Pharm 2 - Antihelminthics Review

drraythe's version from 2015-11-22 18:42

Benzimidazoles (BZDs)

Question Answer
What kind of activity do BZDs have?Antinematodal
Which is the most effective group of BZDs?Carbamates (greater Antihelminthic action, greater affinity, ↓ metabolic inactivation) (Hit the helminths w/ a car)
MOA of BZDs?Irreversibly binds to β-tubulin → cant make microtubules → can't undergo cell division
How is resistance formed against BZDs?Isotypes of β-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 & 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?GI & lung nematodes
Species BZDs work on?ALL species
Contraindications of BZDs?NO PREGGOS (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 & margin of safety 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, ↑ depolarizing NM blockade → paralysis leads to expulsion (Pyrantel & 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?GI & LUNG nematodes (Microfilaria in dogs) (be leva w/ your heart, not just your lungs & gut)
Species Levamisole is used in?Rumis, pigs & dogs (works on microfilaria in dogs) (so not horses, cats or sheep - 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, & 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 no Lactate) (sounds like an anime LOL), no debilitated/sick animals... No horses...Use protective gloves while handling (can cz BM disorders)

Pyrantel & Morantel (group: TETRAHYDROPYRIMIDINES)

Question Answer
What are the 2 Pyrantel salts?TARTRATE & 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 could eat some tar, but that would be SO BAD for a rumen)
Pyrantel Pamoate is used for Txing what?ONLY GI nematodes, PINWORMS & Anaplocephala perfoliata (in horses) bc it is not absorbed well, so it stays in the GI. (Pyrantel Pamoate Pinworms Perfoliata)
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 & safe - even lactating animals w/ no withdrawal period
What is the difference btwn the 2 Pyrantel salts?Pamoate is LESS soluble, so it stays in GI tract & that's how it is able to act on pinworms & Anaplocephala perfoliata
Admin of this group?ORAL ONLY (remember using it in the clinic?)

Dichlorvos (Group: Organophosphates)

Question Answer
MOA?Irreversible inhibition of Acetylcholinesterase (AchE) → accumulation of ACH → sustained muscle contraction & paralysis of nematodes (Chlor → Chol) (DIeing AChEs)
What is the admin of Dichlorvos?Highly volatile & unstable, easy degradation, so usually delivered on an indigestible resin pellet (Dich has a PVC & whip fetish)
Which animals can have Dichlorvos?Pigs
(DI, Pig Crap, Die)
Spectrum of Dichlorvos?GI nematodes, INCLUDING Trichuris (WHIPWORMS) (Dich has a PVC & whip fetish)
Tox/precautions?Narrow margin of safety, never coadmin w/ other AChE inhibitors. Don’t administer to chronically ill or stressed PTxs


Question Answer
What are the 2 subgroups?Avermectins & Milbemycins (mac has 2 friends- aber & miles)
What are Macrocyclic Lactones effective against?GI & lung nematodes & 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 hyperpolarizationflaccid paralysis of parasite & 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 & don't want to reproduce w/ him)
Contraindications of Ivermectin?(Ivermectin) DONT USE IN COLLIES, AUSTRALIAN SHEPHERDS, Murrah gray cattle, crocodilians/chelonians(turtles), horses w/ heavy Onchocerca infxns
Which drugs are SAFE for the species/breeds that are sensitive to Macrocyclic Lactones (& usually, specifically, Ivermectin)?Selamectin, Moxidectin & Milbemycin Oxime (the Milbemycins which are the safe group, as opposed to the Avermectins which is the group w/ Ivermectin in it)
Admin/species for Ivermectin?Oral, SC, topical. All species (aside from collies, Australian shepherds, crocodiles & turtles, Murrah Gray Cattle & SEVERE cases of worms → impaction)
Admin/species for Abamectin?SC, rumis (think of cows singing & dancing to abba as they get SC injxns)
Admin/use for Doramectin?SQ, im, topical (CAN TX SCREWWORMS) super broad spectrum (Dora likes to screw)
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/Txs what?Oral, small animal, GI & lung nematodes, also prophylactic use for heartworms (Milf...I mean, milb, can kill GI & lung nematodes, the usual, but she's got my HEART too, bc she does oral even though im small)
Moxidectin admin/animalsOral/SC/topical, all animals (it has moxi - will do everything but IV - bc mac hates needles)
Remember what drugs are in this categoryMac punching a bunch of collies & turtles

Piperazine & ↓ (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) & only adult stages, so will need re-Tx to get rid of the 1s which weren't killed bc they were immature during the 1st Tx
Which species are Piperazines used in?MONOGASTRICS (Piper is scared of cows)
What is the safety margin of Piperazines?WIDE! Can even Tx little puppies & sick animals, w/ tox affects only in super high doses
Contraindications of Piperazine?DO NOT USE in chronic liver/kidney Dz PTxs & in heavy ascarid infxns (bc they can cz an impaction) (piper gets punched in the liver & kidney in jail, & 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 TX!
Admin of DEC?Oral, & 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, & killing them off can cz 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 PTxs w/ liver or kidney problems) FATAL TO CATS (cats are screwed if they get heartworm anyway bc it eats their lungs & of course the 2 major filters would get blocked up w/ arsenic)
Route of admin for Thiacetarsamide sodium?IV bc it can cz tissue irritation (arent they irritated enough?)
MOA?Inhibits cell ATP production (glycolysis inhibition) (heartworms take all your ENERGY & they arent sweet about it)
How should the animal be Txd/handled during Tx? Explain the reasoningAs the worms are killed, they bcm impacted in the pulmonary artery & act as an emboli. At 1st you must give FULL REST & 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 assess if the animal is experiencing arsenic toxicity from these drugs?Before the next Tx, try to feed it. If it eats, go for it, if not, do not Tx, toxicity present
How do you Tx the arsenic toxicity in these drugs?Dimercaprol (The Tx & the Tx for the Tx will cost you a pretty dime) (Note: we do not accept ugly dimes :P)
How is Melarsomine different from Thiacetarsamide sodium?Melarsomine has a GREATER bioavailability, so only need 1/2 the dose (SAFER & MORE POTENT) (Mel thinks shes so much more efficient...& 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 anticestodal. MOA = acts by uncoupling oxidative phosphorylation–inhibiting ATP production (PHEN NOT VOS. it isnt phen when you uncouple...the relationship DIes & your heart feels small)
Resorantel - which animals, Tx what?RUMINANTS! Tx cestodes & also RUMEN FLUKES (anti-trematodal action) (Resorantel Rumi, Rumen flukes...& obv cestodes) (its a Ruminants last RESort)
Praziquantel - Txs who? Txs 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 & also flukes!)
Praziquantel MOA?Acting against Ca influx to mediate tectanic contraction. Affect general integrity of integument → vacuoles → host cells granules enter & cz parasitic degradation. (ziq - weird word, weird stuff w/ Ca & vacuoles)
Admin/spectrum of Praziquantel?Absorbed via oral widely distributed → acct for broad spectrum! Effective against adult & larvae (you can eat prazi & it goes everywhere → it DONT CARE IF YOU BABY OR ADULT!)
Epsiprantel - use for what, in who? Hows the bioavailability & what is the excretion?Anticestodal ONLY, for sm animals. Low in oral bioavail, excreted in feces
BZDs - which are used to Tx what?Mebendazole & Fenbendazole also active against larval stages of tenia sp, & hydaded cyst (diffuse through cyst wall) (Me think it's no Fen to have tenia cysts)
Difference btwn Praziquantel & Epsiprantel?Prazi is soluble → absorbed systemically, all animals (Prazi Permeable)
Epsipran → least soluble, low oral bioavailability, so only GI Anticestodal action in sm animals (Epsi = around = only around GI in sm animal)


Question Answer
BITHIONOL Txs what?Rumen & liver flukes
NITROXYNIL admin/Txs?Inject-able, Hemonchosis & flukes, BZD resistant H. contortus in sheep.
Closantel MOA? Used to Tx?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?Proton ionophore → transports cation across cell membrane → uncouples oxiphosp → ↓ ATP production
Rafoxanide admin/PK/spectrum?BROAD spectrum! Well absorbed oral admin → WIDELY distributed w/ EXTREME PROTEIN BINDING 99% which makes it have a SUPER LONG HALF LIFE (16 days)
Rafoxanide effective against?Fasciolosis, immature & mature flukes, haemonchosis, bot flies.
Clorsulon - used to Tx what? Admin?FDA approved for liver flukes. Rapid absorbed w/ oral route, oral drench or injectable preparation (FDA likes pokemon)
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 do nematodes. Metabolites bound to plasma proteins, exist for 7 days & have wide spectrum action against liver flukes (adult & larval) bc it is excreted in BILE
Which drug do you use to Tx immature flukes?Diamphenethide
What is Diamphenethide used to Tx?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 we know about this group?Closantel
Oxyclozanide.... ONLY FOR RUMINANTS