Pharm 2 - Antihelminthics 1
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2015-11-21 19:07
Basics
| Question | Answer |
|---|---|
| Define Antihelminthic drugs | Drugs used to kill &/or expel the parasitic helminths in the host animal |
| What are the 2 types of Antihelminthic drugs? | (1) Vermifuges - expels the helminths (2) Vermicides - kills the helminths |
| How is the selectivity of Antihelminthics? Exceptions? | Usually very selective (safe), working on receptors/metabolic processes/accumulation exclusive to the parasite. BUT Organophosphorus Compounds & Levamisole DO have risk for tox since they can affect the Host's cells too |
| Most Antihelminthics can be used in all species, but Levamisole is for only? | Ruminants & Swine |
| Most Antihelminthics can be used in all species, but Praziquantel is for only? | Dogs, cats & horses |
| Most Antihelminthics can be used in all species, but Piperazine is for only? | Monogastric species (NO RUMIS) |
| Most Antihelminthics can be used in all species, but Salicylanilides, Nitroxynil & Clorsulon are for only? | Ruminants |
| How do nematodes develop resistance to Nematodicides? | They develop resistance to the MOA! |
| How do you prevent the development of resistance against Nematodicides? (2) | (1) ROTATE TYPE OF NEMATODICIDE (so the MOA keeps changing...dont change to something w/in the same group) (2) Minimum frequency of Tx |
Benzimidazoles (GI & LUNG NEMATODES)
| Question | Answer |
|---|---|
| Benzimidazoles have what spectrum of activity? What is their safety margin? | BROAD spectrum, WIDE margin of safety |
| What are the 2 Subclasses of Benzimidazoles? | (1) Benzimidazole Thiazoles (2) Benzimidazole Carbamates |
| What drug(s) are in the Benzimidazole Thiazole subclass? | Thiabendazole |
| What drugs are in the Benzimidazole Carbamates subclass? | Albendazole/Netobimin Fenbendazole/Fenbantel Mebendazole Oxfendazole |
| What are the drugs in the Pro-Benzimidazole (PRO DRUG) category? What are they converted into? | Netobimin (converted to Albendazole) Febantel (converted to Fenbendazole) |
| BZD (Benzimidazole) Carbamates (describe their activity & dose needed & why this is so) | Possess greater Antihelminthic activity → EVEN LARVICIDAL!! Since stronger, need a lower dose. This strength is bc they have... (1) Enhanced receptor binding in parasites (2) ↓ metabolic inactivation in host animal |
| Which Benzimidazole subgroup (Carbamates or Thiazoles) has larvacidal activity? | CARBAMATES |
| What is the MOA of Benzimidazole? | BZD binds irreversibly to nematode β-tubulin, prevents dimerization w/ α-tubulin & polymerization of tubulinoligomers into microtubules I.E., INHIBIT MICROTUBULE FORMATION (this is also selective for nematode tubulin not host) |
| How does resistance develop against Benzimidazoles? | Development of β-tubulin isotypes w/ lower affinity for BZDs |
| What is the absorption of Benzimidazoles like? What ↑ the bioavailability of BZDs? | Absorption is LIMITED. Presence of food in stomach ↑ the bioavailability of drug (ex: Fenbendazole) |
| What is the plasma conc of Benzimidazoles like? Who has a higher systemic avail? | BZD level in plasma is always <1% of the dose administered & RUMINANTS have higher systemic avail. |
| Metabolism of Benzimidazoles (general) | Hepatic! |
| Metabolism of BZD Carbamates is special how? | (Hepatic) They are converted into ACTIVE METABOLITES! 1st metabolized to Sulfoxides, which are active & extend effectiveness, before being metabolized again to Sulphones, which are inactive (Albendazole to Albendazole sulfoxide) (Fenbendazole to Fenbendazole sulfoxide) |
| The metabolism of Albendazole & Fenbendazole is more rapid in who? | Cattle & goats |
| Which Benzimidazole has poor metabolism & excreted unchanged in feces? | Mebendazole |
| Benzimidazole clinical efficacy depends on? | Effective concentration at the site of action in the parasite |
| How safe are BZDs? | Well tolerated (safe!) |
| What are the contraindications of BZDs? (Which BZDs have which effects on who?) (2) | (1) Substituted BZDs are not indicated during early pregnancy (2) Parbendazole produces teratogenic effects in pregnant ewes (2nd to 4th week of gestation) |
| How do you admin BZDs? | ORAL!! (Paste or suspension/powder or granules) → Rumis can have gradual release boluses |
| Whats special about the Pro-Benzimidazoles? | (Netobimin & Febantel) they have 2 active metabolites!! |
| Which Pro-BZD is used in Rumis & monogastrics, bc it can be converted via hepatic enzyme & ruminal microorganisms? Explain how it differs in activity btwn the 2 sp. | Netobimin! In RUMIS → Nematocidal & Fasciolicidal activity In MONOGASTRICS → Nematocidal & Cestocidal activity |
| Netobimin metabolic path? | Netobimin → Albendazole - (Hepatic oxidation) → Albendazole Sulfoxide |
| Who can have Febantel? | Horses Dogs Cats |
| Febantel metabolic path? | Febantel → Fenbendazole - (Hepatic oxidation) → Fenbendazole sulfoxide |
| What is Vercom? Effective against? | Combination of Febantel (nematodes) & Praziquantel (cestodes) |
| What is Drontal Plus? For who against what? | 25 mg Febantel, 5 mg Pyrantel Pamoate & 5 mg Praziquantel FOR DOGS!! (Effective against canine Ascarids, Hookworms, Whipworms & Echinococcus sp) |
| How safe is Febantel? | Wide margin of safety |
| Febantel is effective against? | GI & lung parasites |
| Febantel contraindications? | Vercom paste & Drontal Plus are contraindicated in pregnant dogs & cats (NO PREGGOS) |
| Can you use BZDs in birds? | Yes, for lung nematodes |
IMIDAZOTHIAZOLES (GI & LUNG NEMATODES)
| Question | Answer |
|---|---|
| Levamisole is effective against what? | GI & lung nematodes |
| Levamisole routes of admin? | Oral Parenteral Topical (Nice!) |
| How is Levamisole formulated, based on route of admin? | ORAL = Hydrochloride salt paste INJECTABLE = Phosphate salt |
| MOA of Levamisole? (Basic)(2) | (1) Depolarization neuromuscular blockade (2) Acts as immunostimulator (cell mediated) |
| How does Levamisole work as a depolarization neuromuscular blockade? | It acts as a ganglionic stimulant & a direct cholinergic drug → it binds to nicotinic receptors of nematodes → sustained mm contraction & subsequent paralysis |
| What is the speed of the absorption & excretion of Levamisole? What is its pharmacodynamic action? | RAPID absorption & secretion. Pharmacodynamic action is of nicotinic & muscarinic effects |
| How can Levamisole be administered? | Bolus Drench (Topical pour-on) Feed additive SC injxn |
| What special action can Levamisole have, in who? | In DOGS, can act as a Heartworm microfilaricide (along w/ being GI & LUNG nematodes) |
| How is the safety margin of Levamisole? | NARROW (but leva is 4 times more safe than Tetramisole) |
| Tox of Levamisole in who? | SHEEP! (Salivation, Lacrimation, Head shaking, Muscle tremors, Mild excitability) |
| What is the safe route of Levamisole for cats & dogs? | Oral |
| What can make a Levamisole tox worse? | Simultaneous administration of Pyrantel Tartrate or any Cholinesterase Inhibiting drugs |
| When is Levamisole contraindicated? | DAIRY COWS (Excreted into milk & no established withdrawal time) |
| What is the big ol' WARNING about Levamisole for you? | WEAR GLOVES! Leva can have percutaneous absorption (topical absorption) & cz agranulocytosis (LOW WBC count) |
Tetrahydropyrimidines (NEMATODES)
| Question | Answer |
|---|---|
| Tetrahydropyrimidines are most effective against? | GI nematodes |
| What 2 drugs do we care about in the Tetrahydropyrimidines? | Pyrantel & Morantel |
| Pyrantel spectrum? For who? | BROAD spectrum all species |
| What are the 2 forms Pyrantel is available in? | Tartrate or Pamoate salt |
| What solution cz Pyrantel to lose potency? | Aqueous solution undergoes photoisomerization → loss of potency |
| MOA of Pyrantel & Morantel? | Depolarizing neuromuscular blocking agent in nematode parasites. Cz sustained muscle contraction followed by paralysis of worms. (MORE potent than Acetylcholine) |
| Pyrantel Tartrate → How is the absorption? Exceptions? Speed of metabolism? Excretion? Sp. diffs? | WELL ABSORBED (except in ruminants), it is rapidly metabolized (does undergo 1st pass effect), & is excreted in Urine (DOGS) & Feces (RUMINANTS) |
| Pyrantel Pamoate → What worm does Pamoate work on, & how come it's so good at this? | Poorly soluble in water → ↓ absorption from the gut → drug reaches the lower intestine & acts on pinworms (this is the 1 most clinics use) |
| Which 2 drugs have a more potent NM blockade effect than ACh? (Acetylcholine) | Pyrantel & Morantel |
| What is in Drontal Plus for dogs? | Pyrantel Pamoate(5 mg/kg) + Febantel(25 mg/kg) + Praziquantel(5mg/kg) |
| What is in Drontal for cats? | Pyrantel Pamoate(20 mg/kg) + Praziquantel(5 mg/kg) |
| What is in Heartgard 30 Plus? For who? Effective against what? | Contains Ivermectin(6-12 g/kg) + Pyrantel Pamoate(5-10 mg), for DOGS, effective against heartworms, hookworms & ascarids |
| Why would you want to give Pyrantel to a horse? | Effective against Anaplocephala perfoliata tapeworm (ileocecal junction tapeworms) |
| Why would you want to give Pyrantel to a cattle/sheep? | It is effective against BZD RESISTANT STRAINS of Haemonchus contortus (barber pole worm) (GI worm) |
| Safety of Pyrantel salts? | Generally safe in all species EXCEPT FOR HORSES |
| Contraindications of Pyrantel salts? (2) | (1) Not indicated in severely debilitated animals (2) Withdrawal period for food animals needed |
| What is Morantel used for? (In who?) Anything to note about food animals? | RUMNANTS! GI nematode adult & immature stages. Withdrawal period needed!! |
| Whats the route of admin she emphasized for Morantel? | Sustained release ruminal bolus (Morantel slow release trilaminate bolus) ← Cylindrical tri-walled cartridge |
| Which is a safer drug - Pyrantel Tartrate or Morantel Tartrate? | MORANTEL IS SAFER |
