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Antiparasitic Agents
Endoparasites
Antiprotozoals Anthelminthics
Ectoparasites
Enteric amebiasis
lumenal amebicide Metronidazole or tinidazole + lumenal amebicide Metronidazole or tinidazole + lumenal amebicide Metronidazole or tinidazole + lumenal amebicide
Severe disease
Luminal Amebicides
Orally administered and not absorbed Do not work on trophozoites in the intestinal wall or extraintestinal tissue Iodoquinol and paromomycin
Metronidazole
Pharmacokinetics
Administration:
Oral for protozoal diseases - 80+% absorption Parenteral and oral for anaerobic bacterial infections
10% renal - Urine may turn reddish brown, probably from metabolite
Metronidazole
Adverse effects:
Nervous system - headache, dizziness, convulsions (rare, but serious) Mouth - metallic taste, dryness Disulfiram-like effect, like reaction with alcohol Occasional GI disturbance (take w/food) Preg cat B BUT possible developmental effects, avoid in first trimester Increases anticoagulant effect of coumarin-type anticoagulants Enzyme induction increases its clearance
Contraindications / Interactions
Uses of Metronidazole
Must treat sexual partner Two regimes: tid for 7 days or single 2g dose
Giardia Anaerobic bacterial infections: Clostridium difficile or tetani; Bacteroides Gardnerella bacterial vaginosis
Tinidazole
Approved for: intestinal and hepatic amebiasis trichomonas giardia
bacterial vaginosis
PK:
Oral administration with good absorption Excellent distribution - crosses the blood-brain barrier, the placental barrier, and is secreted in breast milk Undergoes hepatic metabolism followed by excretion by the liver and kidneys
Tinidazole
Contraindications / Interactions
First trimester of pregnancy and during lactation Interactions assumed to be the same as metronidazole
Adverse effects
Toxoplasmosis
Toxoplasmosis
Plasmodial dihydrofolate reductase inhibitor Synergistic effect with sulfonamides (sulfadoxine or sulfadiazine) Well tolerated, but may cause blood dyscrasias Severe disease in immunocompetent patient Immunocompromised CNS infection <5 yr old Pregnant w/ (+) amniotic fluid otherwise self-limiting
Only treat:
Antimalarial drugs
Hepatic infection relapsing P. vivax and ovale Erythrocytic only nonrelapsing P. falciparum and malariae
Severity of the malarial disease Accompanying illness or condition Active disease versus prophylaxis
Chloroquine
Oral and parenteral medication Drug of choice for non-falciparum and sensitive falciparum - treatment and prophylaxis
Chloroquine
Adverse effects:
Pruritis (especially Africans) GI disturbance, headache, dizziness, malaise Ocular - Corneal deposits - reversible; Retinopathy - irreversible vision loss
Rare at doses used for tx malaria Monitoring for dose-related ocular effects is important
Contraindications:
Porphyria and psoriasis Retinal/visual abnormalities Liver disease
Mefloquine
Chemically related to quinine Oral administration Used for tx of chloroquine-resistant falciparum and prophylaxis High incidence of nervous system toxicity
Dizziness - 60% Visual disturbances Fatigue Other neurotox effects - psychiatric disorders & neuropathies
Mefloquine
Doses used for prophylaxis are lower and less likely to cause neurotox than doses for treatment
Long half-life: (13-33 days) Detected in blood for months after dosing ceases
Atovaquone
MOA -interferes with mitochondrial electron transfer Used for treatment and prophylaxis Use combined w/proguanil - dihyrofolate reductase inhibitor Administration -oral only
Atovaquone
Adverse effects:
rash (25%) nausea & diarrhea (20%)
Contraindications:
children weighing <5 kg pregnant women severe renal impairment
Artemisinins
From the "quinghaosu" or sweet wormwood plant No resistance (maybe) Artemesunate - IV - short acting
Headache, cough, N/V, abdominal pain, dizziness, diarrhea and pruritis. Lumefantrine may prolong QT interval
Primaquine
Quinine
Older drug; was considered obsolete, but now used again against resistant strains Causes cinchonism: source is bark of cinchona tree (headache, tinnitus)
Quinidine
Isomer
of quinine Established antiarrhythmic agent Investigational as an antimalarial for resistant falciparum strains
Pyrimethamine
See
tx of toxoplasmosis
Prophylaxis
1. Mosquito avoidance measures 2. Medication - Begin before, continue during and after travel
Chloroquine Mefloquine
P. falciparum
P. vivax
Anthelmintic drugs
Enterobius - Pinworms
Roundworms - Ascarids
Mebendazole
MOA:
PK: oral administration, poor absorption in GI tract & 1st pass metabolism very low systemic levels Indications: roundworms, hookworms, pinworms, whipworms
Mebendazole
Contraindications/Interactions
Pregnancy category C, caution w/lactation Caution w/hepatic insufficiency and IBD Systemic drug metabolized by Cyt P 450 enzymes can interactions
Albendazole
Only approved for tx of hydatid cyst disease and cysticercosis Excellent efficacy against hooks, rounds, whips, tapes and pin worms
MOA helminth microtubule inhibition PK: Oral administration then rapidly undergoes first-pass hepatic metabolism --> active metabolite albendazole sulfoxide Distributes well to tissues, and enters bile, cerebrospinal fluid, and hydatid cysts
Albendazole
Contraindications / Interactions:
Caution w/ hepatic disease Metabolism via Cyp P450 enzymes enzyme induction and drug interactions Co-admin with dexamethasone, cimetidine, and praziquantel may increase toxicity Minimal side effects when treating nematodes, only seen with long term treatment of hydatid disease most common - reversible increase in serum aminotransferases (16%); abdominal pain, diarrhea, nausea, dizziness and headache occasionally occur
Adverse effects:
Pyrantel pamoate
MOA: inhibition of cholinesterase and release of Ach depolarizing neuromuscular blockade and paralysis PK: poorly absorbed by host following oral administration (provides selectivity) Adverse effects:
Cestodes - Tapeworms
Praziquantel
MOA - alters cell membrane permeability massive influx of Ca++ leads to paralysis Pharmacokinetics
absorbed (take WITH meals) and metabolized in host liver; metabolites excreted in urine Rapidly taken in by worm, but not metabolized
Praziquantel
Contraindications / Interactions:
Ocular (retinal) cysticercosis Pregnancy category B Lactation - do not breast feed for 72 h Cyt P450 interactions
Ivermectin
MOA: enhance chloride ion channel activity paralysis of the parasite Pharmacokinetics oral use only, widely distributed except CNS, hepatic metabolism for disposition Uses strongyloides (threadworm) and onchocerciasis, scabes, lice, off label for cutaneous larval migrans
Ivermectin
Drug-drug interactions:
may enhance effects of GABAergic compounds CYT P450 interactions possible Preg Cat C
Adverse effects
Dizziness, fatigue Mazotti reaction in onchocerciasis Exacerbation of bronchial asthma