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Antiparasitic Medications

Dr. Meera Ababneh, Pharm.D, PhD

Antiparasitic Agents
Endoparasites
Antiprotozoals Anthelminthics

Ectoparasites

Amebiasis (E. histolytica)

Enteric amebiasis

Asymptomatic cyst passer

lumenal amebicide Metronidazole or tinidazole + lumenal amebicide Metronidazole or tinidazole + lumenal amebicide Metronidazole or tinidazole + lumenal amebicide

Mild to moderate disease

Severe disease

Agents for hepatic (systemic) amebiasis

Luminal Amebicides

Orally administered and not absorbed Do not work on trophozoites in the intestinal wall or extraintestinal tissue Iodoquinol and paromomycin

Metronidazole

MOA: nitro group reduction yield products that


have antimicrobial activity

Pharmacokinetics

Administration:
Oral for protozoal diseases - 80+% absorption Parenteral and oral for anaerobic bacterial infections

Distribution: wide, high CSF levels Disposition: primarily metabolism

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

Amebiasis - tissue infections Trichomonas vaginal infections (DOC)


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

Half life longer than MTZ so treatment time is shorter

Tinidazole

Contraindications / Interactions
First trimester of pregnancy and during lactation Interactions assumed to be the same as metronidazole

Adverse effects

Similar to metronidazole but less frequent

Toxoplasmosis

Toxoplasmosis

Pyrimethamine most effective agent


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

Treatment varies by..

Species of the Plasmodium


Hepatic infection relapsing P. vivax and ovale Erythrocytic only nonrelapsing P. falciparum and malariae

Area where the infection was acquired

Drug resistance status

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

Resistance is high for falciparum

Accumulates in parasitized RBC and disrupts parasitic detoxification of heme

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

absorption enhanced by fatty food

Atovaquone

Adverse effects:
rash (25%) nausea & diarrhea (20%)

Contraindications:
children weighing <5 kg pregnant women severe renal impairment

Highly protein bound drug interactions

Artemisinins

From the "quinghaosu" or sweet wormwood plant No resistance (maybe) Artemesunate - IV - short acting

Severe, resistant disease, need parenteral

Artemether-lumefantrine (Coartem) oral treatment of uncomplicated P. falciparum Generally well tolerated:


Headache, cough, N/V, abdominal pain, dizziness, diarrhea and pruritis. Lumefantrine may prolong QT interval

Primaquine

Active against all stages, least against schizonts


Alternate choice for prophylaxis Use for relapsing infections (P. vivax and P. ovale)

Oral - daily Adverse effects:


Nausea, abdominal cramps & pain Causes hemolytic anemia in persons with G-6PD deficiency

Highest incidence in blacks Greatest deficit in Mediterranean ethnic groups

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

Doxycycline Atovaquone/proguanil Primaquine

CDC recommendations for treatment

P. falciparum

Chloroquine-susceptible chloroquine Chloroquine resistant atovaquone/proguanil


Chloroquine-susceptible chloroquine Chloroquine resistant Mefloquine

P. vivax

Anthelmintic drugs

50% of worlds population infested by helminths (worms) Most common:


Pinworm (ages 5-9) Hookwork Roundworm Tapeworm

Enterobius - Pinworms

Mebendazole Pyrantel pamoate

Hookworm - Necator and Ancylostoma


Albendazole Mebendazole Pyrantel pamoate

Roundworms - Ascarids

Albendazole Mebendazole Pyrantel pamoate

Mebendazole

MOA:

inhibits microtubule synthesis in nematode

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

Adverse effects -generally well tolerated

Transient abdominal pain & diarrhea may occur

Albendazole

Broad spectrum anthelmintic activity


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:

N & V, abdominal pain

Use: pinworms, roundworms and hookworms

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

Indications: tapeworms (except Echinococcus) and schistosomiasis

Praziquantel

Contraindications / Interactions:
Ocular (retinal) cysticercosis Pregnancy category B Lactation - do not breast feed for 72 h Cyt P450 interactions

Adverse effects - generally mild


dizziness( up to 80%) headache abdominal pain Rare: hypersensitivity, arrhythmia exacerbation

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