Classification and Dosage of Antimicrobial Agents in Veterinary Medicine

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