Pharm 2 - Antihelminthics 2

drraythe's version from 2015-11-22 01:08

Organophosphorus Compounds (Nematodes, WHIPWORMS)

Question Answer
What is the drug we focus on w/ Organophosphorus Compounds?Dichlorvos
MOA of Organophosphorus Compounds?Irreversible inhibition of Acetylcholinesterase → accumulation of Acetylcholine → sustained muscle contraction & subsequent paralysis
Which animals do you use Organophosphorus Compounds in?Horses, pigs, dogs, cats & ruminants (everyone)
How do you prevent Organophosphate Antihelminthic resistance?Rotation of Antihelminthics group (remember don't rotate drugs in the same group!!)
4 precautions to be considered w/ Organophosphate Antihelminthics?(1) Animal should not be simultaneously Txd w/ other Acetylcholinesterase 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 Organophosphorus CompoundsFrequent urination
Vomiting (dogs & cats)
Muscle twitching & weakness
How do you Tx Organophos. Toxicity?Atropine & PAM (Pralidoxime)
Dichlorvos is used to Tx what parasites?GI nematodes, 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 & cats. Allows slow release at therapeutic level all throughout the GI → SAFER ADMIN (Dich has a PVC & whip fetish)
Dichlorvos → Special critter we need to know it kills?Whipworms (Dich has a PVC & Whip fetish)

Questions for 1st part (up to this point)

Question Answer
Which is the drug that acts as an immunostimulant?Levamisole
Contraindication of BZDs?NO PREGGOS (Teratogenic)
Prodrugs of BZDs?Netobimin & Febantel
MORE SPECIFIC: Netobimin (converted to Albendazole) & Febantel (converted to Fenbendazole)
Levamisole MOA?(1) Depolarization neuromuscular blockade
(2) Acts as immunostimulator (cell mediated)
Pyrantel & Morantel MOA?Depolarizing neuromuscular blocking agent
Dichlorvos MOA?Irreversible inhibition of Acetylcholinesterase (accumulation of ACH, neuromuscular blockade & paralysis)

Macrocyclic Lactones (nematodes & arthropods)

Question Answer
What are the 2 groups of Macrocyclic Lactones?Avermectin, Milbemycin
What are the drugs in the Avermectin group?Ivermectin
Abamectin (Lung and GI)
Doramectin (Screw worms)
Selamectin (Ectos)
Eprinomectin (can use in dairy cattle)
(end in mectin...easier to memorize)
What are the drugs in the Milbemycin group?Milbemycin oxime
What are Macrocyclic Lactones effective against?Nematodes & arthropods
What is the spectrum of action of Macrocyclic Lactones?BROAD
MOA of Macrocyclic Lactones? (2)(1) Binds selectively w/ high affinity to Glutamate gated chloride channels → ↑ 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 btwn inhibitory & excitatory motor neuron
(2) Arthropods - Myoneural junction
How do Macrocyclic Lactones (Avermectins & Milbemycin) affect the repro of nematodes & arthropods? (3)(1) Abnormal egg formation by nematodes
(2) Sterility of both male & female filarial nematodes
(3) Reduces oviposition by ticks
Explain the selective toxicity of Macrocyclic LactonesMesses w/ mammalian GABA in the CNS
Are Macrocyclic Lactones safe?They are more safe, bc they do not cross the mammalian BBB
**Sensitivities to Macrocyclic Lactones?COLLIES & AUSTRALIAN SHEPHERDS (MDR1 Mutants)
Ivermectin belongs in which group? What is its spectrum?Avermectins. Broad!
Ivermectin is composed of what important major & 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 & URINE & 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 Ivermectin & 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 & certain ectoparasites
DOGS: Intestinal nematodes, ear mites, sarcoptic mange, infective stage heartworm & 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 w/ all Macrocyclic lactones) & also Murrah Gray cattle. Contraindicated in crocodilians & chelonians (Turtles)
Abamectin is usually used in who, w/ what admin?Usually in ruminants as a SC injectable
What bugs does Abamectin work on?Lung & GI nematodes (ABBA's singing (lungs) makes me ill (GI) )
Is Abamectin more or less toxic than Ivermectin?Aba is more toxic than iver
Doramectin is effective against what bugs?(Dora likes to screw)******SCREW WORMS!!!!!****** & myiasis! (Infective stage of fly larvae)(GI nematodes, lungworms, eyeworms, sucking lice, ticks, & mites)
******Which drug kills screwworms? & myiasis (infective stage of fly larvae)?DORAMECTIN (Dora likes to screw)
**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 nematode → hookworm & roundworm infxns) good at ectoparas bc the circulating Selamectin is deposited into the sebaceous glands
Selamectin is useful against ___ in dogs? Noteable thing about it?100% effective against heartworms in dogs
Milbemycin oxime is for what animals & what route?Small animals, oral route
When would you want to use Milbemycin oxime instead of an Avermectin?MDR1 mutants (Collies) w/ HTW
*Which drug is used for PROPHYLAXIS of canine heartworm?Milbemycin oxime
Which drug Txs canine & feline heartworm?Milbemycin oxime (it is a potent & fast-acting microfilaricide)
Why should you be careful about administering Milbemycin oxime?Welp, usually Txing heartworm infxn, can get a hypersensitivity rxn w/ microfilaria dying. Tx is accompanied w/ mild rxns (lethargy, salivation, coughing, tachypnea or emesis) & HEAVY HEARTWORM INFXNS → shock-like rxns & circulatory collapse (Tx w/ corticosteroids)
Why do you need to be careful w/ heavy heartworm infxns & Milbemycin oxime? (What happens, what do you do)The Tx can lead to shock-like rxns & circulatory collapse. You Tx this rxn w/ corticosteroids & IV fluids
Moxidectin is given to who, how?All species & 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 & ruminants (breeding & pregnant animals); used in Ivermectin sensitive Collie breed of dogs

Piperazines (nematodes)

Question Answer
What are the 2 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?Hyperpolarization at neuromuscular junction (GABA agonist) → blocks neurotransmission → flaccid paralysis of worms
What should you know about the Tx regimen of Piperazine?Tx should be repeated at 2 or 4 week intervals
Absorption/metabolism/excretion of Piperazine?Absorbed from GIT
Metabolized in the tissues
Excreted in the urine W/IN 24 HRS OF ADMIN
What bugs are Piperazine effective against? (In who?)DOGS/CATS: GI nematodes (NOT LUNG THO)
HORSES: Equine ascarids & mature pinworms
How safe is Piperazine? Tox?WIDE margin of safety
but In LARGE doses :
Head pressing
When would you contra-indicate Piperazine? (2)(1) NOT USE in CHRONIC LIVER/RENAL DZ!
(2) In HEAVY ascarid infxns, might cz intestinal impaction of dead ascarids
*What is Diethylcarbamazine citrate (DEC) used for? In who? (Unique spectrum)Prophylactic control of heartworm Dz in dogs
MOA of Diethylcarbamazine citrate (DEC)?Inhibits cyclic peroxide production from arachidonic acid metabolism → Inhibits PG synthesis → Vasoconstriction & endothelial adhesion in parasite. So, ↑ CYTOTOXIC ACTION IN HOST GRANULOCYTES
Absorption/distribution of Diethylcarbamazine citrate (DEC)?RAPID absorption from GIT. Peak conc 3hrs after admin & 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 W/IN 24 HRS!!! So you need to administer daily
****Contraindications of Diethylcarbamazine citrate (DEC)?Contraindicated in microfilaria positive dogs!! So, before prophylactic TX (its intended purpose), the infected dog should be cleared of adult heartworms & 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 infxn, or you risk an intestinal blockage
MOA of Macrocyclic Lactones (2) (name the drugs too)(1) Binds selectively w/ high affinity to Glutamate gated chloride channels → ↑ 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. & Milbemycins-Milbemycin oxime, Moxidectin)
MOA of Piperazines? (Name the drugs, too)Hyperpolarization at neuromuscular junction (GABA agonist) → blocks neurotransmission → flaccid paralysis of worms (Piperazine & DEC -Diethylcarbamazine)
Drugs for prophylactic control of heartworm are?DEC - Diethylcarbamazine

Heartworm adulticides (nematodes)

Question Answer
What are the 2 heartworm adulticides?Thiacetarsamide sodium & 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 & NEPHROTOXIC (dont give to liver/kidney PTx)
*Admin of Thiacetarsamide sodium?IV!!! bc irritating to tissues
What is an easy way to know if you should or shouldn't continue Tx w/ 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 bc they are showing signs of tox
Arsenic toxicity signs?Persistent vomiting
Orange-colored urine
How do you Tx Thiacetarsamide sodium/Melarsomine tox?Dimercaprol
How should you be handling the animal during Tx w/ Thiacetarsamide?Adult worms die in 1-2 weeks & they lodge in the pulmonary artery where they take 2-3mo to be absorbed. So, during the FIRST 2 WEEKS AFTER TX THEY NEED FULL REST (if there is an ↑ in temp & 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 2 dosage regimen will be followed after 1 month)
What does an overdose (toxicity) of Melarsomine look like?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 & death