Flashcards in Antihelminthic Drugs Deck (68):
What are the 3 main categories of antihelminthic drug?
1. Drugs against nematodes
2. Drugs against trematodes
3. Drugs against cestodes
Mention 5 drugs used against nematodes.
5. Pyrantel pamoate
Mention 4 drugs used against trematodes.
Mention 4 drugs used against cestodes?
What is the mechanism of action of albendazole?
Inhibition of microtubule assembly.
Larvicidal --> in ascariasis, cystercercosis, hookworm, and hydatid disease.
Ovicidal --> in ascariasis, ancylostomiasis, and thichuriasis.
What is the clinical use of albendazole?
6. Both visceral and cutaneous larva migrans
7. Hydatid disease
8. Active against pork tapeworm in the larval stage (cysticercosis)
What are the side effects of albendazole?
1. Short term --> no side effects.
2. Reversible leukopenia
4. Elevation of liver enzymes
What is the mechanism of action of diethylcarbamazine?
Immobilizes microfilariae by an unknown mechanism, increasing their susceptibility to host defense mechanisms.
What is the clinical use of diethylcarbamazine?
Drug of choice for several filarial infections:
2. Brugia malayi
3. Eye worm disease (loa loa)
What are the pharmacokinetics of diethylcarbamazine?
Undergoes renal elimination, and its half-life is increased significantly by urinary ALKALINIZATION.
What are the main side effects of diethylcarbamazine?
What are the reactions to proteins released by the dying filariae?
3. Ocular damage
4. Joint and muscle pain
In what condition are the reactions to proteins released by the dying filariae more intense?
3. Respiratory distress
What is the mechanism of action of ivermectin?
Intensifies GABA-mediated neurotransmission in nematodes --> immobilization of parasites --> removal from reticuloendothelial system.
Does ivermectin cross the BBB?
No - so no problem with GABA in CNS.
What is the clinical use of ivermectin?
The drug of choice for:
2. Cutaneous larva migrans
4. Some forms of filariasis
What are the side effects of ivermectin?
Single-dose oral Tx in onchocerciasis results in reactions to the dying worms:
7. Pain in joints/muscles/lymph nodes
Are the side effects of onchocerciasis of long or of short duration?
Usually short duration - controlled with anti-histamines and NSAIDs.
What should we remember about ivermectin?
Avoid other drugs that enhance GABA activity.
In what condition is ivermectin contraindicated?
What is the mechanism of mebendazole?
Selectively inhibiting microtubule synthesis and glucose uptake in nematodes.
What is the clinical use of mebendazole?
1. Primary drug --> ascariasis, pinworm, and whipworm infections.
2. Backup drug --> in visceral larval migrans.
What are the pharmacokinetics of mebendazole?
1. Less than 10% of the drug is absorbed systemically after oral use, and this portion is rapidly metabolized by hepatic enzymes.
2. Plasma levels may be DECREASED by carbamazepine/phenytoin.
3. or INCREASED by cimetidine.
What are the side effects of mebendazole?
1. Usually limited to GI irritation, but at high doses agranulocytopenia and alopecia have occured.
2. CONTRAindicated in pregnancy.
What is the mechanism of action of piperazine?
Paralyzes ascaris by acting as an agonist at GABA receptors.
The paralyzed roundworms are expelled live by normal peristalsis.
What is the clinical use of piperazine?
As an alternative drug for ascariasis.
What are the side effects of piperazine?
Mild GI distress is the most common side effect.
In what patients is piperazine contraindicated?
1. Pregnant patiens
2. Hepatic or renal problems
3. Seizure disorders
What is the mechanism of action of pyrantel pamoate?
Stimulates nicotinic receptors at neuromuscular junctions of nematodes --> Contraction of muscle occurs, followed by a depolarization-induced paralysis.
Where has pyrantel pamoate no effect?
On flukes or tapeworms.
What is the clinical use of pyrantel pamoate?
1. Wide activity against nematodes - can't kill the eggs.
2. Drug of choice --> Hookworm and round worm infections.
3. Alternative --> Pinworms.
What are the pharmacokinetics of pyrantel pamoate?
Poorly absorbed when given orally.
What are the side effects of pyrantel pamoate?
1. GI distress
What patients should be treated carefully with pyrantel pamoate?
Patients with hepatic dysfunction.
What is the mechanism of thiabendazole?
A structural congener of mebendazole - similar action on microtubules.
What is the clinical use of thiabendazole?
Alternative in strongyloidiasis and trichinosis (adult worms), due to side effects.
What are the pharmacokinetics of thiabendazole?
Rapidly absorbed from the gut and is metabolized by liver enzymes.
What are the actions of thiabendazole on the host?
Anti-inflammatory and immunorestorative actions on the host.
What are the side effects of thiabendazole?
Much more toxic than the others:
1. GI irritation
6. Allergic reactions --> intrahepatic cholestasis.
What are the reactions caused by the dying parasites when given thiabendazole?
4. Skin rash
What fatal conditions have been reported when thiabendazole is used?
1. Liver failure
2. Stevens-Johnson syndrome
What is the drug to which most fluke infections respond well?
What is the mechanism of action of praziquantel?
Increases membrane permeability to Ca --> marked contraction --> paralysis --> followed by vacuolization and parasite death.
What is the clinical use of praziquantel?
Wide antihelminthic spectrum:
1. Drug of choice in schistosomiasis/ clonorchiasis/ paragonimiasis/ infections by small-large intestinal flukes.
2. Active against immature and adult schistosomal forms.
3. Drug of choice together with niclosamide for infections by cestodes (all tapeworms).
4. Alternative agent to albendazole in Tx of cysticercosis.
What are the pharmacokinetics of praziquantel?
Absorption from the gut is rapid - metabolized by the liver to inactive products.
What are the side effects of praziquantel?
3. GI irritation
4. Skin rash
When can praziquantel lead to neurologic side effects?
In the treatment of neurocyticercosis --> intracranial HTN and seizures.
What reduces the risk of the more serious side effects of praziquantel?
In what condition is praziquantel contraindicated?
In ocular cysticercosis.
What is the mechanism of action of bithionol?
What is the clinical use of bithionol?
1. Codrug of choice (with triclabendazole) for treatment of fascioliasis (sheep liver fluke) and an alternative agent in paragonimiasis.
What are the pharmacokinetics of bithionol?
Orally effective and is eliminated in the urine.
What are the side effects of bithionol?
1. Nausea - Vomiting - Diarrhea
2. Abdominal cramps
5. Skin rash (possibly reaction to dying worms)
Mention some rare side effects of bithionol?
What is the mechanism of action of metrifonate?
Organophosphate PRODRUG that is converted to the cholinesterase inhibitor dichlorvos.
Against what does the active metabolite of metrifonate act?
Schistosoma haematobium (cause of bilharziasis).
What are the side effects of metrifonate?
From excess cholinergic stimulation.
In what condition is metrifonate contraindicated?
What is the mechanism of action of oxamniquine?
It causes paralysis of the worms, but its precise mechanism is not known.
What is the clinical use of oxamniquine?
Effective solely in Schistosoma mansoni infections (intestinal bilharziasis), acting on male immature forms and adult schistosomal forms.
What are the side effects of oxqmniquine?
1. Dizziness (no driving for 24h).
3. GI distress
What are the reactions to the dying parasites in oxamniquine?
3. Pulmonary infiltrates
In what conditions in oxamniquine contraindicated?
1. In pregnancy
What are the 2 primary drugs for treating cestode infections?
Praziquantel and niclosamide.
What is the mechanism of action of niclosamide?
May act by uncoupling oxidative phosphorylation or by activating ATPases.
What is the clinical use of niclosamide?
1. Infections caused by beef, pork, and fish tapeworm.
2. NOT effective in cysticercosis or hydatid disease caused by Echinococcus granulosus.
3. Effective in infections from small and large intestinal flukes.
What are the side effects of niclosamide?
1. GI distress