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pharm final

All anthelmintics are potentially devoid of pharmacological effects Exception organophosphorous compounds & levamisole.
Classification of anthelmintics it is based on chemical structure.
bioavailability of anthelmintic depends on formulation of dosage form.
clinical efficacy varies among species.
Most of the anthelmintics are recommended for clinical use in all species Exception levamisole (ruminant species & pigs)Praziquantel (dogs, cats & horses)Piperazine (monogastric species)Salicylanilides, nitroxynil & clorsulon (ruminant species).
Benzimidazoles (carbamates) Albendazole, fenbendazole, mebendazole, oxfendazole, oxifendazole, parbendazole.
Benzimidazoles (thiazoles) Thiabendazole, cambendazole.
Probenzimidazoles Netobimin, febantel.
Imidazothiazoles Butamisole hydrochloride, levamisole.
Tetrahydropyrimidines Pyrantel, morantel.
Organophosphorous compounds Dichlorvos, coumaphos.
Macrocyclic lactones Avermectins.
Milbemycins Milbemycin oxime, moxidectin.
Phenothiazine derivative Phenothiazine.
Piperazine compounds Piperazine, Diethylcarbamazine citrate (DEC).
Benzenedisulphonamide Clorsulon.
Isoquinoline Praziquantel, epsiprantel.
Salicylanilide Closantel, oxyclozanide, rafoxanide.
Nitrobenzonitrile Nitroxynil.
Arsenical compound Thiacetarsamide sodium.
ANTINEMATODAL DRUGS BENZIMIDAZOLES Broad spectrum of activity,Wide safety of margin.
Subclasses of benzimidazoles Benzimidazole thiazole (Thiabendazole, cambendazole).
Benzimidazole carbamates (albendazole, fenbendazole, mebendazole & oxfendazole)Probenzimidazole.
Metabolically converted to BZD carbamates (netobimin to albendazole; febantel to fenbendazole).
BZD carbamates possess greater anthelmintic activity,requires a lower dose.
This is due to enhanced receptor binding in parasites, decreased metabolic inactivation in host animal.
BZD carbamates possess larvicidal activity.
Mechanism of actionBZD binds irreversibly to nematode β-tubulin-prevents dimerization with a-tubulin & polymerization of tubulin oligomers into microtubules.
BZDs inhibits microtubule formation.
Selective toxicity:BZDs have a greater affinity for nematode tubulin (selective toxicity).
BZD resistance due to development of b tubulin isotypes with lower affinity for BZDs.
Pharmacokinetics of BZDs Absorption is limited (except TBZ, albendazole, oxfendazole).
BZD level in plasma is always <1pct of the dose administered.
Presence of food in stomach increases the bioavailability of drug ex fenbendazole.
In ruminants, the systemic availability of BZDs is more.
Metabolism of BZDs undergoes hepatic metabolism.
BZD carbamates are converted to active metabolites Ex albendazole to albendazole sulphoxide fenbendazole to fenbendazole sulphoxide (oxfendazole).
Sulphoxides metabolized by liver to sulphones (inactive).
In cattle & goats, the metabolism of albendazole & fenbendazole is more rapid.
Oxfendazole when administered as oral suspension/intermittent release ruminal bolus undergoes partial reduction in rumen to form fenbendazole.
Oxfendazole & fenbendazole is oxidized by the liver to inactive sulphone metabolite.
Mebendazole poor metabolism & excreted unchanged in faeces (within 48 hrs.).
Albendazole metabolized to sulphoxide & sulphone derivatives excreted in urine.
TBZ & cambendazole rapidly metabolized,excreted in faeces.
BZD carbamates have a broad spectrum of activity.
Clinical efficacy depends on effective concentration at the site of action in the parasite.
Horses:TBZ & substituted BZDs adult strongyles, cyathostomes, Oxyuris equi, small pinworms & Trichostrongylus axei.
Substituted BZDs Parascaris equorum & immature Oxyuris.
Oxibendazole Strongyloides westeri.
Horses Fenbendazole migrating S. vulgaris & S. edentates,encysted 3rd & 4th cyanthostome larvae.
Mebendazole & albendazole equine lungworms (Dictyocaulus arnfieldi).
Cattle & sheep Substituted BZDs GI nematodes & lung worms in ruminants.
Fenbendazole D. filaria in sheep.
Fenbendazole Mullerius infection in goats & sheep.
Albendazole & fenbendazole tissue stages of Ostertagia.
Swine TBZ Hyostrongylus rubidus, S. ransomi, O. dentatum.
Substituted BZDs effective against all parasites of swine,Swine whipworm (Trichuris suis).
Kidney worm, lungworm, ascarids & nodular worms fenbendazole @ 3mg/kg/day for 3 days.
Swine lungworms fenbendazole @ 25 mg/kg, single dose,albendazole @ 10 ppm in feed for 5 days.
Dogs & cats Mebendazole adult hookworms, ascarids & whipworms.
Fenbendazole Common nematodes of dogs & cats,3rd & 4th stage larvae of canine ascarids,Cat lungworms,Cat stomach worm.
Albendazole T. canis & A. caninum.
Birds effective against GI & respiratory tract nematodes Mebendazole,Fenbendazole.
Turkeys Fenbendazole @45 ppm in feed for 6 days,(ascarids, Heterakis, Capillaria).
Turkeys Parbendazole ascarid worms & heterakids.
Withdrawal period for BZDs Albendazole oral suspension (sheep – 10 days; cattle – 14 days).
Fenbendazole oral suspensions (cattle & sheep - 21 days; pigs – 7 days).
Oxfendazole oral suspension (cattle & sheep - 10 days).
Intermittent release ruminal bolus Albendazole in sheep 100 days.
Oxfendazole in cattle 180 days.
BZDs are well tolerated.
Contraindications:Substituted BZDs are not indicated during early pregnancy.
Parbendazole & cambendazole produces teratogenic effects in pregnant ewes (2nd to 4th week of gestation).
Administration of BZDs Oral administration (suspension/powder or granules).
Horses Fenbendazole & mebendazole as oral paste.
Pigs Fenbendazole as pellets.
Ruminants Intermittent release ruminal bolus of albendazole (sheep) & oxfendazole (cattle).
Continuous release ruminal bolus fenbendazole.
PROBENZIMIDAZOLES ex Netobimin & Febantel.
Netobimin to albendazole (metabolic conversion by ruminal microorganisms).
Febantel to fenbendazole (metabolic conversion by hepatic microsomes).
Netobimin Broad spectrum probenzimidazole anthelmintic drug.
Nematocidal activity in horses & ruminants Netobimin.
Cestocidal & fasciolicidal activity in ruminants Netobimin.
Metabolic activation:Netobimin- albendazole-hepatic oxidation-albendazole sulphoxide.
Febantel broad spectrum anthelmintic drug indicated for horses,dogs & cats.
Metabolic activation:Febantel- fenbendazole-hepatic oxidation-fenbendazole sulphoxide(Oxfendazole).
Anthelmintic spectrum:Febantel Hook worms, ascarids, whipworms.
Commercial anthelmintic preparation Vercom Combination of febantel (nematodes) & praziquantel (cestodes).
Commercial anthelmintic preparation Drontal Plus (35.8 mg febantel, 7 mg pyrantel pamoate & 7 mg praziquantel).
effective against canine ascarids, hookworms, whipworms & Echinococcus sp.
Febantel Cattle, sheep, swine effective against GI & lung parasites.
wide margin of safety Contraindications Vercom paste & Drontal Plus are contraindicated in pregnant dogs & cats.
IMIDAZOTHIAZOLES,Levamisole effective against GIT & lung nematodes.
routes of administration (oral, parenteral or topical) Levamisole.
it is available as hydrochloride (drench) or phosphate (injectable) salt Levamisole.
Mode of action of levamisole It acts as a ganglionic stimulant & a direct cholinergic drug binds to nicotinic receptors of nematode parasites-sustained muscle contraction with subsequent paralysis in nematode parasite (depolarization blockade)acts as immunostimulator (cell mediated i
Pharmacokinetics of levamisole Absorption & excretion is rapid.
Its pharmacodynamic action is of nicotinic & muscarinic effects Levamisole.
administered as bolus/ drench/ feed additive/ SC injection/ topical pour-on Levamisole.
Anthelmintic spectrum for levamisole Cattle & sheep Haemonchus, Ostertagia, Cooperia, Trichostrongylus, Bunostomum, Oesophagostomum, Dictyocaulus, Thelazia.
Swine A. suum, S. ransomi, Metastrongylus sp., O. dentatum, S. dentatus.
Poultry A. galli, H. gallinarum, C. obsignata, fowl eyeworm.
Dogs Tetramisole @ 10 mg/kg/day for 2 days (ascarids & hookworms).
Dogs Levamisole - 5.5 mg/kg twice daily for 6 days (microfilaricide).
Levamisole Safety Narrow margin of safety.
Safety factor of levamisole is twice that of tetramisole.
Toxicity signs are similar to organophosphate poisoning(salivation, lacrimation, head shaking, muscle tremors, mild excitability).
simultaneous administration of pyrantel tartrate enhances levamisole toxicity.
poultry tolerate tetramisole & levamisole.
oral route is more safe in dogs & cats Levamisole.
Contraindication If levamisole used in lactating animals milk should not be used for 48 hrs.
Tetrahydropyrimidines ex pyrantel & morantel.
Pyrantel Broad spectrum anthelmintic for all species.
Imidazothiazole derivative available as tartrate or pamoate salt Pyrantel.
Aqueous solution undergoes photoisomerization loss of potency Pyrantel.
Mode of action of Pyrantel It acts as a depolarizing blocking agent in nematode parasites & in host,causes sustained muscle contraction followed by paralysis of worms.
Pharmacokinetics Pyrantel tartrate well absorbed except ruminants,rapidly metabolized (first-pass effect)excreted in urine (dogs) & feaces (other species).
Pyrantel pamoate poorly soluble in water-decreased absorption from the gut-drug reaches the lower intestine & acts on pinworms.
Pyrantel pharmacologic effects are similar to levamisole, DEC citrate & morantel citrate (depolarization blockade).
pyrantel & morantel are more potent than acetylcholine.
Horses Pyrantel tartrate is available as top-dressed pellet oral paste/granules.
Swine Pyrantel Medicated feed (0.016pct)prevents migration & establishment of A. suum & Oesophagostomum infections.
Dogs Pyrantel pamoate (suspension/tablet)Dose: 5-10 mg/kg.
Drontal Plus for dogs Pyrantel pamoate (5 mg/kg)+febantel (25 mg/kg)+praziquantel (5mg/kg).
Drontal for cats Pyrantel pamoate (20 mg/kg)+ praziquantel (5 mg/kg).
Pyrantel pamoate administration with food increases the contact time of drug with parasites.
Heartgard 30 Plus beef based chewable form in dogs contains ivermectin (6-12 mg/kg) + pyrantel pamaote (5-10 mg).
Heartgard 30 Plus effective against heartworms, hookworms & ascarids.
Anthelmintic spectrum of Pyrantel Horses Parascaris equorum, S. vulgaris, S. equinus & pinworms effective against Anaplocephala perfoliata tapeworm @ 13.2 mg/kg.
Swine (tartrate salt) Pyrantel Ascaris & Oesophagostomum.
Cattle & sheep (tartrate salt) Pyrantel broad spectrum anthelmintic effective against (Haemonchus contortus (including BZD resistant strains), Ostertagia ostertagi, T. axei, Nematodirus battus, Cooperia & Bunostomum sp.
Anthelmintic spectrum of Pyrantel Dogs A. caninum, Uncinaria stenocephala, ascarids.
Dogs Drontal plus for tapeworms, whipworms, hookworms, ascarids.
administered to dogs of 3 weeks of age,Treatment repeated at 2 week intervals Drontal.
Cats Pyrantel pamoate for Ancylostoma tubaeforme, T. cati.
Drontal cats for hookworm, ascarid, tapeworm.
Safety Pyrantel salts are generally safe in all species.
Tartrate salts are less tolerated than pamoate salt in Horses.
Pyrantel salts Contraindications not indicated in severely debilitated animals,withdrawal period for slaughtering animals should be given.
Pyrantel tartrate Horse: 12.5 mg/kg, single dose,Swine: 22 mg/kg; max. 2g/animal,Cattle, sheep & goats : 25 mg/kg.
Pyrantel Pamoate Horses: 6.6 mg base/kg,Dogs: suspension & chewable form -5 mg base/kg.
Morantel Methyl ester analog of pyrantel,formulated as tartrate salt.
Morantel Pharmacological action similar to pyrantel.
Morantel in Ruminants (adult & immature stages)for Haemonchus, Ostertagia, Trichostrongylus, Cooperia, Nematodirus.
Morantel Available as medicated premix (Morantel Premix-88)delivers the drug @ 0.44 g/100 lb BW.
Morantel Slaughter withdrawal period Cattle-14 days,Goats-30 days.
Morantel Sustained release ruminal bolus contains 11.8 g morantel base (Paratect Flex Diffuser)releases drug @ 150 mg/day into rumen/ reticulum for 90 days.
Morantel sustained release ruminal bolus requires no withdrawal period.
Morantel tartrate is a safer drug than pyrantel tartrate.
Organophosphorous compounds Ex Dichlorvos, trichlorfon, coumaphos.
Organophosphorous Mode of action irreversible inhibition of acetylcholinesterase-accumulation of acetylcholine-sustained muscle contraction & subsequent paralysis.
effective against parasites of horses, pigs & dogs OP.
rotation of anthelmintics is recommended to prevent the development of organophosphate anthelmintic resistance OP.
Precautions with Organophosphate anthelmintics,animal should not be simultaneously treated with other acetyl cholinesterase inhibiting drugs/ pesticides/ muscle relaxants or sedatives.
narrow safety margin (proper dosing is required) OP.
withdrawal period of 7 days for slaughtering animals OP.
not recommended in sick/stressed animal OP.
Toxicity signs:Vomition, frequent urination, defecation, urination, diarrhea & muscular weakness OP.
OP Treatment Atropine & PAM.
Dichlorvos volatile & easily degradable in GIT.
dichlorvos incorporated into polyvinyl chloride resin pellets – for administration in pigs, dogs & cats,releases dichlorvos slowly from the indigestible pellets,maintains therapeutic concentration throughout the digestive tract.
this formulation is more safer dichlorvos incorporated into polyvinyl chloride resin pellets.
it is effective against whipworms (Trichuris sp.) dichlorvos incorporated into polyvinyl chloride resin pellets.
Anthelmintic spectrum of Dichlorvos Dogs & cats A. caninum, A. tubaeforme, Uncinaria stenocephala, ascarids, Trichuris vulpis.
Swine first broad spectrum anthelmintic effective against 4th stage larvae, juveniles & adults of Ascaris suum, Oesophagostomum, T.suis & H. rubidus Dichlorvos.
Macrocyclic lactones Consists of 2 groups Avermectin,Milbemycin.
Avermectin includes Ivermectin, abamectin, doramectin, selamectin, eprinomectin.
Milbemycin includes Milbemycin oxime, moxidectin.
active against nematodes & arthropods,broad spectrum action Avermectin,Milbemycin.
Chemistry Avermectin Fermentation product of actinomycete, Streptomyces avermitilis.
Milbemycin D & milbemycin oxime chemistry Streptomyces hygroscopicus aureolacrimosus.
Mode of action of macrocyclic lactones binds selectively to glutamate gated chloride channels-creates an ion imbalance-it increases the release of GABA from synaptosomes of nervous system-it binds to GABA related chloride channels-increase in chloride ion influx-hyperpolarization of post synap
Mode of action of macrocyclic lactones Site of action Nematodes synapse between inhibitory & excitatory motor neuron.
MOA macrolytic lactones site of action Arthropods myoneural junction,It also affects reproduction of nematode/ arthropod by inducing abnormal egg formation by nematodes,sterility of both male & female filarial nematodes,reduces oviposition by ticks.
Selective toxicity of macrocyclic lactones Mammalian GABA – mediated neurotransmission – only in CNS.
Macrocyclic lactones do not cross the mammalian blood brain barrier-more safer drug.
Macrocyclic lactones Sensitivity Collie breed dogs & Australian shepherds.
Ivermectin Semisynthetic derivative of avermectin.
Chemistry Avermectin consists of Major components (avermectin A1a, A2a, B1a, B2a)Minor components (avermectin A1b, A2b, B1b, B2b).
Ivermectin 80pct B1a + 20pct B1b.
Pharmacokinetics of ivermectin It depends on formulation of the dosage form, route of administration & animal species.
Half-life of Ivermectin (IV) Dogs: 1.6-1.8 days,Sheep: 2.7 days,Cattle: 2.8 days.
Ivermectin SC administration longer half-life.
Excretion Faeces (98pct) & urine,Up to 5pct in lactating animals.
Formulations of ivermectin Ivermectin (oral, parenteral, topical).
Ivomec injection 1pct ivermectin in an organic vehicle (60pct propylene glycol+ 40 pct glycerol formal).
It can be administered by SC injection to cattle, sheep & swine Ivomec.
Formulations of ivermectin Controlled release Ivomec ruminal bolus contains 1.72 g of ivermectin delivers ivermectin @12 mg/day for 135 days,withdrawal period: 180 days.
Formulations of ivermectin Equalan liquid for horses 1pct ivermectin in an aqueous micelle form.
Equalan paste for horses 1.87pct ivermectin with propylene glycol as vehicle.
Ivomec Pour-on for cattle 0.5pct ivermectin in 80pct isopropyl alcohol.
Heartgard-30 tablets & Heartgard – 30 chewables for dogs & cats combination of ivermectin & pyrantel pamoate.
Anthelmintic spectrum of ivermectin Cattle, sheep, horses & pigs GI & lung nematodes & certain ectoparasites.
Dogs intestinal nematodes, ear mites, sarcoptic mange, infective stage heartworm & microfilariae.
Poultry GI nematodes, ectoparasites of poultry.
High lipid solubility of ivermectin increased anthelmintic activity.
Ivermectin More safer (about 10 fold safety margin) for ruminants, horses, swine & dog breeds except Collies & Australian shepherds.
This could be due to breed specific compromised blood brain barrier.
Clinical signs of toxicity ataxia, depression, mydriasis, tremor & recumbency.
Horses ivermectin In heavy infection of Onchocerca treatment induces pruritus & cutaneous edema,This is due to sudden death of large numbers of microfilaria of Onchocerca cervicalis (resolves in 3-4 days).
Abamectin Fermentation product of Streptomyces avermitilis,Consists of 80pct B1a & 20pct B1b.
Formulation Avomec (injectable)consists of 1pct w/v abamectin.
Abamectin Anthelmintic spectrum Adults & 4th stage larvae of O. ostertagi, H. placei, Cooperia & Dictyocaulus sp., Trichostrongylus axei.
more toxic than ivermectin Abamectin.
Abamectin Toxicity signs Lethargy, ataxia, paresis, recumbency, decrease in lip & tongue tone, drooling of saliva, mydriasis, coma & death.
Doramectin product of mutational biosynthesis.
broad spectrum of activity against GI nematodes, lungworms, eyeworms, suckling lice, ticks, mites & screwworms Doramectin.
effective against myiasis Doramectin.
Formulation for doramectin Dectomax–sterile 1pct solution of doramectin (sesame oil –ethyl oleate as vehicle).
Doramectin Anthelmintic spectrum similar to ivermectin,it is highly effective against screwworms.
Eprinomectin modified fermentation product of Streptomyces avermitilis,consists of 90pct avermectin B1a + 10pct avermectin B1b.
Eprinomectin Pharmacokinetics absorption is rapid (topical administration)peak concentration reaches after 2-5 days of treatment,undergoes poor metabolism-eprinomectin B1a as tissue residue,low milk plasma coefficient.
Eprinomectin safety More safer.
Selamectin Chemically modified derivative of avermectin.
Indications: Dogs : heart worm, flea & ectoparasite infection.
Cats hookworm & roundworm infections.
Selamectin Pharmacokinetics:absorption is rapid,peak plasma concentration after 8 hrs. of oral administration (3 days of topical administration).
Topical route: Half-life in dogs is 11 days.
Selamectin maintains effective concentration for 30 days in dogs & cats.
Selamectin Absorption into blood-excreted into intestinal tract.
Circualting selamectin deposited in sebaceous glands&–ectoparasitic activity.
Selamectin Formulation: 6pct or 12pct topical formulation (Revolution) for dogs & cats.
Selamectin Anthelmintic spectrum 100pct effective against heartworm.
Selamectin cats Ancylostoma tubaeforme & T. cati.
Safety for selamectin safer drug (breeding & lactating animals)can be used in ivermectin sensitive Collies.
Milbemycin,Milbemycin oxime Fermentation product of Streptomyces hygroscopicus aureolacrimosus
Milbemycin 95pct of dose passes through GIT in unchanged form,5pct of absorbed drug excreted through bile,eliminated through faeces.
Milbemycin oxime Formulations available as chewable tablet for dogs,Cats: Interceptor Flavor tabs; orally administered once a month.
Milbemycin oxime Anthelmintic spectrum: Nematodes & Demodex canis,Dogs: prevention of canine dirofilariasis,Cats: feline heartworm, T. cati, A. tubaeformr infections.
Milbemycin oxime potent & fast acting microfilaricide.
Milbemycin oxime Treatment is accompanied with mild reactions (lethargy, salivation, coughing, tachypnea or emesis).
Milbemycin oxime In animals with heavy heartworm infection shock-like reactions & circulatory collapse.
Moxidectin Fermentation product of Streptomyces cyanogriseus noncyangenus.
Moxidectin Pharmacokinetics more lipophillic,maintains clinically effective concentration for prolonged period,excreted in faeces.
Moxidectin Anthelmintic spectrum Ruminants: O. ostertagi, Haemonchus, T. axei, Oesophagostomum, Bunostomum, Dictyocaulus,Sarcoptes, Psoroptes, ticks & suckling lice.
Sheep: GI nematodes, sheep itch mite.
Horses: GI nematodes.
Dogs: A. caninum @ 25 µg/kg, single oral dose,Prophylactic control of heartworm.
100pct effective against larval stages of D. immitis @ 3 µg/kg,safe to administer in dogs & ruminants (breeding & pregnant animals),used in ivermectin sensitive Collie breed of dogs Moxidectin.
Heterocyclic compounds Phenothiazine used in ruminants, horses & chickens.
Limitation: phenothiazine resistant helminth strains.
Piperazine class Piperazine & Diethylcarbamazine (DEC).
Piperazine wide margin of safety,narrow spectrum of action,clinically effective in monogastric species.
Diethylenediamine strong base & unstable,available as salts of citrate, adipate, hydrochloride, phosphate, sulfate & tartrate.
Piperazine Mode of action Hyperpolarization at neuromuscular junction-blocks neurotransmission-flaccid paralysis of worms.
Pharmacokinetics absorbed from GIT,metabolized in tissues,excreted in urine.
Piperazine Toxicity Wide margin of safety,Large doses – emesis, diarrhea, incordination, head pressing.
Contra-indication Not recommended in chronic renal/liver disease,In heavy ascarid infections–intestinal impaction of dead worms.
Piperazine Anthelmintic spectrum Dogs & cats T. canis, T. cati, T. leonina (citrate or phosphate salts)Efficacy is variable (52-100pct).
Horses Equine ascarids (adipate salts)treatment should be repeated at 8 week intervals – to prevent helminth re-infection,effective against adult pinworms (80pct) (retreatment is required)
Piperazine Anthelmintic spectrum Swine administered through water/ feed,acts on lumen dwelling stages of ascarids & nodular worm (100pct effective)retreated after 1-2 months.
Ruminants effective against nodular worm.
Chickens administered through feed (citrate/adipate salts) or drinking water (hexahydrate)effective against Ascaridia galli.
Diethylcarbamazine citrate (DEC) Indication: prophylactic control of heartworm disease in dogs.
Pharmacokinetics absorption is rapid from GIT,peak concentration reaches after 3 hrs. of oral administration,widely distributed to all organs except fat,rapid metabolism,excreted through urine (within 24 hrs. of administration) Diethylcarbamazine citrate (DEC).
effective against molting stage larvae of Dirofilaria immitis,possess microfilaricidal action-fatal adverse reactions,contraindicated in microfilaria positive dogs DEC.
IMPORTANT:Before prophylactic treatment, the infected dog should be cleared of adult heartworms & microfilariae.
Heartworm adulticides Ex Thiacetarsamide sodium & melarsomine.
Thiacetarsamide sodium: Hepatotoxic & nephrotoxic (not recommended in animal with liver & kidney dysfunction)Irritable to tissue – administered by IV route.
Animal feeding behavior indicative of dog’s general condition during treatment Thiacetarsamide sodium.
Toxicity:Arsenic toxicity signs – persistent vomiting, icterus, orange-colored urine TS.
Treatment for TS toxicity Dimercaprol (8.8 mg/kg/day in 4 divided doses).
Created by: alljacks



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