INTRODUCTION TO ANTIMICROBIALS Antibiotics asre the substances prioducd by the microorganisms which suppress rthe growth/ kill the microorganism at a low concentration without affecting/ causing much damage to the host. These exclude the other substances which also inhibit/ kill the microorganisms, but are produced synthetically( eg: sulphonamides) or those substances needing higher concentration to inhibit, though produced by the microbes (eg; ethanol). Since many antibiotics and their analogues have been synthesized both synthetically and microbially, these agents are together termed as antimicrobial agents (AMA) . Since antimicrobial agents belong to diverse chemical class, they can be classified based on their chemistry, mechanism of action. spectrum of activity, source from which they are obtained etc A.
Based on type of organism against which they are primarly active a. Antibacterial –eg: penicillin b. Antifungal-eg: clotrimazole c. . Antiviral- eg: amantidine d. . Antiprotozoal-eg: tinidazole e. . Antiparsitics /Anthelmintic-eg: albendazole f. Antirickettsial-eg: tetracycline g. Antineoplastic eg: bleomycin Again, based on the specific pathogenic organism against which they are acting , these agents can be subclassified in to various groups like antistaphylococca, antipseudomonal,antitubercular, antileprosy, antimalarial, antitrypanosomal, antischistosomal etc. B. Based on the source from which they are derived a. Fungal –eg: penicillin, cephalosporin b. Bacterial-eg: colistin, polymixinB c Synthetic- eg: sulphonamides C. Based on chemistry: a. Beta-lactam antibiotics:eg: Penicillins and Cephalosporins b. Aminoglycosides: eg: Streptomycin, Gentamicin etc., c. Tetracyclins: eg:Tetracycline, Oxytetracycline etc., d. Nitro-benzene derivatives: eg: Chloramphenicol e. Fluoroquinolones: eg: Enrofloxacin, Norfloxacin ete., f. Macrolides: eg:Erythromycin, Roxithromycin etc., g. Lincosamides: eg:Lincosamine h. Glycopeptide: eg:Vancomycin i. Polypeptide: eg:Bacitracin j. Sulphanilamide derivatives/Sulphonamides eg: sulphadimidine k. Steroidal : eg: Fusidic acid l. Quinolones: eg: nalidixic acid m. Diaminopyrimidines: eg: trimethoprim n. Oxazolidinones: eg: linezolid o. Nitrofurans: eg: nitrofurazone p. Polyene : eg:nystatin q. Azole : eg: miconazole
r. Nicotinic acid derivatives: eg: isoniazid s. Miscellaneous: eg: rifampin, cycloserine t. Nitroimidazoles: eg: metronidazole D. Based on mechanism of action: a. Inhibitor of folate synthesis: eg: Sulphonamides b. Cell wall synthesis inhibitors: eg: Beta-lactam antibiotics c. Protein synthesis(30 S’ ribosomal activity)inhibitors: eg:Aminoglycosides, Tetracyclines d. Protein synthesis (50 S’ ribosomal activity) inhibitors: eg: Chloramphenicol, Tylosin e. Inhibition of energy metabolism: eg: Nitrofurazones f. Interfering with plasma membrane permeability: eg:Ionophoric antibiotics- monensin g. Inhibiting DNA gyrase: eg: Fluoroquinolones i. Inhibiting RNA polymerase: eg: Rifampin j. Inhibiting DNA polymerase: eg: Aciclovir j. Disruptor of microtubule function.eg: albendazole k. Disruptor of muscle fibre function. eg: ivermectin E.Based on spectrum of activity a. Narrow spectrum: eg: benzyl penicillin b.Broad spectrum: eg: tetracyclines c. Extended spectrum: eg: aminopenicillins F .Based on type of action a. Bacteriostatic: eg: chloramphenicol b. Bacteriocidal :eg: cephalosporins CATEGORISATION OF ANTIBIOTICS AND ANTIBACTERIALS (The list is not exhaustive) 1. PENICILLINS a. Natural Penicillins – penicillin G (benzyl penicillin),phenoxymethyl penicillin,(penicillinV) Penethamatehydroxide, Penicillin procaine b. Amdinopenicillins- mecillinam c. Aminopenicillins (Semisynthetic, broad spectrum)-amoxycillin, ampicillin, hetacillin d. Aminopenicillin plus betalactamase inhibitorampicillin, ticaricillin, piperacillin or amoxycillin plus clavulanic acid, sulbactum, or tazobactum e. Carboxypenicillins -carbenicillin,ticarcillin, tobicillin f. Ureido Penicillin-aspoxicillin ,aziocillin, mezlocillin, and piperacillin. g. Phenoxypenicillins-phenoxymethylpenicillin(penicillinV), Phenethicillin h. Long acting – benzathine penicillin, procaine penicillin, PAM(procaine ppenicillin with aluminium monostearate)
i. Extended spectrum penicilins: i.Antistaphylococcalcloxacillin,dicloxacillin, nafcillin, oxacillin ii.Betalactamase/Penicillinaseresistantnafcillin,methicillin,oxacillin,cloxicillin, dicloxacillin, and flucloxacillin. iii.Anti-pseudomonal- piperacillin,azlocillin,ticarcillin,carbenicillin 2. CEPHALOSPORINS a. First generation-cefacetrile, cephalexin, cefalothin, cefaridine, cefatrizine,cefazolin,cefalonium,cefadroxil,cefapirin, cefradine and cephaloglycin b. Second generation- cefaclor, cefamandole,cefmetazole, ceforanide, cefonicid, cefacetrile, cefmenoxime, cefotiam cefotetan, cefprozil, and cefuroxime. c. Third generation - cefixime, cefoperazone,cefotaxime, cefpodoxime, ceftazidime, ceftizoxime, ceftiofur ceftriaxone, cefdinir,ceftibuten,cefsulodin,latamoxef(moxalactam)and cefodizime d. Fourthgeneration-cefquinome,cefepime,cefpirome,cefmetazole,cefditoren 3. CARBAPENEMS- imipenem, meropenem, faropenem 4. MONOBACTAMS-aztreonam 5. AMINOGLYCOSIDES
a. Aminocyclitol- spectinomycin
b. Aminoglycosides- streptomycin, dihydrostreptomycin framycetin, kanamycin, neomycin, paromomycin, apramycin, gentamicin, , amikacin, sisomycin, netilmicin and tobramycin 6. PHENICOLS- florphenicol, thiamphenicol, chloramphenicol 7. SULFONAMIDES- Sulfachlorpyridazine,sulfadiazine,Sulfadimerazine,Sulfadimethoxine Sulfadimidine,Sulfadoxine,Sulfafurazole,Sulfaguanidine,Sulfamethazine, sulfadimethoxazole,Sulfamethoxine,Sulfamonomethoxine,Sulfanilamide, Sulfaquinoxaline.Sulfonamides+Diaminopyrimidinessulfamethoxypyridazine,Trimethoprim+Sulfonamide.DiaminopyrimidinesBaquiloprim,Trimethoprim 8. STREPTOGRAMINS-virginiamycin, quinupristin ,dalfopristin 9. TETRACYCLINES-chlortetracycline,doxycycline,oxytetracycline,tetracycline, Demeclocycline, methacycline, lymecycline, minocycline 10.
QUINOLONES- QUINOLONES 1G- flumequin,miloxacin,nalidixic acid, oxolinic acid 11. FLUOROQUINOLONES (Quinolones2G) ofloxacin, norfloxacin, ciprofloxacin, pefloxacin, enrofloxacin danofloxacin,difloxacin, ,marbofloxacin, , orbifloxacin, gatifloxacin, sparfloxacin,levofloxacin, moxifloxacin, lomefloxacin 12.LINCOSAMIDES- pirlimycin,lincomycin , clindamycin 13.MACROLIDES- tulathromycin, erythromycin, josamycin, kitasamycin, spiramycin tilmicosin, tylosin, mirosamycin, terdecamycin, roxithromycin, azithromycin, clarithromycin, olendomycin ,troleandomycin, carbomycin,
rosamicin, , clarithromycin, dirithromycin 14. NOVOBIOCIN-novobiocin 15. ORTHOSOMYCINS- avilamycin 16. ANSAMYCIN – RIFAMYCINS- rifampicin, Rifaximin 17. BICYCLOMYCIN- Bicozamycin 18. FOSFOMYCIN-fosfomycin 19. STERDOIDAL -fusidic acid 20. IONOPHORES- lasalocid,maduramycin,monensin,narasin,salinomycin, semduramicin 21. QUINOXALINES-carbadox 22. PLEUROMUTILINS-tiamulin, valnemulin, 23. POLYPEPTIDES- enramycin, gramicidin, bacitracin, colistin, polymixin 24. GLYCOPEPTIDES-vancomycin, teicoplanin 25. OXAZOLIDINONE- linezolid 26. NITROFURANS- furazolidone, nitrofurazone, and nitrofurantoin 27. NITROIMIDAZOLES -metronidazole, orindazole, secnidazole,satranidazole, tinidazole Drug sagainst specific organisms: 1. ANTI TUBERCULAR DRUGS- capreomycin, soniazid, rifampin, ethambutol, streptomycin, Pyrazinamide 2. ANTI LEPROSY DRUGS- Dapsone (diamino diphenyl sulfone), rifampin, ethionamide, ofloxacin, minocycline, clarithromycin 3. ANTIMALARIAL DRUGS- Quinine, arteether, artesunate, chloroquine, bulaquinemefloquine, primaquine
CATEGORISATION OF IMPOPRTANT ANTIFUNGAL DRUGS 1. ANTIBIOTICS:
a. Polyene- amphotericin B, nystatin, hamycin,nafamycin b. Heterocyclic benzofuran-griseofulvin 2. ANTIMETABOLITES : flucytosine (5-FU/ flurouracil) 3. AZOLES: a. Imidazole- clotrimazole, econazole, miconazole, ketoconazole b. Triazole- fluconazole, itraconazole,voriconazole 4. ALLYLAMINE: -terbinafine 5. OTHERS- tolnaftate, undecylenic acid, quinidochlor, benzoic acid, ciclopirox olamine, sodium thiosulfate
Spectrum of activity of common antibacterial drugs Group
Class of microorganisms Bacteria Mycoplasma Rickettsia Chlamydia Protozoa Aerobic Anaerobic Gram Gram Gram Gram + ve - ve + ve -ve Aminoglycosides + + --+ ---Penicillins + + ------Potentiated + + + + ----penicillins Cephalosporins + + + + ----Chloramphenicol + + + + + + + -Lincosamides + + + + + --+ Macrolides + -+ + + -+ -Pleuromutilins + -+ + + -+ -Tetracyclines + + + + + + + -Fluorouinolones + + + + + + + -Sulfonamides + + --+ -+ + Trimethoprim + + -----+ Nitroimidazoles --+ + ---+ Polymixin -+ ------Bacitracin + -+ ------
DOSAGE REGIMENS FOR ANTIMICROBIAL DRUGS IN DOGS AND CATS
Drugs PENICILLINS Penicillin G, Na or K Penicillin G, procaine Penicillin G, benzathine Penicillin V Cloxacillin Dicloxacillin Methacillin Oxacillin Amoxicillin Amoxicillin-clavulanate Ampicillin Carbenicllin Hetacillin Ticarcillin CEPHALOSPORINS First Generation Cefaclor Cefadroxil Cephalexin Cephradine Cephaloglycin Cefazolin Cephapirin Cephradine Second Generation Cefamandole Cefotaxime Cefachlor Cefoxitine Cefotetan Cefomandole Third generation Cefotaxime Ceftriaxone Ceftazidime Cefoperazone Cefoxitin
Dose in mg/kg (Except as indicated)
Route of administration
Dose Interval (hr)
20000-40000 U/kg 20000 U/kg 40000 U/kg 10 30 50 25-50 15-25 10-20 12.5-25 (Comb) 20-30 10-20 10-50 20-30 40-75
IV, IM, SC
6-8
IM, SC IM PO PO, IV, IM PO, IV, IM IV, IM PO, IV, IM PO, IV, IM, SC PO PO IV, IM, SC PO, IV, IM, SC PO, IV, IM, SC
24 72-120 8 8 8 6 8 8-12 8-12 8 8 8 8 6-8
10-15
PO
8
10-20 10-25 15-30 10-20 10-30 20-40 6-25
PO PO PO PO IV, IM, SC IV, IM, SC IV, IM, SC
12 8-12 6-8 6-8 6-8 8 6-8
15-30 20-80 15-30 10-20 30 10-30
IV, IM, SC IV, IM, SC IM,IV PO IM,IV IM,IV
8 8
20-40 15-50 30-50 30 20-40
IM, IV IM, IV IM,IV IM IV, IM, SC
8 24 8-12 6-8 6-8
8-12 8 8
Moxalactam AMINOGLYCOSIDES Amikacin Dihydrostreptomycin Gentamicin Kanamycin Neomycin Netilmicin Streptomycin Tobramycin FLUOROQUINOLONES Ciprofloxacin Enrofloxacin Norfloxacin TETRACYCLINES Chlortetracycline Doxycycline Minocycline Oxytetracycline
50
6-8
IV, IM, SC PO IM, SC IV, IM, SC PO IV, IM, SC PO IV, IM, SC PO IM, SC IV, IM, SC
20-40 10-20 10 2-4 10 10 10 1-2 20 10 1-2
6-8 6 12 8 6 6-8 6 8 6 12 8
PO PO PO
5-15 2.5-15 5-20
12 12 2
20-30 5-10 5-15 20-30 10 20 10 5-10 PO IM,IV
8 12 12 8 12 8 12 12 8 12
5-10 10-20 10-20 10-20 10 5-10
8-12 8-12 8-12 12-24 8 12
50-100 (double first dose in dog) 30 (comb) 30 (comb) 27.5 (double first dose in dog) 55
12
PO PO, IV PO PO IV, IM Tetracycline PO IV, IM Rolitetracycline IM,IV Demeclocycline 20-30 Methacycline 5-10 MACOLIDES AND LINCOSAMIDES Clindamycin PO, IV, IM, SC Erythromycin PO Lincomycin PO IV, IM Tylosin PO IV, IM SULPHONAMIDES Sulfadiazine PO, IV Sulfadiazine-trimethoprim Sulfamethoxazole-trimethprim Sulfadimethoxine
IV, IM
PO, IV, IM, SC PO IV PO
12-24 12-24 12-24
MISCELLANEOUS ANTIMICROBIALS
Chloramphenicol
PO IV, IM, SC
Clofazimine Dapsone Ethambutol Isoniazid
PO PO PO PO
Metronidazole Nitrofurantoin Rifampin
PO, IV PO PO
ANTIPROTOZOAL, ANTIRICKETTSIALS Amprolium PO Clindamycin
PO, IM, SC
Difluoromethylornithine Diminazene acetate Furazolidone Imidocarb dipropionate Meglumine antimonite Metronidazole
PO IM PO IM, SC IV, SC PO
Parvoquone Pentamidine isethionate Phenamicine isethinate Primaquine Pyrimethamine Quinacrine
IM, SC IM SC IM PO PO
Sodium stibogluconate Thiacetarsamide Tinidazole ANTIFUNGALS Amphotericin B
IV, SC IV PO
Fluconazole
PO
IV
Dog 50 Cat 50 mg total Dog 50 Cat 20-30 Cat 2-8 Cat 50 mg total Dog 15 Dog 10-20 (max 300 mg daily) 10 5 10-20 (dog max 600 mg daily)
8 12 8 12 24 12-24 24 24
Dog 100-400 mg total Dog 10-20 Cat 12.5-25 Dog 100 Dog 3.5 or 7 8-10 Dog 5 Dog 100 Dog 15-30 Cat 10-25 Cat 10-20 Dog 4 Dog 15 0.5 0.25-0.5 Dog 50-100 mg total,Cat 10 Dog 30-50 Dog 2.2 Dog 44
24
Dog 0.25-0.5 Cat 0.25 Dog 5-10
48 48 12-24
8 8 24
12 12 8 Once 12-24 Once 24 12-24 12-24 24 24 24 Once 12 8 24 24 24 24
Flucytosine
PO
Griseofulvin, microsized Itraconazole Ketoconazole
PO PO PO
Thiabendazole
PO
Cat 50 mg total Dog 50-75 Cat 50 25-60 5-10 5-10 Cat 10 Dog 10
12 8 8 12 12-24 12 12-24 12
DOSAGE OF ANTIMICROBIAL AGENTS in ANIMALS PENICILLINS Drug
Route
Penicillin G sodium aqueous Procaine Penicillin G Benzathine Penicillin G Cloxacillin, Oxacillin Methicillin Ampicillin sodium Ampicillin Amoxicillin Amoxicillin trihydrate 10 % aq. susp. 5 % aq. susp. Carbenicillin sodium Carbenicillin Ticarcillin sodium
Dosage (IU/KG or mg/kg)
Interval (h)
IM, IV IM IM Oral, IM IM, IV IV, IM Oral Oral
15-20,000 IU 25,000 IU 40,000 IU 40-60 25-50 10-20 20-30 20-30
6-8 24 72 8 6 6-8 8 8-12
IM Oral Oral IM, IV IM, IV
10 30 50-100 50 50-75
12 8 8 6-8 6-8
AMINOGLYCOSIDES AND AMINOCYCLIOTOLS Drug
Amikacin Apramycin Gentamicin
Route
IMb IM, SC PO IM IM(IV)
Dosage (mg/kg)
4-8 10 20-40 20 2-4
Intreval (hr)
8-12 8-12 12 12 8-12
Comments
Horses Dog, cat Enteric infection Swine only Dogs, cats-2 x day
Kanamycin Neomycin Spectinomycin Streptomycin Tobramycin
PO IM(IV) PO PO IM IM IM(IV)
10 4-8 10 20-40 20 8-12 1-2
1, 1 x thereafter Enteric infection
6 8-12 6 8 12 8 8
Enteric infection Enteric infection Swine only Need more data
CHLORAMPHENICOL Species
Dosage form
Route
Dose (mg/kg)
Interval (hr)
Dogs, Cats
Base, palmitate
Horses
Sodium succinate Sodium succinate
Oral dog, cat IV, IM, SC IM
50 50 mg/cat 25-50 30-50
12 12 12 8-12
Ruminants
Sodium succinate
IV, IM
25
8-12
Pigs
Sodium succinate
IM
25
12
Comment
50-100 mg/kg priming dose 50 mg/kg Priming dose 50 mg/kg Priming dose
TETRACYCLINES Species
Dosage Form
Route
Dose (mg/kg)
Interval (hr)
Tetracycline, Oxytetracycline, Doxycycline
IV, IM
10
12
IV
5-10
12
Horses
Oxytetracycline
IV
3-5
12
Slow IV
Ruminants
Tetracycline, Oxytetracycline
IV, IM
10
12-24
Slow IV
Long acting tetracycline (2PVP)
IM
20
48
Same as ruminants.
Oral
10-30
24
Dogs, cats
Pigs
Comment
IM
Tetracycline, Oxytetracycline, Chlortetracycline
Injection
ORAL DOSAGE OF TETRACYLINES FOR MONOGASTRIC ANIMALS Tetracycline Preparation
Route
Priming Dose
Maintenance Dose (mg/kg)
Dosage Interval (h)
PO PO PO PO
30 40 10 10
15 20 5 5
6 12 12 12
Tetracycline Hcl Oxytetracycline Hcl Minocycline Hcl Doxycycline hyclate
SULFONAMIDES AND TRIMETHOPRIM-SULFONAMIDE COMBINATIONS Drug
Route
Short acting Sulfadiazine, sulfamethazine, tri sulfapyramidine (triple sulfas) Intermediate acting Sulfadimethoxine Sulfadimethoxine Sulfisoxazole Sulfamethoxazole Gut-Active Phthalysulfathiazole Other Salicylazo sulfapyridine Trimethoprim-sulfonamide combination
Dose (mg/kg)
Interval (h)
Comment
IV, PO
50-60
12
100 mg/kg priming dose
IV, SC PO PO PO
27.5 55 50 50
12-(24) 12-(24) 8 12
55 priming 100 priming U. T. infection
PO
100
12
PO IV, IM PO
25 24-30 36
12 12 12
Meningitis (TID)
Usual systemic dosages of currently available fluoroquinolones Species
Cattle, sheep, goats Swine Poultry
Drug
Enrofloxacin Enrofloxacin Enrofloxacin
Route
Dose (mg/kg)
Interval (h)
Comment
PO IM, SC IM, PO PO IM
2.5-5 2.5-5 2.5-5 50 ppm 0.5 mg/bird
24 24 24 Water SID
Preruminants Ruminants Turkey, Salmonella
Common antimicrobial drug dosage in horses Drug
Amphotericin B Amikacin sulfate Ampicillin sodium
Dose
0.3-0.6 mg/kg in 5% dextrose 6.6 mg/kg 10-20 mg/kg
Frequency
Route of administration
TID
IV
TID TID
IV or IM IV or IM
Cefazolin Ceftiofur Cephalexin Cefotaxime Chloramphenicol palmitate Erythromycin estolate Isoniazid Gentamicin sulfate Ketoconazole Metronidazole Oxytetracycline HCl Penicillin-G, K or Na Penicillin-G procaine Rifampin Sodium iodine Streptomycin sulfate Ticarcillin disodium Ticarcillin and calvulanic acid Trimethoprimsulfonamide (oral preparation)
15-20 mg/kg 2.2 mg/kg 20-25 mg/kg 20-40 mg/kg 25-50 mg/kg 25 mg/kg 5-15 mg/kg 2.2 mg/kg 10 mg/kg 15 mg/kg 5 mg/kg 20,000-40,000 IU/kg 20,000 IU/kg 5-10 mg/kg 20% solution, 10-40 ml /day 8-12 mg/kg 50-75 mg/kg 50 mg/kg of ticarcillin 5.5 mg/kg of trimethoprim
TID BID QID QID QID
IV or IM IM PO IV PO
QID BID QID SID/BID BID/TID BID QID
PO PO IV or IM PO PO IV IV
BID BID
IM PO IV
TID QID QID
IM IV, IM IV
BID
PO
ANTIMICROBIAL DRUGS THAT ARE POTENTIALLY HAZARDOUS IN RENAL FAILURE, LIVER FAILURE, PREGNANCY OR NEONATES
Renal failure
Aminoglycosides Amphotericin B Cerbenicillin Cephaloridine Chloramphenicol Flucytosine Fluoroquinolones Nalidixic acid Nitrofurantoin Polymyxins Tetracyclines --
Liver failure
Chloramphenicol Clindamycin Erythromycin Linocomycin Oxacillin Tetracyclines -------
Pregnancy
Aminoglycosides Amphotericin B Chloramphenicol Flucytosine Fluoroquinolones Griseofulvin Ketoconazole Metronidazole Nitrofurantoin Polymyxins Sulphonamices (L.A) Tetracyclines
Neonates
Aminoglycosides Chloramphenicol Fluoroquinolones Nalidixic acid Nitrofurantoin Polymyxins Sulphonamides Tetracyclines Trimethorpim ----
--
--
Trimethoprim
--
SUGGESTED ORAL ADMINISTRATION IN RELATION TO FEEDING
Better if administered on an empty stomach( 2 hours before or after food intake) Cephalosporins Erythromycin base Erythromycin stearate Isoniazid Lincomycin Most penicillins Rifampin Most sulphonamides Most Tetracyclines
Better if administered with food
Indifferent/ No effect of food
Chloramphenicol palmitate(cats) Doxycycline
Chloramphenicol caps and tabs, palmitate (dog) Erythromycin coated formulations Ethambutol Fluoroquinolones Hetacillin
Erythromycin estolate Erythromycin ethyl succinate Griseofulvin Ketoconazole Metronidazole Nitrofurantoin
ADVERSE EFFECTS OF COMMON ANTIBACTERIAL GROUPS Sl no 1
Antibacterial group Penicillins
Adverse effects Hypersensitivity reactionsanaphylaxis, skin rashes, angioedema, Super infection- GIT disturbances
Effect in Pregnancy Nonteratogenic, may modify infant bowel flora, increase penicillin resistant bacterial
Na salt- sodium overload in population CHF 2 Cephalosporins Nephrotoxic, painful IM Nonteratogenic injection, phlebitis on repeated IV, occasional vomition, diarrhoea, superinfection 3 Aminoglycosides Ototoxicity, nephrotoxicity, Nonteratogenic, renal failureneuromuscular but dose related blockade, Ototoxicity and nephrotoxicity 4 Quinolones and Neurutoxic, high doseNonteratogenic fluoroquinolones convulsions, vomition , Arthropathy, diarrhoea, dermal reactions, phototoxicity phototoxicity High dosescartilaginous erosions, embryonic loss lameness in young ones and maternal toxicity 5 Sulphonamides Hypersensitivity, crystalluria, Nonteratogenic haematuria, tubular obstruction Neural tube defect 6 Tetracyclines GI disturbances, Ca chelation, Nonteratogenic,c hinders host defense Inhibit bone mechanisms,nephrotoxic,Rapid growth of foetus, IV- hypotension, collapse yellow PG base- Intravascular discoloration of haemolysis bone and teeeth 7 Chloramphenicol Blood dyscrasias, bone marrow Bonemarrow depression, aplastic anaemia, depression, “Grey suppress immune response baby syndrome” in Rapid IV-haemolysis, collapse, humans death 8 Macrolides Occasional hypersensitivity, GI Nonteratogenic disturbances,Erythromycin Erythromycin estolate- hepatotoxic, estolateTilmicosin- cardiac toxicity hepatotoxic SUGGESTED DOSAGE REGIMENS FOR ANTIMICROBIALS IN REPTILES Drug Ampicillin Carbenicillin Piperacillin Ceftazidime
Species tortoise Snakes, tortoise Snakes Snakes
Route of administration IM IM IM IM
Dose(mg/kg) 50 400 400 100 20
Frequency of administration 12 hour 24 hour 48hour 24 hour 72 hour
Doxycycline Chloramphenicol Sulphadiazine+TMP Gentamicin Amikacin Ciprofloxacin Enrofloxacin Tylosin Ketoconazole Nystatin
Tortoise Snakes All species Alligators, Snakes Snakes tortoise
IM SC IM IM IM IM IM
50 50 30 1.75 2.5 5 5
72 hour 12 hour 24 hour 72-96 hour 48-120 hr 72 hour 48 hour
Snakes Tortoise All species All species All species
Oral IM IM Oral Oral
2.5 5 5 15-30 100000IU/kg
48-72 hour 24-48 hour 24hour 24hour 24 hour
ANTI-NEOPLASTIC DRUGS DRUGS ALKYLATING AGENTS Cyclophosphamide Melphalan
MECHANISM OF MAJOR ACTION INDICATIONS
Dose& Route of Adm.
alkylate DNA, Lymphoma, sarcomas, cross-linking of mammary DNA strands adenocarcinoma, lymphocytic leukemia Alkylates DNA Multiple myeloma causing miscoding and cross-linking of DNA strands
60mg/kgBW daily oral 150mcg/kgBW daily or 250mcg/kgBW daily for 4 weeks oral
Chlorambucil Carboplastin
Alkylates DNA causing miscoding DNA strands Inhibits both DNA and RNA synthesis
Streptozocin
Inhibits synthesis
Dacarbazine
alkylate inhibits synthesis
Busulfan
Chronic lymphocytic 100mcg/kgBW leukemia, lymphoma daily oral
CNS neoplasias ,GI carcinomas, multiple myeloma DNA Temporary remission of hypoglycemia resulting from functional pancreatic islet cell tumor DNA, Lymphoma RNA
300-360mg/m2 BSA by IV 100mcg/kgBW daily
2-4.5mg/kgBW daily for 10 days IV1015mg/day for 48days oral Alkylates DNA, Chronic myelogenous 60mcg/kg BW causing miscoding of leukemia, polycythemia daily oral DNA strands vera
ANTIMETABOLITES Methotrexate Inhibits formation of tetrahydrofolate, a necessary cofactor in thymidylate synthesis, essential for DNA synthesis and repair Fluorouracil Pyrimidine analog, interferes with DNA synthesis and may be incorporated into RNA to cause toxic effects Cytarabine Pyrimidine analog, incorporates into DNA causing stereo hindrance and inhibition of DNA synthesis ANTIBIOTICS Dactinomycin disrupting helical (Actinomycin D) structure and DNA template, inhibits RNA and DNA polymerases Doxorubicin Disrupts helical structure and DNA
Lymphoma, Sertoli cell 10-15mg/day tumor, osteosarcoma, for 4-8 days oral metastatic transmissible venereal tumor
GI, lung, liver, and mammary carcinomas (systemic); cutaneous carcinomas (topical)
15mg/kgBW once a week oral 15mg/kgBW in 500ml DNS
Lymphoma (including 100mg/m2 BSA CNS), leukemias bid by rapid inj.IV.& Ithecal 10-30mg/m2for meningitis Choriocarcinoma, testicular carcinoma, rhabdomyosarcoma, lymphoma Lymphoma, lymphocytic
15mcg/kgBW per day or400600 mcg/m2 BSA IV
acute 60-75mg/ and BSA IV
m2
Mitoxantrone Bleomycin
MITOTIC INHIBITORS Vinblastine Vincristine
MISCELLANEOUS Cisplatin
L-Asparaginase
template, inhibits RNA and DNA polymerases DNA aggregation, oxidation, and strand breakage generates oxygen radicals that cause chain scission and fragmentation of DNA
granulocyticleukemia, sarcomas carcinomas,
Lymphoma,carcinomas, fibrosarcoma, hemangiopericytoma Carcinomas (testicular, squamous cell of head and neck, cervical, penile)lymphoma, seminoma,malignant teratoma disruption of mitotic Lymphoma and spindle apparatus leukemias, and arrest of cell mastocytoma cycle disruption of mitotic Transmissible venereal spindle apparatus cell tumors, lymphoma and arrest of cell and leukemias, CNS cycle tumors, mammary adenocarcinoma, softtissue sarcomas, immune-mediated thrombocytopenia Reacts with proteins and nucleic acids; forms cross-links between DNA strands and between DNA and protein; disrupts DNA synthesis Inhibits protein synthesis
Mitotane (o,p¢DDD)
Destroys adrenal zona fasciculata and zona reticularis
Hydroxyurea
Inhibits conversion of ribonucleotides to deoxyribonucleotides
8-12mg/ BSA IV
m2
15,000IU thrice a week IM/IV
0.10.5mg/kgBW IV 25-75 mcg/kg or 1.4mg/m2 IV
Osteosarcoma, 50-120mg/m2 carcinomas (transitional BSA with % cell, testicular, NS, IV squamous cell of head and neck, ovarian, cervical, bladder, and lung), mesothelioma Acute lymphocytic and 1000units/kg lymphoblastic leukemia BW/10days and lymphoma with NSor Dextrose 5% Pituitary hyperadrenocorticism, palliation of adrenal cortical tumors Polycythemia vera, 20-30 mastocytoma, mg/kgBW oral granulocytic and basophilic leukemia, thrombocythemia
Causes Carcinomas (testicular, 50-100mg/m2 topoisomerase-IIsmall cell lung) IV mediated DNA scission
Etoposide
HORMONES Prednisolone
inhibits mitosis in Lymphoma, mast cell lymphocytes tumors, palliative treatment of brain tumors Anti-estrogenic; Estrogen-receptorblocks the effects of positive mammary estrogen on target carcinomas tissues Anti-androgenic; Testosterone-receptorcompetes with positive prostatic testosterone for tumors; surgical binding to androgen castration preferred receptors GnRH analog that Testosterone-receptor initially stimulates, positive prostatic then decreases, the carcinomas or perianal secretion of FSH and tumors, surgical LH,lead to decreased castration preferred concentrationof testosterone (males) and estrogen (females)
Tamoxifen
Flutamide
Leuprolide
60mg/m2 IM,IV
20mg/day single dose oral 250mg TID oral
1-3.5mg IM or SC
APPENDIX The relation of body weight to surface area in square meters for dogs is given in the following table: Kg
0.5 1 2 3 4 5
m2
0.06 0.10 0.15 0.20 0.25 0.29
Kg
17 18 19 20 21 22
m2
Kg
m2
0.66 0.69 0.71 0.74 0.76 0.78
34 35 36 37 38 39
1.05 1.07 1.09 1.11 1.13 1.15
6 7 8 9 10 11 12 13 14 15 16
0.33 0.36 0.40 0.43 0.46 0.49 0.52 0.55 0.58 0.60 0.63
23 24 25 26 27 28 29 30 31 32 33
0.81 0.83 0.85 0.88 0.90 0.92 0.94 0.96 0.99 1.01 1.03
40 41 42 43 44 45 46 47 48 49 50
1.17 1.19 1.21 1.23 1.25 1.26 1.28 1.30 1.32 1.34 1.36
Body surface area in ‘ square meters’ for dogs and cats may be obtained from the following formula: K x W2/3 BSA = ---------------104 Where, K = constant (10.1 for dogs ; 10 for cats) W = weight in grams BSA = Body surface area in square meters Doses for anticancer drugs are calculated as a function of body surface areas (m) rather than body weight because the blood supply to the organs responsible for detoxification, kidney and liver, is more closely related to surface area than body weight
DOSAGES OF SOME OF THE ANTIMICROBIALS USED IN BIRDS. Drug Enrofloxacin
Doxycycline Oxytetracycline Tylosin
Dose in mg/kg 10 5ml/litre water/50ppm or iml per kg feed 20 50 200
Route of administration
Dose Interval (hr)
IM PO
12 12
PO IM PO
12 12 SD
25 Ampicillin 100-150 Amoxycillin 100-200 25-100 Amoxycillin+clavulanate 100 Cloxacillin 250 Cephalexin 35-50 Lincomycin 50 Clindamycin 20-100 Gentamicin 75-200mg totaldose Tobramycin 2 Potentiated sulphonamides 20 Metronodazole 50 Ronidazole 5mg/100ml water Itraconazole 5-10 Nystatin 300000units/kg Aciclovir 50mg/ 100ml water Ivermectin 200µg/kg Levamisole 15-25 Fenbendazole 20-50 Praziquantel 5-10
IM IM IM PO PO PO PO PO PO IM IM PO PO PO PO PO PO PO,SC PO PO PO
12 12 24 12 12 24 6-8 24 12 12 12 12 12 12 12 SD 24 SD SD SD SD
CLASSIFICATION OF COMMONLY USED ANTHELMINTICS
Sl no 1
Group Benzimidazoles
2
Probenzimidazoles
3
Imidothiazoles Imidazothiazoles
4
Pyrimidines(Tetra hydrop yrimid ines) Salicylanilides
5
6
Substituted phenols
7
Organophosphates
Examples Mode of action on parasites thiabendazole, Interfers with energy parbendazole, production, cambendazo inhibit fumarate le, reductase, mebendazol block tubulin e, synthesis oxfendazole Inhibit glucose transport- all , resulting in starvation of oxibendazol parasite, ovicidal effect e, fenbendazol e triclabendazole, albendazole thiophinate Metabolized invivo to febantel Benzimidazole netobimin carbamates to result in the same effect as above levamisole Ganglionic stimulants- result tetramisole in spastic paralysis pyrantel pamoate Cholinergic(ganglionic) pyrantel tartrate agonosts – morantel citrate result in spastic oxantel paralysis rafoxanide Uncouple oxidative oxyclozanide phosphorylatio niclosamide n resulting in closantel energy resorantel depletion nitroxynil Uncouple oxidative niclofolan phosphorylatio bithional n resulting in hexachlorophene energy hexechloroethane depletion carbon tetrachloride trichlorphon Irreversible cholinesterase dichlorovos inhibition haloxan leading to coumaphos spastic fenchlorphos paralysis uredophos
8
Piperazine
9
piperazine diethylcarbamazine citrate (DEC)
Neuromuscular hyperpolarisati on resulting in flaccid paralysis
Macrolide ivermectin,doramectin endecticid moxidectin es/Averme selamectin ctins abamectin milbemycine
10
Pyrazinoisoquinolones and benzazepi nes
praziquantel epsiprantel
11
Miscellaneous
Phenothiazine Disophenol Dithiazine Thiacetarsamide clorsulon
GABA potentiation – flacci d paral ysius Ionic balance altera tion to cause vacou lation and disru ption of tegu ment Interfere with repro ducti on Inhibit oxidative phosphorylation Inhibit glycolysis
DOSAGE OF ANTHELMENTICS IN DOMESTIC ANIMALS Drug/Chemical nature
Bunamidine HCl
Indication
Dose/Route
Dichlorovos (OPC)
Cestodes, 25-50 mg/kg P.O. Echinococcus Ascarids, Hook and Whip worms 11 mg/kg P.O.
Disophenol
Hook worms
10 mg/kg S/C
DEC Fenbendazole
Ascarids and spirocerca lupi Ascarids, Hook , Whip worms ,Larvicidal, Ovicidal effect Ticks/mites/ Nematodes. Larvicidal and ovcidal effects. Ticks/mites/ Nematodes
55-110 mg/kg P.O. 5-10 mg/kg for 3 days P.O.
Nitroxynil Levamisole
Ascarids, Hookworm Cestodes Ascarids Echinococus Diphylobothrium latum Liverflukes and Amphistomes GI nematodes
Hexachlorophene Carbon tetra chloride
Adult and immature liver flukes Adult flukes
Phenothizine
Haemonchus Oesophagostomum Strongyles
22 mg/kg for 3 days P.O. 150 mg/kg P.O. D:110 mg/kg P.O D:5-10 mg/kg P.O D: 25 mg/kg. P.O C: 10 mg/kg, S/C C: 7.5 mg/kg S/C (large animals) D: 7.5 mg/kg P.O. (Dogs) 2.5mg/kg- immunomodulatory dose C:20-25 mg/kg P.O. S-4 ml P.O. C-5 ml P.O. C-20gm/45 kg (Max. 80 g) H-3g/45 kg
Pyrantel pamoate/tartrate Morantel citrate/tartate
Broad spectrum antinematodal
Ivermectin Doramectin Mebendazole Niclosamide Piperazine Praziquantel
Closantel
Haemonchus Trichostrongyles Liverflukes, Nematodes, Cestodes
Chlorsulon
Liver flukes
Triclabendazole
Liver flukes (mature & immature) Nematodes larvicidal, ovicidal Liver flukes
Thiophinate Oxyclonazide Antimony potassium tartarate (Tartar emetic)
S.nasalis
Lithium antimony thiomalate
S.nasalis Filariasis and Leishmaniasis
Note :
S= Sheep & Goat
C= Cattle
H = Horse
200 g/kg, S/C.PO 200 g/kg, S/C
25 mg/kg P.O. (Tartarate 5% drench 5 mg/kg P.O. Pamoate) S-10 mg/kg P.O. C-8.8 mg/kg S/C 5mg/kg IM 15 mg P.O.
S-7mg/kg P.O C-4mg/kg S/C 20 mg/kg., P.O. C-10g/100 kg P.O C-10mg/kg S-10-15mg/kg C-3 mg/kg IV only C-6% Solution of (50 ml IM) given as 20 ml + 15 ml +15 ml for 3 days. D-1ml IM C&S 3.5 mg/kg SC or IM D= Dog
