Pharm 2- Anthelmintics 2

kelseyfmeyer's version from 2015-05-10 01:45

Organophosphorous compounds (nematodes, WHIPWORMS)

Question Answer
what is the drug we focus on with organophosphorous compounds?Dichlorvos
MOA of Organophosphorous compounds?irreversible inhibition of acetylcholinesterase--> accumulation of acetylcholine--> sustained muscle contraction and subsequent paralysis
which animals do you use organophosphorous compounds in?horses, pigs, dogs and ruminants (so......cats not said here, but mentioned a few slides past)
how do you prevent organophosphate anthelmintic resistance?rotation of anthelmintics
4 precautions to be considered with organophosphate anthelmintics?(1) animal should not be simultaneously treated with other acetyl cholinesterase inhibiting drugs/ pesticides/ muscle relaxants or sedatives (2) narrow safety margin (proper dosing is required) (3) withdrawal period of 7 days for slaughtering animals (4) not recommended in sick/stressed animal
Toxicity signs of organophosphorous compoundsVomiting (dogs & cats), frequent urination, diarrhea , muscle twitching and muscular weakness
how do you treat organophos. toxicity?Atropine and PAM (Pralidoxime)
Dichlorvos is used to treat what parasites?GI nematodes, and esp **whipworms
unique way dichlorvos is administered, in who? benefits of this?polyvinyl chloride resin pellets (indigestible, just acting as a vehicle) for administration in pigs, dogs and cats. allows slow release at therapeutic level all throughout the GI--> SAFER ADMIN
dichlorvos--> special critter we need to know it kills?whipworms

Questions for first part (up to this point)

Question Answer
Which is the drug that acts as an immunostimulant?levamisole
Contraindication of BZDs?pregnancy!!! (teratogenic)
Prodrugs of BZDs?Netobimin, febantel. MORE SPECIFIC: netobimin (converted to albendazole), and febantel (converted to fenbendazole)
levamisole MOA?(1) depolarization neuromuscular blockade (2) acts as immunostimulator
pyrantel & morantel MOA?depolarizing neuromuscular blocking agent
dichlorvos MOA?irreversible inhibition of acetylcholinesterase

Macrocyclic lactones (nematodes and arthropods)

Question Answer
what are the two groups of macrocyclic lactones?Avermectin, Milbemycin
what are the drugs in the avermectin group?Ivermectin, abamectin, doramectin, selamectin, eprinomectin (end in mectin...easier to memorize other group)
what are the drugs in the Milbemycin group?Milbemycin oxime, moxidectin
what are macrocyclic lactones effective against?nematodes and arthropods
what is the spectrum of action of macrocyclic lactones?BROAD
MOA of macrocyclic lactones? (2)(1) binds selectively with high affinity to glutamate gated chloride channels--> inc GABA release/binds to GABA gated chloride channels--> flaccid paralysis of parasites--> expulsion (2) It also affects reproduction of nematode/ arthropod
site of action for macrocyclic lactones? (depending on who it's affecting) (2)(1) Nematodes –synapse between inhibitory and excitatory motor neuron (2) Arthropods –myoneural junction
how do macrocyclic lactones (avermectins and milbemycin) affect the repro of nematodes and arthropods? (3)(1) abnormal egg formation by nematodes (2) sterility of both male and female filarial nematodes (3) reduces oviposition by ticks
explain the Selective toxicity of macrocyclic lactonesmesses with mammalian GABA in the CNS
are macrocyclic lactones safe?they are more safe, because they do not cross the mammalian BBB
**Sensitivities to macrocyclic lactones?COLLIES AND AUSTRALIAN SHEPHERDS
Ivermectin belongs in which group? what is its spectrum? avermectins. broad!
ivermectin is composed of what important major and minor component?Major-B1a, 80%. Minor- B1b, 20%
ivermectin admin--> who has the longer half life, IV or SC? apprx iv half life?SC is longer. (IV apprx 2-3 days)
EXCRETION OF IVERMECTIN?98% FECES AND URINE and in lactating animals, 5% in milk
pharmacokinetics of ivermectin depends on what?route of admin
weird admin of ivermectin for cattle?pour-on formula (oily topical vehicle)
Heartgard-30 contains what drugs?combination of ivermectinand pyrantel pamoate
why dont you need a huge dose of ivermectin for it to be effective?HIGH lipid solubility
what kinda stuff does ivermectin kill? sp diffs?farm animals- GI/lung nematodes and certain ectoparasites. DOGS-intestinal nematodes, ear mites, sarcopticmange, infective stage heartworm and microfilariae. POULTRY- GI nematodes, ectoparasites of poultry
how safe is ivermectin?SUPER SAFE! 10 fold safety
**who is sensitive to ivermectin/contraindications?COLLIES/AUSTRALIAN SHEPHERDS (as with all macrocyclic lactones) and also Murrah Gray cattle. Contraindicated in crocodiles & chelonians
abamectin is usually used in who, with what admin?usually in ruminants as a SC injectable
what bugs does abamectin work on?lung and GI nematodes
is abamectin more or less toxic than ivermectin?aba is more toxic than iver
doramectin is effective against what bugs? ******SCREWWORMS!!!!!********** and myiasis! (infective stage of fly larvae)(GI nematodes, lungworms, eyeworms, suckling lice, ticks, and mites)
******which drug kills screwworms? and myiasis (infective stage of fly larvae)?DORAMECTIN
**whats special about Eprinomectin?YOU CAN USE IN DAIRY CATTLE!!! (quite safe)
selamectin is useful for killing what? why?can kill ECTOPARASITES (as well as heart worm, flea, GI nematodes-->hookworm and roundworm infections) good at ectoparas because the circulating selamectin is deposited into the sebaceous glands
selamectin being useful against what in dogs, and noteable thing about it?100% effective against heartworms in dogs
Milbemycin oxime is for what animals, and what route? Small animals, oral route.
when would you want to use milbemycin oxime instead of a avermectin?milbemycin
*which drug is used for PROPHYLAXIS of canine heartworm?Milbemycin oxime
which drug treats canine AND feline heartworm?milbemycin oxime (it is a potent and fast-acting microfilaricide)
why should you be careful about administering milbemycin oxime?welp, usually treating heartworm infection, can get a hyersensitivity rxn with microfilaria dying. Also--> Treatment is accompanied with mild reactions (lethargy, salivation, coughing, tachypnea or emesis), AND HEAVY HEARTWORM INFECTIONS-->shock-like reactions and circulatory collapse
why do you need to be careful with heavy heartworm infections and milbemycin oxime? (what happens, what do you do)the treatment can lead to shock-like reactions and circulatory collapse. You treat this reaction with carticosteroids, IV fluids
Moxidectin is given to who, how?All species, and oral/parenteral/topical
how well does moxidectin maintain its clinically effective concentration? where is it excreted?lipophilic!! so lasts a while. also excreted in feces
*Moxidectin is used for what in dogs?Prophylactic control of heartworm
*how safe is moxidectin?safe to administer in dogs and ruminants (breeding and pregnant animals); used in ivermectin sensitive Collie breed of dogs

Piperazines (nematodes)

Question Answer
what are the two groups in the piperazine class?Piperazine, Diethylcarbamazine(DEC)
what is the spectrum for Piperazine? how safe is it?narrow!!!!! spectrum. wide margin of safety
who do you use piperazine in?MONOGASTRIC species
MOA of piperazine?Hyperpolarizationat neuromuscular junction (GABA agonist)--> blocks neurotransmission--> flaccid paralysis of worms
what should you know about the treatment regimen of piperazine?Treatment should be repeated at 2 or 4 weeks interval
absorption/metabolism/excretion of piperazine?absorbed from GIT. metabolized in the tissues. excreted in the urine WITHIN 24 HRS OF ADMIN
what bugs are piperazine effective against? (in who?)DOGS/CATS: GI nematodes (NOT LUNG THO). HORSES: Equine ascarids and mature pinworms
how safe is piperazine? tox?WIDE margin of safety. In LARGE doses, show tox of emesis, diarrhea, incordination, head pressing
when would you contra-indicate piperazine? (2)(1) NOT RECC in CHRONIC LIVER/RENAL DZ! (2) in HEAVY ascarid infections, might cause intestinal impaction of dead ascarids
*what is Diethylcarbamazine citrate (DEC) used for? in who? (unique spectrum)prophylactic control of heartworm disease in dogs
MOA of Diethylcarbamazine citrate (DEC)?inhibits cyclic peroxide production from arachidonic acid metabolism--> Inhibits PG synthesis → vasoconstriction & endothelial adhesion in parasite. so, INC CYTOTOXIC ACTION IN HOST GRANULOCYTES
absorption/distribution of Diethylcarbamazine citrate (DEC)?RAPID absorption from GIT. peak conc 3hrs after admin, and is widely distributed in all tissues except fat!
metabolism/excretion of Diethylcarbamazine citrate (DEC)?RAPID metabolism, excreted through urine (W/IN 24 HRS OF ADMIN!)
*what should you know about the admin of Diethylcarbamazine citrate (DEC)?IT IS METABOLIZED/EXCRETED WITHIN 24 HRS!!! so you need to administer daily
****contraindications of Diethylcarbamazine citrate (DEC)?contraindicated in microfilaria positive dogs!! so, Before prophylactic treatment (its intended purpose), the infected dog should be cleared of adult heartworms and microfilariae

Questions for the section so far

Question Answer
Ivermectin toxicity-->sensitive breeds?COLLIES/AUSTRALIAN SHEPHERDS, Murrah Gray cattle, crocodiles & chelonians (turtles)
Contraindication of piperazines? (2)(1) NOT IN LIVER/KIDNEY DZ PTS (2) dont give in HEAVY ascarid infection, or you risk an intestinal blockage
MOA of macrocyclic lactones (2) (name the drugs too)(1) binds selectively with high affinity to glutamate gated chloride channels--> inc GABA release/binds to GABA gated chloride channels--> flaccid paralysis of parasites--> expulsion (2) It also affects reproduction of nematode/ arthropod (Avermectins-Ivermectin, abamectin, doramectin, selamectin, eprinomectin. and Milbemycins-Milbemycin oxime, moxidectin)
MOA of piperazines? (name the drugs, too)Hyperpolarizationat neuromuscular junction (GABA agonist)--> blocks neurotransmission--> flaccid paralysis of worms (piperazine and DEC-diethylcarbamazine)
Drugs for prophylactic control of heartworm are?DEC- diethylcarbamazine

Heartworm adulticides (nematodes)

Question Answer
what are the two heartworm adulticides?Thiacetarsamide sodium and melarsomine
What is unique/important to know about this group of drugs?THEY HAVE ARSENIC IN THEM! be careful, yo
*counterindications of thiacetarsamide sodium? (2)(1) HEPATOTOXIC and NEPHROTOXIC (dont give to liver/kidney pts) (2) FATAL IN CATS
*admin of thiacetarsamide sodium?IV!!! because irritating to tissues
what is an easy way to know if you should or shouldn't continue treatment with thiacetarsamide sodium or melarsomine?Try to feed them before their next dose. IF they eat, go ahead. If they don't, or vomit/etc, DONT administer because they are showing signs of tox
Arsenic toxicity signs?persistent vomiting, icterus, orange-colored urine
how do you treat thiacetarsamide sodium/melarsomine tox?Dimercaprol
how should you be handling the animal during tx with thiacetarsamide?adult worms die in 1-2 weeks, and they lodge in the pulmonary artery where they take 2-3mo to be absorbed. so, during the FIRST TWO WEEKS AFTER TX THEY NEED FULL REST (if there is an inc in temp and coughing, it's the pulmonary rxn to the emboli)
how is Melarsomine different from thiacetarsamide?Greater boiavail of drug--> need less. also contains more arsenic, lasts longer. peak conc after 8min!
admin of melarsomine?2 IM doses at 24 hr, repeated after 90-120 days (If severe, 1 IM dose Then the two dosage regimen will be followed after one month)
Tox/overdose of melarsomine?mild localized edema at IM inject site. Overdose--> distress, restlessness, pawing, salivation, glazed corneas, tachycardia, tachypnea, abdominal pain, hindlimb weakness, recumbency, difficulty in rising. in severe cases, circulatory collapse, orthopnea, coma and death