ANTIBIOTICS TONGUE-IN-CHEEK REMINDERS Hello people :D This chapter is driving me CRAZY!! took me two entire days to do and STILL i feel confused about some stuff in it. So I decided to gather up the key points and share them with whomever is as confused as i am about this chapter. There we go... ----------------------------------------------------------------------------------------------------------Jarisch-Herxheimer Jarisch-Herxhe imer reaction (jarisch SEXheimer!! SEXheimer!!)) - hypersensi hypersensitivity tivity after FIRST injection of penicillin in ttt of syphilis (syphilis (syphilis is sexually t ransmitted) Red man syndrome - due to histamine release if vancomycin is injected rapidly (remember Fanta is red too!!) Fanconi syndrome (F*** syndrome!! syndrome!!)) - due to F***ing expired tetracyclins (the bad word should make you remember LOL) Pseudotumorr cerebri - due to minocyclin toxicity Pseudotumo Diabetes insipidus-like sundrome - due to demeclocyclin Grey baby syndrome - in premature neonates due to chlorampheni chloramphenicol col toxicity ---------------------------------------------------------------------------------------------------------
Penicillin + aminoglycosides aminoglycosides (gentamicin especially) = synergy and complementary spectrum (but NOT in the same vial) Penicillin + tetracyclin = antagonism (since tetracyclin prevent formation of prtns which are the target of penicillin) Benzathine penicillin penicillin + local anesthetic (lidocaine - to avoid pain at site of injection)
Amoxiicillin Amoxiicilli n + calvulanic acid = Augmentin (suicide (suicide substrate that blocks beta lactamase lactamase)) Ampicillin + Sulbactam = Unasyn Unasyn Piparcillin Piparcilli n + Tazobactam = Tazocin
Cefoperazone + sulbactam = sulperazone (beta lactamase inhibition) Ceftriaxone + calcium = Biliary sludge :D Cephalosporins Cephalospori ns + local anesthetic (lidocaine - to avoid pain at site of injection) Cefoxitin + vit K (to prevent hypoprothrombinemia) hypoprothrombinemia)
Imipenem + cilastatin = Tienam (to inhibit dihydropaptidas dihydropaptidase) e)
Tetracyclin + milk/Ca/Mg/Fe/Al = chelation Tetracyclin + streptomycin (to treat brucellosis and tularemia)
Chloramphenicol Chlorampheni col + penicillin = ANTAGONISM in meningiococcal meningitis (fakreen el micro :D) Chloramphenicol Chlorampheni col + ampicilli ampicillin n = SYNERGISM in H. influenzae meningitis!! meningitis!! Chlormphenicol Chlormpheni col + Aminoglycoside = antagonism (chloramph blocks the O2 dependent pump that gets them inside)
Aminoglycoside Aminoglycosid e + amphotiricin amphotiricin B/polymixins/cephalosp B/polymixins/cephalosporins/fur orins/furosamide osamide = more nephrotoxicity nephrotoxicity Aminoglycosides Aminoglycosid es + loop diuretics/chloroqui diuretics/chloroquine/aspirin ne/aspirin = ototoxicity Aminoglycosides Aminoglycosid es + curare = more N-M blockade blockade
Streptomycin IM + rifampin + isoniazid + pyrazinamide = anti-TB Streptomycin IM + penicillin G = endocarditis ttt Streptomycin IM + tetracyclin = plague, tulatremia and brucellosis ttt
Gentamycin + penicillin (mentioned (mentioned before) to ttt serious infections (pneumonia, (pneumonia, UTI, septicemia, osteomyelitis) Gentamycin + carbenicillin/ticarcillin carbenicillin/ticarcillin (extended spectrum) = ttt pseudomonal infection Gentamycin + benzyle penicillin = prophylaxi prophylaxiss of bacterial endocarditis
Neomycin + bile acids = management of hyperlipidemia
Erythromycin + lincomycin/ lincomycin/clindamycin/ clindamycin/fucidic fucidic acid = mutual antagonism (same binding site)
Erythromycin + clindamycin = mutual antagonism Erythromycin and clarithromycin # cyt P450 Erythromycin # intestinal flora (less metabolism of digoxin)
Clindamycin + aminoglycosides = ttt anaerobic infections 30% Quinopristin Quinopristin + + 70% Dalfopristin Dalfopristin = STREPTOGRAMIN STREPTOGRAMIN!! !!
Fusidic acid + nafcillin = t tt of severe staph infection (including osteomelitis)
Ciprofloxacin / ofloxacin # cyt P450 Cimitidine decreases metabolism of fluoroqui fluoroquinolones nolones Sucralfate/antacids and food supplements decrease absorption of fluoroqui fluoroquinolones nolones Fluoroquinolones Fluoroquinol ones + NSAID's = seizures!!
Trimethoprim + sulphamethoxazole = Co-TRIMOXAZOLE!!
Rifampin is HME inducer
Metronidazole sensitizes Metronidazole sensitizes tumor cells to ionizing radiation
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Drug of choice (DOC) of...
Syphilis - penicillin Vincent gingivitis gingivitis - penicillin + metronidazole Mycoplasma pneumonia - tetracyclin Rickettsial infection - tetracyclin
Weird upper/lower respiratory tract infections ( Pertussis, Diphtheria , Mycoplasma, Legionella, Legionella, chlamydia ) - Macrolides Nocardiosis - Co-Trimethoxazole HIV associated pneumocystis jivorneci - Co-Trimethoxaz Co-Trimethoxazole ole (I.V.) Prophylaxis of meningiococcal meningitis - rifampin Protozoa (ameba, trichomonas, giardia) - Metronidazole Certain upper and lower GIT infections (acute ulcerative gingivitis, dental abcess/inf abcess/infection, ection, peptic ulcer with H pylori, pseudomembranous pseudomembranous colitis, sepsis with anaerobic bacteroides) - Metronidazol Metronidazole e (though it's not DOC for H pylori, of course) -----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------*** AS A GENERAL RULE: most antibiotics cause GIT upset, do not pass BBB, cause nephrotoxicity so the dose should be modified in renal failure patients. * Broad spectrum penicillin - not against K.P.P (Klebsiella, proteus, pseudomonas) * Carboxypenicillin - platelet dysfunction and bleeding * Penicillin passes placental barrier but is NOT teratogenic! * Nafcillin Nafcillin is is the only penicillin excreted in bile so enterohepatic circulation (useful (useful in renal imparement) * B-lactamase producing bacteria - PEPSI (pesudomon (pesudomonas, as, E.coli, proteus, staph aureus, influenzae) * Gonorreal neonatal ophthalmia - benzyl penicillin eye drops * Na and K salts with penicillin - might overload patients with renal/cardia impairment!! impairment!! * Ampicillin - skin rash in ALL patients with infectious mononucleosis, mononucleosis, allopurinol or leukemia!! * Methicillin - nephritis and nephrotoxic so is not obsolete except for S. aureus * Cephalosporins are not are not active against MRSA, C. difficile, enterococci * Cephazoline concentrates in bone - thus treats osteomyelitis * Cefuroxime - only 2nd generation cephalosporin to pass BBB * Ceftriaxone and Cefoperazone - excreted in BILE (allowed in renal patients without altering the dose + ttt typhoid)
* Cefoperazone and ceftazidime- especially at pseudomonas * Monobactams - NO cross allergy with penicillin penicillinss * Imipenem - half of patients get seizures!! (this is less marked with meropenem) * Vancomycin - ttt gram positives INCLUDING MRSA, C.dificil and enterococci * Vancomycin - ototoxic and nephrotoxic * PHOTOTOXICIT PHOTOTOXICITY Y - tetracyclins, sulfonamides sulfonamides (and of course co -trimethoxazole) and quinolones * Demeclocyclin # ADH receptors so ttt syndromes of inappropriate inappropriate ADH secretion (SIADH) * Minocyclin - to eradicate meningiococcal carrier * Minocyclin - vestibular disturbance, disturbance, vertigo and pseudotumor cerebri * Tetracyclin - to ttt amebiasis too!! * Chloramphenicol absorption affected by crystal shape and size (polymorphism (polymorphism ) * Chloramphenicol - ttt vancomycin-resistant ENTEROcocci * Chloramphenicol BM inhibition - either dose dependent (# Mt ptn synth) or fatal dose-independent aplastic anemia (less with thiamphenicol thiamphenicol)) * Chloramphenicol - kernecterus in premature infants + grey baby syndrome * Aminoglycosides - NOT effective against anaerobes (O2 dependent intake into bacteria) * Aminoglycosides - polycations so only extracellular, no passage to BBB or eye, NOT mixed with penicillic ACID in the same container, concentrate in kidney and endolymph leading to ototoxicity and nephrotoxicity * Streptomycin - optic nerve dysfunction * Neomycin - ointment * Neomycin - oral in hepatic coma (plus lactulose) * Neomycin - oral in hyperlipidemia
* Erythromycin - conc in prostatic fluid, PMN's and macrophages * Erythromycin - motilin receptor-stimulating receptor-stimulating (prokinetic) action * Macrolides - cholestatic jaundice, reversible ototoxicity * Clindamycin - conc in bone and teeth (NOT ppt like tetracyclin, but concentrates and REMAINS active) * Clindamycin - fatal pseudomembranous colitis * Liezolid - thrombocytopenia , neutropenia
* Fusidic acid - a STEROID!! * Fusidic acid - concentrates in bone , in SEVER staph infection incl osteomyelitis * CONCENTRATE IN BONE: Tetracyclins (but becomes inactive), Clindamycin and Fusidic acid (so used in ttt of osteomyelitis). * Quinolones - not against spirochaetes/ana spirochaetes/anaerobes/MRSA erobes/MRSA/pneumococci /pneumococci * Fluoroquinolones 60 times more potent than quinolones * Fluoroquinolones - conc in prostatic tissue (not fluid) , low CSF levels, intracellular * Fluoroquinolones - CHONDR CHONDROLYTIC OLYTIC , tendinitis and RUPTURE of t endons (esp Achillis) * CRYSTALURIA - quinolones, sulfinamides sulfinamides (and Co-trimethoxazole, of course) * Co-trimethoxazone side effects (due to sulfa) - megaloblasti megaloblastic c anemia + ABCDDDD (Allergy, Blood dyscriasis, Crystalluria, Diarrhea, Damage, Displace bilirubin, Drug interactions) * Co-trimethoxazole - contraind in infants less than two months, pregnancy and lactation (kernicterus) and if creatinine clearance less than 15 ml/min * Rifampin - orange red discoloration of all body fluids * Metronidazole - disulfram-lik disulfram-like e action , METALLIC SENSATION
BLOOD PHARMA - REMINDERS What's up guys? Hope you're not as late as I am with t he studies :D
I'm just finishing up with blood pharmacology now and there's been a few points that i often forget, so instead of writing them on paper I thought i write them here so that others could benefit as well. There we go ...
* Heparin is a mucopolysaccharide * We use PTT (2-2.5 times normal, which is 30-40 seconds) and coagulation time (which is 5-7 minutes) to monitor heparin * we use PT (2-2.5 times normal which is 12-15 seonds) ,internation ,international al normalized ratio (PT of patients/control PT) * Heparin might cause paradoxical thromboembolism and thromboembolism and its chronic use leads to REDUCED antithrombin antithrombin III activity!! -------------------------------------------------------------------------------------------------------------------------------------------HERE'S A LITTLE SOMETHING :) Do you know what the mechanism of the paradoxical thromboembolism is? Heparin, being a polysaccharide, might bind to some receptors on the surface of platelets, causing them to be literally OPSONIZED and taked by spleen and liver macrophages!!! Besides, it causes them to look foreign and become attacked by antibodies and complement -type II hypersensitivity-----------------------------------------------------------------------------------------------------------------------------------------* Heparin might also lead to hypersensitivity, transient alopecia and osteoporosis. (dunno why that occurs!) * Warfarin might cause skin necrosis... necrosis ... -----------------------------------------------------------------------------------------------------------------------------------------------... AND HERE'S THE REASON!! Protein C and protein S are also vitamin K-dependent factors that require gamma carboxylation, just like the clotting factors. So, warfarin prevents synthesis of protein S and C as well!! and since the half-life of them is shorter than the halflife of coagulation factors, they get affected BEFORE the clotting factors are decreased. Thus, if heparin is not coadministered at the beginning of the warfarin therapy, thrombosis resulting in skin necrosis or even toe gangrene can result!! Cooooool!! And what's its treatment? treatment? Hirudin and Lipirudin.. Lipirudin.... --------------------------------------------------------------------------------------------------------------------------------------------------* Heparin and warfarin is contraindicated in liver and kidney disease as well as surgeries in which the threat of bleeding is bad (brain, (brain, eye or spinal cord). It's also contraind in bleeding disorders , active TB, ulceration of gut and subacute bact endocarditis> * Drug interactions of oral anticoagulants - look at them carefully!! * Fondaparin Fondaparinu u X - selective inhibitor inhibitor of factor factor X X a, a, greater efficacy than LMWH but no antidote * Hirudin Hirudin and Lipirudin Lipirudin - are heparin analogues, the first from leeches and the second by recombinant DNA in yeast * Ticlopidin and clopidogril are used routinely in stent insertion * Ticlopidin might cause neutropenia while clopidogril doesn't. * Dipyridamol is is # PDE (coronary VD) but is ineffective alone * Cilostazole is used for ttt of intermitten intermittentt claudification
* Streptokinase is not an enzyme (it binds to and activated proactivator plasminogen) * Steptokinase causes hypersensitivity and might be inhibited by antibodies against streptococci * Altepla Alteplase se (tPA) has a local fibrinolyti fibrinolyticc activity (greater clot selectivity) * Aminocaproic / tranexamic acid # plasminogen activation (antidote to streptokinase) * Oxycel (Ox Oxidized idized Cel Cellulose) lulose) - surgical gauze applied to surf to stop bleeding BUT # epithelialization * Sclerosing agents (sodium morhuate , sylnasol and sodium ricinoleate) - for varicose veins -------------------------------------------------------------------------------------------------------------------------------------------------------------- And here's here's something something nice... Do you you know why why statins cause cause myositis myositis and rhabdomyol rhabdomyolysis? ysis? Because one of the intermediates in the cholesterol-makin cholesterol-making g pathway is farnesyl pyrophosphate pyrophosphate which is needed foor the production of coenzyme Q of the respiratory chain!! And since muscle are very active cells, this resulting decrease in ATP significantly inhibits the Na/K pump and hence, Na accumulates inside the cell, followed by hydropic swelling and even, possibly apoptosis!!!
Ok, 7aga tanya ... Do you know why they cause hepatotoxicity? Simply because they cause retention of the fat and cholesterol within the hepatocyte causeing fatty swelling and apoptosis!!! ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
* Fibrates might lead to cholesterol gall stone formation and thus are contraindicated in gall bladder disease, simply because the retained cholesterol increases the formation of stones :) * Niacin causes significal cutaneous flush but... ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Is this cutaneous flush due to histamine? Of course not, otherwise we would've treated it with an antihistamenic. It's actually due to prostaglandins which is why an aspirin a day prevents it... -----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------* Ezetim Ezetimib ib (easy-te3em-3eeeeeb!!) - lowers intest abs of cholesterol * Aplastic anemia- don't forget the haemopoeitic growth factors in t he ttt (erythropoeitin, GM-CSF, G-CSF, IL1,3,5,6,9,11 and thrombopoeitin)
ENDOCRINE PHARMA – LITTLE REMINDERS Here are some of t he points I often forget in endocrin pharmacology :) In case they show up in MCQ or something... ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
* Islet cell antibodies and HLA association is only in type ! diabetes * Alloxan and Strptozotocin inhibit insulin synthesis - thus causing secondary DM * Immunosupp Immunosuppressives ressives inhibit insulin synthesis causing secondary diabetes (Wonder why?? "The " The diabetogenic effect is due to a direct effect of both drugs on the beta pancreatic cell, in particular on intracellular Ca++ metabolism, which is involved in the insulin secretion and in the reduction of the number of the secretory granules." granules.")) * Insulin glargine forms microprecipitates at injection sites * Adverse effects of insulin include include insulin resistance ( may be improved by insulin sensitizers) * First gen sulfonylu sulfonylureas reas - Tolbutamide Tolbutamide,, Acetohexamide and chloropropamide ( increases secretion of ADH) * Second gen sulfonylure sulfonylureas as - Gl Glipi ipizide zide,, Gl Glicla iclazide zide,, Gl Glybu yburide ride,, Gl Glimipi imipiride ride * Adverse effects of sulfonylurea sulfonylureass include PRIMARY PRIMARY or SECONDARY SECONDARY failure. * Drug interactions of sulfonylureas - look at them carefully!! * Meglitinides ( Repaglinide Repa glinide and Nateglinide Nateglinide)) have more rapid onset, shorter duration, are take before eac h meal and cause less hyperglycemia than sulfonylureas. * Metformin LOWERS apetite (good for obese type II DM) but major risk is lactic acidosis, especially especially:: in renal failure, liver failure, alcohol, CHF and COPD. * Thi-azo-lidine-diones = Glit-azo-nes !!! They work on Peroxisome Proliferator Proliferator Activated Receptor gamma (PPAR) * Glitazones cause hepatotoxi hepatotoxicity city (must moniter liver function) + M.I. + weight gain and edema and anemia + OSTEOPOROSIS!!! * alpha glucosidase inhibitors inhibitors (Miglitol and Acarbose) make it necessary to give GLUCOSE (not sucrose) in case of hypoglycemic coma.
* Exentaide commonly causes nausea and has to be injected - thus lower patient compliance * Sitaglipidine is often combined with metformin ( JANUMET) * Therapeutic uses of glucagon - just look at its action on liver/muscle (hypoglycemic (hypoglycemic coma), heart (BB toxicity), pancreas (Glucagon (Glucagon test to see islet reserve) and smooth muscle (radiology of bowel). ---------------------------------------------------------------------------------------------------------------------------------------------* L4 is preferred to L3 in primary hyperthyrodism hyperthyrodism because L4 has better stability, content uniformity lower cost, can be given once daily, is less antigenic and easily monitored. This is in contrast to T3 which has a rapid onset (up to HF) and is more expensive, more frequent dosing etc. * Thionamides/Thiourea derivates include Carbimazole Carb imazole (PRODRUG, converted to >>>), Methimazole Methimazole and propyluraci propyluracil. l. * Propyluracil is highly bound to plasma proteins (unlike methimazole) and thus does not cross the placental barrier (safe in pregnancy) ... They both cause hypersentitivity however (due to -thio group) -----------------------------------------------------------------------------------------------------------------------------------------------** Agranuloc ** Agranulocytosis ytosis and hepatitis are are side effects effects of thionamides thionamides - they are triggered by AUTOIMMUNE MECHANISM MECHANISM
** Loss of hair and abnormal hair pigmentation are also side effects ----------------------------------------------------------------------------------------------------------------------
* Iodides might be used PROPHYLACTICALLY PROPHYLACTICALLY in endemic areas * Thyroid gland adaptation occurs after two weeks of iodide therapy * HYPOTHYRO HYPOTHYROID ID goitre is a side effect of chronic iodide use (colloid goitre due to high TSH) * There are two opposing side effects of radioactive iodine - hypothyroidism and thyroid storm (from release of stored colloid) * Bis-phosp Bis-phosp--onates (Eto (Etodronate, dronate, Pami Pamidronate, dronate, Ali Alidronate dronate and Risedronate Risedronate)) are used for osteoporosis ttt and are contraindicated in renal failure and peptic ulcer (patient should take them while standing to avoid esophageal ulcer!!!!) * TeriPARA TeriPARAtide tide - is a para parathormone thormone fraction that should be given INTERMITTENTLY to stimulate bone formation ( a little endocrin trick since, as we know, parathormone increases bone resorption) * Monoclonal anti-RANKLE antibodies - for t tt of osteoporosis * Corticosterone withdrawal syndrome - fever, myalgia, myalgia, arthralgia and malaise. malaise. * Mestra Mestranol nol - is stored in adipose tissue so has a long duration of action * Estrogen preparation can be used for ttt of acne, osteoporosis, prostate cancer (!!), hirsutism and preventing atrophic vaginitis. * Estrogen synthesis inhibitors include GnRH, Danazol (
!!) and Aromatase inhibitors inhibitors..
* AI's are either STEROIDAL, such as exemastane exemastane (the INSANE one causing suicide inhibition) or NON-STREOIDAL such as letrezole letre zole (
)
