Pharm 2- Anthelmintics Review

kelseyfmeyer's version from 2015-05-10 01:46

Benzimidazoles (BZDs)

Question Answer
what kind of activity do BZDs have?Antinematodal, also anticestodal and antitrematodal
which is the most effective group of BZDs?carbamates (greater anthelmintic action, greater affinity, dec metabolic inactivation) (like they're hit by a car)
MOA of BZDs?irreversibly binds to beta-tubulin--> cant make micotubules
how is resistance formed against BZDs?isotypes of beta-tubulin (so the drug doesn't bind to the isotypes, so they aren't rendered ineffective)
what are the kinetic features of BZDs? (absorption, metabolism, plasma binding?)POOR oral absorption, but they undergo a rapid metabolism which produces the sulfoxides (drug name-sulfoxide) which are ACTIVE METABOLITES and these stay in the plasma (eventually converted into inactive sulfoxones...I before O) (ben doesnt like you putting things in his mouth, but he ACTIVELY puts it in plasma)
spectrum of BZDs?GIT and lung nematodes
species BZDs work on?ALL species
contraindications of BZDs?NOT IN PREGNANT ANIMALS (teratogenic) (BEN will hurt your baby)
what are the PROBENZIMIDAZOLES? what are they converted to? (2)(1) Netobimin--> albendazole--> albendazole sulfoxide (2) febantel--> fenbendazole---> fenbendazole sulfoxide


Question Answer
where does levamisole come from?L-isomer of tetramisole (spectrum and margin of saftey is better than parent drug)
route of admin of levamisole?ALL ROUTES! this is super awesome(LEVALL)
MOA of levamisole?acts as ganglionic stimulant, cholinergic agonist, inc depolarizing NM blockade--> paralysis leads to expulsion (pyrantel and morantel also have this MOA) (also an immunostimulant for CMI response) (Leva-tation using neuromuscular powers)
one of the cool things levamisole does that isnt its MOAacts as an immunostimulant--> CMI---> T-cell mediated immunity (the level of immunostimulant is T-CELLS for CMI--> LEVA T)
spectrum of levamisole?GIT and LUNG nematodes (microfilaria in dogs) (be leva with your heart, not just your lungs and gut)
species levamisole is used in?rumis, pigs, and dogs(works on microfilaria in dogs) (so not horses and cats, and said sheep was toxic too-- theyre on leva impossible)
what should you know about tox of levamisole?toxicity more pronounced in debilitated/sick animals, never coadmin any other drugs, esp pyrantel, morantel, organophosphates. (it's on it's OWN level, by itself, and that level is toxic...if you're sick, you wont be able to handle it)
contraindications of levamisole?do not give to lactating dairy animals! (leva, lactate), no debilitated/sick animals... No horses...Use protective gloves while handling (can cause blood disorders)

Pyrantel and Morantel (group: TETRAHYDROPYRIMIDINES)

Question Answer
what are the two pyrantel salts?TARTRATE and PAMOATE
MOA? DEPOLARIZATION BLOCKADE-->Sustained muscle contraction--> Paralysis of nematodes (Pyrantel paralysis) (same as levamisole.)
pyrantel tartrate is for who?well absorbed in MONOGASTRICS! NOT RUMIs (you can i could eat some tar, but that would be SO BAD for a rumen)
pyantel pamoate is used for treating what?ONLY GI nematodes and PINWORMS, and in horses, Anaplocephala perfoliata because it is not absorbed well, so it stays in the GI. (pyrantel pamoate pinworms)
which animals are the pyrantel salts able to be used in?ALL animals, including horses(Anaplocephala perfoliata)
tox of pyrantels?NOT FOR USE IN SICK/debilitated levamisole, since they have the same MOA
how is morantel different from pyrantel? what can you use morantel in?more potent AND safe--even lactating animals with no withdrawal period
what is the difference between the two pyrantel salts?pamoate is LESS soluble, so it stays in GI tract and that's how it is able to act on pinworms and Anaplocephala perfoliata
admin of this group?ORAL ONLY (remember using it in the clinic, dumbass?)

Dichlorvos (Group: Organophosphates)

Question Answer
MOA?Irreversible inhibition of acetylcholinesterase (AchE) --> accumulation of ACH --> sustained muscle contraction and paralysis of nematodes (Chlor--> Chol) (DIeing AChEs)
what is the admin of dichlorvos?highly volatile and unstable, easy degradation, so usually delivered on an indigestible resin pellet (steady DIet of PELLETS)
which animals can have dichlorvos?pigs, dogs, and cats (DI, Pig Crap, Die)
spectrum of dichlorvos?GI nematodes, INCLUDING trichuris (WHIPWORMS) (WHIP you till you DI)
tox/precautions?narrow margin of safety, never coadmin with other AChE inhibitors. Don’t administer to chronically ill or stressed patients


Question Answer
what are the 2 subgroups?Avermectins and Milbemycins (mac has two friends- aber and miles)
what are macrocyclic lactones effective against?GI and lung nematodes, AND ectoparasites (mac is enough to kill the repro of even ECTOPARASITES)
MOA of macrocyclic lactones?bind to glutamate gated Cl- channels = ↑ GABA = ↑ Cl influx leading to hyper polarization --> flaccid paralysis of parasite and expulsion. ALSO affect the repro ability in ticks (Mac swim in the chlorinated pool, hoping girls will GAB at him, but they merely are expulsed and don't want to reproduce with him)
contraindications of ivermectin?(Ivermectin) DONT USE IN COLLIES, AUSTRALIAN SHEPHERDS, murrah gray cattle, crocodillains/chelotians(turtles), horses w/ heavy onchocherca infxns
which drugs are SAFE for the species/breeds that are sensitive to macrocyclic lactones (and usually, specifically, ivermectin)?Selamectin, Moxidectin and Milbemycin Oxime (the milbemycins which are the safe group, as opposed to the Avermectins which is the group with ivermectin in it)
admin/species for ivermectin?oral, SC, topical. all species (aside from collies, Australian shepherds, crocodiles and turtles, murray grey cattle and SEVERE cases of worms-->impaction)
admin/species for abamectin?SC, rumis (think of cows singing and dancing to abba as they get SC injections)
admin/use for doramectin?SQ, im, topical (CAN TREAT SCREWWORMS) super broad spectrum (screws in the doors made of boards)
eprinomectin admin/use?topical admin. Very safe! Ok for dairy cows--> low milk plasma ratio. However, Poor metab--> forms tissue residue (need withdrawal for meat) (eprino makes primo milk, but the meat is lacking)
selamectin admin/animals/use?(aka revolution) oral/topical, sm animals--> circulating drug gets deposited in the sebaceous glands which allows the ectoparasitic activity
Milbemycin Oxime admin/animals/treats what?oral, small animal, GI and lung nematodes, also prophylactic use for heartworms (Milf...i mean, milb, can kill GI and lung nematodes, the usual, but she's got my HEART too, because she does oral even though im small)
Moxidectin admin/animalsOral/SC/topical, all animals (it has moxi-- will do everything but IV--because mac hates needles)
remember what drugs are in this categoryMac punching a bunch of collies and turtles.

Piperazine and DEC (diethylcarbazine) (Group: Piperazines)

Question Answer
MOA of piperazine?Hyperpol of neuromuscular junction --> inhibit neurotrans--> worm paralysis (NM blockade!)
spectrum of piperazines? very narrow (only certain GI nematodes) and only adult stages, so will need re-treatment to get rid of the ones which weren't killed b/c they were immature during the first tx
which species are piperazines used in?MONOGASTRICS (piper is scared of cows)
what is the safety margin of piperazines?WIDE! can even treat little puppies and sick animals, with tox affects only in super high doses
contraindications of piperazine?DO NOT USE in chonric liver/kidney disease patients, and in heavy ascarid infections (because they can cause an impaction) (piper gets punched in the liver and kidney in jail, and also is scared of worms)
DIETHYLCARBAZINE (DEC) MOA?inhibits cyclic peroxide production from arachidonic acid metabolism. This inhibits PG synthesis → vasoconstriction. (immobilizes, then destruction via host cell granulocytes)
what is diethylcarbazine(DEC) used for?PROPHYLACTIC HEARTWORM TREATMENT!
admin of DEC?Oral, and DAILY (DEC will stick a gun in your mouth every day till you give up)
contraindication of DEC?DO NOT USE IF ANIMAL IS ACTIVELY INFECTED! it is a microfilarialcide, and killing them off can cause the animal to go into hypovolemic shock.

THIACETARSAMIDE sodium, MELARSOMINE (Group: heartworm adulticides)

Question Answer
THIACETARSAMIDE sodium contraindications/toxicity?Arsenic toxicity, nephrotoxicity, hepatotoxicity (so, no pt's with liver or kidney problems) FATAL TO CATS (cats are screwed if they get heartworm anyway. and of course the two major filters would get blocked up with arsenic)
route of admin for thiacetarsamide sodium?IV because it can cause tissue irritation (arent they irritated enough?)
MOA?inhibits cell ATP prodcution (glycolysis inhibition) (heartworms take all your ENERGY and they arent sweet about it)
how should the animal be treated/handled during treatment? explain the reasoningas the worms are killed, they become impacted in the pulmonary artery and act as an emboli. At first you must give FULL REST, and slowly work up to mild exercise.
how long does it take for the dog to be fully cured?heartworms dead after 1-2 weeks, BUT, dissolving the dead-worm-emboli will take 2-3mo to resolve
how can you access if the animal is experiencing arsenic toxicity from these drugs?before the next treatment, try to feed it. If it eats, go for it, if not, do not treat, toxicity present
how do you treat the arsenic toxicity in these drugs?Dimercaprol (the treatment and the treatment for the treatment will cost you a pretty dime)
how is melarsomine different from thiacetarsamide sodium?melarsomine has a GREATER bioavailability, so only need 1/2 the dose (SAFER and MORE POTENT) (Mel thinks shes so much more efficient...and i guess she is)
describe how the tx regimen is diff for melarsomine as opposed to thiacetarsamide sodium?milarsomine--> GREATER bioavail. deep IM route in 2 doses. if HEAVY infestation, 1st dose, wait 1 mo, then do 2 dose regimen


Question Answer
dichlorphen- which animals, MOA?sm animals, efficacious cestodals. MOA= acts by uncoupling oxidative phosphorylation–inhibiting ATP production (PHEN NOT VOS. it isnt phen when you uncouple...the relationship DIes and your heart feels small)
resorantel- which animals, treats what?RUMINANTS! treats cestodes and also RUMEN FLUKES (anti trematodal action) (Resorantel Rumi, Rumen flukes...and obv cestodes) (its a Ruminants last RESort)
praziquantel- treats who? treats what?ALL SPECIES! Anticestodal, also antitrematodal-->lung fluke in dog, intestinal fluke in pig, pancreatic fluke in sheep (prazi is a big gun, so everyone and also flukes!)
praziquantel MOA?acting against Ca influx to mediate tectanic contrction. affect general integrity of integumen--> vacuoles--> host cells granules enter and cause parasitic degredation. (zip-- weird word, weird stuff with Ca and vacuoles)
admin/spectrum of praziquantel?absorbed via oral widely distributed--> acct for broad spectrum! effective against adult and larvae (you can eat prazi and it goes everywhere--> it DONT CARE IF YOU NO BABY OR ADULT!)
epsiprantel- use for what, in who? hows the bioavailability and what is the excretion?anticestodal ONLY, for sm animals. low in oral bioavail, excreted in feces
BZDs- which are used to treat what?Mebendazole and fenbendazole also active against larval stages of tenia sp, and hydaded cyst (diffuse through cyst wall) (Me think it's no Fen to have tenia cysts)
difference between praziquantel and episprantel?prazi is soluble--> absorbed systemically, all animals (Prazi Permeable). Episipran-->least soluble, low oral bioavailability, so only GI anticestodal action in sm animals (Epi=around=only around GI in sm animal)


Question Answer
BITHIONOL treats what?rumen and liver flukes
NITROXYNIL admin/treats?inject-able, Hemonchosis & flukes, BZD resistant H. contortus in sheep.
Closantel MOA? used to treat?uncouples oxidative phosphorylation (inhibits ATP production) Effective against resistant strains of H. contortus (closeted barber pole addict...makes it hard to be in a relationship-- you get uncoupled a lot)
Rafoxanide MOA?Protein ionophore --> transports cation across cell membrane --> uncouples oxiphosp --> decrease ATP production
Rafoxanide admin/PK/spectrum?BROAD spectrum! Well absorbed oral admin--> WIDELY distributed with EXTREME PROTEIN BINDING 99% which makes it have a SUPER LONG HALF LIFE (17 days)
rafoxanide effective against?fasciolosis, immature and mature flukes, haemonchosis, bot flies.
clorsulon- used to tx what? admin?FDA approved for liver flukes. rapid absorbed with oral route, oral drench or injectable preparation (FDA likes pokemons too)
MOA of clorsulon?Inhibits glycolytic pathway--> deprive fluke of energy
what to know about albendazoleFDA approved for liver flukes
Triclabendazole- pk? effective against?Trematodes!! are major thing this kills, unlike the other BZDs which are nematodes. Metabolites bound to plasma proteins, exist for 7 days and have wide spectrum action against liver flukes (adult AND larval) because it is excreted in BILE
which drug do you use to treat immature flukes?Diamphenethide
what is Diamphenethide used to treat?100% effective against IMMATURE LIVER FLUKES ((Deacetylation by liver enzymes--> active amine metabolite (LIVER flukes)-->Affects integument
which drugs are in the Salicylanilides group? what must i know about this group?closantel, rafoxanide, oxyclozanide.... ONLY FOR RUMINANTS