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112 Cards in this Set

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  • Back
3 different approaches of how antiparasitics affect parasites
1. Affect neuromuscular function at principal neurotransmitter
2. Affecting metabolism
3. Affecting parasite reproduction
How do antiparasitics affect parasite metabolism?
1. inhibition of microtubules
2. inhibition of folic acid synthesis
3. inhibition of thiamine utilization
4. uncoupling of oxidative phosphorylation
5. Inhibition of chitin formation in arthropods
6. Simulation of insect juvenile hormones
7. Facilitation of ion transport
8. Denature of cysteine
9. Inhibition of electron transport
Acetylcholine receptors are excitatory in which parasites?
Nematodes and arthropods
Acetylcholine receptors are inhibitory in which worms?
cestodes and trematodes
Glutamate gated chloride channels are inhibitory in which parasites?
Nematodes and arthropods
Octopamine work on:
1. Which receptors?
2. how?
3. what parasites?
4. excitatory/inhibitory
1. alpha2 adrenergic receptors
2. mimics them
3. arthropods (though cestodes and trematodes also)
4. inhibitory
5HT is what?
receptors in which parasites?
inhibitory or excitatory?
2. cestodes - excitatory
trematodes - excitatory
nematodes - inhibitory
GABA are receptors in which parasites?
2. inhibitory or excitatory?
1. nematodes - inhibitory
2. Arthropods - inhibitory
lindane blocks which receptors in which parasites?
GABA receptors in arthropods
piperazine uses which receptors in which parasites?
GABA receptors in nematodes
The ideal antiparasitic should have what characteristics?
1. must be effective in removing parasites from the body
2. must have a wide therapeutic index (the toxic dose should be at least 3times greater than the therapeutic dose)
3. low cost
4. easy to administer
5. one dose treatment
6. no residual problems
7. effective against immature form of parasites also
3 problems with continuous antiparasitic administration?
1. may be expensive
2. Development of resistant strains
3. Inhibition of the host's immunity
4 current trends of parasitic chemotherapy?
1. adopting broad spectrum drugs
2. adopting a mixture of drugs (usually to broaden the spectrum, though this may backfire)
3. Seeking persistent control
4. Convenient administration
What is the MOA of piperazine?
acts on neuromuscular transmission-GABA receptor agonist to induce hyperpolarization of excitable cells
What is the MOA of pyrantel?
It causes sustained contractions followed by paralysis.

Do NOT use concurrently with piperazine or macrocyclic lactones

It is similar to levamisole.
What is the MOA of Fenbendazole?
it inhibits microtubule formation
it is a benzimidazole
What is the MOA of Dichlorvos?
It is an organophophate so it inactivates cholinesterase receptors by binding to them with a covalent bond which leads to an increase in Anticholinesterase
What is the MOA of Ivermectin
it is a macrocyclic lactone.
1. hyperpolarization of nerves and pharyngeal muscles
2. opens glutamate gated chloride channels.
What is the MOA of Levamisole?
Acts on neuromuscular transmission. It is a nictonic like drug so it activates nicotine receptors and causes sustained contractions which lead to paralysis.
This drug is similar to pyrantel so if you have resistance to pyrantel you will have resistance to levamisole.
What is the MOA of Febantel?
It is a Probenzimidazole. It will be metabolized into a benzimidazole where it becomes fenbendazol and oxfendazole.
Benzimidazoles inhibit microtubule formation.
Adverse effects of Fenbendazole?
a Benzimidazole.
1. safe in general, but may be toxic to liver and bone marrow in dogs.
2. Liver Toxicity
Adverse effects of Albendazole?
a Benzimidazole
1. safe in general, but may be toxic to the liver and bone marrow in dogs.
2. in dogs and cats may cause anorexia, weight loss, neutropenia, and/or depression.
3. liver toxicity
4. Bone marrow depression
5. Teratogenicity
Adverse effects of Ivermectin?
a Macrocyclic lactone
1. Very safe in most animals, including pregnant females.
2. Some breeds are sensitive due to the P-glycoprotein mutation.
3. there may also be some CNS disturbances causing lethargy, recumbency, mydriasis, and/or impaired vision.
4. CNS Depression because it opens chloride channels which causes hyperpolarization and therefore inhibits neurotransmission which leads to depression.
Adverse effects of Levamisole?
1. Dyspnea because of nicotinic like effect stimulates skeletal muscle contractions and paralyzes it. Atropine doesn't help a lot because it only works on muscarinic receptors.
2. SLUDD = due to nicotinic- like actions and cholinergic stimulation
3. Cardiac arrhythmias
4. SQ is the most dangerous injection method.
5. pigs are more susceptible than sheep which are more susceptible than cattle.
Why is piperazine, which is a relatively safe antinematodal drug, rarely used in ruminants?
Because there are few economically important ascarids in cattle which is what piperazine is primarily effective against.
Which position of the structure of benzimidazoles is important with regard to metabolism?
Position #5
Why are fenbendazole and albendazole resistant to metabolism?
These two benzimidazoles have a side group attached to the 5' position which inhibits their metabolism.
It also makes them more persistent in the body because it takes a lot to break their side chains.
Discuss the metabolism of benzimidazoles.
They stay mostly in the gut (except for albendazole which is about 50% absorbed). They are very lipid soluble so they have a long withdrawal period. They are metabolized in the liver by 5'-hydroxylation. The mode of excretion varies between urine and feces.
Name 4 broad spectrum antinematodal drugs.
1. levamisole
2. Pyrantel
3. Morantel
4. Dichlorvos
Which of the 4 broad spectrum antinematodal drugs cause cholinergic stimulation?
1. levamisole
2. pyrantel
3. morantel
4. Dichlorvos

What is the most fatal consequence that pyrantel and levamisole can lead to in the host?
asphyxia due to respiratory paralysis
Can atropine be useful as an antidote for levamisole and pyrantel toxicity?
No, because it only works on the muscarinic receptors.
Can pyrantel be used to kill levamisole-resistant nematodes?
NO... because they have the relatively same method of action
Is levamisole a good dewormer for Strongyles?
It is not a good dewormer for Strongyles. It is also not legal to use in horses.
Which drugs are effective against Strongyles?
1. Benzimidazoles
a. Fenbendazole
b. Oxfendazole
c. Oxibendazole
2. Macrocyclic lactones
a. ivermectin
b. moxidectin
3. Tetrahydropyrimidines:
a. pyrantel
b. morantel
Levamisole is FDA approved in which species?
Cattle and swine
Why is levamisole not FDA approved in other species?
The margin of safety is very narrow. Horses can be killed at 20 mg/kg.
What are the preslaughter withdrawal periods for the use of benzimidazoles?
Albendazole: 27 days because of the better absorption rate in the gut.
Fenbendazole: 8 days because of the reduced absorption in the gut. This is the only one that can be used in lactating dairy cattle.
Oxfendazole: 7 days... same as fenbendazole
What are the preslaughter withdrawal periods for macrocyclic lactones?
1. cattle:
Pour on: 49 days
SQ: 35 days
Swine: PO: 45 days
SQ: 18 days
Sheep: PO: 11 days
2. Eprinomectin:
Cattle: No Meat or Milk Withdrawal times if used topically.
3. Doramectin:
Cattle: PO: 45 days
SQ: 35 days
Can be used in freshening cows older than 20 months of age
4. Moxidectin:
Cattle: No Withdrawal times if used topically. similar to Eprinomectin.
What drugs have been used in the treatment of bots?
Macrocyclic lactones:
Which drugs are used for the treatment of equine ascarids?
1. Macrocyclic lactones:
a. ivermectin
b. moxidectin
2. Tetrahydropyrimidines:
a. pyrantel
b. Morantel
3. Benzimidazoles: LIMITED ACTIVITY... must use at higher dose to be effective.
4. Piperazine and diethylcarbamiazine (these are of limited use in cattles)
Which drugs are used for the treatment of whipworms?
1. Benzimidazoles in cattle, dogs, and cats
2. Macrocyclic latones
a. ivermectin: ruminants, pigs, and dogs
b. eprinomectin: ruminants, pigs, and dogs
c. Doramectin: cattle
d. Milbemycin oxime: dogs
e. Selamectin: dogs (if swallowed may kill whipworms but failures have been reported)
3. Organophosphates
a: Dichlorvos (pigs and dogs)
Why is there a difference in the administration schedule of benzimidazoles in the dog, cat, and pig as compared to the herbivores?
In herbivores, the benzimidazoles only have to be given once (except in the case of Strongylus vulgaris) because their gut is much larger than that of dogs, cats, and pigs. The drug stays in the gut much longer in herbivores.
What are the most concerning adverse effects of benzimidazoles in dogs?
They are generally pretty safe, but there is concern about liver toxicity and bone marrow toxicity.
What is the only drug (or group of drugs) used to treat Trichinosis in humans?
Mebendazole (a benzimidazole)
Humans tolerate it well, but it much too risky to use in animals.
What is the side effect of Macrocyclic lactones (macrolide endectocides). What is its mechanism of action?
The method of action of macrocyclic lactones is that of opening glutamate gated chloride channels which causes hyperpolarization of the nerves and pharyngeal muscles. This can cause CNS disturbances such as lethargy, recumbency, mydriasis, and impaired vision. They can cross the BBB and accumulate in the brain cells.
There is also a breed sensitivity.
Which drugs can be used in cats to treat GI nematodes?
1. Benzimidazoles
2. Piperazine and diethylcarbamazine (?)
3. Selamectin, if over 1 month of age, (a macrocyclic lactone)
4. Pyrantel (a tetrahydroprimidine)
5. Dichlorvos (an organophosphate)
What is the primary drug available for removal of adult heartworms?
1. melarsomine
2. macrocyclic lactones, also work
What is the primary drug available for elimination of microfilariae?
1. macrocyclic lactones
What is the primary drug available for elimination of infective heartworm larvae (for prophylaxis)?
1. Macrocyclic lactones
What is the antidote for a melarsomine overdose?
1. dimercarol (BAL) for the treatment of nephrotoxicity caused by arsenic poisoning
2. anti-inflammatories, antibiotics (?), and absolute rest for 2 weeks for the treatment of thromboembolism
3. a glucocorticoid to prevent pneumonia
What is the mechanism of action for Melarsomine?
It denatures cysteine which is required for the protein structure of the heartworm. This is also what harms the liver and kidney.
What is the mechanism of action for Ivermectin?
It causes the opening of Chloride channels with causes hyperpolarization of nerves and pharyngeal muscles.
What are the adverse reactions associated with Melarsomine?
1. local irritation, pain, and distress at the sight of injection. It is given in the deep lumbar muscles only! Can cause weakness or paralysis in the hind limbs)
2. Liver Toxicity: anorexia, persistent vomiting, depression, jaundice, melena, increased ALT, AP, and bilirubin; recumbency, or circulatory collapse.
3. Nephrotoxicity: Azotemia with a high BUN, albuminuria
4. Thromboembolic pneumonia: caused by dead worms within 3 weeks of treatment
5. Liver and Renal Toxicity are the most important side effects!
What are the adverse reactions associated with ivermectin?
1. Breed sensitivity due to a P-glycoprotein mutation
2. CNS Depression (lethargy, recumbency, mydriasis, or impaired vision)
3. Generally, ivermectin is quite safe in most animals, including pregnant females
Which stage of heartworm larvae are most susceptible to diethylcarbamazine?
1. L3 stage
2. This stage lasts approximately 3 days, which is why this drug was given on a daily basis.
Which stage of heartworm larvae are most susceptible to Macrolide endectocides?
1. L3 and L4 stages
2. These stages last for about 90-100 days which is why you only need to give this heartworm medication once a month.
Which macrocyclic lactone that is used for heartworm prevention also kills ascarids, hookworms, and whipworms?
Milbemycin oxime
What is the mechanism of action of Dichlorophene?
It uncouples oxidative phosphorylation which leads to a decrease in ATP synthesis.
What is the mechanism of action for praziquantel?
It paralyzes the worm by producing irreversible focal vacuolization which causes the integument to disintegrate. The host then digest the worm so you won't see the dead worm in the feces. It also increases the intracellular Ca+ as well.
What is the mechanism of action for Fenbendazole?
It inhibits microtubule formation. It has a colchicine-like mode of action.
What are the toxic effects associated with dichlorophene?
1. This is a fairly safe drug.
2. vomiting, diarrhea, and ataxia may occur
What are the toxic effects associated with Praziquantel?
1. It is a very safe drug even for pregnant animals.
What are the toxic effects associated with Fenbendazole?
1. Liver toxicity in dogs
2. Bone marrow toxicity in dogs
Which anticestodal is the safest ?
Which anticestodal is the most effective?
Which anticestodal has the broadest spectrum?
Praziquantel, kills both juveniles and larvae in the intermediate host.
Which anticestodal can be used to treat hydatid disease?
Fenbendazole (a benzimidazole)
What is the diference between Epsiprantel and praziquantel?
Praziquantal has good GI absorption while Epsiprantel, an analog of praziquantal, is not as readily absorbed in the GI tract.
Would you expect to see scolex in the feces after dosing an animal with a taeniacide? Why or why not?
No, some drugs, such as praziquantal, break down the integument of the worm and then it is ingested by the host in which case you would not see the worm in the feces.
What is the most significant disadvantage with most antitrematodal drugs?
Most are only effective against the mature flukes and not effective against the immature flukes which are the cause of a great amount of damage to the liver and lungs.
Which anticestodal drugs have significant antitrematodal activity?
1. Albendazole (a benzimidazole)
2. praziquantel
Which drug is effective against immature flukes?
1. Clorsulon, which is a sulfonamide, is effective against both immature and mature liver flukes.
What is the mechanism of action of Decoquinate (quinolone)?
It inhibits DNA gyrase.
What is the mechanism of action of Monensin(an ionophore)?
It is a Na⁺ ionophore. It facilitates the movement of monovalent transport into cells which leads to increased osmolarity in the cell and eventual destruction of organelles and cell death.
What is the mechanism of action of Amprolium?
It is a thiamine antagonist. It is a quaternary compound.
What is the mechanism of action of Lasalocid?
It is an ionophore which facilitates the monovalent transport (of Na+ mainly) into cells which increase the intracellular osmolarity which leads to the destruction of the organelles and cell death.
What is the mechanism of action of Sulfadimethoxine?
It is an antifolate and used with dihydrofolate reductase inhibitors.
What is the mechanism of action of Metronidazole (nitroimidazole)?
Its active metabolites disrupt the helical structure of the protozoal DNA.
What is the mechanism of action of Ponazuril?
It kills schizonts by inhibiting nuclear division in the DNA.
It is only approved to treat EPM (Equine Protozoal Myeloencephalitis)
What is the mechanism of action of Nitazoxanide?
It creates the formation of a toxic free-radical from the nitro group which blocks the cellular respiration of the protozoa.
Name the ionophores that are available in the US as coccidiostats.
1. Monensin
2. Lasalocid
What are the side effects (and their mechanism of actions) of ionophores?
The side effects are excess sodium in the striated muscles (cardiac and skeletal). The mechanism of action is the same as that against the protozoa. Increased Na⁺ entry into the cell which leads to increased Ca⁺⁺ entry into the cell which leads to increased myocardial contractility and catecholamine release.
Are sulfonamides used predominantly for prevention or for treatment of coccidiosis?
For Treatment of acute outbreaks.
Are sulfonamides used in conjunction with other anticoccidials?
yes, they are used with dihydrofolate reductase inhibitors which cause a synergism.
Name 3 dihydrofolate reductase inhibitors that are used as anticoccidials.
1. Trimethoprim
2. ormetoprim
3. Pyrimethamine
Which dihydrofolate reductase inhibitor is not used as an antiprotozoal drug? Why?
Methotrexate because it has no antiprotozoal activity. It is an analog of folic acid which protozoans can't utilize because it is too to get through the protozoal membrane.
Which anticoccidial drugs do not require a preslaughter withdrawal?
1. amprolium
2. Decoquinate
3. Monensin (though don't use in veal calves)
4. lasalocid
5. Only the sulfa drugs have a preslaughter withdrawal period.
1. Name a broad-spectrum antiprotozoan drug?
1. Metronidazole (nitroimidazoles)
What parasites is Metronidazole effective against?
1. giardiasis
2. histomoniasis
3. babesiosis
4. trichomaniasis
5. amebiasis
What are the adverse effects of metronidazole?
1. Because it can cross the BBB, you will see CNS disturbances such as ataxia and seizures.
2. GI disturbances (diarrhea, vomiting, and anorexia)
3. Teratogenicity (mutagenicity, carcinogenicity)
4. Reversible leukopenia
What drugs can be used for the treatment of Equine Protozoal Myeloencephalitis?
1. Ponazuril
2. Nitazoxanide
3. Trimethoprim-sulfadiazine, pyramethamine, daily for 30 days
What are the side effects of Ponazuril?
blisters on nose & mouth, skin rash & hives, GI disturbances, colic, seizures
What is the mechanism of action of Ponazuril?
work against schizonts by inhibiting nuclear division
What are the side effects of Nitazoxanide?
ADR: GI disturbances (anorexia, diarrhea, colic, fever), enterocolitis, anaphylaxis (laminitis, edema, etc) - treatment crisis – may need to suspend therapy
What is the mechanism of action of Nitazoxanide?
albumin bound; metabolized into acetyl-nitazoxanide and eliminated in 24 h
What are the side effects of Trimethoprim-sulfadiazine?
Folic acid/folinic acid for protecting bone marrow?
What is the mechanism of action of trimethroprim-sulfadiazine?
It is combination of a dihydrofolate reductase inhibitor and an antifolate drug. This combination has a synergistic affect.
Which drugs can be used to treat giardiasis?
1. Nitazoxanide
2. metronidazole
3. Albendazole/Fenbendazole (Benzimidazoles)
Which drugs can be used to treat toxoplasmosis?
1. tetracyclines (doxy, or minocycline)
2. Clindamycin (controversial)
3. Pyrimethamine + sulfadiazine
4. Ponazuril
What is the Mechanism of action for Nitazoxanide?
It creates the formation of a free-radical from the nitro group at 5' position which blocks cellular respiration of the protozoan.
What is the mechanism of action for Metronidazole?
It creates the disruption of the helical structure of DNA by its active metabolites
What are the side effects of Metronidazole?
CNS disturbances
GI disturbances
What are the mechanism of action of albendazole/fenbendazole?
They inhibit microtubule formation.
The side effects of albendazole/fenbendazole?
Liver and bone marrow toxicity in dogs.
What is the mode of action of Ponazuril?
It inhibits nuclear division of the protozoa.
What are the side effects of ponazuril?
GI Disturbances, hypersensitivity (blisters on teh nose and mouth, skin rash and hives), and/or seizures
Which drugs work for both toxoplasmosis and giardiasis?
Tetracyclines (doxycycline) and clindamycin
What drug is used for the treatment of cryptosporidiosis?
1. Paromomycin
2. Nitazoxanide ??? Used in humans, but unknown about other animals...
What is the mechanism of action for Paramomycin?
Binds to the 50S ribosomal unit which inhibits translocation and stops the addition of amino acids to the protein chain.
What are the side effects of Paramomycin?
1. Vomiting
2. Diarrhea
3. colic
4. renal toxicity
5. deafness
Azithromycin is a human drug, but is sometimes used in animals instead of paromomycin. Why?
Paromomycin is very expensive. Azithromycin is less expensive and therefore more cost effective.