Notes in Pharmacology

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PHARMACOLOGY - came from from the Greek word "Pharmakon" which means "Drug" and "Logos" "Logos" which means "Discourse" / "Logia" (Latin) - "Study". - it is a science that deals with the chemical and physical physical properties of drugs, their their sources, effects, biotransformation and excretion. - it is the study of the effects of chemical substances upon living tissues. tissues. HISTORY OF PHARMACOLOGY Pharmacologic thought had its beginning when early humans began to wonder why the chewing of certain plant roots or leaves altered their awareness or functions. As experience in root and leaf chewing progressed into therapeutic berry picking and smoke smelling, the experiences were spread and shared. As time progressed, some some individuals became more astute in observing and remembering remembering that plant products produced predictable effects. effects. Thus, the first pharmacologist pharmacologist was born. Clearly this humble beginning beginning has evolved through the years into a huge industrial and academic community that is concerned with the study and development of drugs. Drugs that evolved are then prescribed and dispensed through the practice of medicine, dentistry, and pharmacy. (for continuation - refer to Holroyd) The history of pharmacology can be divided into 2 periods: the early period dates back to antiquity and is characterized characterized by empirical observations in the use of crude drugs. It is interesting that even primitive people could discover relationships between drugs and disease. The use of drugs has been so prevalent throughout history that Sir William Osler stated (1894) with some justification that man has an inborn craving for medicine. In contrast to this ancient period, modern pharmacology is based on experimental investigations concerning the site site and mode of action of drugs. The application of the scientific method to studies on drugs was initiated in France by Francois Magendie and was expanded by Claude Bernard (1813-1878). The name of Oswald Oswald Schiemie Debug (1838 (1838 1921) is commonly associated with the development o f Experimental Pharmacology - in Germany and John Jacob Abel (1857-1938) (1857 -1938) played a similar role in the U.S. The growth of pharmacology was greatly g reatly stimulated by the rise of synthetic organic chemistry which provided new tools tools and new therapeutic agents. More recently, pharmacology has benefited from developments of other basic sciences and in turn has contributed to their growth. Some of the greatest changes in medicine that have occurred during the last few decades are directly attributable to the discovery of new drugs.

Claude Bernard - expanded application application in scientific scientific method. Alexander Fleming - discovered penicillin. Hippocrates - father of medicine John Jacob Abel - development of experiments in pharmacology pharmacology Oswald Schieme Debug - development of experimental pharmacology Joseph Lister - antiseptic technique BRANCHES OF PHARMACOLOGY 1. Pharmacokinetics - concerned with the absorption, distribution, biotransformation, and excretion of drugs. - movement of drugs in the body. "How the body handles the the drug?"

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2. Pharmacodynamics - deals with the effects of drugs in the body; deals with the mechanism of action/effect of a drug in living organisms and their corresponding responses and the physiologic and biochemical effects of the drug. "How the drug produces its its effect?" "What the drug does to the body?" 3. Pharmacognosy - identification and procurement procurement of crude and naturally occurring drugs. drugs. Former name: "Materia Medica" 4. Pharmacy - procurement, preparation and dispensing of drugs. 5. Pharmacogenetics - effects of drug on people with with congenital abnormalities of metabolism. metabolism. e.q. Eskimos - hydrolyze hydrolyze isoniazid = faster than than other races. barbiturates - geriatrics = stimulation instead instead of depression depression 6. Posology - study of dosage of drugs. 7. Toxicology - study of the adverse effects of drugs. 8. Biochemorphology - alteration of the chemical structure of drugs to p roduce a different effect. 9. Developmental pharmacology - effects of drugs in fetal development. e.q. Thalidomide babies - teratogenic. 10. Pharmacotherapeutics - "clinical pharmacology' - the uses/application of drugs in the treatment of disease; disease; the art and science science of using drugs drugs in the diagnosis, treatment, and prevention of disease. 11. Descriptive pharmacology - qualitative effects of drugs in man. 12. Clinical Pharmacology –  the study of the effects of drugs in man. 13. Molecular pharmacology –  the study of drug effects at the molecular level.

IMPORTANCE OF PHARMACOLOGY TO DENTISTRY 1. To be able to cure diseases 2. To be able to prescribe drugs to the patient appropriate for his condition. 3. To be able to communicate with the medical staff and practitioners.

***The dentist should be able to obtain the maximal advantage while producing the minimal disadvantages. ***The prescriber should be aware of how drugs may modify the physiology of the patient. affects / modifies the biologic biologic system. DRUGS - any chemical substance that affects - chemical necessary for the maintenance maintenance of life processes by their ability to act selectively in biologic systems to accomplish a desired effect. - a single entity that may be one of the constituent of medicine. Medicine - may contain one or more active constituents constituents (drugs) together with with additives to facilitate administration. *** "All medicines are drugs, but not all drugs are medicine."

SOURCES OF DRUGS 1. Natural a. Animals - glandular products are the chief medicinal currently obtained obtained form animal sources. e.q. thyroid hormone, insulin from pancreas of cattle and pigs, epinephrine and ACTH.

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b. Plants - crude drugs maybe maybe obtained from any part of various plants used medicinally. medicinally. E.q Leaves - Pito-pito, Alagaw, Banaba, etc.; digitalis digitalis from foxglove plant. c. Minerals - iron, commonly used in the form of ferrous sulphate 2. Synthetic/Chemical Substances Substances - done in the laboratory by chemists. chemists. a. Pure drugs and other simple substances b. Products of complex synthesis (antibiotics, sulfonamides and adrenocorticosteroids). STAGES IN THE DEVELOPMENT OF A DRUG Evolution of a New Drug Drug development Strategies Experimental Pharmacology Toxicological Assessment Clinical Evaluation Marketing and Promotion STRATEGIES * Serendipity (luck and intuition) * Molecular Roulette (random clinical synthesis) * Program Basic Research with Synthesis of Specific Chemicals. * Clinical Observation of Drug Action in the Practice.

PRINCIPAL INDIVIDUAL(S) CONCERNED

STAGES IN THE DEVELOPMENT OF A DRUG

Various Chemist Pharmacologists Biochemists Toxicologists

Ideas Natural or synthetic chemical compounds Pharmacological Tests Performs "biologic assays" Acute toxicity Chronic toxicity tests Mutagenicity Teratogenesis Carcinogenecity Pharmaceutical formulation / Clinical trials Phase 1: A pilot investigation made in a small number  of normal volunteers Phase 2: An open clinical trial carried out in a small number of patients Phase 3: Large scale clinical trial Phase 4: Monitored release and post- marketing surveillance of new drug Accepted drug

Pharmacists Clinical Pharmacologists   Normal Volunteers Dentist/Doctor/Patients Clinical Pharmacologists   Nurse Patients Statistician Practicing Dentists/Doctors and their patients

CLINICAL EVALUATION Phase I * A pilot study that uses small numbers of human volunteers * Initially, low doses of drug that are gradually increased are used and the toxic or exaggerated effects are monitored Phase II * The drug is tested in in limited numbers of hospitalized hospitalized patients with the disease disease the drug is

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intended to treat * The test drug is compared to established drugs and placebo Phase III * Testing is intended to large group of outpatients to permit evaluation of the drug under  conditions that may exist if the drug is marketed. * If the drug is safe and effective for its intended use, the FDA may app rove the drug for  marketing. Phase IV * A new drug is usually marketed only after a few hundreds, or at most few thousand patients have been exposed to it for a relatively short period of time. * Post-marketing surveillance is necessary to assess efficacy and toxicity of a new drug on a larger scale. * 3 MAJOR PHASES IN A PRE-CLINICAL TESTS 1. Acute Toxicity Test 2. Sub-acute (prolonged) Toxicity Test 3. Chronic Toxicity Test PRINCIPLES OF DRUG ACTION 1. Cure disease 2. Alleviate symptoms 3. Replace deficiencies FUNDAMENTAL ACTION OF DRUGS 1. STIMULATION - drugs that increases increases the overall activity of specialized organs, tissue, tissue, or cell. e.q. caffeine (coffee (coffee - CNS stimulant; can cause tachycardia (inc. (inc. heart activity). 2. DEPRESSION - drugs that decreases the overall functional activity of cells, tissues, or organs. e.q. alcohol, barbiturates. 3. IRRITATION - either inc. or dec. but it is said that stimulation stimulation is pushed too far to the point of injuring the cell.; manifested as nausea, vomiting, itchiness, redness. 4. REPLACEMENT / SUPPLEMENT - drugs that can be used as substitutes substitutes for what is lacking in the body. e.q. vitamins. 5. ANTIMICROBIAL / ANTIBACTERIAL ANTIBACTERIAL - when the action of the drug is directed directed towards the invading microorganism in the body. e.q. antibiotics. 6. ANESTHETIC - a solution that tends to produce a temporary block or nerve conduction. 7. PROPHYLACTIC - to prevent any untoward occurrences/illnesses in the body. e.q. DPT, polio vaccines, etc.

*All drugs exert some effect on a biologic system * In most instances, a given effect can be related to drug dosage in a quantitative fashion. *Two important expressions of drug action can be demonstrated: POTENCY and EFFICACY. required to produce the desired effect or action Potency - amount/strength of a drug required - is a measure of drug activity in terms of the amount required to produce an effect of  given intensity. Efficacy - ability of the drug to elicit its maximum inherent physiologic effect. - the "Maximum Intensity of Effect" of a certain drug.

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* For example, one drug (drug A) produces complete eradication of premature p remature ventricular  contractions (PVCs) at a dose of 10 mg. A second drug (drug B) produces complete eradication of PVCs at a dose of 20 mg. Therefore, both drugs have the same efficacy efficacy (complete eradication of PVCs), but drug A is more potent than drug B. It takes less of drug A to produce the same effect. A third drug (drug C) can reduce the PVCs by only 60%, and it takes a dose of 50 mg. to to achieve the effect. Therefore, drug C has less efficacy and less potency in the reduction of PVCs compared with both drug A and drug B. CHARACTERISTICS OF DRUG ACTION 1. According to Biochemical Action E.q. Hypoglycemic agents; Hemostatic agents 2. According to Physiologic Effects E.q. Muscle relaxants; Anti-hypertensive agents 3. According to the Organ System on which they exert their Therapeutic Action E.q. CNS stimulants USES OF DRUGS 1. Diagnosis - e.q. barium enema 2. Prevention - e.q. DPT vaccine 3. Contraception - e.q. pills, deprovera, etc. 4. Treatment - e.q. analgesics, antibiotics MECHANISM OF DRUG ACTION 1. Action on a Receptor  2. Action on an Enzyme 3. Action on Membrane Ionic Channels 4. Cytotoxic action

I. ACTION ON ON A RECEPTOR  Receptor - a specific macromolecule usually a protein to which a specific specific group of drug or naturally occurring substances such as neurotransmitter or hormone can bind. RECEPTORS INVOLVED IN THE ACTION OF COMMONLY USED DRUGS RECEPTOR

ADRENOCEPTOR  1 2 B1 B2

CHOLINERGIC Muscarinic

MAIN ACTION OF NATURAL AGONISTS

Vasoconstriction Hypotension ; Sedation Heart Rate Bronchodilation Vasodilation Uterine Relaxation Heart Rate Secretion

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Nicotinic HISTAMINE H1

Gut Motility Bronchoconstriction Contraction of Striated Muscle

H2

Bronchoconstriction Capillary Dilation Increased Gastric Acid

DOPAMINE OPIOD

CNS Neurotransmitter  CNS Neurotransmitter 

II. ACTION ON ENZYME Enzyme - protein macromolecule macromolecule with which substances interact to to produce “activation” or “inhibition”. *Drugs in clinical use which exert their effect thru enzyme action generally do so by “inhibition”. E.q. Aspirin inhibits platelet platelet cyclo-oxygenase; Allopurinol inhibits xanthene oxidase. III. ACTION ON MEMBRANE IONIC IONIC CHANNELS The conduction of impulse in nerve tissues and electrochemical coupling in muscles depends on the movement of ions particularly sodium, calcium, and potasium through membrane channels. *Several group of drugs that interfere interfere with these processess: processess: Antiarrythmic drugs, General and local anesthesia, Anticonvulsant. IV. CYTOTOXIC ACTIONS This mechanism have been defined in terms of effects on specific receptors or enzymes. But in other cases, chemical action (Alkylation) damages DNA or other macromolecules and results in cell death or failure of cell division. E.q. Drugs used in cancer or in treatment of infection infection may kill malignant cells or  Microorganisms.

PUBLICATIONS IN PHARMACOLOGY U.S.P. United States Pharmacopoeia - Representatives from school of medicine and pharmacy - American medical Association - American Pharmaceutical Association - State Medical Societies - American Chemical Society - Other scientific organization and federal agencies

Purpose of U.S.P. : It sets the official chemical and physical standards that relate essentially to strength and purity of drug.

7 N.F. National Formulary - issued every 5 years - establishes official standards for drugs not described in the U.S.P. - described extent of drugs' use and therapeutic value British Pharmacopoeia - English equivalent equivalent of U.S.P. (Great Britain and Canada) Pharmacopoeia Internationalis - issued by W.H.O. A.D.T. Accepted Dental Therapeutics A.D.R. Accepted Dental Remedies - biennial publication of the Council on Dental Therapeutics (CDT) of the American Dental Association - drugs of recognized value that are labeled and advertised in accordance with CDT are included. - Primarily Primarily a handbook of dental pharmacotherapeutics and intended to assist the dental practitioner in the selection of drugs. P.D.R. Physician's Desk Reference - a handbook published annually by some 200 manufacturers Special Value: 1. Published annually and therefore includes relatively up to date information 2. It is cross-indexed to include the use of proprietary names Disadvantages: 1. Products or drugs are arranged by manufacturers rather than by pharmacologic class 2. Information may be "biased".

* REPUBLIC ACT 6675 - known as the GENERIC ACT OF 1988 - an act to Promote, Require and Ensure the production of an adequate supply, distribution, use and acceptance of drugs and medicines identified by their generic n ames. AIM: 1. To promote, encourage and require the use of generic terminology in the importation, manufacturing, distribution, distribution, marketing, advertising and promotion, prescription and dispensing of drugs. 2. To ensure the the adequate supply of drug with generic names through a rational system system of  procurement and distribution. 3. To encourage the extensive use of drug with generic names through a national system of  procurement and distribution.  Importance of R.A. 6675 1. For health professionals to become more aware and cognizant of their therapeutic effectiveness. 2. To provide drugs to indigent patients at the lowest possible cost. 3. To have healthy competition among drug manufacturers

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Who Shall Use Generic Terms? All government health agencies All medical, Dental and Veterinary practitioners All drug establishments All drug outlets Penalty for NOT complying to R.A. 6675  First Offense Reprimand which will be recorded in the Professional Regulation Commission Book. Second Offense Fine : Not less than P2,000.00 but not greater than P5,000.00. Third Offense Fine : Not less than P5,000.00 but not greater than P10,000.00.  Fourth and Succeeding  Fine : Not less than P10,000.00 and suspension suspension of license to practice for for one year. year.

DRUG NOMENCLATURE 1. CHEMICAL NAME "FIRST NAME" given to compound of known composition - conveys the chemical structure of the compound. E.q. N-Acetyl p-aminophenol

CODE DESIGNATION DESIGNATION - convenient means of referring to to the compound before it has been assigned either a generic or trade name. 2 Types of Code Designation 1. A letter and number combination e.q. SH 567 letter/s - research laboratory involved involved number/s - arbitrarily assigned 2. Letter combination e.q. AZT - Azothymidine TPA - Tissue Plasminogen Activator  ASA - Acetyl Salicylic Acid 2. TRADE NAME (Commercial Name; Proprietary Name; Brand Name) - name of the company who manufactured the drug - gives no or little information about the drug itself  BRAND NAME - name of the company marketing the product - distinguishes its product from others. - E.q. Biogesic, Ponstan, Ponstan, Flanax, Amoxil,

Two Important Disadvantages of Trade Name: 1. Makes the problem of drug identification more complex 2. Deprive the patient to avail of a less expensive generic preparations.

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Advantages of Trade Names: 1. They are convenient and saves time when writing prescriptions for for multiple-entity multiple-entity drugs 2. Trade names are usually shorter shorter and easier to remember than than generic names. 3. The use of trade names demands the product of a specific manufacturer manufacturer in whose manufacturing practices the practitioner may have special confidence. "Non-Proprietary name. 3. GENERIC NAME - "Official" name of the drug; "Non-Proprietary Advantages of using Generic Names 1. Healthy Healthy compet competiti ition on among among drug manufac manufactur turers ers 2. Provid Provides es a wide wide sele selecti ction on of of drugs drugs 3. It is is unive univers rsal ally ly acc accept epted ed.. Disadvantages of using Generic Names 1. Not all all preparat preparations ions are prepare prepared d as they should should be. 2. It is hard hard to reme rememb mber er.. 3. It is is incon inconveni venient ent when writte written. n. E.g. : Chemical : Generic Trade Name :

2-diethylamino 2,6 acetoxylidide Lidocaine Xylocaine Dolicaine Octocaine L-caine

: : : : : :

N-acetyl p-aminophenol Acetaminophen Tylenol Tempra Valadol Datril

*** How to use the PIMS / MIMS PIMS - Philippine Index for Medical Specialties therapeutic index. MIMS - Monthly Index for Medical Specialties. It is a global term for a therapeutic

Brand Name /Manufacturer / Distributor  Contents (C) Indication/s (I) Dosage (D) Contraindications ( C/I ) Special Precautions ( SP ) Adverse Reactions ( AR ) Drug Interactions ( DI ) Presentation / Price ( P/P )

Example: (Based from MIMS MIMS Dental Phils. Phils. 2002 page 68) ATMOSE Morishita-Seggs Rx (Metro Drug) C. Mefenamic Acid I. Relief of mild to moderate pain including

(Atmose is the proprietary name of the drug; Morishita-Seggs is the name of the company who manufactured the drug

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headache, dental pain, post-op and postpartum Metro Drug is the name of the   pain, dysmenorrhea, osteoarthritis and RA. company marketing the product D. Adult and children > 14 yr. Initially 500 mg. Rx means this drug needs prescription then 250 mg 6 hrly. P/P. Atmose is available in capsule CI. Peptic ulceration or inflammatory bowel disease. form at a dosage of 500 mg.; SP. Hepatic or renal impairment; epilepsy. X100 means in one box there are 100 capsules that costs AR. GI disturbances; peptic ulceration, GI bleeding; drowsiness; dizziness; nervousness; visual Php357.63 disturbances; skin rash; urticaria; blood dyscrasias. DI. Enhances the effects of the coumarin anticoagulants. P/P. Cap 500 mg X 100’s (P357.63)

PHARMACOLOGICAL CLASSIFICATION INDEX Pharmacological Classes and Sub-classes (based on MIMS Dental Phils 2002) I.

ALIMENTARY SYSTEM 1. Antac Antacid idss and Antiu Antiulc lcer eran ants ts 2. GIT regulat regulators, ors, Antifl Antiflatule atulents nts and Anti-Infl Anti-Inflammat ammatories ories 3. Anti Antisp spas asmo modi dics cs 4. Anti Antidi diar arrh rhea eals ls 5. Laxa Laxati tives ves,, Pur Purga gati tive vess 6. Digestives 7. Cholagogues, Cholagogues, Cholelitho Cholelitholyti lytics cs and and Hepatic Hepatic Protector Protectorss

II. CARDIOVASCULAR AND HEMATOPOIETIC SYSTEM 1. Card Cardiiac Drug Drugss 2. Anti Anti-a -ang ngin inal al Drug Drugss 3. ACE ACE Inhi Inhibi bittors ors 4. Beta Beta Bloc Blocke kers rs 5. Calc Calciu ium m Anta Antagon gonis ists ts 6. Diuretics 7. Ant Antidiur diuret etic icss 8. Peripheral Vasodilators and Cerebral Activators 9. Vaso Vasoco cons nstr tric icto tors rs 10. Migraine Migraine Drugs 11. Haemostati Haemostatics cs 12. Anticoagulants, Antithrombotics Antithrombotics and Fibrinolytics Fibrinolytics 13. Haemorrhoidal, Phlebitis and Varicose Preparations 14. Haemorrheol Haemorrheological ogicalss 15. Haematopoetic Haematopoetic Agents Agents 16. Other Cardiovasc Cardiovascular ular Drugs Drugs III. RESPIRATORY SYSTEM 1. Resp Respir irat ator ory y Stimu Stimula lant ntss 2. Antias Antiasthm thmati aticc Prepar Preparati ations ons

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3. Cough Cough and and Cold Cold Reme Remedi dies es 4. Deconge Decongesta stants nts and other other Nasal Nasal Prepar Preparati ations ons 5. Other Other drugs drugs acti acting ng on Respi Respirat ratory ory Syst System em IV. NEUROMUSCULAR SYSTEM 1. Anti-i Anti-infl nflamm ammato atory ry Enzyme Enzymess 2. Analges Analgesics ics and Antipy Antipyret retics ics 3. Antirheumat Antirheumatic, ic, Anti-infla Anti-inflammat mmatory ory Analgesics Analgesics 4. Gout Gout Pre Prepa para rati tion onss 5. Minor Minor Tran Tranqu quil ilis iser erss 6. Majo Majorr Tranq Tranqui uili lise sers rs 7. Hypn Hypnot otic icss and and Seda Sedati tives ves 8. Anti Antico conv nvul ulsa sant ntss 9. Anti Antide depr pres essa sant ntss 10. CNS Stimulant Stimulantss 11. Nootropics Nootropics and Neurotonic Neurotonicss 12. Antiemetics and Antivertigo Drugs 13. Neurodegenera Neurodegenerative tive Disease Disease Drugs 14. Antiparkins Antiparkinsonism onism Preparati Preparations ons 15. Neuromuscul Neuromuscular ar Disorder Drugs Drugs 16. Muscle Relaxants V. HORMONES 1. Androgens and Related Synthetic Drugs 2. Oestrogens Oestrogens and Progestero Progesterones nes and Related Related Synthetic Synthetic Drugs 3. Comb Combin ined ed Sex Sex Hor Hormo mone ness 4. Cort Cortic icos oste tero roid id Horm Hormone oness 5. Trophic Hormones and Related Synthetic drugs 6. Anab Anabol olic ic Agen Agents ts 7. Othe Otherr Horm Hormon onee Relat Related ed Drug Drugss VI. CONTRACEPTIVE AGENTS 1. Depot Depot Cont Contra race cept ptiv ives es 2. Oral Oral Cont Contra race cept ptiv ives es 3. Othe Otherr Contr Contrac acep epti tive vess VII. ANTIBIOTICS 1. Amin Aminog ogly lyco cosi side dess 2. Ceph Cephal alos osph phor orin inss 3. Chlo Chlora ramp mphe heni nico cols ls 4. Macrolides 5. Peni Penici cilllins lins 6. Quin uinolones 7. Tet Tetracy racycl clin ines es 8. Ant Antifung fungal alss 9. Antiba Antibacte cteria riall Combin Combinati ations ons 10. Other Antibiotic Antibioticss

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VIII. OTHER CHEMOTHERAPEUTICS 1. Antit Antitub uber ercul culous ous Agent Agentss 2. Sul Sulphon phonam amiides des 3. Ant Antiamoe amoebi bics cs 4. Ant Anthelm helmiinti ntics 5. Ant Antilepr leprot otic icss 6. Anti ntivirals 7. Anti Antine neop opla last stic icss 8. Ant Antimal malaria arialls 9. Leishm Leishmani aniaci acides des,, Trypan Trypanoci ocides des 10. Filarici Filaricides des

IX. GENITO-URINARY SYSTEM 1. Prepar Preparati ations ons for for Vagin Vaginal al Condi Conditi tions ons 2. Urin Urinar ary y Anti Antise sept ptic icss 3. Drug Drug actin acting g on on Uter Uterus us 4. Other Drugs Acting on Genito-Urinary System X. METABOLISM 1. Insulins 2. Oral Oral Ant Antid idia iabet betic ic Agen Agents ts 3. Thyr Thyroi oid d Pre Prepar parat atio ions ns 4. Ant Antithy thyroids oids 5. Antihy Antihyper perlip lipidae idaemic mic Agents Agents 6. Other Other Agen Agents ts Affe Affecti cting ng Metab Metaboli olism sm XI. VITAMINS AND MINERALS 1. Vit Vitami amins A, D, E 2. Vita Vitami min n B’s B’s / wit with hC 3. Vitamin C 4. Calc Calciu ium m / with with Vita Vitami mins ns 5. Multi Multivit vitami amins ns / with with Minera Minerals ls 6. Vitamins with Hormones / Geriatric Preparations 7. Pediat Pediatri ricc Vitam Vitamins ins and Minera Minerals ls 8. Elec Electr troly olyte tess and Mine Minera rals ls 9. Antian Antianemi emics cs / Pre Pre and Post Post Nata Natall Vitami Vitamins ns XII. NUTRITION 1. Infant Infant / Follow Follow-On -On Formul Formulae ae 2. Entera Enterall / Nutrit Nutrition ional al Prod Product uctss 3. Pare Parent nter eral al Nutr Nutrit itio ion n 4. Tonics 5. Appet Appetit itee Stim Stimul ulant antss 6. Anti Antiob obes esit ity y Agent Agentss

13 EYE, EAR, MOUTH / THROAT THROAT

*EYE 1. Eye Anti Anti-in -infec fecti tives ves and and Antise Antisepti ptics cs 2. Eye Eye cort cortic icos oste tero roid idss 3. Eye Antiseptics with Corticosteroids 4. Mydr Mydria iati ticc Drug Drugss 5. Miot Miotiic Drug Drugss 6. Glau Glauco coma ma Prep Prepar arat atio ions ns 7. Othe Otherr Eye Eye Prepa Prepara rati tion onss *EAR  1. Ear Anti Anti-in -infec fectiv tives es and Anti Antisep septi tics cs 2. Ear Ear Corti Cortico cost ster eroi oids ds 3. Ear Anti Antisep septic ticss with with cortico corticoste steroi roids ds 4. Othe Otherr Ear Ear Prep Prepar arat atio ions ns *Mouth / Throat 1. Mout Mouth h / Throa Throatt Prepa Prepara rati tion onss XIV. DERMATOLOGICALS 1. Topi Topica call AntiAnti-in infe fect ctiv ives es 2. Topical Anti-infectives with Corticosteroids 3. Topi Topica call Corti Cortico cost ster eroi oids ds 4. Acne Treatm Treatment ent Prepar Preparati ations ons 5. Antise Antisepti ptics cs and Disinf Disinfect ectant antss 6. Medica Medicated ted Surgic Surgical al Dressi Dressings ngs 7. Topica Topicall Fungici Fungicides des and and Antipa Antiparas rasite itess 8. Psoriasis, Psoriasis, Seborrhea Seborrhea and Ichthy Ichthyosis osis Preparatio Preparations ns 9. Topi Topica call Antiv Antivir iral alss 10. Keratolyt Keratolytics ics 11. Skin Protective Protectivess 12. Topical Antihistamines Antihistamines / Antipruritics Antipruritics 13. Topical Analgesics Analgesics and Anti-inflammatories 14. Other Dermatol Dermatological ogicalss XV. ANAESTHETICS 1. Loca Locall Anes Anesth thet etic icss 2. Gener General al Anest Anesthe heti tics cs XVI. DIAGNOSTIC AGENTS

1. Urin Urinal alys ysis is Age Agent ntss XVII. ALLERGY AND IMMUNE SYSTEM 1. Antihi Antihista stamin mines es and and Antia Antiall llerg ergies ies 2. Vaccines, Antisera and Immunologicals 3. Immu Immuno nosu suppr ppres essa sant ntss

14 ANTIDOTES AND DETOXIFYING AGENTS INTRAVENOUS AND AND OTHER STERILE STERILE SOLUTIONS XX. MISCELLANEOUS

Different Factors Affecting Response: Routes of Drug Administration Passage of Drug Across Body Membranes Molecular Mechanism of Action

Absorption Distribution Metabolism Excretion

FATE of a DRUG

ROUTES OF DRUG ADMINISTRATION ENTERAL Oral Rectal PARENTERAL   Hypodermic Routes Intravenous Intramuscular  Subcutaneous Intradermal Intrathecal Intraperitoneal

  Additional Routes Topical Inhalation Sublingual Transdermal LOCAL ROUTE Topical Intradermal Intrathecal Intranasal Intraconjuctival Intra-oral Intra-articular  Intra-arterial Other special routes

15 SYSTEMIC ROUTES Enteral Parenteral

*** Locally administered drugs may be absorbed at a rate and to an extent sufficient to result in the production of systemic effects. ENTERAL ROUTES - drug is placed directly into the GIT from where absorption occurs. A. ORAL ROUTE - simplest and most convenient for self administration.

Contraindication for Oral Route 1. Patients with gastrointestinal intolerance 2. Patients Patients preparing for anesthesia 3. Patients with gastrointestinal surgery 4. Precluded in coma Disadvantages of Oral Route 1. Irritant Irritant drugs drugs cannot cannot always always be given by mouth mouth for it it may cause cause sickness. sickness. 2. It is not feasibl feasiblee to give drugs drugs by this this route to patien patients ts who are vomiti vomiting ng or moribund. moribund. 3. Many drugs drugs are destroy destroyed ed by the action action of the digesti digestive ve ferments ferments before before they can can be absorbed. 4. Intestinal Intestinal absorpt absorption ion may be irregul irregular ar due to other other substances substances in the the git. 5. Intestinal Intestinal absorpt absorption ion may be affect affected ed by changes in in gastric gastric emptying emptying which which may increase or decrease the rate of absorption. metabolism of a drug en route from from the gut lumen to "First Pass Effect" - refers to the metabolism the systemic circulation. - a process that rapidly deactivate some drugs in the liver that was given orally and was initially perfused perfused into the hepatic portal circulation. Some drugs do not go directly d irectly into the systemic circulation following absorption but pass from the intestinal intestinal lumen to the liver, liver, by the portal vein. In the liver, most of  the drug is metabolized to an inactive drug form for excretion, reducing the amount of  active drug. Importance of First Pass Metabolism 1. It is one of the reasons for the apparent differences in drug absorption between individuals. 2. In patients with severe liver disease, first-pass metabolism may be dramatically reduced leading to the absorption of greater amounts of parent drug. Drugs with High First Pass Metabolism Analgesics Aspirin Morphine Paracetamol Pentazocine

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Pethidine Respiratory Drugs Salbutamol Terbutaline Drugs Acting on Central Nervous System Chlormethiazole Chlorpromazine Imipramine Levodopa Nortriptyline Oral Contraceptives Cardiovascular Drugs Glyceryl Trinitrate Isoprenaline Nifedipine Prazosin Propanolol Verapamil Lignocaine Metropolol RECTAL ROUTE - drugs are given via the rectum. E.q. solid form form – suppositories; liquid form – enemata. - used when oral administration administration is impossible. - avoids the the acidity and enzymes of the gastric juice and first pass metabolism. - Both local and systemic systemic effects are obtained but absorption of many drugs are often irregular and incomplete. Indications: Pediatrics / Geriatrics PARENTERAL ROUTES - generally chosen when speed or reliability reliability are specially desired. A. Injection – essential if the drug is to be absorbed in in active form. form. - absorption is usually more predictable predictable and more rapid rapid - requires special skill; drugs cannot be withdrawn easily. easily.  Disadvantages 1. Difficult Difficult for for the patient patientss to perform perform the the injectio injection n by themselves themselves.. 2. Strict Strict asepsis asepsis must be maintai maintained ned to to avoid avoid infectio infection n 3. Usuall Usually y more more cost costly ly and less less safe. safe. 4. Can Can cau cause se pai pain. TYPES OF INJECTION Intravenous (IV) - route of choice for emergency cases - Most rapid route / method to elicit drug response. Advantages 1. Rapid ac action 2. Can be used used for drugs which are are irrita irritant nt by IM injecti injection. on. 3. Useful for ill, ill, hospitali hospitalized zed patients patients when a slow slow IV infusio infusion n provides provides a steady steady flow without disturbing the patient

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Disadvantages 1. Tend to produce produce more immediate immediate adverse adverse reactio reactions. ns. 2. Too high concent concentration ration of the drug is is readily readily obtained obtained when injecte injected d rapidly. rapidly. 3. The chance chance of penetratio penetration n into an artery artery instead instead of a vein vein is a possibili possibility. ty. Complications: 1. Drug Shock  2. Acute, serious, allergic responses 3. Phlebitis 4. Necrosis around the injection site. Intradermal (cutaneous) - E.q. skin testing.

Action: - local effect - small amount is injected into the epidermis of the skin so that volume does not interfere with wheal formation or cause a systemic reaction. - used for observation of an inflammatory (allergic) reaction to foreign proteins. - rarely employed except in certain Diagnostic and test procedures (screening for  allergic or local irritant responses). - takes the longest time for drug absorption. Sites: inflammatory reaction can be observed. Preferred areas - Locations are chosen so that inflammatory are lightly pigmented, thinly keratinized, and hairless such as ventral mid-forearm, clavicular area of chest, scapula area of back, and medial aspect of thighs. Equipment: Needle: Syringe:

26 – 27 gauge 1 ml. calibrated in 0.01 ml. increments Usually 0.01 – 0.1 ml. injected.

Technique: Cleanse area using circular motion; observe sterile technique. Hold skin taut. Insert needle, bevel up, at a 15 degree angle; outline of needle under the skin should be visible. Inject medication slowly to form a wheal (blister or bleb). Remove needle slowly. Make a mark or encircle the bleb with a pen. Do not massage area; instruct client not to do so. Assess for allergic allergic reaction in 24 – 72 hours; measure diameter of local reaction. Subcutaneous - for drugs which are not irritant to tissues. E.q. morphine sulphate, sulphate, adrenaline, and insulin. - volume is usually 1 ml. ml. or less; seldom exceeds 2 ml. - cutaneous blood flow is is slower compared compared to IM

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- sustained effect can be obtained by placing a pellet of drug subcutaneously; e.q. Estradiol plants. - drug is injected in the subcutaneous layer into the the alveolar connective tissue just below the the skin. Action: - Systemic effect - Sustained effect; absorbed mainly through capillaries; usually slower in onset than with intramuscular route. - Used for small doses of non-irritating water-soluble drugs. Sites: - Locations for subcutaneous injection are chosen for adequate fat pad size and include the abdomen, upper hips, upper back, lateral upper arms, and lateral hips. Equipment: Needle: Syringe:

25 – 27 gauge ½ - 5/8 in. in length 1 – 3 ml. Usually 0.5 – 1.5 ml. injected. Insulin syringe measured in units for use with insulin only.

Technique: Cleanse area with circular motion using sterile technique Pinch the skin. Insert needle at angle appropriate to body size. 45 to 90 degrees. Release skin. Aspirate, except with heparin. Inject medication slowly. Remove needle quickly. Gently massage area, unless contraindicated with heparin. Apply plaster if needed. Advantages: 1. Spread Spread the the action action out out over a number number of hour hours. s. 2. Avoid Avoid too too inten intense se or too shor shortt respo response nse 3. Avoi Avoid d frequ frequent ent inj injec ecti tions ons..

 Layer of skin and site of injections: Epidermis Cutaneous Dermis Membrane Fascia Subcutaneous

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Muscle Intramuscular (IM) - more dangerous than IV; better for irritant tissues. tissues.

Action: - systemic effect. - Usually more rapid effect of drug than with subcutaneous. - Used for irritating drugs, aqueous suspensions, and solutions in oils. is not required but a prompt prompt effect is desirable.desirable.- 10 –  - indicated when an immediate effect is 30 minutes absorption. Sites: Locations are chosen for adequate muscle size and minimal major nerves and blood vessels in the area. Preferred locations include include ventrogluteal, dorsogluteal, deltoid, and vastus lateralis. Equipment: Needle: Syringe:

18 – 21 gauge 1 – 1.5 in. in length length 1 –3 ml. Usually 0.5 – 1.5 ml. injected

Technique: Same as for subcutaneous injection except that needle is inserted at 90 degree deg ree angle into the muscle.

Figure:

Angles for injections. (A) IM 90 (B) (C) (D) SC 90 , 60 , 45

(E) ID 10=15 .

Intraperitoneal – injected into the peritoneal cavity by absorption of messenteric veins

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Intrapleural - introduce into into the pleural cavity; cavity; for aspiration of fluids.

analgesia into the spinal spinal subarachnoid space. Intrathecal / Intraspinal - for spinal analgesia - administered into the cerebrospinal fluid at any level o f the cerebrospinal axis. in trigeminal trigeminal neuralgia. Intraneural - used in Intrasternal - drugs which normally do not cross the blood brain barrier. barrier. BUCCAL and SUBLINGUAL route - an enteral enteral route route infrequ infrequently ently used but but useful useful in in drugs with first first pass hepati hepaticc metabolis metabolism. m. E.q. glyceryl trinitrate trinitrate for angina attack but ineffective ineffective when swallowed as its first pass metabolism approaches 100 per cent - drug drugss that that are are susc suscep epti tibl blee to degra degrada dati tion on by the GIT GIT and and even even the the live liverr are are safe safely ly administered sublingually. INHALATION - E.q. inhalation anesthetics, aerosol aerosol inhalation for asthma. inhalation is via the mouth; mouth; absorption occurs in the small small bronchioles. E.q. disodium cromoglycate via a “Spinhaler”. - drug is absorbed absorbed through through the pulmonary pulmonary endothelium endothelium at the alveoli alveoli to gain rapid access to the general circulation.

Reasons for rapid absorption 1. Alveolar Alveolar and vascular vascular epitheli epithelial al membranes membranes of the the lungs are are quite permeable permeable.. 2. Bloo Blood d flo flow w is is abun abunda dant nt.. 3. There There is al al large large surfa surface ce for absorp absorptio tion. n. Particle Size 1. Particles Particles greater greater than than I um in diamete diameterr - tend to settl settlee in the bronchi. bronchi. 2. Particles Particles less than 0.5 um - fail to settle; settle; mainly mainly are are exhaled exhaled.. TOPICAL - least effective. - drug drug is applie applied d to the skin skin and othe otherr epithe epitheli lial al surfa surface cess with with glove glove,, tong tongue ue blade, blade, or  cotton-tipped applicator. - util utiliz ized ed for for loca locall dru drug g eff effec ect. t. - Use appro appropri priate ate techni technique que to remove remove medic medicati ation on form conta containe inerr and apply apply to clean, clean, dry skin, when when possible. possible. Do not contaminate contaminate medicatio medication n in container, container, use gloves or an applicator.

Methods of enhancing drug absorption via the Topical route Ionotophresis - uses galvanic current Inunction - mechanical rubbing of drug into the skin. TRANSDERMAL - stored stored in a patch patch placed placed on the skin skin and and absorbed absorbed through through skin, skin, having having systemi systemicc effect effect

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-

Transderma Transdermall drugs drugs provide provide more more consist consistent ent blood levels levels and avoid GI absorpt absorption ion associated with oral products.

PHARMACEUTICAL PHARMACEUTICAL PREPARATIONS AND DOSAGE FORMS Pharmaceutical preparations are the forms in which drugs are prepared by the pharmacist or   pharmaceutical chemist for administration in the treatment of the sick.   SOLID PREPARATIONS  compressed gas under pressure for topical application. Upon release, the the Aerosols - packed with compressed aerosol takes the form of a fine mist, foam, semisolid fluid or solid. Ampules - are hermetically sealed glass containers for medicinal substances substances containing a sterile solution for parenteral use. gelatin receptacles of various sizes for oral administration. Generally dissolve dissolve Capsules - small gelatin in the stomach except the enteric capsules capsules which dissolves in the the intestines. They maybe of firm or flexible consistency. both ends with rubber stoppers, one acting as a plunger, Carpules - are glass tubes enclosed on both the other as a diaphragm. diaphragm. Contain a drug drug in solution and designed for parenteral medication Confections - medicinal substances formed into a mass with sugar, honey, and water as confection of rose. Effervescent Salts - powdered drug which give off CO2 gas and go into solution when added to to water. (thin sheets of dried flour paste) – sometimes used to Konseals - (rice flour capsules) or wafers (thin enclose drug powders. Papers - paper impregnated with medicinal substances. E.q. mustard paper  swallowing covered with various substances substances Pills - small spherical masses of drugs intended for swallowing as gelatin, salol, sugar, chocolate, etc. and generally generally colored; powdered drugs drugs mixed with adhesive substances like glucose or honey and molded in spherical or o r ovoid forms. orifices Suppositories - solid bodies of various weights and shapes adapted for introduction into orifices (vagina, rectum, urethra, urethra, etc.) of the human body and usually melting, softening, or dissolving at body temperature. For urethral use, they they are called bougies. Rectal Suppositories Suppositories - conical or bullet-shaped, usually usually weigh about 2 grams. Used to produce local and systemic effects and to produce catharsis. Vaginal Suppositories - conical or spherical in shape and weigh from 4 – 10 grams. Used to confer antisepsis, to combat various infections, and as spermatocides. Urethral Suppositories Suppositories - pencil-shaped and weigh for 2 – 4 grams. grams. Used mainly for local treatment of the female urethra Tablets - solid dosage forms containing containing granulated or powdered drugs that are compressed compressed or  molded into round or discoid shapes.contains medicinal substances with or without suitable diluents. They vary in shape, size and weight. It may be classed according to the method of manufacture, as molded tablets or compressed tablets. Troches - lozenges intended to be dissolved in the the mouth for local effect on the mucous membrane of the mouth and throat.

22   SEMI-SOLID PREPARATIONS  Cerates - unctuous preparations having for for their bases the simple simple cerate. Similar Similar to ointments ointments in consistency but do not melt melt at body temperature. E.q. Cantharides cerate. emulsions of either the oil-water or the water in oil type for topical Creams - semi-solid emulsions application. Extracts - concentrated preparation of vegetable or animal drugs. Made in 3 forms: 1) Semi Semi liquids or liquids of syrupy consistency 2) Plastic masses (pilular or solid e xtracts) and 3) Dry powders (powdered extracts. Ointments - for external external application. Medicinal substances substances are combined with a base of  sufficient softness which tend to fall into two groups: hydrophilic such as the lanolin and the lipophilic, lipophilic, such as the petrolatum. E.q. ZOE ointment ointment Pastes - comprise two classes of ointment-like preparations intended intended for external application: 1)Hydrogels – such as hydrated hydrated pectin; and 2) Fatty pastes – such as ZOE paste, paste, which consist of thick, stiff ointments which do not ordinarily flow at body temperature and therefore serve as protective coatings over the areas they are applied. Plasters - adhesive, fatty or resinous resinous compounds spread on textile fibers, fibers, leather, muslin, etc., Either soft or dry and intended for local application. E.q. Belladone plaster, etc.. Poultices (Cataplasma) - semi-liquid mixtures of such substances as flaxseed, elm bark, or  bread, etc., with hot water or milk, milk, spread upon cloth and used as a means for applying heat and moisture or stimulation to the the body surfaces. E.q. Cataplasma Kaolini. active remedy triturated with with sugar or milk, usually usually of  Triturations - powders consisting of an active 10% strength. E.q. Triturations of Elaterin.   LIQUID PREPARATIONS  Aromatic waters - saturated (0.2%) aqueous solutions of volatile volatile substances, usually volatile oils. Generally used as vehicle for water-soluble drugs. E.q. peppermint water. Collodions - liquid preparations having for their their base a solution of guncotton (pyroxylin) in a mixture of ether ether and alcohol. E.q. Flexible collodion. collodion. Collyria - Medicinal eyewashes. Decoctions - solutions of vegetable substances prepared prepared by boiling with water in in a closed container for 15 minutes and strained – as decoction of coffee and sarsaparilla. liquids intended for oral use. Contains flavoring flavoring Elixirs - clear, sweetened, hydroalcoholic liquids substances. Because of alcoholic content, they are miscible miscible with tinctures. tinctures. Two types: 1. Aromatic Aromatic elixir elixir - used mainly mainly for for diluting diluting other liquid liquid preparat preparations ions 2. Medicated Medicated elixirs elixirs - include include Phenobar Phenobarbital bital elixir, elixir, Diphenhydram Diphenhydramine ine Hydrochlori Hydrochloride de Elixir, and Terpin Hydrate and Codeine elixir. Emulsions - aqueous preparations in which oils, oleoresins, balsams, resins, or other substances which are insoluble in water are suspended by means of gum or other viscid excipients. E.q. Cod liver oil emulsion, milk and eggyolk. Fluid extracts - liquid extractions extractions of drugs prepared prepared by percolation. Concentrated tinctures in which 1 g. of the drug corresponds to 1 ml. of the finished product. product. E.q. Ergot fluid extract. Gargles - mixtures or hydroalcoholic hydroalcoholic solutions for application to to the pharynx and mouth. Gels - suspension in a water medium, medium, of insoluble drugs in hydrated hydrated form wherein particle particle size approaches or attains colloidal dimensions. Glycerites - mixtures or solutions of medicinal substances with or in glycerin. glycerin. E.q. Tannic acid

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glycerite. Honeys - solutions of drug in clarified honey. E.q. Honey of rose. Injections - sterile preparations for parenteral use. Comprise of 1) Solutions for injection 2) Dry solids, which upon the addition of suitable solvents yield solutions conforming in all respects to the requirements for injections injections 3) Solids suspended in a suitable fluid medium which are not to to be injected IV or into into the spinal canal 4) dry solids, which upon the addition of suitable vehicles, yield preparations conforming to the requirements for sterile sterile suspensions and 5) emulsions of fluids fluids in fluid media, suitable for parenteral administration, but are not to be injected in the spinal canal. applied with friction friction to the skin. Liniments - liquid ointments applied solutions of medicinal agents intended for external application with Lotions - mixtures or solutions soothing and protective effect. Milks - suspension of poorly soluble soluble drugs in water medium and distinguished from gels mainly mainly in that the suspended particles particles are larger. They tend to separate on standing standing and must be shaken well before use. E.q. Milk of magnesia. Mixtures - suspension of drugs in an aqueous vehicle. E.q. Brown mixture. metallic salts or alkaloids in oleic acid. E.q. Oleate of Mercury. Oleates - solutions of metallic Solutions - liquid preparations that contain one or several soluble chemical substances substances (non volatile) in water. substances dissolved in alcoholic solution. Many are flavoring Spirits or Essences - volatile substances agents. E.q. Peppermint spirit –also used as a carminative. Aromatic Ammonia Spirit – a medicated spirit used as a reflex stimulant. Suspensions - finely divided drugs either intended for suspension in some suitable liquid liquid vehicle prior to use or already in suspension in a liquid vehicle. Syrups - highly concentrated solutions of sugar such as sucrose in water, carrying flavors or  medicinal substances – as syrup syrup of Orange, Syrup of Wild cherry. Syrups serves as vehicle or preservatives. preservatives. Some contain active therapeutic agents. agents. 2 Classes of Syrups: 1. Flavored syrups - employed to mask the taste taste of unpleasant tasting drugs and to add stability to preparations. preparations. E.q Acacia syrup, Cocoa syrup. 2. Medicated syrups syrups - E.q Ipecac syrup syrup (emetic, expectorant); Chloral Hydrate syrup (hypnotic), contain some added medicinal substances. Tinctures - hydroalcoholic solutions of medicinal substances usually obtained by extractin of  vegetable drugs; generally alcoholic extracts extracts of vegetable or animal drugs obtained obtained by percolation. E.q. Belladona tincture; tincture; Vanilla tincture (used as flavoring agents); Iodine tincture (used as antiseptic). distilled and de-ionized to form a more more Waters - may be a natural product, as tap water, or distilled purified and sterile sterile product. E.q. Water for injection. SYSTEMS OF MEASUREMENT Three systems of measurement (metric, apothecary, and household) are used in measuring drugs and solutions. The metric system system developed in the late eighteenth century, is is the internationally accepted system of measure. It is replacing the the apothecary system, which dates  back to the middle ages and had been used in England since the 17th century. It is proposed that the apothecary system will will phase out by the end of this century. Household measurement is commonly used in community and home settings.

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I. METRIC - to measure based on decimals and Arabic Arabic numbers; the official system used in the USP.

Units:

Meter (m) = for length Liter (l) = for capacity Gram (gm.) = for weight

Metric Tables: Table of Length 1 km. = 1,000 m. 1 hm. = 100 m. 1 dkm = 10 m. 1 dm. = 0.1 m. 1 cm. = 0.01 m. 1mm. = 0.001 m.

1 kl. 1 hl. 1 dkl 1 dl. 1 cl. 1ml.

Table of Capacity = 1,000 l. = 100 l. = 10 l. = 0.1 l. = 0.01 l. = 0.001 l.

1 kg. 1 hg. 1 dkg 1 dg. 1 cg. 1mg.

Table of Weight = 1,000 gm. = 100 gm. = 10 gm. = 0.1 gm. = 0.01 gm. = 0.001 gm.

Procedure for Conversion Between Units of the Metric System: 1. To change milligrams to grams, grams, milliliters milliliters to liters, or grams grams to kilograms, divide by 1000. 2. To change liters liters to milliliters, milliliters, grams to milligrams, kilograms to grams, multiply by 1000.

Examples: a. 64 mg. = ? gm. 1000 mg. : 1 gm. = 64 mg. : x gm. 1000 x = 64 x = . 64 . 1000 = 0.064 gm.

  b. 325 ml. = ?L 1000 ml. : 1L. = 325 ml. : x L. 1000 x = 325 x = . 325 . 1000 = 0.325 L II. APOTHECARIE’S OR ENGLISH SYSTEM - In this older system, Roman numerals numerals and common fractions are used to designate designate units. Also, the units of measure precede the numeral in correct form. e.q the correct way to signify 20 grains would be “gr.xx.” A line is often written above the numerals, and a dot is placed above the numeral I to distinguish more clearly between the two I’s and a V or X hastily written. When using the apothecary system in calculations, however, the Arabic numbers are used.

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Procedure for Conversion Within the apothecary System 1. Write Write the equivalent equivalent between between the terms terms to be convert converted ed as the first first two two terms of the  proportion. 2. Being careful careful to keep keep the units units in the last last two terms terms in in the same order order as they they occur  in the first, write the known quantity and the unknown equivalent as the third and fourth terms of the proportion. Examples: a. 6 drams = ? ounces 8 drams : 1 ounce = 6 drams : X ounces 8x = 6 x = . 6 . = . 3 . ounce 8 4 b. 2 drams = ? minims 60 minims : 1 dram = x minims : 2 drams 1 x = 120 x = 120 minims TABLE OF WEIGHT 60 grains = 1 dram 8 drams = 1 ounce 12 ounces = 1 lb. TABLE OF CAPACITY 60 minims = 1 fluidram 480 minims or 8 fluidrams = 1 fluid ounce 7680 minims or 16 fluid ounces = 1 pint 2 pints = 1 quart 4 quarts = 1 gallon III. HOUSEHOLD SYSTEM - The household system of measurement is not as accu rate as the metric system because of the lack of standardization of spoons, cups, and glasses. The measurements are approximate.

HOUSEHOLD UNITS OF MEASUREMENT 60 drops (gtt) = 1 teaspoon 3 teaspoon = 1 tablespoon (tbs) 6 teaspoon = 1 ounce 2 tbs = 1 oz. 6 oz. = 1 tea cup 8 oz. = 1 glass 8 oz. = 1 measuring cup OTHER EQUIVALENTS 1,000 cc. = 1 L = 1 quart 500 cc. = 1 pint 30 cc. = 1 fluidounce = 2 tbsp.

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5 cc. = 1 fluidram = 60 minims = 1 tsp. 1 cc. = 15 minims 1 kg. = 1000 gms. = 2.2. lbs. 4 gms. = 1 dram = 60 grains TEMPERATURE CONVERSION Celsius to Farenheit: ( C ) (9/5) + 32 Farenheit to Celsius: ( F – 32 ) (5/9)

METRIC DOSES with APPROXIMATE APOTHECARY EQUIVALENTS ( by Musser/O’Neil * reprinted from USP XVI)

METRIC

1000 ml. 750 ml. 500 ml. 250 ml. 200 ml. 100 ml. 50 ml. 30 ml. 15 ml. 10 ml. 8 ml. 5 ml. 4 ml.

METRIC

3 0 Gm . 1 5 Gm . 1 0 Gm . 7.5 Gm. 6 Gm. 5 Gm. 4 Gm. 3 Gm. 2 Gm. 1.5 Gm. 1 Gm.

LIQUID MEASURE Approximate APOTHECARY METRIC equivalents 1 quart 3 ml. 1 ½ pints 2 ml. 1 pint 1 ml. 8 fluid ounces 0.75 ml. 7 fluid ounces 0.6 ml. 3 ½ fluid ounces 0.5 ml. 1 ¾ fluid ounces 0.3 ml. 1 fluid ounce 0.25 ml. 4 fluid drams 0.2 ml. 2 ½ fluid drams 0.1 ml. 2 fluid drams 0.06 ml. 1 ¼ fluid drams 0.05 ml. 1 fluid drams 0.03 ml. WEIGHT Approximate APOTHECARY METRIC Equivalents 1 ounce 30 mg. 4 d r am s 25 mg. 2 ½ drams 20 mg. 2 d r am s 15 mg. 90 grains 12 mg. 75 grains 10 mg. 60 grains (1 dram) 8 mg. 45 grains 6 mg. 30 grains 5 mg. 22 grains 4 mg. 15 grains 3 mg.

Approximate APOTHECARY equivalents 45 minims 30 minims 15 minims 12 minims 10 minims 8 minims 5 minims 4 minims 3 minims 1 ½ minims 1 minim ¾ minim ½ minim Approximate APOTHECARY equivalents ½ grain 3/8 grain 1/3 grain ¼ grain 1/5 grain 1/6 grain 1/8 grain 1/10 grain 1/12 grain 1/15 grain 1/20 grain

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0.75 Gm. 0.6 Gm. 0.5 Gm. 0.4 Gm. 0.3 Gm. 0.25 Gm. 0.2 Gm. 0.15 Gm. 0.12 Gm. 0.1 Gm. 7 5 mg. 5 0 mg. 6 0 mg. 4 0 mg.

12 grains 10 grains 7 ½ grains 6 grains 5 grains 4 grains 3 grains 2 ½ grains 2 grains 1 ½ grains 1 ¼ grains 1 grains ¾ grain 2/3 grains

2 mg. 1.5 mg. 1.2 mg. 1 mg. 0.8 mg. 0.6 mg. 0.5 mg. 0.4 mg. 0.3 mg. 0.25 mg. 0.2 mg. 0.15 mg. 0.12 mg. 0.1 mg.

1/30 grain 1/40 grain 1/50 grain 1/60 grain 1/80 grain 1/100 grain 1/120 grain 1/150 grain 1/200 grain 1/250 grain 1/300 grain 1/400 grain 1/500 grain 1/600 grain

APPROXIMATE HOUSEHOLD EQUIVALENTS HOUSEHOLD APOTHECARY METRIC 1 drop (gt) 1 minim (m or min) 0.06 milliliter (ml.) 15 drops (gtt) 15 min 1 ml. (cc.) 1 teaspoon (tsp) 1 fluidram (60 minims) 5 or or 4 ml. * 1 tablespoon (tbsp) 4 fluid dram 15 ml. 2 Tbs. 1 fluid ounce 30 ml. 1 ounce 1 fluid ounce 30 ml. 1 tea cup 6 fluid ounce 180 ml. 1 glass 8 fluid ounce 240 ml. 1 measuring cup 8 fluid ounce 240 ml. 2 measuring cups 1 pint (pt) 500 ml.

DOSE CALCULATIONS Children Children are not able to tolerate tolerate adult doses of drugs. drugs. There are several several formulas formulas for  graduating dosage according to age and weight. weight. The recommended dosage dosage for kg. or lb. of body weight is is more accurate accurate than calculat calculating ing dosage accordi according ng to age. Other factors factors beside beside age and weight enter enter into dosage for children. children. For this reason, reason, some physicians, physicians, use the :body surface surface area” method method to estimate estimate the dosage for children. children. Charts Charts are available available to determine determine the body surface area in square meters according to height and weight. For Infants and Preschool children

Clark’s Rule

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Weight (lbs.) X Adult dose --------------------------------------- --------------------------- = Infant dose 150

Fried’s Rule - sometimes used in calculating dosages for infants less than 2 years old.

Age (mos.) X Adult dose --------------------------------- = Infant dose 15

For Preschool to Adolescent years:

Young’s Rule - not valid after 12 years of age. If the child child is small enough to warrant a reduced dose after 12 years of age, the reduction should be calculated on the basis of  Clark’s rule.

Age (yr.) X Adult dose ----------------------------------------------------------------- = Child dose Age (yr.) + 12 Cowling’s Rule

Age (at next b-day) X Adult dose ------------------------------------------- = Child dose 24

Calculation based on Body Surface Area (BSA) : - considered to be the most accurate accurate way to calculate the drug dose for infants, children, older adults, and clients who are on antineoplastic agents or whose body weight is low. The BSA, in square meters meters is determined by where the person’s height and weight intersect the nomogram scale.

Surface area area X Adult dose dose ----------------------------------- = Child dose 2.00 OR 

Multiply the drug dose ordered by the number n umber of square meters. Example: Order: Cyclophosphamide (Cytoxan) 100 mg. / m2 / day, PO

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Patient is 5 ft. 10 in. (70 in.) tall and weighs 160 lbs. a. 70 in. and 160 lbs. lbs. intersect the nomogram at 1.97 m2 (BSA)  b.  b. 100 mg. mg. x 1.97 1.97 = 197 197 mg. mg. Answer: Administer Cyclophosphamide 197 mg. or 200 mg./day. mg./day.

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31

PRESENTLY USED DOSE CALCULATION: Weight: (Ideal Body Weight)

At Birth: 3000 Grams Less than 6 months: Weight In Grams Age in Months X 600 + Birth Weight 6 – 12 Months: Weight in Grams Age in Months X 500 + Birth Weight 1 – 6 Years: Weight in Kilograms Age in Years X 2 + 8 7 – 12 Years: Weight in Kilograms Age in Years X 7 - 5 2 Suggested Dose: Age 13 – 18 years = 250 mg. 19 – above = 500 mg. Example: Given:

Age of child = 2 years old Recommended dose = 10 mg. Available dose: 250mg./5ml. x 30 ml.

Formula: Age in years X 2 + 8 Solution: 2 X 2 + 8 = 12 kg. 10 mg. X 12 Kg. = 120 mg. (dose needed by a 2-year old child) What part of 250 mg. is 120 mg.? To compute for the exact dose/ml., multiply multiply 120 mg. to 5ml. and 250mg. to X(ml.) X(ml.) then divide to 250mg. 250mg. / 5ml.

=

120mg / X(ml.)

5ml. X 120mg. = 600mg./ml. 250mg. X ?ml = 250mg. Then divide:

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600mg./ml. 250 mg. = 2.4 ml.

*120mg. computed dose of the child is 2.4ml. in a 250mg./5ml. preparation of the drug. DOSE CALCULATION ACCORDING TO KEE AND HAYES Basic Formula: D -----X V = A H

Where: D = is the desired dose; drug dose ordered by the physician do se; drug dose on label of container (bottle, vial). H = is the on hand dose; V = is the vehicle; drug form in which the drug comes (tablet, capsule, liquid) A = is the amount calculated to be given to the client. Example: Order: Ampicillin (Polycillin) 0.5 g., PO, bid Available (drug label): Polycilin 250 mg./capsule Solution: The unit of measure that is ordered, grams, and the the unit on the bottle, milligrams, are from the same system of measurement, the metric system. Conversion to the same unit is is necessary to work the problem. Since the  bottles is in milligrams, milligrams, convert grams to milligrams. To convert grams (large value) to milligrams (small value), move the decimal po int three spaces to the right. 0.5 G. = 0.500 mg. or 500 mg.

D ------ x V H

=

500 mg. 500 --------- x 1 capsule = ------- = 2 capsules 250 mg. 250

RATIO AND PROPORTION: - the oldest method currently used in calculating drug dosage.

Known H :

V

: : means extremes x =

Desired D :

x

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Example: Order: Ampicillin 100 mg., PO, qid Available: Ampicillin (Polycillin) 250 mg./5ml. Solution: Conversion is not needed needed since both are expressed expressed in the same unit unit of measure. H : V :: D : x 250 mg. : 5 ml. :: 100 mg. : x ml. means extremes

250x = 500 x = 2 ml. Answer: Ampicillin 100 mg. = 2 ml.

DRUG LIST: NARCOTIC ANALGESICS 1. MEPERIDINE HCL (DEMEROL) Elixir: 50mg/5ml. Tablet 50,100 mg. Injection 100 mg./ml. Dose: 6mg./kg./Day or 0.5 – 1.0 mg./Kg./Dose

2. NALBUPHINE (NUBAIN) Injection 10 mg./ml. Dose: 0.1 – 0.2 mg./Kg./Dose mg./Kg./Dose NON-NARCOTIC ANALGESIC 1. ASA (ASPIRIN) 60, 81, 200, 300, 600, mg. Tablet Dose: 6.5 mg./Kg./Day

2. ACETAMINOPHEN Afebrin, Tempra, Tylenol, Calpol, Rexidol, Naprex, Panadol 100 mg./5ml., 120mg./5ml., 250mg./5ml. Syrup 60mg./0.6 ml. Drops Dose: 10 – 20 mg./Kg./Dose

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3. MEFENAMIC ACID Ponstan, Dolfenal 50 mg./5ml. Suspension 250, 500 mg. Tablet, Capsule Dose: 6.5 mg./Kg./Dose (Pedia) BETA-LACTAM ANTIBIOTICS PENICILLIN G 1. PENICILLIN G BENZATHINE BENZATHINE Usual Dose: Newborn(NB), Infants (IN): 50,000 – units/kg/single dose IM Children (CH) (>60 lbs.) and Adults (A): 600000-1200000 units IM q 3 weeks for rheumatic fever prophylaxis 2.4 million units IM once (divided into 2 injection sites at one visit) for  three treatment of early syphilis, weekly X 3 doses for syphilis of more than one year duration. Preparation: (Penadur L-A): L-A): 1.2 M units and 2.4 M units/vial.

2. CRYSTALLINE PEN G (BENZYLPENICILLIN) Usual dose: NB - 25,000 U/Kg. q 6, 8, 12 IN, CH - 100,000 – 250,000 U/Kg. U/Kg. div. div. q4h. Preparation: Pen G: 1 M units/vial units/vial and 5 M units/vial units/vial 3. PHENOXYMETHYLPENICILLIN (PENICILLIN V) Usual Dose: IN, CH - 25-50 mg./Kg./Day or 25,000-100,000 U/Kg./Day div.q6-8 h, PO 1-2 g/d or 1.6-3.2 million u/d div.q6h, div.q6h , PO Preparation: Oral - 250, 500, 625 mg. capsule 125 mg./5ml; 25mg./5ml, suspension 60 ml. Note: Administer on empty empty stomach (1-2 hours after meal) meal) BROAD SPECTRUM PENICILLINS 1. AMOXICILLIN Usual Dose: IN, CH- 20-40 mg./kg./day div.by 3 doses (q8h) PO Adults- 750-1500 mg./day div. q8h, PO Preparations: Drops - 100mg./ml. Granules/Powder for suspension, 10ml. drops 125, 250 mg./5ml. 60-70 ml. Capsule- 250, 500 mg. Injection- 250,500mg./vial

2. AMPICILLIN Usual Dose: NB- 25-50 mg./kg. Q6-12 IV IN, CH- 100-200 mg./kg./day div.q4-6 h. A- 2-12 Grams infusion div. q6h. (Ampicin, Amopen drops: 100 mg/ml.; suspension 125, 250 mg./5ml.; capsule- 250,500mg.; Injection- 100, 250, 500 mg./vial)

COMBINATION OF A PENICILLIN AND BETA-LACTAMASE INHIBITOR 

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1. BACAMPICILLIN Usual Dose: IN, CH - 25-50 mg./kg./day div.by 2 doses (q12) PO A- 800-1600 mg. mg. bid (Penglobe susp. 200mg./5ml.; Tablet- 200, 400, 800 mg. 2. CO-AMOXICLAV Usual Dose: NB- not recommended IN, CH- 40 mg./kg./day div. q8h PO and IV. A- 750 – 1.5 Grams/d Grams/d div.q8 PO and IV. Preparations: 156.25 mg./5ml (30-60 ml) 375, 625 mg. tablet 600,1200 mg./vial PENICILLINASE RESISTANT PENICILLIN 1. CLOXACILLIN Usual Dose: IN, CH - 50-100 mg./kg./day mg./kg./day div.q6h (4 doses) PO Adults - 2-4 Grams/day div.q6 PO Preparations: Suspension - 125 mg./5ml x 60 ml. Capsule - 250 mg., 500 mg. Injection - 250, 500 mg./ vial CEPHALOSPORINS First Generation A. CEPHALEXIN Usual Dose: IN, CH - 25-50 mg./kg./day div.q6h, PO Adults - 1-4 Grams/day div.q6h, PO Preparations: 125 mg./ 5ml. Granules/Powder for Suspension (50-70 ml). 100 mg./ 5 ml. Granules/Powder for drops (10 ml.) Capsule - 250, 500 mg.

B. CEPHAZOLIN Usual Dose: NB - 20 mg./kg. q12h IN, CH - 50-100 mg./kg./day div. q8h, IM or IV Adults - 1-6 Grams/day Grams/day div.q8h, div.q8h, IM or IV. Preparation: 1 Gram vial Second Generation A. CEFACLOR  Usual Dose: IN, CH - 20-40 mg./kg./day q8-12h, PO Adults - 750 – 1500 mg./day div.q8-12 h, PO Preparations: Suspension 125mg./5ml. Granules/ Powder for suspension Puvule 250, 500 mg. 50 mg./ml. Granules/Powder for drops (20ml.)

B. CEFUROXIME Usual dose - 30-50 mg./kg./day Injection 250-750 mg./vial

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Third Generation A. CEFTRIAZONE Usual Dose: 50-100 mg./kg./day Injection 250, 500 mg., 1 G / vial

B. CEFTAZIDIME Usual Dose: 30-50 mg./kg./day Injection 250, 500 mg., 1 G./ vial AMINOGLYCOSIDES 1. GENTAMYCIN SULFATE Usual Dose: IN, CH, A - 3.5-8 mg./kg./day div.q8 IM or IV Preparation: Injection - 20, 40, 80 mg./ml. (vial)

2. AMIKACIN SULFATE Usual Dose: IN,CH,A - 15mg./kg./day loading, 10mg./kg./day maintenance Preparation: Injection - 50, 125, 250 mg./ml. (vial)

DRUGS THAT ACT ON 30 S RIBOSOMAL SUBUNIT TETRACYCLINE Usual Dose: CH(>8years) - 25-50 mg./kg./day div. q6h, PO Adults - 1-2 Grams / day div.q6h, PO Preparations: Oral - 250, 500 mg. capsules Other preparations: Doxycycline - 2-4 mg./kg./day Doxin capsule capsule - 100 mg. Minocycline (Minocin) - capsule: 50 mg., 100 mg. DRUGS THAT ACT ON 50 S SUBUNIT CHLORAMPHENICOL Usual Dose: IN, CH - 50-100 mg./kg./day div.q6h, PO, IM, IV Adults - 50-100 mg./kg./day div.q6h, PO, IM, IV Preparations: Oral - 125 mg./5 ml., 60 ml. suspension 250, 500 mg. capsules Injection - 1 Gram Gram vials ERYTHROMYCIN Usual Dose: IN, CH - 30-50 mg./kg./day, div. q6h PO, IV Adults - 1-2 Grams/day div. q6 PO, IV Preparations: 250, 500 mg. tablet; 500 mg. capsules; 100mg./2.5 ml. (30 ml. drops); 200, 400 mg./5ml. (60 ml. suspension) CLINDAMYCIN Usual Dose: IN, CH - 10-25 mg./kg./day, div. q6h PO, IV IV Adults - 600-1800 mg./day div. q6 PO Preparations: Oral - 150, 300 mg. capsule; 75 mg./5 ml. x 30 ml. suspension

37 TRIMETHOPRIM - SULFAMETHOXAZOLE (COTRIMOXAZOLE) Usual Dose: IN, CH - 8 mg. TMP and 40 mg. SMX/kg./d div.q12h PO Adults - 320 mg. TMP and 1600 SMX/d div.q12h PO Preparations: Oral - 100,000 units/ml. 30 ml. suspension; 500,000 units per tablet Vaginal - 100,000 units tablets KETOCONAZOLE Usual Dose: CH - 5-10 mg./kg./day div. q12-24 h, PO Adults - 200 – 400 mg. qd PO Preparations: Oral - 200 mg. tablets ISONIAZID Usual Dose: 10-20 mg./kg./day Preparation: Syrup - 150 mg./5ml. Tablet - 400 mg. METRONIDAZOLE Usual Dose: For amoebiasis and Anaerobic Anaerobic Infections: Infections: IN, CH - 35-50 mg./kg./d div. q8h, PO Adults - 750 mg. tid, PO Preparations: Oral - 250, 500 mg. tablets; 125 mg./5ml. (60 ml. suspension) Injection - 5mg./ml. 100 ml. vial Rectal - 1 G Suppository QUINOLONES Usual Dose: Adults - 400-800 mg./day divq12h, PO, IV Preparations: Ofloxacin (Inoflax), Ciprofloxacin (Coprobay) - 200, 400 mg. tablets RIFAMPICIN Usual Dose: 10-20 mg./kg./day PO Preparations: Syrup - 100 mg./ml. and 200 mg./5ml. (50-60 ml. suspension) Capsule - 150, 300, 450, 600 mg.

ANTIFUNGALS AMPHOTERECIN B Usual Dose: IN, CH - 0.1-0.25 mg./kg./day (single IV dose) Adults - 0.25-1 mg./kg./day Preparation: Injection - 5 mg./ml. (10 ml. vial) NYSTATIN Usual Dose: NB - 400,000 units/day units/day div.q4-6 h PO PO IN, CH - 400,000-800,000 units / day div.q4-6 h PO Adults - 800,000 – 2,000000 units/day units/day div. q4-6 h PO

38 PRINCIPLES OF PRESCRIPTION ORDER WRITING Prescription - a written order for medicines medicines written by a qualified Medical, Dental or Veterinary Veterinary practitioner to the pharmacist for a patient. “ Simple” - if containing containing only one ingredient. “Compound ” - if containing more than one ingredient. Drugs may be combined in prescriptions for the following reasons: 1. To obtain obtain the conjoint conjoint effect effect of two or more active active substances. substances. 2. To diminish diminish or annul annul undesirabl undesirablee effects effects produced produced by one or more more of the active active ingredients. 3. To increase increase the solubil solubility ity or aid aid in the dispensi dispensing ng of the active active substances substances.. 4. Occasi Occasional onally, ly, to to produce produce a new comp compound ound..

PARTS OF AN IDEAL IDEAL PRESCRIPTION PRESCRIPTION   ________Doctor’s Name_________   _____________Address______________   ________Tel. No.________  ---------------------------------------------------------------------------------------------------------------------Patient’s name: _________________________ __________________________________ _________ Date:_____________  Address:________________________________________________________________________  Tel. No. __________________ Age: ______ Sex: ______ 

Rx Generic name of drug, dosage form and amount . (Brand name of drug) Direction to the pharmacist

.

Direction to the patient

.

__________________ D.M.D. Prescriber’s Signature PRC License Number  P.T.R. Number

.

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 Narcotic License Number ( S-2) T.I.N. Tax Identification Number 

 ____________________  Refill Information Parts of the Prescription Superscription : Patient’s name, address, and age; date and the the symbol symbol Rx. form, and amount. Inscription : Name of drug, dosage form, to the pharmacist Subscription : Directions to Transcription / Signature : Direction to the patient HEADING  Name, address and phone number of the prescriber. Name, address, age, and phone number of the patient, and date BODY The symbol Rx Name and dosage unit or concentration concentration (liquids) of the drug. Amount to be dispensed Directions to the patient CLOSING Prescriber’s signature Space for DEA number  Refill instructions “Please place name of drug on label”

Importance of placing the name of the drug on label: 1. In case of of overdose overdose or advers adversee reactions, reactions, the the drugs’ drugs’ identity identity can can be quickly quickly obtained. obtained. 2. Other practit practitioner ionerss can identify identify drugs the the patient patient is taking. taking. 3. In most most cases, cases, the patient patient has has the right right to to know what what drug he or she she is taking. taking. Hints for Prescription Prescription Writing 1. Write Write legib legibly ly in ink ink or have have it type typewri writt tten en 2. Use Use the the metr metric ic syst system em 3. Avoid Avoid abbr abbrevi eviat atio ions ns 4. Keep a copy of each prescript prescription ion or transcr transcribe ibe the informat information ion to the the patient’s patient’s record. record. 5. Includ Includee complete complete inform informati ation on for the the patient patient.. a. Never use use “take “take as directe directed” d” unless unless a written written instru instruction ction sheet sheet is provided. provided.  b. Includ Includee the the intend intended ed purpos purpose. e. c. Use precautions precautions to remind remind a patient patient of a drug’s drug’s side effects. effects. E.q. “Caution: “Caution: Sedation Sedation or drowsiness.” d. Add remind reminder er phrases phrases to increas increasee the the patient’ patient’ss complian compliance. ce. E.q. “Take until all are gone.” 6. It must must contain contain the the follow following ing parti particula culars: rs: a. The address address and usual usual signatur signaturee of the the practiti practitioner oner giving giving it. it.

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 b. The date date on which it was was signed signed by the the practit practitioner. ioner. c. An indication indication of whethe whetherr the practition practitioner er is a dentist, dentist, doctor, doctor, or veteri veterinary nary surgeon. surgeon. d. The name, name, address, address, age (if (if under under 12) of the person person whose whose treatment treatment is given. 7. The prescript prescription ion shall shall not be dispensed dispensed not later later than than six months months after after the date date of  signature.

Considerations in Drug Administration / Prescribing Tolerance – the ability of a client to respond to a particular dose of a certain drug may diminish after days or weeks of repeated administration. A combination of  drugs may be given to decrease or delay the development of tolerance for a specific drug. 1. Pathologic Pathologic State State / Pre-exi Pre-existin sting g Disease Disease State State - Liver, Liver, kidney, kidney, heart, heart, circulat circulatory ory and and gastrointestinal disorders are examples of preexisting states that can affect a response to a drug. For instance, diabetics should should not be given elixirs or syrups syrups than contain sugar. Age - The age of a patient will will affect his or her response to drugs. Children and elderly persons are more more sensitive to drugs; they require less than the usual adult dose. 2. Weight - the more a person weighs, the more dilute the the drug will become and a smaller  smaller  amount will accumulate in the tissues. tissues. On the other hand, the less a person weighs, the greater accumulation in the tissues and a more powerful drug effect is produced. 3. Sex - Women are more more suscept susceptible ible to the the action action of certain certain drugs drugs and and are usually usually given given smaller doses. 4. Drug-Drug Drug-Drug Intera Interaction ction - the effects effects of a combinatio combination n of drugs drugs may be be greater greater then, equal to, or less than the effects effects of a single drug. drug. Some drugs may compete for the same receptor sites. An adverse reaction may lead to toxicity or complication complication such as anaphylaxis. 5. Psychologi Psychological cal factors factors / Emotional Emotional factors factors - A person’s person’s personal personality ity often often plays plays an important part in his response to drugs; comments about the drug and its side effects may influence its effects. 6. Genetic Genetic factors factors - drug idiosy idiosyncrasy ncrasy is an abnormal abnormal suscepti susceptibilit bility y of some some individ individuals uals that that causes them to react differently than most people. This intolerance intolerance to small amounts of  some drugs is thought to be due d ue to genetic factors. If your mother or father has an adverse reaction to a drug, you may also. 7. Environmenta Environmentall factors factors - the setti setting ng in which the drugs drugs are given given and and the attitude attitude of the  person giving the medication may influence the effects of drugs. 8. Method of adminis administrat tration ion - generally, generally, larger doses are ordere ordered d when a medicatio medication n is given by mouth or by rectum and smaller doses when the parenteral route is used. Blood level curves and dosing regimens Pregnant and breastfeeding mothers - Administration of medication in the early weeks of pregnancy may cause damage to to the fetus. During the third trimester, trimester, there is the possibility of premature labor caused by drugs that may stimulate muscular contractions.

LATIN PHRASES and ABBREVIATIONS Used in PRESCR PRESCRIPTION IPTION WRITING WRITI NG

Abbreviations

a. aa a . c. ad ass. ad lib. acq. agit. a q. aq. dest. amp. b. bene b.i.d. c c. cap. co. ; comp. coch. mag. coch. med. coch. parv. cong. d. da d. in p. acq. d.t.d. dieb alt. dil disp. div. dos. E.C. elix. Et Ex Ext ex aq. e.m.p. f. F ac fl. or fld. Ft. gm. gr. gtt. h h.s. hypo

Latin

English

ante before ana of each ante cibum before meals ad to, up to adde, addantur add, let them be added ad libitum at pleasure acqualis equal agita shake aqua water   aqua distilata distilled water   --ampule bis twice bene well bis in die twice a day cibum meal cum with capsula capsule compositus compound cochleare magnum a tablespoonful cochleare medium a dessertspoonful cochleare parvum a teaspoonful congium a gallon dies a day da give dividatur in in partes ac acquales let it be di divided in into equal parts dentus tales doses give such doses diebus alternis every other day dilitus dilute dispensa, dispensetur dispense divide divide dosis a dose --enteric coated elixir elixir   et and ex out of   extractum extract ex aqua with water   ex modo prescripto after the manner pr prescribed fiat, fiant make, let be made face make fluidus fluid fiat make --gram --grain gutta, guttae a drop, drops hora hour   hora somni at bedtime(hour of sleep) --hypodermically

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DRUG THERAPY Pharmaceutical Process Pharmacokinetics Process Pharmacodynamics Process Therapeutic Process PHARMACEUTICAL PROCESS Is the drug getting into the patient? Approximately 80% of drugs are taken by mouth; therefore, the pharmaceutic phase is the first phase of drug drug action. In the gastrointestinal tract, tract, drugs need to be in solution solution to be absorbed. A drug in solid form (tablet or pill) must disintegrate disintegrate into smaller particles in order  for it to dissolve into a liquid. Disintegration is the breakdown of the tablet or pill into smaller particles. Dissolution is the dissolving of smaller particles in gastrointestinal gastrointestinal fluid for absorption. absorption. Rate Limiting is the time it takes for the drug to disintegrate and become available for the body to absorb it.

Factors to consider  1. Particle Particle size size - the smaller smaller the particl particlee size, size, the faster faster it can can be absorbed absorbed in the the body. body. 2. Excipients Excipients of drug - fillers fillers and inert inert substan substances ces are used in drug drug preparat preparation ion to allow allow the the drug to take on a particular particular size and shape and to enhance dissolution of the drug. Some additives such as K and Na in penicillin K and penicillin Na, increase the absorbability of  the drug. 3. Coating Coating materia materiall - Enteric-coat Enteric-coated ed (EC) (EC) drugs drugs resist resist disin disintegra tegration tion in the the gastric gastric acid in the stomach, so disintegration does not occur until the drug reaches the alkaline environment in the small intestine. PHARMACOKINETIC PROCESS Is the drug getting into its site of action? - is the process of drug movement to achieve drug action. action. - concerned with with the absorption, distribution and elimination (metabolism and excretion) of drugs. ABSORPTION - process by which drug molecules are are transferred form the site of administration administration in the body to the circulating fluids

Factors Affecting Absorption 1. Physico-chemical factors 2. Site of absorption / Blood flow at the site 3. Drug Solubility 4. Effects of food a. Blood flow b. Gastric emptying

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•

•

•

the non-ionized portion behaves as a non-polar lipid soluble compound which readily traverses body membranes. The amount of ionization that any weak electrolytes undergoes depend on the pH at the drug site in the tissues and its dissociation characteristics. Increase pH (weak acids) - the greater the degree of ionization ionization Decrease pH (weak bases) – the greater the degree of ionization.

Oral absorption – depends on the dosage form of drugs. Absorption on injection injection sites - depends on the solubility solubility of drug drug and the blood flow flow at the site; also affected by dosage form. E.q. drugs in suspension are absorbed much ore ore slowly than those in solution. Effects of food on drug absorption - by affecting affecting the blood flow and gastric emptying. E.q. liquid glucose meal decreases flow and a meal rich in protein increases flow. - some drugs are irritating irritating to the stomach mucosa, so fluids fluids or food are necessary necessary to dilute drug concentration - there are drugs that are absorbed easily in the presence of food. Factors that Modify the Rate of Absorption 1. Drug Concentration at the Site 2. Circulation to the Site of Absorption 3. Area of Absorptive surface FACTORS GOVERNING THE FATE OF A DRUG 1. Mole Molecu cula larr Weigh Weightt - substances with high molecular weight are not usually absorbed intact intact except in minute quantities. - they are absorbed by enzymatic actions. actions. E.q. insulin is is a protein – it undergoes enzymatic breakdown in the git and is not absorbed. 2. Chem Chemic ical al Stab Stabil ilit ity y - unstable drugs maybe inactivated inactivated in the git. E.q. Benzylpenicillin in in unstable in acid medium and cannot be effective if given given by mouth. Phenoxymethylpenicillin is more more stable in acid medium. 3. Lipi Lipid d Solu Solubi bili lity ty - if the drug is lipid lipid soluble, it can easily easily pass through the membrane. 4. Degr Degree ee of of Ioni Ioniza zati tion on - the unionized portion of a drug is lipid soluble and so is is readily absorbed; ionized portion is lipid insoluble. THE CELL MEMBRANE Composition: Lipids (40%) phospholipids - makes membrane relatively impermeable to ions and polar molecules Proteins (50-60%) - make up the structural structural components of the membrane

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- acts as enzyme during transport Carbohydrates (remainder) Oligosaccharide - linked covalently to form complexes of glycoproteins and glycolipids

*PRINCIPAL MECHANISMS INVOLVED IN THE PASSAGE OF DRUGS ACROSS CELL MEMBRANE Lipid Diffusion (Simple Diffusion ) - drug molecules dissolves in the membrane to penetrate through the other other side. Can take place either via: Lipoprotein membrane Paracellular spaces 2. Aqueous Aqueous Diffu Diffusion sion (Filt (Filtrati ration on throug through h Pores) Pores) - the size of the drug molecule molecule is relative to the size of the pores. - water soluble drugs with molecular molecular weight less than 100 Daltons are able to cross cross the cell membrane by passing through the polar pores. E.q. Ethanol (46); Urea (60) 3. Specific Carrier Mediated Transport System Active Transport - process by which a substance substance is transported against a concentration concentration gradient. Drug molecules are mediated by transport transport “carrier” that furnish energy for the transportation of drug from lower concentration through higher con centrations. E.q. Na, K, Ca, Fe, amino acids, and glucose. 1.

3 Features 1. Abil Abilit ity y to work work agai agains nstt conc concen entr trat atio ion n grad gradie ient nt,, osmo osmoti tic, c, elec electr tric ical al,, or  hydrostatic gradient 2. Specif Specifici icity ty – ability ability to concen concentra trate te a selecte selected d substance substance on one side side of the cell cell membrane. 3. Each system system require require an energy energy source (ATP), (ATP), to which which it it is directly directly coupled. coupled. Facilitated Diffusion - a passive process whereby drugs can move across cell membranes more more rapidly than simple diffusion. - involves the action of a specific specific but saturable carrier system system - can only work in the presence of an appropriate appropriate concentration gradient. gradient. DISTRIBUTION - the passage of drug into various body fluids compartments such such as plasma, intestinal fluids and intracellular fluids; fluids; process by which the drug drug becomes available available to body fluids and body tissues.

Factors affecting Distribution 1. Blood fl flow 2. Affi Affini nity ty to the the tis tissu suee 3. Prot Protei ein n bind bindin ing g Forms of Drug inside the Body

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1. Free / Unbound state - free active drug 2. Bound - inactive drug Binding to Plasma Proteins Proteins - e.q. salicylic acid and warfarin bind bind to Albumin Basic drugs bind bind to acid glycoproteins and lipoproteins Binding to Cells - drugs become bound onto the surface or inside the cells. *Only free drugs or drugs not bound to protein are active and can cause a pharmacologic response. As the free drug in the the tissues decreases, more bound drug is released from the protein to maintain the balance ba lance of free drug. Checking the protein-binding percentage of all drugs administered is important in order to avoid possible drug toxicity. toxicity. E.q. Drug accumulation accumulation and toxicity toxicity can result if  two highly protein-bound drugs are given concurrently because they will compete for protein binding sites causing more free free drug to be released into into the circulation; Also, a low protein level decreases the number of protein binding binding sites, causing an increase in the amount of  free drug in the plasma. Drug overdose may result because drug dosage is prescribed according to the percentage in which the drug binds to protein. STORAGE DEPOT (Non-specific Site) - helps prevent prolong the action action or areas for  transient storage. AFFINITY TISSUES TISSUES - maybe sites of action or areas for transient transient storage; some drugs accumulate in particular tissues such as fat, bone, liver, eye, and muscle. E.g. Guanethidine - binds to heart and skeletal skeletal muscle Quinacrine - binds to liver liver and skeletal skeletal muscles Tetracycline - bone and enamel Thiopental - adipose tissue METABOLISM - Liver – main organ of metabolism - most drugs are inactivated inactivated by liver enzymes and are then then converted by hepatic enzymes to an inactive metabolite or water soluble substance for excretion. However, some drugs are transformed into active metabolites causing an increased p harmacologic response. Example of liver disease that affects metabolism - cirrhosis and hepatitis.

1. 2.

Excretion Excretion in the original original form e.q. Hexamethoni Hexamethonium um – a highly ionized ionized antihypert antihypertensive ensive compound excreted in the urine unchanged. Transf Transform ormati ation on into into one or more more Meta Metabol bolite itess Other organs: G.I.T., Lung, kidney, kidney, skin skin and placenta. placenta.

BIOTRANSFORMATION - a process wherein parent drug is converted co nverted by enzymes into drug metabolites ready to to perform its its action. Biotransformation of Drugs has Two Effects 1. It alters alters the pharmac pharmacolo ologica gicall activi activity, ty, usually usually decreas decreasing ing it but sometim sometimes es convertin converting g the drug to a compound similar or greater activity (potency) (potency) than the original. 2. Results Results in in metabolit metabolites es that that are more water-solu water-soluble ble and and less less lipid lipid soluble soluble than than the parent compounds and therefore more readily excreted in the urine.

46

* Two General Types of Chemical Reaction Phase 1 (Non-Synthetic reaction) 1. Oxi Oxidati dation on - Diaz Diazep epam am 2. Reduc Reducti tion on - Nitr Nitraz azep epam, am, Cort Cortis ison onee 3. Hydrol Hydrolysi ysiss - Suxameth Suxamethoni onium, um, Ametho Amethocai caine ne Phase 2 (Synthetic (Conjugation) Reaction) -It involves conjugation to form one or o r more of the following: 1. Glucor Glucoroni onide de e.g. e.g. Morphi Morphine, ne, Parace Paracetam tamol ol 2. Sulp Sulpha hate te e.g. e.g. Isop Isopre rena nali line ne 3. Aceta Acetate te e.g. e.g. Ison Isonia iazi zid, d, Hydr Hydral alaz azin inee 4. Glut Glutat athi hione one e.g. e.g. Para Parace ceta tamo moll

BIOLOGIC HALF-LIFE (t1/2) - is the time it takes for one half of the the drug concentration to be eliminated. - a drug goes through several half-lives half-lives before more than 90% is is eliminated.

Example: 650 mg. of Aspirin Number (t1/2) 1 2 3 4 5 6

Time of Elimination(h) 3 6 9 12 15 18

t1/2 = 3 hours Dosage Remaining (mg) 325 162 81 40.5 20 10

%left 50 25 12.5 6.25 3.1 1.55

- it takes three three hours for the first half-life to eliminate 325 mg and the second half-life (6h) for an additional 162 mg. to be eliminated, and so until the 6th half-life (18h) when 10 mg. of aspirin is left in the body. - a short half-life is 4-8 hours. - a long half-life half-life is 24 hours or longer (e.q Digoxin 36 hours); it takes several days until the body completely eliminates the drug. Factors Affecting Drug Metabolism 1. Ag e 2. Sex 3. Liver Di Disease 4. Envi Enviro ronm nmen enta tall Fact Factor orss 5. Gen Genetic Fa Factors ors 6. Rout Routee of Admi Admini nist stra rati tion on MICROSOMAL DRUG DRUG METABOLIZING SYSTEM - the most important of the many biochemical system in the body involved in biotransformation. - located primarily primarily in the smooth Endoplasmic Reticulum of hepatic cells.

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CYTOCHROME P450 - the most important enzyme in the microsomal enzyme enzyme system involved in the oxidative transport processes. EXCRETION - major way by which the the activity of the drug is is terminated - mainly in the Kidney; some via via the (Extra Renal Route) .Bile, Skin (sweat), (sweat), Lungs (expired air), Saliva, Feces and Breast Milk  - expressed in terms of “Renal Plasma Clearance” – the volume volume of plasma effectively cleared cleared of the drug by the kidney in unit time.

RENAL EXCRETION - most important important route of drug elimination *3 Processes Implicated in Renal Excretion 1. Glomerular Filtration - depends upon the plasma concentration of drugs and molecular weight. - 125 ml./min. 2. Tubular Reabsorption / Active / Active Secretion in the Proximal tubule 3. Tubular Secretion / Passive Re-absorption in the distal tubule

PHARMACODYNAMICS Is the Drug producing the required Pharmacological Effect? - study of a drug’s effect on cellular physiology and biocehmistry and the drug’s mechanism of action.

I. Drugs which act via Pharmacological Receptors: 1. Act Act at low low conce concent ntra rati tion on 2. React React with with spec specifi ificc rece recepto ptors rs 3. Show Show struc structur turee activi activity ty rela relati tion on 4. Can be anta antagon gonize ized d by speci specific fic anta antagoni gonist st e.q. acetylcholine; adrenaline; noraduraline and histamine e II. Drugs which DO NOT act via Pharmacological Receptors: f 1. Act Act at high higher er conc concen entr trat atio ions ns g 2. Do not react react with with spec specif ific ic rece recept ptor orss h 3. Tend to show struct structure ure-ac -activ tivity ity relati relations onship hipss i 4. Do not not have have spec specif ific ic anta antago goni nist stss e.q. General anesthetics and non-specific destructants of cell membranes such as detergents. DRUG-RECEPTOR INTERACTION macromolecule with special sites sites to which specific substances binds. Receptor - a macromolecule (Drug/Ligands – Receptor).

SITES OF RECEPTORS 1. On or with within in Cell Cell Membr Membran anes es 2. Inside Cells

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Most receptors, protein in in structure, are found on cell cell membranes. Drugs act through receptors by binding to the receptor to produce (initiate) a response or block (prevent) a response. The activity of many drug is determined by the the ability of the drug to to bind to a specific receptor. The better the drug drug fits at the receptor site, the more more biologically active active the drug is. It is similar similar to the fit of the right key in a lock.

Two drug agonists attach to the the receptor site. The drug agonist that has an Figure: exact fit is a strong agonist and is more biologically active than the weak agonist.

neurotransmitter) which combines with its specific receptor, Agonist - a drug (hormone or neurotransmitter) activates it and initiates a sequence of effects. effects. E.q. Isoproterenol stimulates the beta1 receptor. which interferes with the action of an agonist but does not have any Antagonist - a drug which effect itself unless it possess partial agonist ag onist activity. E.q. Cimetidine blocks the the H2 receptor thus preventing excessive gastric secretion. Partial Agonist - a drug that that act on a receptor with an intrinsic activity activity or efficacy efficacy of < 1. Mixed Agonist-Antagonist - a drug that act simultaneously on a mixed group of  receptor with an agonist action on one set and an antagonist action on another. ***DRUG ANTAGONISM - occurs when their biological effect is less than the expected sum of  their individual effects.   Pharmacological Antagonism: 1. Reversible Reversible Competitive Competitive / Equilib Equilibrium rium Antagonis Antagonism m - substances are competing dynamically for the the same pharmacological receptor  2. Irreversible Competitive / Non-Equilibrium Antagonism - drugs form very strong bonds  Non-Competitive Antagonism - block action of an agonist not at the receptor level but at some point between receptor and effector that leads to the action of the agonist. Physiological Antagonism - occurs when two drugs that act on different receptors receptors produce opposite effects. effects. E.q. Adrenaline antagonizes the effects of histamine histamine on bronchial smooth muscle. Chemical Antagonism - occurs when one drug combines chemically with another to

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produce inactive product. Pharmacokinetic Antagonism - occurs when one drug effectively reduces the concentration of another at its site of action by altering its its absorption, distribution distribution or  elimination. ***Relationship Between the Dose of Drug and the Effect it produces: Two Types of Relationship: Relationship: 1. Qu Quant antita itativ tivee (G (Grad raded ed)) resp respon onses ses or effec effects ts - the effect increases as the dose is increased until until the maximum is reached. Beyond this point, any increase in the dose is not accompanied by an increase in effect or  response. Graded - refers to that characteristic of an effect which begins at some low level and increase through progressive stages until it reaches some higher level. 2.

Quanta Quan tall resp respon onse sess or effe effect ctss - “All or None” response. E.q. In toxicity toxicity test, a dose could either kill or not.

Definition of Terms: plasma and lasts until it it reaches minimum Onset of Action - begins when the drug enters the plasma effective concentration (MEC). Peak Action - occurs when the drug reaches its its highest blood or plasma concentration. concentration. Duration of Action - is the length of time time the drug has a pharmacologic effect. Time-response-curve - evaluates three parameters of drug action: the onset of drug, peak action, and duration of action. Biologic Variation - connotes the sum total of all the sources of variation that combine to cause one biologic unit to vary from one another. Threshold Dose - lowest case of a drug that that will produce a measurable response. response. Plateau - endpoint/terminal point in in a graded dose response curve. Therapeutic Index - the difference between the dose which will produce the desired effect and that which will cause adverse effect. - estimates the margin of safety of a drug by using a ration that measures measures the effective therapeutic dose in 50% of animals an imals (ED50) and lethal dose in 50% of animals (LD50). The closer the ratio is to 1, the greater the danger of  toxicity. - a figure that gives measure measure as to the amount by which which therapeutic dose made exceeded before eliciting eliciting a toxic effect. effect. For clinical situation, situation, a  better measure would be adverse effect dose ED50 in which a specific adverse effect is considered, rather than the lethal median dose. Median Effective Dose (ED 50) - smallest dose causing the given pharmacologic effect in 50% of the individuals of a sample. Relative Safety - dose of the drug required to produce the desired therapeutic effect relative to the dose of the drug required to produce toxic or lethal effects. Therapeutic Effects - desirable clinical action of a drug. "Risk - Benefit Ratio" - toxicity taken into consideration consideration --- "the risk of treatment weighed against the risk of disease" e.q. the use of known highly toxic drugs such as those used in the treatment of cancer applies this principle.

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THERAPEUTIC PROCESS Is the Pharmacological effect being translated into a de sired therapeutic effect? Factors which Determine the Relationship Between Prescribed Drug Dosage and DRUG Effect  

Dosage Pathway

Prescribed dose Administered dose

Concentration at locus of action

Intensity of effect

Influences on Drug Effect 

Patient compliance Medication errors Rate and extent of absorption Body size and composition Distribution in body fluids Binding in plasma and tissues Rate of elimination Physiological variables Pathological factors Genetic factors Interaction with other drugs Development of tolerance Drug receptor interaction Functional state Placebo effects

PHARMACOLOGY OF INFLAMMATION - a reaction of the vascular and supporting elements of a tissue to injury which results in in a protein-rich exudate, provided the injury has no t been so severe as to destroy the area. CLINICAL SIGNS OF INFLAMMATION 1 Rubor - Redness 2. Tumor - Swelling 3. Calor - Hotness 4. Dolor - Pain 5. Functio Laesa - Loss of function CLINICAL MEDIATORS  HISTAMINE  a vas vasoa oact ctiive ami amine foun found d in in mos mostt ti tissue ssuess of of the the body body form formed ed by the the dec decar arbo boxy xyla lati tion on of the the ami amino no acid acid hist histid idin ine. e. PHARMACOLOGICAL PROPERTIES OF HISTAMINE - relaxation of the vascular smooth muscle - contraction of the bronchi and gut wall - secretion of exocrine glands - production of pain and itch - acts as neurotransmitter in the CNS (control of thirst, thirst, secretion of antidiuretic hormone,

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control of blood pressure, and pain perception). TYPES OF HISTAMINE RECEPTORS related to smooth m. activity H1 = primarily related H2 = primarily involved with the stimulation of gastric secretions secretions H3 = mediates CNS effects effects of histamine on histaminergic nerve terminals terminals Effects of Histamine: Heart - increase heart rate rate & force of contraction which results in an increase in cardiac output - increase histamine may cause arrhytmias arrhytmias due to slowing slowing of A-V conduction - dilation of small b.v leads leads to flushing, lowered peripheral peripheral resistance, and a drop in blood pressure.

Smooth muscles - “Bronchial muscle’ - activation of H1 receptor results to bronchoconstriction. - Patients who suffer from asthma asthma are particularly sensitive to the action of histamine on the bronchial musculature however, antihistamines are of no value value in the treatment of  asthma. Gastric secretion - even a slow concentration can cause copious secretion secretion of the gastric gastric juices mediated by H2 receptor. Pain and Itch - caused by direct stimulation of free nerve endings when injected. - Subcutaneous injection of histamine causes sharp pain of short duration like a wasp’s sting but when injected into a more superficial layer of the skin, causes itching. ANAPHYLAXIS AND ALLERGY reaction occurring hour after drug Anaphylactic reaction – most dangerous acute allergic reaction administration. - histamine will be released released due to an antigen combining with specific specific antibody attached to the surface of mast cells (DEGRANULATION) causing causing the extrusion of histamine from the secretory granules in the mast cells. - e.q. of substances that can cause anaphylaxis anaphylaxis and allergy: Penicillin, animal fur, fur, pollen. Adverse Effects - undesirable clinical action of a drug; a range of untoward effects (unintended and occurring at normal doses) of drugs that cause mild to severe side effects, including anaphylaxis; Always undesirable. desirable or  Side Effects - are physiologic effect not related to desired rug effects; Maybe desirable undesirable and are predicted. Toxic Effects - adverse effects of an unexpected nature resulting from the direct action of a drug. Allergy - altered capacity of the body to react to various antigens. Idiosyncracies - covers unusual or bizarre drug effects that cannot readily be explained in an individual recipient.

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(self) and ‘akas” (remedy). (remedy). It refers refers AUTOCOIDS – derived from the Greek word “autos” (self) substances which have local hormone-like activity at o r near the site of  production. EICOSANOIDS  – a term that denotes the metabolites of certain 20-carbon polyunsaturated fatty acids, mainly arachidonic acid. - products of arachidonic acid metabolism are divided into two main groups on the basis that they are ultimately derived from the action o f one of the two enzymes systems (cyclo-oxygenase (cyclo-oxygenase or lipoxygenase) on arachidonic arachidonic acid.

ARACHIDONIC ACID ACID - a 20 - polyunsaturated fatty fatty acid Two sources : 1. Metabolic Metabolic pool - endogenous endogenous synthesis synthesis of arachidonic arachidonic acid 2. Cell membrane membrane pool - stimulate stimulated d synthe synthesis sis such as trauma; trauma; major source source of the eicosanoid precursor in inflammation.

Arachidonic acid -----metabolized------ results to metabolites (eicosanoids - a term…) by the action of the 2 enzyme (cyclo-oxygenase and lipoxygenase) lipoxygenase) *In most cells and tissues, phospolipids are thought to b e the major source of arachidonic acid. 1. The first step in eicosanoid synthesis: liberation of the Arach. Acid from cell membrane phospolipids by the action of a group of enzymes known as the phospolipases particularly phospolipase A2 responsible for its bulk. 2. The second step : formation of cyclo-oxygenase cyclo-oxygenase on free arachidonic acid ( results in the the insertion of 2 oxygen molecules into the fatty acid carbon chain to form PGG2 which is rapidly transformed by the peroxydase-like activity of cyclo-oxygenase into the hydroxyperoxide, PGH2). This is followed by the formation formation of one of the three groups depending on the particular cell and circumstances involved, the prostaglandins, thromboxane, and prostacyclin. CYCLO-OXYGENASE PRODUCTS: PROSTAGLANDIN - 1st identified in 1930 but their structure and function were elucidated until 1960. - occur in every tissue tissue and body fluid. –  vasodilators = fall in blood pressure 2 Types: PGE and PGF series THROMBOXANE AND PROSTACYCLIN THROMBOXANE A2 - Main synthesis in in platelets plays an important important role in platelet aggregation  PROSTACYCLIN  - a potent vasodilator and acts as an antagonist of platelet aggregation; main synthesis in vessel walls. *T and P are biologically opposite poles of the mechanism for regulating the platelet vessel wall interaction interaction and the formation of hemostatic hemostatic plug. Both are unstable, with very short half lives.

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LIPOXYGENASE PRODUCTS: LEUKOTRIENES - has potent chemotactic properties; properties; probably involved in the process of cellular infiltration that accompanies inflammation. Types: LTA4; LTB4; LTC4; LTD4; LTE4 PLATELET ACTIVATING FACTOR  - a lipid autocoid synthesized mainly mainly by platelets, leukocytes, leukocytes, and endothelial cells. - action includes vasodilation, inc. in vascular permeability, white blood chemotaxis, chemotaxis, and the release of lysosomal enzymes. - a potent stimulator stimulator of platelet aggregation. - may also be important in the the pathogenesis of asthma. asthma.

Arachidonic Acid Metabolism Product

Cyclo-oxygenase product

Lipoxygenase product

Prostaglandins Thromboxanes Prostacyclin

Leukotrienes Compounds based on eicosatetraenoic acid

BRADYKININ AND KALLIDIN - Polypeptides formed from the plasma alpha globulins by a complex series of  proteolytic reactions. - Potent vasodilators - Increase capillary permeability = oedema - Cause bronchoconstriction - Bradykinin: 10X active than histamine; effects are are brought by:  Kinin Receptors : B1 and B2

 j k 

l

5-HYDROXYTRYPTAMINE (5-HT) - amine formed by the hydroxylation of tryptophan stored in gastric mucosa - dilatation of arteries and constriction constriction of veins via receptors receptors 5HT1 ; 5HT2 ; 5HT3 - high high conce concent ntra rati tion onss are are foun found d in plat platel elet ets. s. - pharmacologic properties: role in inflammation inflammation is uncertain and maybe insignificant; dilation of arteries and constriction of veins. CYTOKINES - Proteins secreted by cells that have effects effects on other cells LYMPHOKINES - cytokines produced by sensitized T lymphocytes and to a lesser 

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extent by B lymphocytes in response to antigenic challenge Actions of Lymphokines: 1. Chem Chemot otact actic ic for for macro macroph phage agess 2. Macr Macroph ophag agee acti activa vati tion on 3. Macr Macroph ophag agee inh inhib ibit itio ion n 4. Chemot Chemotacti acticc for othe otherr monon mononucl uclear ear WBC WBC 5. Mutagen Mutagenic ic for other other lymp lymphoc hocyte ytess 6. Increa Increased sed vascul vascular ar permea permeabil bility ity 7. Activa Activatio tion n of osteoc osteoclas lasts ts.. INTERLEUKINS - cytokines from macrophages and lymphocytes lymphocytes during inflammation and immune immune response. - exerts a number of inflammatory actions which include the stimulation of PG and collagenase production, chemoattraction for WBC and enhancement of the hepatic synthesis of acute phase proteins. - Has 8 types: types: Interleukins 1 – 8. COMPLEMENT - consist of a series of protein that react in in a cascade fashion ANTIHISTAMINES - antagonize histamine at the receptor sites; do not alter the formation or release of histamine from tissues or mast cells. - classified as H 1 or H2 receptor blockers (antagonists)

H1 Receptor Antagonists - interact with H1 receptor on cell membranes - results in a decrease in the availability of  these receptors for the action action of histamine; well absorbed from the git; git; therapeutic effects can be observed within 15-30 min. after dosage; widely distributed in the body and broken down in the liver. - Therapeutic uses: Treatment and prevention of a variety variety of allergic conditions (e.q. rhinitis, hay fever, and certain allergic allergic dermatoses such as acute urticaria). urticaria). Topical application is useful in relieving the itching associated with insect bites; widely used as common cold remedies usually combined with decongestants (e.q. Actifed). - no effect on bronchospasm or severe severe hypotension associated with anaphylactic anaphylactic shock; no value in the treatment of asthma. Unwanted effects: Sedation; may cause stimulation; stimulation; dryness of the mouth; variety of g.i disturbances. *** Alcohol should be avoided while taking H1 blockers as it enhances the sedative seda tive effect. H 2   Receptor ecepto r Antagonists Antago nists - antagonizes the action of histamine at H2 receptor. - commonly used are Cimetidine Cimetidine and Ranitidine. - reduce gastric secretion; Treatment of duodenal ulcers and gastric hypersecretion.

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Unwanted effects: slight such as headache, dizziness, constipation or diarrhea, and skin rashes that are antagonists antagonists for  5-HT ANTAGONISTS - Ergot alkaloids are a group of compounds that 5-HT, Ergotamine. anti-inflammatory properties; widely used in the treatment CORTICOSTEROIDS - have potent anti-inflammatory of recurrent oral ulceration and other oral o ral mucosal lesion such as erosive lichen planus, erythema multiforme, and pemphigus. E.q. 0.1% Triamcinolone (topical) ; hydrocortisone sodium succinate 2.5 mg. ; Bethamethasone 17-valerate (topical spray) ; etc. - pulpal inflammation; TMJ pain; Bell’s palsy; post-operative pain and swelling after after dental surgery; Anaphylactic and allergic reactions.

PHARMACOLOGY OF PAIN Pain - an unpleasant sensory and emotional experience experience associated with actual or potential potential tissue damage, or described in terms of such damage. Analgesia - absence of pain in response to stimulation stimulation which would normally normally be painful. Hyperalgesia - an increased response to a stimulus stimulus which is normally normally painful Neuralgia - pain in the distribution of a nerve. Neuritis - inflammation of a nerve or nerves. Nociception - activity in a nerve fiber fiber which arises as the the result of stimulation stimulation of nociceptors. If nociception reaches consciousness, it is perceived as pain. stimulus or to a stimulus stimulus which Nociceptor - a receptor preferentially sensitive to a noxious stimulus would become noxious if prolonged. prolonged. Pain threshold - the least stimulus intensity at which a subject perceives pain. Pain tolerance level - the greatest stimulus intensity causing pain that a subject is prepared to tolerate. Allodynia - pain due to a stimulus which does not normally provoke pain. sustained burning pain, allodynia and hyperpathia after after a traumatic Causalgia - a syndrome of sustained nerve lesion, often combined with vasomotor va somotor dysfunction and later trophic changes. Hyperaesthesia - increased sensitivity sensitivity to stimulation stimulation excluding special senses. senses. characterized by increased reaction to a stimulus, stimulus, especially Hyperpathia - a painful syndrome characterized repetitive stimulus, as well as an increased threshold. Neuropathy - a disturbance of function or pathological pathological change in a nerve; in one nerve, mononeuropathy; in several nerves, mononeuropathy multiplex; if diffuse and  bilateral, polyneuropathy. Two Main Types of NOCICEPTORS 1. High High Thresh Threshold old Mechano Mechanorec recept eptor  or  2. Polymodal Nociceptor  THEORIES OF PAIN 1. SPECIFIC SPECIFICITY ITY Theory Theory - concerned concerned primaril primarily y with the sensory sensory discrim discriminati inative ve aspects aspects of   pain and its quality, location on the skin, intensity and duration. 2. CENTRAL CENTRAL SUMMATIO SUMMATION N (PATTERN) (PATTERN) Theory Theory – pain is not a separat separatee entity, entity, but results from over stimulation of other primary sensations.

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3. SENSORY SENSORY INTERACTI INTERACTION ON Theory – stresse stressess inhibition inhibition as an important important physiolo physiological gical mechanism in pain transmission. 4. GATE CONTROL CONTROL Theory Theory - stress stressed ed the the importan importance ce of both descending descending contro controll mechanism and activity in large sensory fiber in modulating the pain experience. PERIPHERAL MEDIATORS OF PAIN 1. BRADYKININ 2. HISTAMINE 3. EICOS ICOSAN ANOI OIDS DS Four Main Groups of Eicosanoids 1. Pros Prosttagl aglandi andin n 2. Pros Prosttacyc acycllin 3. Thrombox boxane 4. Leuk Leukot otri rien enes es CENTRAL MEDIATORS OF PAIN 1. Amino Acids 2. Peptides METHODS TO RELIEVE PAIN 1. Remo Remove ve perip periphe hera rall stimu stimulu luss 2. Inte Interr rrup uptt nocice nocicept ptiv ivee input input 3. Stimu Stimulat latee nocicepti nociceptive ve inhibit inhibitory ory mechani mechanism sm 4. Modulate Modulate central central appreciat appreciation ion of pain pain and/or and/or emotional emotional concomit concomitants ants 5. Block or remove remove secondary secondary factors factors mainta maintaining ining pain.

I. NON – NARCOTIC ANALGESICS ANALGESICS General Characteristics 1. Reliev Relieves es pain witho without ut alteri altering ng conscio consciousn usness ess.. 2. Safe Saferr tha than n nar narcot cotic ics. s. 3. Produ Produce ce fewe fewerr side side effe effect cts. s. 4. Not Not add addiictin cting. g. 5. Act princ principa ipall lly y on periphe peripheral ral nerve nerve endin endings. gs. 6. Inhibi Inhibits ts the synth synthesi esiss of prostag prostaglan landin dins. s. PharmacologicAction 1. Analgesia 2. Ant Antipyr pyresi esis 3. Anti Antiin infl flam amma mato tory ry SALICYLATES – extracts of willow bark containing the bitter glycoside salicin. Therapeutically Useful SALICYLATES 1. Salicylic Acid - parent compound., toxic internally, topical fungicide, keratolytic agent. less effective than aspirin, may be 2. Sodium Salicylate - internal use as an analgesic, less used in patients allergic to aspirin.

57 Methyl Salicylate (oil of wintergreen) – external use as a counterirritant, flavoring in cooking. 4. Acetylsalicylic acid - widespread use as an analgesic, antipyretic antipyretic and antirheumatic 5. Salicylamide – internal use as an analgesic; less effective than aspirin; less G.I. irritation. 6. Difflunisal – an investigational salicylate; possibly better tolerated , effective at lower  doses; apparent therapeutic advantage over aspirin aspirin and perhaps other inflammatory agents. 3.

ASPIRIN - absorbed from the git; partly from stomach but mainly mainly in the upper small intestine Pharmacological Properties - Analgesic (mild analgesic) – due to inhibition of the synthesis of PGE. Suitable regimen: 600-1200mg. every 4-6 hours. - Anti-inflammatory – inhibit synthesis of eicosanoids; High concentrations can inhibit the function and activity of PMN leukocytes - Antipyretic – lowers an elevated body temp. (pyrexia) due to to infection, tissue damage, malignancy or other disease states; states; due to inhibition of prostaglandin prostaglandin  production in the hypothalamus. - Antithrombotic effect Unwanted effects - Gastrointestinal – epigastric epigastric pain, nausea, gastric erosions leading to blood loss - Haemostatic effects – prolongs bleeding time; inhibiting the synthesis synthesis of platelet platelet thromboxane. - Tinnitus – hearing loss due to rise in labyrinth labyrinth pressure - Uricosuric effect effect – increase plasma uric acid. Should Not be given to patients with gout(a disorder of uric acid metabolism). - Effects on kidney – decrease renal blood flow; also enhances sodium and water  retention.

Aspirin Hypersensitivity – from rhinitis to life threatening laryngeal edema. Aspirin Overdose – 10-30 gm. can be fatal. Aspirin and Reye”s Syndrome – an acute acu te encephalopathic illness and fatty degeneration of the viscera, especially the liver that arises after an infectious illness such as chickenpox or influenza. - interaction between aspirin and the viral viral infection leads to damage of cell mitochondria in genetically susceptible individuals. PARA-AMINOPHENOLS A. Acetaminoph Acetaminophen en (parace (paracetamol, tamol, N-acetyl) N-acetyl) B. Phenace Phenaceti tin n (acetophe (acetophenet netidi idin) n) ACETAMINOPHEN Pharmacologic Properties 1. Analgesic 2. Ant Antipyr pyretic etic

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3. 4. 5. 6. 7. 8.

Antiinflamm Antiinflammatory atory (not clinicall clinically y signif significant icant)) Do not not produce produce gastri gastricc bleedi bleeding ng Do not not affec affectt plate platelet let adhesiv adhesivene eness ss Do not not aff affect ect uric uric acid acid excr excreti etion on Enhance Enhancess water water trans transpor portt in the the kidne kidney. y. Peak plasma plasma concent concentratio ration n usually usually occur occur 30 minutes. minutes. After dosage, dosage, and the the half life is usually 2 hours. 9. Conjuga Conjugated ted in the the liver liver and excre excreted ted in in the urine. urine. Adverse Effect: 1. Methem Methemogl oglobi obinem nemia ia (Phenac (Phenaceti etin) n) - condition that results from from conversion of the iron in hemoglobin to an oxidized state that cannot effectively carry oxygen. Signs: 1. Cyanosis 2. Dyspnea on exertion 3. Anemia 2. Hemo Hemoly lyti ticc Ane Anemi miaa - Hemolysis is caused by minor metabolites that that oxidize glutathione in the RBC and thereby labilize the erythrocyte membrane to oxidative destruction. Signs: 1. Abdominal or lower back pain 2. Jaundice 3. Hemoglobinuria 4. Anemia 3. Hepa Hepati ticc Nec Necro rosi siss - may occur after ingestion ingestion of a single dose of 10 to 15 Grams. 4. Neph Nephro roto toxi xici city ty Adult dose: 325 to 500 mg. or 2 tablets tablets or capsules; not more than 4 Grams in 24 hours. Unwanted effects: few; most serious is hepatoxicity Paracetamol Overdose: 10-15 gm. – acute liver damage – manifests manifests between 2-6 days after overdose 25 gm. – fatal Treatment: Gastric lavage provided it is is in the first first hour after dosage; <12 hrs. hrs. – N acetylcysteine; after 24 hrs. – the success of treatment depends on the the magnitude of the initial dose. (px will suffer a slow and distressing distressing death). - In postoperative dental pain, efficacy is NOT dose-related.

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) - share many of aspirin’s pharmacological properties. - anti-inflammatory and analgesic analgesic because they can inhibit the synthesis synthesis of eicosanoids. - produce unwanted effects similar to those of aspirin. aspirin. A.

PHENYLPROPIONIC ACID DERIVATIVES  – Ibuprofen, Naproxen, Flurbiprofen and Fenoprofen

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Pharmacologic Properties 1. The mechanism mechanism of action action appears appears to be relate related d to inhibition inhibition of prostagl prostaglandin andin synthetase. 2. Analgesic, Analgesic, antipyret antipyretic, ic, and anti-infl anti-inflammato ammatory. ry. 3. Indicated Indicated for the symptom symptomatic atic treatmen treatmentt of rheumatoi rheumatoid d arthritis arthritis.. Adverse Reaction 1. Gast Gastoi oint ntes esti tinal nal upse upsett 2. CNS effects effects such as dizziness, dizziness, headaches headaches,, drowsiness drowsiness and tinnitus tinnitus.. Naproxen: t1/2 13 hours. Ibuprofen – peak plasma concentration – 1.5 hrs. after dosage and the plasma half life is 2 hours; broken down in the liver; excreted excreted in the urine; has similar  similar  unwanted effects as aspirin. B. INDO INDOLE LEAC ACET ETIC IC ACID ACID 1. Indom ndomet etha haci cin n - most potent inhibitors of cycloxygenase - analgesic, antipyretic, antipyretic, powerful anti-inflammatory anti-inflammatory agent. - used in rheumatoid arthritis. arthritis. - first drug of choice to treat gout. Adverse reaction: - GI complaints - CNS - dizziness, headache, tinnitus, vertigo, confusion – unknown, but may be due to PG inhibition 2. Sulindac - has analgesic, antipyretic effect. - treatment of rheumatoid arthritis. arthritis. C. PYRR PYRROL OLAC ACET ETIC IC ACID ACID Tolmentin Zomepirac D.

FENAMIC ACID DERVIATIVES (FENAMATES) 1. Mefe Mefena nam mic aci acid - treatment of pain, dysmenorrhea - sedation can occur  - absorbed after oral dose; peak plasma plasma concentrations – after 2 hrs.; hrs.; half-life is 3-4 hours. - metabolized in liver, half of metabolites excreted in the urine, half half in the feces. - Diarrhea occurs in 25% of patients - as active active as aspirin; - incidence of unwanted effects effects esp. GI disturbance is high. high.

2. Meclofenamate - treatment of arthritis - dose: initial – 500 mg. followed followed by 250 mg. every six hours.

60 E. PYRA PYRAZO ZOLO LONE NES S Phenylbutazone Oxyphenbutazone F.

DIFFLUNISAL - a difluorophenyl derivative of salicylic acid; has similar pharmacologic properties as aspirin - long plasma half-life half-life – 8 hrs. hrs. (only b.i.d.)

II. NARCOTIC ANALGESIC Similarities: They all produce: 1. Pote Potent nt anal analge gesi siaa 2. Addiction 3. Resp Respir irat ator ory y depr depres essi sion on 4. Sedation 5. Emesis 6. Cons Consti tipa pattion ion CLASSIFICATION 1. OPIU OPIUM M ALKA ALKALO LOID IDS S 2. SEMIS SEMISYNT YNTHET HETIC IC DERIVA DERIVATIV TIVES ES 3. SYNT SYNTHE HETI TIC C DERI DERIVA VATI TIVE VES S I. OPIUM ALKALOIDS - opium is the dried juice juice obtained from the unripe seed capsules of the poppy plant (Papaver somniferum) A. Morp orphine ine  – most potent analgesic in use  – named after Morpheus (Greek God of Dreams)  – undergoes extensive first pass metabolism in the liver.  – Parenteral solutions of morphine sulfate and oral preparations are available.  – t1/2 = 3 hours to 15 mg. subcutaneously subcutaneously every 4-6 hours.  – Dosage: Adult – 10 to Children – 0.1 to 0.2 mg/kg/dose Maximum dose: 15 mg.

Pharmacological Properties 1. Analgesia Analgesia - effective effective against against continuous continuous dull pain. 2. GIT – used used to treat treat diarrhea diarrhea and and dysentery dysentery;; produce produce degree degree a degree degree of  constipation. 3. Cough Cough suppre suppressi ssion on - effect effective ive antitu antitussi ssive. ve. 4. Cardio Cardiovas vascul cular ar - cause cause the releas releasee of of hist histami amine. ne. Unwanted Effects 1. Resp Respir irat ator ory y depr depres essi sion on 2. Depend endence

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3. Naus Nausea ea and Emet Emetic ic eff effec ectt 4. Cause Cause constr constrict iction ion of the the pupil pupil (MIO (MIOSIS SIS)) 5. Acti Action onss on on the the blad bladde der. r. B. Codei Codeine ne or Methy Methyll Morphi Morphine ne - Dose: Adult – 15-60 mg (1/4 to 1 grain)

Pharmacological Properties 1. Effe Effect ctiv ivee when when taken taken by by mout mouth h 2. Use in trea treati ting ng mild mild to to moder moderate ate pain pain 3. Very Very effect effective ive antitu antitussi ssive. ve. Unwanted Effects 1. Nausea Nausea,, vomiti vomiting, ng, sedat sedation ion,, dizzin dizziness ess 2. Can Can depr depres esss res respi pira rati tion on 3. Can Can cau cause se const constip ipat atio ion n C. Heroin - produced by acetylation of morphine - 2 to 5X as potent as morphine as an analgesic. - highly euphoric and addicting drug II. SEMISYNTHETIC DERIVATIVE OF MORPHINE MORPHINE OR CODEINE A. Hydromorphone - more potent than morphine. morphine. - principal use is for acute pain. B. Hydrocodone (Codone, Dicodid) C. Oxymorphone - extremely addicting and a potent respiratory respiratory depressant. - Dose: Adult - 1mg. subcutaneously. - Available only for parenteral parenteral use. III. SYNTHETIC NARCOTICS A. Meper Meperidi idine ne (Demer (Demerol ol)) - most common narcotic abused by professionals. professionals. - Dose: Adult – 50 to 100 mg. mg. orally, subcutaneously, or intramuscularly. - Preparation: Tablets, elixir, and solutions solutions for injections. injections. - available in combination with acetaminophen or promethazine. promethazine.

Adverse Effect 1. Sedation 2. Resp Respir irat ator ory y depr depres essi sion on 3. Increa Increased sed tone tone and secret secretion ionss of GIT 4. Prod Produc uces es addi addict ctio ion n 5. Tole Tolera ranc ncee deve develo lops ps..

62 B. Alpa Alpapr prod odin inee C. D. Anileridine - Dose: usual Adult dose – 25 to 50 mg. every six hours. - can be give orally, orally, intramuscularly or subcutaneously. - available in tablets and injection. OPIOID ANTAGONIST Naloxone - mainly used to treat opioid opioid overdose, particularly the effects effects on respiration. - must be given intravenously. intravenously. - 0.4 to 0.8 mg for immediate effect - t1/2 1 hour 

COMPREHENSIVE DRUG ABUSE PREVENTION and CONTROL ACT OF 1970

SCHEDULE 1 SUBSTANCES Drugs with a high potential for abuse and no currently accepted medical use. •  Not for prescription use but may be obtained for research purposes. • E.q. Heroin Ketobemidone Marijuana Benzylmorphine Peyote Nicomorphine Mescaline Methaqualone LSD Dihydromorphine Nicodeine Racemoramide Morphine methylsulfonate Levomoramide SCHEDULE II SUBSTANCES Drugs with a high potential for abuse with severe liability to cause psychic or physical • dependence. Consists of certain certain opioid drugs and drug containing amphetamines or metaamphetamines as • the single active ingredient or in combination with each other. Categorized as “Class A Narcotic Drugs.” • E.g. Opium Morphine Codeine Hydromorphone Amobarbital Methadone Meperidine Cocaine Oxycodone Pentobarbital Diphenoxylate Phemetrazine Methylphenidate Secobarbital Methamphetamine Dextroamphetamine Etorphine hydrochloride

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SCHEDULE III SUBSTANCES Drugs with a potential for abuse that is less than those in schedules I and II substances. • Their abuse may lead to moderate moderate or low physical dependence or high psychological • dependence. Drugs included was formerly formerly known as “Class B Narcotic Narcotic drugs” plus a number of non• narcotic agents. E.q. Chlorhexadol Gluthethimide Methylprylon Sulfodiethylmethane Sulfonmethane Nalorphine Benzphetamine Chlorphentermine Phendimetrazine Certain barbiturates except those listed in another schedule. SCHEDULE IV SUBSTANCES Drugs with with low potential for abuse that leads only to limited physical physical or psychological psychological • dependence relative to drugs in Schedule III. E.q. Barbital Phenobarbital Ethinamate Paraldehyde Phentermine Methohexital Fenfluramine Methylphenobarbital Chloral betaine Chloral hydrate Meprobamate Propoxyphene Benzodiazepines Mebutamate Ethchlorvynol SCHEDULE V SUBSTANCES Drugs have a lower potential for abuse than those in Schedule IV for which there is currently • accepted medical use in the U.S. Drugs are categorized as “Exempt Narcotics.” •

HEMOSTATICS Locally applied substances that are employed to arrest excessive bleeding or hemorrhage. Sympathomimetics - reduce bleeding bleeding by local vasoconstriction. E.q. Epinephrine Styptics and Astringents - precipitates the tissue tissue proteins in in the immediate area. E.q. Zinc Chloride, Chloride, Aluminum Chloride, Ferric Sulfate Mechanical Agents - acts as matrices in in which blood cells / fibrin fibrin can be entrapped. E.q. Gel foam, Oxidized Cellulose, Oxidized Regenerated Cellulose. Thrombin - normal constituent of the blood coagulation scheme, scheme, combines with fibrinogen. fibrinogen.

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HEMOSTASIS AND HEMOSTATIC AGENTS Factors in the Arrest of Hemorrhage 1. Vessel wall contraction - of short duration (5-20 minutes) - can be prolonged by topical or local infiltration infiltration of Adrenaline. Adrenaline. 2. Adhesion and Aggregation of Platelets - Platelets are non-nuclear cells with a cytoplasm rich rich in granules. - normal count: 150,000 – 4000,000 cells/ml. - half life is 7 to 10 days - releases Adenosine Diphosphate (ADP) and Thromboxane A2 - forms Platelet PLUG 3. Ability of blood to coagulate Stage I - Activation of Factor X --- Xa Stage II – Prothrombin Prothrombin (II) --- Thrombin Stage III - Fibrinogen (I) --- Fibrin --- Clot Stage IV - Fibrin Clot - Lysed fibrin and fibrin peptides. 4. Fibrinolysis (The breakdown of blood clot) - can be influenced by age, sex, diet, smoking, altitude, exercise.

VITAMIN K  - fat soluble vitamin that is essential for the normal hepatic biosynthesis of  several factors required for blood clotting. (II, VII, IX, X) ANTICOAGULANTS - they directly or indirectly interfere interfere with the normal clotting mechanism mechanism of blood. - patients receiving are those with with a history of myocardial myocardial infarction, cerebrovascular  thrombosis, venous thrombosis, and pulmonary embolism. A. Heparin - enhances the activity of antithrombin antithrombin III (neutralizes several of the activated clotting clotting factors Ixa, Xa, Xia, and XIIa. XIIa. It also inactivates prothrombin prothrombin by forming an irreversible complex with it). - must be administered parenterally. parenterally. - half life is between 1 to to 5 hours (the higher the the dose, the higher the half life) life) - Unwanted effects: Heamorrhage and Thrombocytopenia. - the effect can be reversed by the the specific antagonist (Protamine (Protamine Sulphate) at eh dose regimen of 1 mg. of protamine p rotamine for every 100 units of heparin. B. Coumarin Anticoagulants - Oral anticoagulants - includes Warfarin Sodium and Phenindione. - antagonist to to vitamin vitamin k  - reduces synthesis of vitamin vitamin K dependent clotting factors (II, (II, VII, IX, X). X). - affected by diet, bowel disease, pyrexia, pyrexia, age, pregnancy, liver disease.

65 ANTIPLATELET DRUGS - Antithrombotic - decrease thrombin formation E.q. Aspirin, Diprydamole, Sulphin Sulphin Pyrazone. Pyrazone. FIBRINOLYTIC DRUGS - promotes the breakdown of thrombi thrombi by activation of plasminogen to form plasmin. E.q. Streptokinase, Urokinase, Urokinase, Tissue Plasminogen Activator. Activator. ANTIFIBRINOLYTIC DRUGS - these encourage the stabilization of fibrin fibrin by inhibiting inhibiting plasminogen activator. E.q. Tranexamic acid - effects: Nausea, diarrhea, hypotension.

DENTAL MANAGEMENT OF PATIENTS WITH HEMOSTATIC PROBLEMS 1. Impaired Platelet Function - due to reduction in platelet count or impaired aggregation due to drug therapy. therapy. - Treatment: Low platelet platelet count – Platelet Platelet transfusion before surgery. Thrombocytopenia due to immune destruction of p latelet – Administration of corticosteroid - it is a wise precaution to suture and pack the socket to to minimize the risk of post extraction hemorrhage. - drugs that impair platelet platelet aggregation and increase bleeding time includes Aspirin, Aspirin, NSAID’s, Sodium Valproate, and Phenytoin. 2. Vascular Defects - associated with vitamin C deficiency and long term corticosteroid corticosteroid therapy. - patients have increased capillary fragility fragility which can cause bleeding problems after  surgery. - can be controlled by pressure, suturing, and packing. 3. Impaired Coagulation A. Haemophilia - sex-linked; affects affects only males. - patients have reduced factor VIII VIII activity. activity. - can be corrected by replacement therapy of freeze-dried factor VIII VIII (cryoprecipitate). - drugs used in conjunction with factor factor VIII include anti-fibrinolytic anti-fibrinolytic agents, epsilon aminocaproic acid which should be started pre-operatively. B. Christmas Disease - associated with a deficiency of factor IX (derived from from plasma but not present in cryoprecipitate). - Replacement therapy. C. Von Willebrand’s disease - inherited disorder associated with both prolonged bleeding time time and deficiency deficiency of  factor VIII.

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- replacement therapy is necessary. necessary.

LOCAL ANESTHETICS - reversible Blockade of Peripheral Nerve Conduction; drugs that have little little or no irritating irritating effects when injected into the tissues and that will temporarily interrupt conduction when absorbed into the nerve. Autonomic Losses in the usual order Sense of Cold 1. 2. Warmth 3. Pain 4. Touch 5. Pressure 6. Vibration 7. Proprioception 8. Motor function Components of Local Anesthetics A. Anes Anesth thet etic ic Drug Drug B. Vaso Vasoco cons nstr tric icto tor  r  e.g. epinephrine, levonordefrin

m n

Role of Vasoconstrictor in Local Anesthetics Prolong Local Block  Delay Systemic Absorption Limit Toxicity C. Antioxidant e.g. Sodium Bisulfite Bisulfite or Sodium Pyrosulfite D. Antiseptics methy ethyllpara parabe ben n Ideal Properties of Local Anesthetics 1. Potent Local Anesthesia 2. Reversible Local Anesthesia 3. Absence of Local Reactions 4. Absence of Systemic Reactions 5. Absence of Allergic Reactions 6. Rapid Onset 7. Satisfactory Duration 8. Adequate Tissue Penetration 9. Low Cost 10. Stability in Solution (long shelf life) 11. Sterilization by Autoclave 12. Ease of Metabolism and Excretion

67 Two Groups: ESTER group and AMIDE group CHEMISTRY OF LOCAL ANESTHETICS

 

Aromatic Nucleus

Linkage

Amino Group

ESTER  O R1 ------

-- C – O – R2 --

R3 ------ N 

R4  ____________________ o r ____________________________  AMIDE H O R1 ------

R3

-- N – C – R2 -- ------ N R4

Absorption: Increase vasodilation = Increase speed of circulation Distribution: Brain, liver, kidneys, lungs, spleen. Metabolism: Ester – hydrolyzed in in plasma by plasma cholinesterase. cholinesterase. Amide – Liver  Prilocaine – Lungs Excretion: Kidney Pharmacologic Effects 1. Revers Reversibl iblee periphe peripheral ral nerve nerve condu conducti ction on 2. Smooth Smooth muscle effects effects – relaxation relaxation of smooth smooth muscle muscle because because sensory sensory receptor receptorss are depressed. 3. Anal Analge gesi sicc effe effect ct 4. Anti Antico conv nvul ulsa sant nt effe effect cts. s. Most Local Anesthetics are Synthetic except Cocaine 1. An Aro Aroma mati tic, c, Lip Lipop ophi hili licc Grou Group p 2. An Interm Intermedi ediate ate Chain Chain (Ester (Ester or Amide Amide Linkag Linkage) e) 3. A Hydrop Hydrophil hilic ic 2º or 3º amino amino group, group, which which forms forms water water solubl solublee salts salts when when combined with acids. Generally almost without exception, exception, Drugs thus formed formed are: White and Odorless Viscid Liquids or Amorphous Solids Fat Soluble but relatively Insoluble in water  All are Bases and form form Water Soluble Salts with Acids

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Toxicity of Local Anesthetics: Descending stimulation of the C.N.S. followed by DEPRESSION of certain areas of the brain

o

Classic Progression: 1. Restlessness, Apprehension and Tremors progressing to Excitement and Convulsions 2. Increase Blood Pressure and Pulse Rate 3. Increase Respiratory Rate 4. Respiratory Respiratory and cardiovascul cardiovascular ar depression depression with Loss of reflexes reflexes and consciousnes consciousness. s. Characteristics of Lidocaine Toxicity:  DEPRESSION, generally the cause of Death, may appear without initial stimulation.

GENERAL ANESTHESIA - the drug induced absence of the perception of all all sensation allowing surgery or other painful procedures to be carried out. - depresses the CNS; alleviate alleviate pain and cause a loss of consciousness. HISTORY Nitrous Oxide “laughing Gas” described by john Priest Horace Wells observed its effects as anesthetics. Ether – by T.G. Morton and C.T. Jackson Highly flammable, volatile, pungent odor. Chloroform - volatile liquid; liquid; by J.Y. J.Y. Simpson THEORIES ON MECHANISM OF ACTION OF G.A. 1. Lipi Lipid d or Meye Meyerr Overt Overton on Theor Theory y 2. Inhibi Inhibitio tion n of biochem biochemica icall Actio Action n 3. Mole Molecu cula larr theor theorie iess Pharmacologic Effects 1. CNS CNS depr depres essa sant ntss 2. CVS CVS dep deprressi ession on 3. Urin Urinee outp output ut is redu reduce ced d 4. May May pro produ duce ce liv liver er dam damage age.. 5. Release Release of ACTH, ACTH, antidiureti antidiureticc hormone, hormone, sympathetic sympathetic neurotra neurotransmi nsmitters tters.. STAGES OF ANESTHESIA (Guedel’s (Guedel’ s Classification) Stage I : ANALGESIA - from administration administration of anesthesia – loss of consciousness Analgesia Euphoria Perceptual distortions Amnesia

Stage II : DELIRIUM - loss of consciousness – beginning of surgical surgical anesthesia Excitement

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Involuntary muscular activity (Increase muscle tone) Irregular breathing Hypertension Tachycardia Stage III : SURGICAL ANESTHESIA ANESTHESIA - state of analgesia associated with with majority of surgical surgical procedures - spontaneous respiration ceases * 4 Planes based on: Respiration Size of pupils Reflex characteristics Eyeball movement Stage IV : -

MEDULLARY DEPRESSION DEPRESSION / RESPIRATORY PARALYSIS PARALYSIS begins with cessation cessation of respiration respiration – circulatory collapse Pupils fixed and dilated No lid or corneal reflexes If not reverse immediately, Death occurs. •

PHASES OF  ANESTHESIA (Flagg) INDUCTION - encompasses all the preparation and medication medication necessary for a patient patient up to the time the surgeon is ready to begin. MAINTENANCE - begins with the patient at a depth of anesthesia sufficient sufficient to allow surgical manipulation manipulation and continues until completion of procedure. RECOVERY - begins with the termination termination of the surgical procedure and continues through through the post operative period until the patient is fully responsive to the environment.

CLASSIFICATION OF G.A. BY ROUTE OF ADMINISTRATION Inhalation

Gases

 

Nitrous Oxide

Intravenous Agents

Volatile liquids

Halogenated Hydrocarbon Chloroform

Neuroleptics Fentanyl with Droperidol

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Ethyl Chloride Trichloroethylene (Trilene, Trimar) Halothane (Fluothane)

Cyclopropane Ethylene

Halogenated Ether Methoxyflurane (Penthrane) Enflurane (Enthrane) Isoflurane (Forane) Ether Diethyl Ether (Ether) Vinyl Ether  (Vinethene)

(Innovar) Dissociative Ketamine (Ketalar, Ketaject) Barbiturates Methohexital (Brevital) Thiamylal Sodium (Surital) Thiopental Sodium (Pentothal) Narcotics Fentanyl (Sublimaze) Morphine

“BALANCED ANESTHESIA” - PRE-ANESTHETIC MEDICATION- INDUCTION- NEUROMUSCULAR BLOCKING -AGENT - ANESTHETICSGOAL: ANALGESIA SLEEP MUSCLE RELAXATION ABOLITION OF REFLEXES PREMEDICATION Features Required of PREMEDICATION Agents 1. Allevi Alleviate ate pre-op pre-opera erativ tivee anxiet anxiety. y. 2. Provide Provide some some degree degree of post-ope post-operati rative ve amnesia amnesia esp. esp. in children. children. 3. Make the induction induction and maintenance maintenance anaesthesia anaesthesia easier. easier. 4. Reduce the the amount of anaesthet anaesthetic ic agents agents required required by enhanci enhancing ng their their effects effects 5. Provi Provide de additio additional nal analges analgesia. ia. 6. Reduce Reduce sali salivar vary y and bronch bronchial ial secr secreti etions ons.. 7. Reduce activity activity in in the parasympat parasympathetic hetic nervous nervous system. system. PREMEDICATION AGENTS OPIOIDS - e.q. Morphine, Pethidine, Papaverum

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Therapeutic Effects: Analgesic, Sedative, Euphoriant, Respiratory depression, depression, Suppression of cough reflex Unwanted Effects: Effects: Nausea, Vomiting ANXIOLYTICS - e.q. Benzodiazepines - used orally to provide post-operative sedation. sedation. ANTIPSYCHOTICS (Neuroleptics) e.q. Penothiazines derivatives – promethazine and Trimeprazine. - pre-anaesthetic sedatives; anti-emetic; for patients patients who who fear or has predisposition predisposition to to post-operative vomiting; depresses d epresses respiration: cause varying amount of hypotension. ANTICHOLINERGIC Atropine Sulphate; Hyoscine; Glycopyrrolate - reduce secretions; prevent overactivity of the parasympathetic nervous system. system. Atropine Sulphate - commonly used to reduce salivary and bronchial secretions during anesthesia by antagonizing the actions of acetylcholine at muscarinic receptors.

muscarinic receptors; Hyoscine - antagonizes the effect of endogenous acetylcholine at muscarinic given IM 30-60 minutes before induction anesthesia; a CNS depressant – causes drowsiness and depression of the vomiting center -anti-emetic. -anti-emetic. Athigh doses, it may act as stimulant of the CNS. Both atropine a nd hyoscine block the action of  acetylcholine released from the vagal nerve endings which gives some protection against vagal stimulation. Glycopyrrolate - a quarternary ammonium; produces prolonged and good control of  salivary and pharyngeal secretions; less effect on the cardiovascular system; used as   preoperative or intraoperative antimuscarinicto antimuscarinicto attenuate or prevent the intra-operative bradycardia sometimes associated with the use of suxamethonium or  due to cardiac vagal reflexes.. NEUROMUSCULAR BLOCKING AGENTS - by specific blockage of the neuromuscular junction, they enable light levels of ane sthesia to be used with adequate relaxation of the muscles of the abdomen and diaphragm;   produce relaxation of the abdominal muscles, and paralysis of the respiratory muscles; relaxes the vocal cords allowing the passage of a tracheal tube. Two Types of Neuromuscular Blocking Agents I. NON DEPOLARIZING MUSCLE RELAXANTS(competitive) Tubocurarine - highly ionized; ionized; given IV ; produce paralysis of all voluntary muscles; action commences 3-4 mins. mins. and lasts up to 40 mins.; used as an adjunct to G.A.; action may be reversed by administration of neostigmine neostigmine ; a weak ganglion blocker   – causes the release of histamine histamine -- peripheral vasodilation - - will lower the b.p. ; may also cause flushing and bronchospasm due to the release of histamine; does not cross the blood brain barrier or the placenta.

72 Pancuronium - more potent than Tubocurarine but has a shorter action; acts by competitive block but does not normally n ormally block transmission in autonomic ganglia and so does not significantly significantly alter the blood pressure. pressure. However, if rapidly injected injected IV, it may cause a rise in bp due to vagal blocking and tachycardia; does not cause histamine to be released; may also be used to produce relaxation in a number of  pathological conditions such as tetanus; also used extensively in ICU. the present time; have little little effect Atracurium and Vecoronium - most often used at the on the cardiovascular system; system; may release little little of histamine; more advantageous to patient’s with renal or hepatic impairment.

II. DEPOLARIZING MUSCLE RELAXANTS Suxamethonium - depolarizes the postsynaptic membreane and maintains this state so that the adjacent m. fibers are electrically inexcitable; inexcitable; injected IV; produces complete muscular relaxation in half a minute; has a number of muscarinic action action including increase in salivary secretion, muscle injury occasionally due to direct action on the muscle or may follow K depletion from muscles.; may cause malignant hyperpyrexia – maybe treated by rapid cooling, inhalation of 100% oxygen and IV of Dantrolene 1 mg/kg of body weight. * MUSCLE CONTRACTION  action potential ---- travels travels down the motor nerve---- release of packets of acth (quantamillions of acth molecules) molecules) ----- acth crosses crosses the synaptic cleft and interacts with the cholinergic receptors on the end plate of a muscle fiber ------- surge of acth brings brings a massive increase in the permeability of the post-synaptic membrane to Na ions and to a < extent to K ions (Na ions enter and generate a local end plate potential potential (depolarization) until it reaches a critical threshold --- triggers off a muscle action potential propagated along the muscle fiber causing it to contract. Acth is then broken down by cholinesterase in the neuromuscular junction; the motor end  plate polarizes and is then ready to be stimulated again. INDUCTION AGENTS (IV ANESTHETIC AGENTS) - widely used to induce anaesthesia

acting barbiturate; given IV; produces loss of  Sodium Thiopentone - an ultra short acting consciousness in 10-20 seconds. Max. depth occurs 40 secs. ; px becomes conscious 2-3 mins. after dosage; provide anes. for short operative procedures; induce unconsciousness prior to to inhalation inhalation anaesthesia; rapidly enters the the brain; 85% bound to plasma plasma protein; protein; metabolized in the liver; excreted in the kidney; depresses many of the the functions of CNS; no analgesic properties; low doses may increase increase sensitivity to pain; an anticonvulsant; often associated associated with laryngospasm; bronshospasm; cough; extravascular injection may cause pain and necrosis when the concentration is > 2.5%; endothelial and deeper layer  may be damaged when inadvertently injected into an artery; must not be given to patients with porphyria no effect on the uterus but can cross the placenta and a nd depress the fetal cardiovascular system; there is transient transient drop in blood pressure. Methohexitone - an ultra short acting acting barbiturate; Pharmacological properties – same with Thiopentone Unwanted effects - pain on injection, injection, involuntary movements, cough, and laryngospasm;

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has convulsant properties Etomidate - a carboxylated imidazole derivative; derivative; rapid recovery and lack of “hangover’ effect may be due to short plasma half life; life; does not release histamine; painful, cause involuntary movements; prolonged use may cause adrenocortical suppression suppression in ICU; has little or no effect on the cardiovascular system. Ketamine - given IV but can be given IM; associated with profound profound sedation sedation and analgesia; produces dissociation but not sedation and so airway reflexes are maintained; vivid hallucinations hallucinations and nightmares; raises b.p. and pulse rate; rate; useful in management management of  mass casualties. Propofol - a new phenolic IV induction agent and maintenance anaesthesia provided provided the the surgical procedure does not exceed 1 hour.; recovery is usu. rapid and often accompanied by euphoria; sexual fantasies can also occur; highly lipophilic; More expensive. Unwanted effects - cardiac respiratory respiratory depression; depression; apnea and marked hypotensive effect; effect; pain on injection. INHALATION ANAESTHESIA - most widely used form of maintenance anaesthesia

INHALATION ANAESTHETIC AGENTS Nitrous Oxide - E.q. Entonox colorless, odorless gas; weak anaesthetic; an adjunct to other inhalation agents; may produce severe hypoxia when used alone; an excellent analgesic agent; a direct myocardial depressant; stimulates sympathetic nervous system; may cause nausea, vomiting, (megaloblastic anemia and neuropathy in animals); suppresses spermatogenesis and production of WBC and RBC in bone marrow; Uses: changing painful dressing, an aid to post-operative physiotherapy and emergency ambulances. colorless at room temperature; temperature; has pleasant Halothane - a halogenated hydrocarbon; colorless smell;not inflammable; non explosive; causes dose-related reduction in b.p.,slowing of  heart rate; severe dysrhythmia; dysrhythmia; bronchodilation ; depresses respiration; no analgesic property and does not produce a degree of relaxation; may cause hepatic necrosis. Enflurane - a halogenated ether; colorless at room room temperature; non flammable with with a mild sweet odor; alters electrical activity in the brain; 80% excreted unchanged in expired gases, 2.5 % metabolized in the liver and excreted in the kidney; produces a dose-related reduction in b.p.; causes respiratory depression; twitching of the limbs, jaws, face and neck but self limiting; no significant effect on the liver  physical properties Isoflurane - isomer of enflurane; a halogenated methylethyl ether; physical similar to enflurane; reduction in b.p. but has little or no effect on cardiac output; increase in heart rate but no arrythmias; depresses respiration and stimulates airway reflexes causing increased secretion, coughing and laryngospasm. safest volatile liquids irritating to the mucus membrane; Ether - one of the earliest and safest inflammable and explosive; often associated with nausea and vomiting; now rarely used. ANAESTHETIC EMERGENCIES 1. Resp Respir irat ator ory y Obstr Obstruc ucti tion on

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2. Hypers Hypersens ensiti itivit vity y reacti reaction on

ANTISEPTICS AND DISINFECTANTS - substance that kill or prevent the growth of microorganism Antiseptics - used on living tissues. Disinfectants – applied on inanimate objects. 1. ALCOHOLS A. Ethyl Alcohol and Isopropyl Alcohol B. Chlorhexidine and Iodine C. Surgical Spirits – mixture of ethyl/methyl alcohol

 p q r 

s t u v

2. ALDEHYDES A. Formaldehyde – bactericidal activity on bacteria, fungi, and viruses; action is very slow  – 0.5% will take 12 h rs.; 2-8% concentrations to disinfect inanimate objects. B. Glutaraldehydes – acts against all microorganisms; less viruses, odor; 2% concentration; for cold sterilization; sterilization; for articles contaminated contaminated by hepatitis B virus that cannot be heat sterilized; 1 – 12 hour exposure. C. Chlorhexidine (Hibitane) – antiseptic and disinfectant 1. Hibiscrub ICI – pre-operative preparation of skin and hand disinfection. 2. Hibisol ICI – disinfection of sin and hands. 3. Corsodyl ICI – in dental gel; mouthwash 0.2% solution.

Hibita Hibitane ne Obstet Obstetri ricc cream cream (ICI) (ICI) – pre-ope pre-operat rative ive prepar preparati ation on of hands hands and skin skin of  midwife/docto ctor. Hibitane Concentrate – general purpose antiseptic

w 3. DYES – complex organic substances from coal tar e.q. aniline dyes, gentian violet, brilliant green, acnidine dyes, acriflavin and proflavine. 4. HALOGENS – reacts with bacterial proteins. 5. CHLORINE – has a rapid, potent and brief action; effective against most bacteria, some fungi, yeast, and viruses; in the form of hypochlorites, organic chloramines, chlorinated isocyanurates; inactivated by organic matter. 6. IODINE – acts as much the same way as chlorine but not readily inactivated by organic matter; bactericidal and fungicide; present in weak solution of 2.5% iodine in potassium iodine, water and alcohol; stains skin. 7. IODOFORM – mild antiseptic antiseptic E.q. whiteheads varnish incorporated into ribbon ribbon gauze for  infected sockets and dressing for surgical removal; contains iodoform with benzoin, storax, and balsam of tolu in solvent ether; Kri-paste- used as root canal filler; Kri liquid - sterilize root canals. 8. IODOPHORS – combination of iodine and surface active detergents; effective against

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gram + - organisms after 15 secs.; doesn’t stains skin. E.q. Povidone Povidone Iodine 9. OXIDIZING AGENTS – liberates oxygen which oxidizes proteins of bacteria and tissue proteins. Hydrogen Peroxide – mild antiseptic; 30% aqueous solution to bleach discolored root filled teeth; mouthwash in acute ulcerative gingivitis. Sodium Perborate – treatment of acute ulcerative gingivitis; liberates oxygen when in contact with organic matter. 10. PHENOLS, CREOSOLS and their derivatives Phenol - 80% in water; irritant and caustic producing a burning pain; produces feeling of  anesthesia CMCP (Camphorated para-aminophenol) – 35% in camphor; medicament in root canals. also toxic E.q. Metacrsyl acetate (Cresatin) (Cresatin) –  Cresol – 3x bacteridal potency of phenol; also irrigation of root canals; not irritant to periapical tissues. Chloroxylenols – less effective than phenolic agents; activity reduced in the presence of  organic matter. E.q. Dettol (5% chloroxylenol). Hexachloropane – excellent disinfectant; for gram + cocci; not very irritant to tissues but has neurotoxic effects on babies (dusting powders).

11. SURFACE ACTIVE AGENTS Classification according to ionic charge: CATIONIC CATIONIC - positive charge; includes quarternary ammonium compounds such as: 1. Benzalkonium ch chloride (Z (Zepiran) 2. Cetylpyridinium (C (Ceepryn) 3. Cetrimide (Cetavlon)

- bactericidal against some gram + and some gram negative bacteria; little little effect on tubercle bacilli, spore forming microbes and psuedomonas aeruginosa;  ANIONIC  - negative charge; not bactericidal, only o nly enhances physical removal of bacteria; effective against gram + microorganism; E.q. Sodium lauryl sulfate and green soap. DENTAL USES OF ANTISEPTICS 1. Skin Skin preparat preparation ion before before surge surgery ry or injec injectio tion n 2. Pre-o Pre-oper perati ative ve prepara preparatio tion n of the oral muco mucosa sa 3. Someti Sometimes mes as an an ingredi ingredient ent of dentr dentrif ifice icess 4. Inhi Inhibi biti tion on of den denta tall plaqu plaquee 5. Clea Cleani ning ng of ope opera rati ting ng area areass 6. Cold sterilizat sterilization ion of instru instruments ments and equipm equipment ent 7. Stora Storage ge of steri sterili lized zed surgi surgical cal equip equipmen mentt 8. Prepar Preparati ation on of surgeon surgeon’s ’s hand 9. Irrig Irrigati ation on of root root canal canalss in endodo endodonti ntics. cs.

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DEFINITION OF TERMS Antimicrobial Agents – substances that kill or suppress the growth or multiplication or prevent the action action of microorganisms Anti-infective Agents – substances that act against or tend to destroy infection. Antibacterial Agents – substances that destroy or suppress the growth or multiplication of  bacteria. Antiviral Agents – substances that destroy or suppress the growth or multiplication of viruses. Anti-fungal Agents – substances that destroy or suppress the growth or multiplication of fungi. b y microorganisms that have the capacity, in Antibiotic Agents – chemical substances produced by dilute solutions, to destroy destroy or suppress the growth or multiplication of  organisms or prevent their action.

Antibacterial (Antimicrobials) – are obtained from natural sources or are manufactured Antibiotic – chemicals that are produced by one kind of microorganism that inhibit or kill another  kind of organism. * The difference between antibiotic an tibiotic and synthetic antibacterial agents is that antibiotics are produced by microorganisms and the antibacterial an tibacterial agents are made in the laboratory. Classification of Antibacterials According to its ACTION

1. Bacteriostatic  – inhibit or retard the the multiplication or growth of bacteria but does not kill them. E.q. Tetracyclines, sulfonamides, chloramphenicol - bacteria can grow again when drug is withdrawn. - Host defense mechanism (e.q. phagocytosis) phagocytosis) are required to kill the microorganism. 2. Bactericidal – drugs that kill bacteria. E.q. Penicillin, Cephalosphorins, Cephalosphorins, Aminoglycosides, Vancomycin, Metronidazole, Imipenem. - best choice in treatment especially especially in life threatening threatening infections, endocarditis and in patients whose leukocyte count is <500μ/L * some drugs may be bacteriostatic at low concentrations and bactericidal at high concentrations against the same or different microorganisms; In patients with impaired defense mechanism, a bactericidal is preferred over a bacteriostatic agent because the body’s b ody’s ability to fight infection is compromised. c ompromised. Classification According to RANGE OF ACTIVITY Spectrum – the range of activity of a drug. 1.  Narrow Spectrum – acts against either gram positive or  gram negative organisms. one type of organism; only selective. E.q. Penicillin and erythromycin – gram + bacteria.

2.  Broad Spectrum – acts against a wide variety of organisms – effective on both gram + and gram –   bacteria as well as some viruses; treats infection not

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identified by culture and sensitivity test. E.q. Tetracylcine and Cephalosphorins. INFECTION – invasion of the body by pathogenic microorganism and the reaction of the tissues to their presence and to the toxins generated by them. Principal factors that determine a microorganism causing an infection 1. Virule Virulence nce of the microo microorga rganis nism m 2. Numb Number er of orga organi nism smss pres present ent 3. Resi Resist stan ance ce of the the hos hostt How do Microorganism cause an infection? 1. Infectivit Infectivity y (must (must enter the right right portal portal of entry) entry) 2. It must must be able able to multiply multiply on the body body of the the susceptib susceptible le host. host. 3. Invasiveness Invasiveness (effective (effective mechanism mechanism for transmiss transmission) ion) 4. It must be be able to produce produce toxins, toxins, enzymes enzymes and other other metaboli metabolites tes that affect affect the the cell or toxigenecity.

Two Goals to be achieved to prevent infection 1. Reduce the number number of bacteri bacteriaa in the surgic surgical al wound. wound. 2. Enhance the the host’s host’s defenses defenses so as to prevent prevent the the bacteria bacteria that entered entered the wound wound from causing clinically clinically evident infection. INDICATION FOR ANTIMICROBIAL AGENTS A. Prophylactic Indications - used for high risk patients whose immune system system are weak. E.q. in rheumatic or  congenital heart disease, Renal dialysis patients, or the presence of a heart prosthesis. Any dental procedure may precipitate a bacteremia, therefore, prophylactic antibiotics must be given to prevent b acterial endocarditis. B. Therapeutic Indication - for the treatment of infection. “Does this particular patient need the assistance of antimicrobial agents to resolve this particular infection?" * NOT ALL INFECTIONS REQUIRE ANTIBIOTIC THERAPY, THERAPY, it all depends on: 1. The patient . “host responses” - Defense mechanism mechanism is considered. - The presence or absence of systemic systemic manifestation such as fever, fever, malaise, and lymphadenopathy are indicators of how well the p atient is doing without antimicrobial therapy. 2. The Infection. - The virulence and invasiveness of the the etiologic microorganism are important important in determining the acuteness, severity, and spreading tendency of the infection which is obviously need to be treated with antimicrobial agents. Five Basic Principles in the Use of Antibiotics / Antimicrobials 1. Infection must be present present or imminent - consider the the signs signs of inflammation. 2. Identify the organism organism - accomplished through through culturing, culturing, gram stain or educated guesses. Purpose: To determine the specific type type of antimicrobial sensitive sensitive to the specific type type of 

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microorganism. 3. Choose the specific specific type of antibiotic --------------------------------------------------------------------------------------------------------Antibiotics G- & G+ G-------------------------------------------------------------------------------------------------------Phenoxymethyl Penicillin ++++ + Penicillin G ++++ + Ampicillin +++ Erythromycin +++ ++ Clindamycin +++ + Cephalosporins +++ + Tetracycline ++ +++ Aminohlycoside + ++++ ---------------------------------------------------------------------------------------------------------4. Administer antibiotics properly 5. Prevent and minimize toxicity and hypersensitivity. hypersensitivity. a. right dose  b.  b. right right dose dose inte interv rval al c. righ rightt dos dosee for form m d. right right dura durati tion on of ther therapy apy Duration of dosage: - An antimicrobial agent should be continued long enough to prohibit a regrowth of the causative microorganism, but not so long to induce toxic drug symptoms symptoms or alter the normal flora to the extent that superinfection results ** It should continue 48 hours after the symptoms symptoms of infection infection are absent. If beta hemolytic streptococci are the causative organisms, usually penicillin should be continued for at least 10 days. For osteomyelitis, it should be con tinued for 14 days after  fever and tenderness are absent and drainage has ceased. In patients with a depressed immune system or history of prolonged healing, coverage usually needs to be continued longer than in normal patient. MECHANISM OF ACTION OF ANTIBACTERIALS 1. Inhibition of cell wall synthesis a. Inhibition of cross linking (transpeptidation) of peptidoglycan. e.q. Penicillins; Cephalosporins. b. Inhibition of other steps in peptidoglycan synthesis. synthesis. e.q. Vancomycin, Cycloserin, Bacitracin. 2. Inhibition of protein synthesis x a. Action Action on 50S ribosomal ribosomal subunit subunit e.g. Chlorampheni Chloramphenicol, col, Erythromy Erythromycin, cin, y Clindamycin. z b. Action Action on 30S ribosomal ribosomal subunit. subunit. e.q. Tetracycli Tetracyclines nes and Aminoglyco Aminoglycosides sides.. 3. Inhibition of nucleic acid synthesis aa a. Inhibitio Inhibition n of nucleotide nucleotide synthesis synthesis e.q. Sulfonami Sulfonamides des and trimethopr trimethoprim im   bb b. Inhibition Inhibition of DNA synthesis synthesis e.q. Quinolones Quinolones (Ofloxacin (Ofloxacin)) cc 4. Alterati Alteration on of cell membran membranee func function tion a. Antiba Antibacte cteria riall activi activity ty e.q. e.q. Polymy Polymyxin xin

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 b. Antifungal Antifungal activity activity e.q. Amphoterici Amphotericin n B, Nystatin, Nystatin, ketoconazole ketoconazole.. 5. Uncertain mechanisms E.g. Isoniazid, Metronidazole. Resistance – ability of a microorganism to be unaffected by an antimicrobial agent.  Natural resistance – occurs when an organism has always been resistant to the antimicrobial Agent; occurs without previous exposure to the drug.  Acquired resistance – occurs when the organism that was previously sensitive to an antimicrobial agent develops resistance/ caused by prior exposure to the drug. Cross Resistance - occurs with antibacterials that have similar actions. E.q. Penicillin; Penicillin; Cephalosporins.

Genetic recombination including conjugation, transformation transformation , and transduction, can result in the passing on of resistance resistance from one bacterial strain strain to another. The second strain becomes resistant to the same same antibiotics as the first first strain without without having been exposed to the antibiotic. **Action depends on depends on several variables: 1. Usual therapeutic concentration of that agent 2. Type of organism 3. The mech mechani anism sm of of acti action on of that that agent agent.. GENERAL ADVERSE REACTIONS TO ANTIBACTERIALS 1. Allergy Allergy / Hypersen Hypersensiti sitivity vity - may be be mild to to severe. severe. E.q rash, rash, prurit pruritus, us, hives-tr hives-treated eated with antihistamine. 2. Anaphylacti Anaphylacticc Shock - shortness shortness of breath breath is is the first first symptom symptom;; treatment treatment is epinephrine bronchodilators and antihistamines. 3. Superinfect Superinfection, ion, Suprainfect Suprainfection ion - infecti infection on caused by by prolifera proliferation tion of microorgani microorganisms sms that are different than those causing the original infection. - a secondary infection infection that occurs when the normal microbial flora of the body are disturbed during antibiotic therapy. E.q. Fungal infections. - often caused by broad spectrum antibiotics such as tetracycline tetracycline CULTURE AND SENSITIVITY TESTS - only way in which one can reasonably ensure that a particular particular drug will kill or inhibit the growth of an infecting microorganism. However, it will not show the potency of the drug nor differentiate between bactericidal and bacteriostatic effects, they will only show which drug adversely affect the the growth of the microorganism on the culture plate. Culture – a sample from the infected site is taken and grown grown on culture media. After the pathogen is grown, sensitivity test can be conducted. Sensitivity  – after the organism is identified, it is again grown on culture media and the effect of different antimicrobial agents on the organism is tested. One to two days are required before the result of this test are available Advantages of Culture and Sensitivity tests 1. An early early correction correction of therapy therapy is possible possible if the drug selecte selected d is ineffective ineffective against against the

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2.

microorganism causing the infection Pathogens Pathogens grown grown on culture culture before before antibio antibiotic tic therapy therapy is begun can can be more more easily easily identified than after a therapeutic failure has occurred.

Blood level – the concentration of the antibacterial an tibacterial agent present in the blood or serum; an important index to drug dosage, since certain concentration of the drug is required in the body fluids to inhibit or kill the microorganism. Synergism – effect when a combination co mbination of two antibiotics is more rapidly bactericidal than either  drug used alone. Combinations of antibiotic that that are bactericidal generally generally are synergistic. Combinations of those that are bacteriostatic are merely additive. Antagonism  – effect when the bactericidal rate for the combination of two drugs is less than that for either drug used alone; often exhibited when a bateriostatic bateriostatic and a bactericidal agent are used in combination.

DENTALLY USEFUL ANTI-INFECTIVE AGENTS 1. PENICILLINS - can be divided into three groups A. Peni Penici cill llin in G and and V B. Penicilli Penicillinase-r nase-resist esistant ant penicillins penicillins (Methacillin, Cloxacillin, Nafcillin, Floxacillin, Dicloxacillin) C. Extended-Spectrum penicillins (Ampicillin-like agents, carbenicillin-like agents and amino-penicillin group. Administration and Body handling  - can be administered orally or parenterally. - should not be applied applied topically because of its allergenecity. allergenecity. - Penicillin V is better absorbed orally than than penicillin G - degraded by the gastric fluid-it fluid-it should be administered administered one hour before meals or 2 hours after meals. - crosses placental barrier and a small amount appears to be excreted excreted in the milk and saliva. Spectrum: - very potent bactericidal agent that acts by interfering interfering with the synthesis of the bacterial cell wall. - its narrow spectrum spectrum of activity includes gram positive aerobic and facultative facultative organism(cocci: Streptococcus,and Staphylococcus; rods: Bacillus, Bacillus, Corynebacterium and Clostridium; Spirochetes:Treponema pallidium; and certain gram negative aerobic cocci: Neisseria gonorrhea and N. meningitidis)  Adverse reactions : - most common cause of drug allergies. 1. Toxicity - large doses of penicillin penicillin G have been associated with renal damage manifested manifested as fever, eosinophilia, rashes, albuminuria. - gastrointestinal irritation irritation can manifest itself itself as nausea with or without without vomiting.

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2. Allergy and Hypersensitivity Hypersensitivity Immediate - less than 30 minutes includes anaphylaxis. anaphylaxis. Accelerated - 2 to 48 hours includes serum sickness and laryngeal edema. Late - 3 or more more days includes rashes, oral lesions, and other symptoms. symptoms. Uses: - for dental infections a. ANUG ANUG – pen penic icil illi lin nV  b. Period Periodont ontal al absces abscesss - penici penicilli llin nV c. Abscess, Abscess, celluliti cellulitis, s, perico pericoronit ronitis is – penici penicillin llin V d. Osteom Osteomyel yeliti itiss - penicil penicilli lin nV e. Rheuma Rheumatic tic heart heart diseas diseasee - penicil penicillin lin V.

2. ERYTHROMYCIN - administered orally; available available in tablets and capsules, oral suspensions and IV and IM forms. - formulated as enteric-coated tablet, tablet, capsule or insoluble ester to reduce degradation by the stomach acid. - it should be administered administered 2 hours before meals or several hours after meals.  Activity and Spectrum: - usually bacteriostatic but may be bactericidal at normal therapeutic doses. - used against gram positive positive bacteria. - also a drug of choice for whooping cough, diphteria, syphilis, and gonorrhea. gonorrhea. - cross-resistance has been reported between erythromycin erythromycin and clindamycin. clindamycin. - poor second choice to treat treat dental infections. infections. Adverse Effect: 1. Gastrointestinal Effects - include stomatitis, abdominal cramps, nausea, vomiting vomiting and diarrhea. 2. Cholestatic Jaundice - symptoms include nausea, vomiting vomiting and abdominal cramps followed by jaundice and elevated liver enzyme levels. 3. Allergy - very uncommon. Drug Interaction: - patients taking Theophylline chronically for asthma or acutely acutely for bronchitis may exhibit a drug interaction with erythromycin. - has been implicated in the failure failure of oral contraceptive efficacy. efficacy. Uses: - drug of first choice choice in patients allergic to penicillin. - indicated certain situations for for the prophylaxis of rheumatic rheumatic heart disease. - usual adult dose is between 250 and 500 mg qid. - for bacterial prophylaxisprophylaxis- 1 gm 1 hour before the dental dental appointment

3. TETRACYCLINE

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-

dd

broad spectrum antibiotics antibiotics affecting a wide range of microorganisms. microorganisms. most commonly given by mouth. secreted in the saliva and milk milk of lactating mothers. mothers. stored in the dentin and enamel of unerupted teeth. also concentrated in the gingival crevicular fluid.

Types: 1. Doxycy Doxycycli cline ne - excrete excreted d in the feces feces 2. Tetracycli Tetracycline ne – elimi eliminated nated by glomerul glomerular ar filtra filtration, tion, - oral absorption is decreased by administration of food with with high calcium content, dairy products, oral iron supplements or antacids. 3. Minocycline - metabolized in the liver liver and excreted excreted in in urine. urine. - may be given to patients patients with renal dysfunctio dysfunction n

Spectrum: Bacteriostatic and interfere with the synthesis of bacterial protein Broad spectrum Adverse Reactions: 1. Gast Gastro roin inte test stin inal al effe effect ctss - anorexia, nausea, vomiting, diarrhea, gastroenteritis, gastroenteritis, glossitis, stomatitis, stomatitis, xerostomia, and superinfection (moniliasis) 2. Hepatoxicit Hepatoxicity y - large dose of parenteral parenteral tetracycl tetracycline ine 3. Rena Renall toxi toxici citty 4. Hematologic Hematologic effects effects - hemolyt hemolytic ic anemia, leukocyt leukocytosis, osis, thromboc thrombocytope ytopenic nic purpura purpura 5. Effe Effect ctss on teet teeth h and and bone boness 6. Supe Superi rinf nfec ecti tion on 7. Photos Photosens ensit itivi ivity– ty– exagger exaggerate ated d sunburn sunburn 8. Allergy Uses: 1. 2.

3. 4. 5. 6.

Alternative drug to treat chlamydial and rickettsial infections Used to treat cholera, acne, and pulmonary infections Doxycycline Doxycycline is used to treat treat travelers travelers diarrhea diarrhea Indica Indicated ted for the the treatm treatment ent of perio periodont dontiti itiss Mixture Mixture of equal parts parts of tetracycli tetracycline ne syrup and and lidocaine lidocaine viscous viscous for the the management of recurrent aphthous stomatitis ANUG ANUG may also also be be treate treated d with with tetrac tetracycl ycline ine

4. CLINDAMYCIN - bacteriostatic antibiotic effective effective primarily against gram-positive gram-positive organisms. - administered orally, intramuscularly, or intravenously. ee - food does not interfere interfere with absorption absorption ff - cross-resista cross-resistance nce between between Clindamyci Clindamycin n and tetracycli tetracycline ne (competiti (competition on for binding binding site) site)

Adverse Reaction: 1. Gastrointe Gastrointestin stinal al effects effects (Pseudo (Pseudo Membran Membranous ous ColitisColitis- PMC PMC ) -severe, persistent diarrhea and the passage of blood and mucus in in the stool

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2. Supe Superi rinf nfec ecti tion on 3. Allergy Uses: Should be used only when specifically indicated 2. Mixed infections infections insensiti insensitive ve to penicillinpenicillin- anaerobes anaerobes 1.

5. METRONIDAZOLE - taken orally - bactericidal and penetrates penetrates all bacterial cells. cells.

Adverse Reactions: 1. Gastrointe Gastrointestin stinal al effects effects - nausea, nausea, anorexia anorexia,, diarrhea diarrhea and vomiti vomiting, ng, epigast epigastric ric distress and abdominal cramping 2. Oral effects effects - unpleasant unpleasant metallic metallic taste; taste; altered altered taste of alcohol; alcohol; glossiti glossitis, s, stomatitis and a black furred tongue; dryness of the the mouth 3. Effects Effects on CNS CNS - headache, headache, dizzines dizziness, s, verti vertigo, go, ataxia, ataxia, confusi confusion, on, depression, depression, weakness, insomnia, insomnia, and convulsive seizures 4. Renal toxicity toxicity - cystitis cystitis,, polyuria, polyuria, dysuria, dysuria, incontinence incontinence 5. Disulfiram Disulfiram-like -like reaction reaction - alcohol alcohol should should be avoided; avoided; symptoms symptoms include include nausea, abdominal cramps, flushing, vomiting or headache Uses: Treatment of trichomoniasis, amebiasis 2.  Not the drug of choice for any dental infections (alternative drug) 3. Shown to be effective for the treatment of B. fragilis infections following mandibular fracture 1.

6. CEPHALOSPHORINS - chemically related related to penicillin - bactericidal agents - can be administered orally, orally, intramuscularly, intramuscularly, or intravenously. intravenously. Adverse Reactions: 1. Gast Gastro roin inte test stin inal al effect effectss 2. Neph Nephro roto toxi xici city ty 3. Supe Superi rinf nfec ecti tion on 4. Local ocal rea react ctiion 5. Allergy 6. Cross Cross sens sensit itivi ivity ty with with penic penicill illin in Uses: 1. For infections that are sensitive to these agents but resistant to penicillin

7. VANCOMYCIN - administered only intravenously - bactericidal - narrow spectrum of action against many gram positive cocci.

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Adverse Reactions: 1. Otot Ototox oxiicit city 2. Neph Nephro roto toxi xici city ty 3. Anaphylaxis 4. Supe Superi rinf nfec ecti tion on Uses: 1. Useful in the prophylaxis prophylaxis of infective endocarditis for for patients with prosthetic prosthetic heart valves who are allergic to penicillin. 2. Used orally to treat PMC.

8. AMINOGLYCOSIDES (Neomycin, Streptomycin, Kanamycin, Gentamycin, Tobramycin, Amikacin, Netilmicin) - bactericidal - have a broad antibacterial antibacterial spectrum - poorly absorbed after oral administration & so must must be administered by IM IM or IV injection for a systemic effect - used for the treatment treatment of aerobic gram-negative gram-negative infections infections

Adverse Reaction: 1. Otot Ototox oxic iciity - toxic to the 8th cranial nerve, which can lead to auditory au ditory and vestibular  disturbances. Patients may have difficulty in maintaining equilibrium and can develop vertigo. 2. Nephro Nephrotox toxici icity ty - can cause cause kidney kidney damage damage 3. Neuromuscula Neuromuscularr blockade blockade - act as as weak weak neuromu neuromuscula scularr blocking blocking agents, agents,  potentially producing apnea Uses: - reserved for hospitalized patients patients with the serious gram-negative infections Gentamicin is used in dentistry to prophylaxis patients with prosthetic heart valves 9. CHLORAMPHENICOL - broad spectrum gg - bact bacter erio iost stat atic ic - active against a large number of gram-positive and gram negative organisms, organisms, rickettsiae, and some chlamydiae. Particularly active against Salmonella typhi. - has serious side effects effects like fatal blood dyscracias dyscracias (aplastic anemia, and thrombocytopenia) - “Grey baby syndrome” syndrome” occurs when infants given cannot conjugate it. it. - Antibiotic of first choice in the treatment of life-threatening influenza and typhoid typhoid fever. SULFONAMIDES - cannot be classified as an antibiotic antibiotic because they are not produced by living organisms. - bacteriostatic against many many gram positive positive and gram negative bacteria.

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Adverse Reaction: 1. Allergic Allergic reaction reaction (rash, urticari urticaria, a, pruritus, pruritus, fever, fatal fatal exfoliative exfoliative dermatiti dermatitis). s). 2. Nausea, Nausea, vomiting, vomiting, abdomin abdominal al discomfor discomfort, t, headache headache and dizziness. dizziness. 3. Liver damage, depressed depressed renal renal function, function, blood blood dyscras dyscrasias. ias. Uses: - used when antibiotics are ineffective or cannot be used. - should not be used used topically for oral lesions ANTIFUNGAL DRUGS 1. NYSTATIN - effective against against candida albicans - not absorbed from the skin or mucuos membranes. - used for local effects in the treatment of candidiasis candidiasis on the skin or any part of the alimentary tract. - has a very unpleasant taste. Uses: a.  b.  b. c. d.

Thrush Dent Dentur uree stom stomat atit itis is Anti Antibi biot otic ic stom stomat atit itis is Some Some forms forms of mucocu mucocutan taneou eouss candidi candidiasi asis. s.

2. AMPHOTERICIN B - poorly absorbed from the GIT and probably not all from the unbroken skin. - used locally to treat conditions for which nystatin nystatin could be used. - available in intravenous injection. 3. IMIDAZOLE AGENTS (Miconazole, Ketoconazole) - used in the treatment of systemic fungal infections infections and candidiasis

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G EN ER AL

R EF ER EN CE S

Ansel, H.C., Popovich, N.G., and Allen, L.V.: L.V.: “Pharmaceutical Dosage forms and Drug Delivery Systems”, Sixth edition, William and Wilkins, USA, 1995. Asperheim, M. K.: “Pharmacology AN INTRODUCTORY TEXT”, Seventh Edition W.B. Saunders Company, Philadelphia, Pennsylvania, USA, 1992. Grajeda-Higley, L.: L.: “Understanding Pharmacology: Pharmacology: A Physiologic Physiologic Approach”, Appleton and

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Lange, Stanford, Stanford, USA 2000. Kee, J.L. and Hayes, E.R.: “Pharmacology: A Nursing Process Approach”, 1st edition, W.B. Saunders Company, Philadelphia, Pennsylvania, USA. Musser, R. D. and O’Neil, J. J.: “Pharmacology and Therapeutics”, 4th edition. The McMillan Company, London, 1969. Mycek , M. J., Harvey, R. A., and Champe, P. C.: “Lippincott’s Illustrated Reviews: Pharmacology”, 2nd edition, Lippincott-Raven Publishers, Inc. New York 1997 Olson, J.: “Clinical Pharmacology Made Ridiculously Simple”, international international editions 2000, McGraw-Hill Book Company, Singapore, 1997. Stringer, J.L.: “Basic Concepts in Pharmacology”, A Student’s Student’s Survival Guide, 2nd edition, McGraw-Hill Companies, Inc., Singapore, 2001. Walton, J. G., Thompson J. W., and Seymour, R. A.: “Textbook of Dental Pharmacology and Therapeutics”, Second edition, Oxford University Press, New York, 1994 ---------------------------------------------------------------------------------------------------------------------CENTRO ESCOLAR UNIVERSITY College of Dentistry

Course Title: PHARMACOLOGY Course Number: PHA100/PHA100L Units: Lecture – 2 Laboratory – 1

Hours / Week: Lecture – 2 hours/week  Laboratory – 3 hours/week 

Pre-requisites: Anesthesiology Course Description: The course presents the principles in the use u se of drugs for the diagnosis, prevention, and treatment of diseases. Each drug is considered according to its its indication, mechanism of action, action,  pharmacokinetics, contraindications and precautions, unwanted effects and drug interactions. The course deals more on the commonly co mmonly prescribed drugs used and related in the practice of Dentistry. General Objectives: 1. To explain explain the basic basic and clinical clinical pharmacolog pharmacology y upon which which drug therapy therapy is based based with with  particular emphasis on drugs used in Dentistry. 2. To demonstrate demonstrate the physical physical and biologic biological al behavior behavior of some drugs drugs in order to familia familiarize rize students with the actual effects of drugs.

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3. To expose student studentss to the type type of questions questions they they will will encounter encounter in the licensur licensuree examinations.

COURSE PLAN:

Course Content

Specific Objectives

Introduction To introduce the to general principles of  Pharmacology  pharmacology Drug To identify drugs  Nomenclature according to their  generic, chemical, and trade names Drug Therapy To kno know w an and understand the different processes involved in drug therapy. Route of Drug To effectively apply Administration drugs according to its A. IM/ route of administration Subcutaneous B. Cutaneous Dosa Dosage ge For Forms ms To fam famil ilia iari rize ze stu stude dent ntss on the different dosage forms of drugs; differentiating one from the other  Drug To interpret different Literature drug literature Systems of  Measurement Conversion Computation of a child’s dose Prescription Writing and Prescription Orders

To know how to convert units and doses of drugs To know how to  properly compute for a child’s dose. To equip students with the knowledge of   prescription writing. To learn how to interpret prescription order.

Suggested Teaching Methodology/ Strategy and Materials

Time Allotment (no. of hours)

Evaluative Measures and Requirements

Lecture

Lec. = 4 Lab. = 3

Recitation/Quizzes Laboratory Manual

Lecture

Lec. = 2 Lab. = 3

Recitation/Quizzes Laboratory Manual MIMS

Lecture

Lec. = 4

Recitation/Quizzes

Lecture

Lab. = 3 Lab. = 3

Practical exercise Quizzes

“Show and Tell Method”

Lab. = 6

Written Report Oral Report Laboratory Manual Practical/Written Quiz

Lecture

Lab. = 3

Lecture Board exercises Lecture Board exercises Lecture Board exercises

Lec. = 2 Lab. = 3

Interpretation of   literatures Laboratory Manual Exercise/Quizzes Laboratory Manual

Lec. = 2 Lab. = 3

Exercise/Quizzes Laboratory Manual

Lec. = 2 Lab. = 6

Quizzes Laboratory Manual

demonstration

method

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Pharmacology To know the different Lecture of Pain and  processes involved Inflammation with pain. To know the different mediators of  inflammation. Analgesics To know the Lecture mechanism of action Prescription and application of the Writing different groups of  exercises analgesics. Antihistamines To know the Lecture  pharmacokinetics and  pharmacodynamics of  antihistamines Hemostasis / To know the Lecture Hemostatic mechanism of action Test for  agents of hemostatic agents  bleeding and its importance in time/clotting Dentistry. time of white mice Anesthetic To describe the Lecture agents  pharmacokinetics and Tests the  pharmacodynamics of  effects on these drugs. white mice Antimicrobials To know the different Lecture types of antimicrobials Inoculation and its corresponding of bacteria mechanism of action. Culture and To apply through sensitivity  prescription writing Test the antimicrobials learned. Antiseptics and To know the Lecture Disinfectants  pharmacokinetics and  pharmacodynamics of  these drugs. Drugs acting on To describe the Lecture the Central mechanism of action  Nervous of sedative-hypnotics System Therapeutic Measures of  Common Dental Conditions and Emergency Drugs.

To familiarize students Lecture with common dental diseases and its therapeutic measures. To understand the  proper management of 

Lec. = 2

Recitation Quizzes

Lec. = 4

Recitation Quizzes

Lec. = 2

Recitation Quizzes

Lec. = 2 Lab. = 3

Recitation Quizzes Laboratory Manual

Lec. = 2 Lab. = 3

Recitation Quizzes Laboratory Manual

Lec. = 4 Lab. = 3

Recitation Quizzes Practical exercises Laboratory manual

Lec. = 2 Lab. = 3

Recitation Quizzes Laboratory manual

Lec. = 2 Lab. = 3

Recitation Quizzes Laboratory manual

Lec. = 6 Lab. = 9

Research papers Recitation Quizzes Laboratory manual

89

some dental office emergencies. To understand the  pharmacologic orientation of AIDS and Hepatitis.

Suggested References: Textbook of Dental Pharmacology and Therapeutics by: John G. Walton Pharmacology by: Goodman and Gillman Pharmacology by: Katzung Clinical Pharmacology in Dental Practice by: Sam V. Holroyd

LABORATORY TOPICS

MANUAL TOPICS

1. Introduction and definition definition 1. Introduction to of terms Pharmacology 2. Demonstration of Routes of  2. Dr Drug Nomenclature Administration 3. Skin Testing 3. Routes of Drug Administration 4. Interpretation of Drug 4. Skin Skin Test Testin ing g Inserts 5. Conversion of doses and 5. Drug Dosage Forms measurements 6. Prescription Writing 6. Drug Literatu atures 7. Prescription Orders 7. System of measurements PRELIM EXAM 8. Conversions 8. Narcotics and Non Narcotics Analgesics 9. Histamine and Antihistamines 10. Hemostasis and Hemostatic Agents

LECTURE TOPICS

1. Introduction and definition definition of terms 2. Dr Drug Nomenclature 3. Drug Therapy 4. Route Routess of Drug Drug Administration 5. Dosage Forms

9. Pr Prescription Writing

6. Drug Literatures 7. System of Measurements 8. Prescription Writing / Orders 9. An Analgesics

10. Prescription Orders

10. General Anesthetics

11. Analgesics

11. Local Anesthetics

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11. General Anesthetics

12. Antihistamines

12. Lo L ocal Anesthetics

13. Hemostasis and Hemostatics Agents 14. General Anesthetics

12. Histamines and Antihistamines 13. Hemostasis and hemostatic Agents 14. Antimicrobials

15. Local An Anesthetics 16. 16. Anti Antimi micr crob obia ials ls 17. 17. Sed Sedat ativ ivee-Hy Hypno pnoti ticc Dru Drugs gs

15. Antiseptics / Disinfectants 16. 16. Seda Sedati tive ve-H -Hyp ypno noti ticc Drug Drugss 17. 17. Off Offic icee Eme Emerg rgen enci cies es

18. Antise Antisepti ptics cs / Disinf Disinfect ectant antss 19. Common Dental Diseases 20. Office Emergencies 21. AIDS and Hepatitis

18. Common Common Oral Oral diseas diseases es 19. AIDS / Hepatitis

13. Antimicrob Antimicrobials ials – culture culture and Sensitivity 14. 14. Seda Sedati tive ve – Hypn Hypnot otic icss 15. Antisepti Antiseptics cs and Disinfectants 16. Common Common Oral Oral Diseas Diseases es 17. Office Emergencies 18. AI AIDS an and He Hepatitis

OUTLINE OF TOPICS IN PHARMACOLOGY PRELIM LECTURE

1st Meeting  Orientation 2nd Meeting  Definition of terms Introduction History of pharmacology Branches of Pharmacology Importance of Pharmacology to dentistry Fundamental action of drugs Uses of Drugs Drug Nomenclature

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Drug Publications Quiz 3rd Meeting  Stages in the development of a drug Introduction to Drug Therapy Quiz 4th meeting  Process of Drug Therapy Quiz 5th meeting  Continuation of Drug Therapy Quiz LECTURE PRELIM EXAM LABORATORY

1st Meeting  Orientation 2nd Meeting  Exercise 2 & 3 *Exercise 1 will be given as a quiz How to use MIMS Quiz 3rd Meeting  Exercise 4 Routes of Drug administration Quiz 4th meeting  Exercise 5 Quiz LABORATORY PRELIM EXAM

General Principles / Factors / Terminologies 1. Factors affecting Patient's Reaction to Drugs A. Routes Routes of Drug Drug Adminis Administra tratio tion n 1. Enteral 2. Parenteral B. Passage of Drug Across Body Membrane

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1. Active Transfer  2. Passive Transport C. Fate of Drug 1. Absorption 2. Distribution 3. Metabolism / Biotransformation Biotransformation 4. Excretion / Elimination

2. Considerations in Drug Administration A. Tolerance B. Pathologic State C. Age and Weight 3. Action vs. Effect Anaphylaxis Placebo Immunity Idiosyncrasy Tolerance Tachyphylaxis Drug Resistance Refractory Hyporeaction Hyper-reaction Hypersensitivity Supersensitivity 88888888888888888888

3rd Meeting  General Anesthetics Local Anesthetics Locally Acting Medication: Antimicrobials, Hemostatics and Protectives 4th Meeting  Diuretics and Antihypertensive Sedative Hypnotics Psychotherapeutic 5th Meeting  Central Nervous Nervous System System Stimulants Anticonvulsant Antineoplastic Adrenocorticosteroids

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FINALS

* SPECIAL TOPICS 1st Meeting  Emergency Drugs 2nd Meeting  Pharmacologic Considerations 3rd Meeting  Disease Status of Common Interest 4th Meeting  Pharmacologic Management of Certain Common Oral Disease Entities 5th Meeting  Drug Interactions Predictable Reaction: 1. Excess pharmacological activity 2. Rebound response upon discontinuation Excessive Pharmacological Effects: 1. Respiratory depression in severe bronchitic patients given morphine morphine or benzodiazepine hypnotics 2. Hypotension resulting in stroke, myocardial infarction or renal failure in patients receiving excessive doses of antihypertensive drugs. 3. Bradycardia in patients receiving excessive DIGOXIN Withdrawal Symptoms: 1. Extreme agitation, tachycardia, confusion, delirium and convulsions may occur following the discontinuation of long-term CNS depressants such as barbiturates, barbiturates, benzodiazepine and alcohol. 2. Acute Addisonian crisis may be precipitated by the abrupt cessation of corticosteroid therapy. 3. Severe hypertension and symptoms of sympathetic overactivity may arise shortly after  discontinuing clonidine therapy. 4. Withdrawal symptoms after narcotic analgesics. Allergic Responses:

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to react to various antigens with with which it comes in Allergy - altered capacity of the body to contact. * 2 Types of Hypersensitivity: 1. Immediate - antibody is circulating or fixed to certain tissues. - Antigen reacts reacts to antibody. 2. Delayed - a reaction of T-cells that have been stimulated by antigen to react against targets such as infectious agents. - Antibody is not involved. Genetically Determined effects effects - major toxicity of some drugs is restricted restricted to individuals with  particular  genotype or genetic make-up. DEFECT Pseudocholinesterase Deficiency Glucose-6-Phosphate Dehydrogenase deficiency

Acetylator-Polymorphism

Hepatic Porphyria

TOXIC DRUG

Succinylcholine

Sulfonamides Quinidines Primaquine Procainamide Hydralazine Isoniazid Barbiturates

SYMPTOMS

Paralysis Apnea

Hemolysis Systemic Lupus Neuropathy Symptomatic prophyria

Idiosyncratic Drug Reaction: Idiosyncracy - used primarily to cover unusual, unexpected, bizarre drug effects that cannot readily explained or predicted in individual recipients. *DRUG INDUCED MALIGNANT DISEASE IS FORTUNATELY RARE...

PHARMACOLOGY OF THE AUTONOMIC NERVOUS SYSTEM: - generally, all drugs influence influence blood pressure, heart rate, potassium potassium pump

Diversity of ANS on Body functions specific to Dentistry: 1. Practical application of vasoconstrictors in local anesthetic solutions. 2. Agents that reduces salivary flow 3. Alterations of the ANS mechanism both centrally and peripherally antihypertensive drug. 4. Significant peripheral changes in ANS activity produced b y antipsychotic phenothiazines and antidepressants.

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5. Entire concept of chemical chemical neurotransmitters neurotransmitters and receptors are founded on the principles of the ANS. *2 Divisions of the ANS 1. Sympathetic 2. Parasympathetic

* Both are regarded as peripheral in modes of action and drug reactions even though these cell  bodies are located within the CNS and receive considerable CNS input. Autonomic Nervous System - concerned with the the maintenance of a constant internal environment to provide for optimal cellular function and survival. Functions: Reflex vasodilation Regulates Body temperature Blood glucose level Cardiac Rate Water Balance SYMPATHETIC DIVISION - designed to cope with sudden emergencies. E.q. Fright and flight  phenomenon PARASYMPATHETIC DIVISION - conservation of bodily processes processes E.q. Reflex slowing slowing of  the heart Action Potential - bioelectric signals / self propagated impulses along the nerves. Neurotransmitters - chemical mediators that transmit transmit signals across nerve to nerve, or nerve to effector tissue.

mediator at all autonomic ganglia and parasympathetic parasympathetic post Acetylcholine - specific chemical mediator ganglionic synapses. - transmitter substance of the neuromuscualr junction in skeletal skeletal muscle. Norepinephrine - principal chemical mediator mediator of the sympathetic sympathetic postganglionic neuron.

released by the adrenal medulla. Epinephrine - major mediator released Cholinergic - nerves releasing acetylcholine. acetylcholine. Adrenergic - nerves releasing norepinephrine.

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