Antiparasitic Agents

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Antiprotozoal Therapies : Intraluminal Agents

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Iodoquinol
Paromomycin

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Antiprotozoal Therapies: Extraluminal Agents

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Metronidazole
Pentamidine

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Iodoquinol (Yodoxin): Indications, MOA, ADE

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Indications- intestinal amebiasis
MOA- exact MOA unknown, poorly absorbed in GI tract, works on trophozoites and cysts of entamoeba histolytica in large intestine
ADE- Optic neuritis, optic atrophy, and peripheral neuropathy;
also skin eruptions, urticaria, pruritis, n/v, abdominal cramps, diarrhea, chills, fever, headache, vertigo, thryoid enlargement

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Paromomycin (Humatin): Indication, MOA, ADE

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Indication: acute and chronic intestinal amebiasis
MOA: Amebicidal and antibacterial aminoglycoside
ADE: Secondary enterolcolitis (may enter systemic circulation if ulcerative bowel lesions are present), ototoxicity;
also diarrhea, abdominal cramps, nausea, vomiting, heartburn

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Metronidazole (Flagyl): Route, Indications, MOA, ADE, Contraindications

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Route: PO, IV/IM, topical gel
Indications: DOC for extraluminal amebiasis, MUST be used with a luminal agent! Giardiasis
MOA: Inhibits protein synthesis and causes cell death; mechanism of antiprotozoal action is unknown
ADE: SEIZURES (lowers seizure threshold), METALLIC TASTE, DARK URINE, NEUROPATHY, DISULFIRAM-TYPE RXN WITH ALCOHOL, dizziness, headache, n/v, loss of appetite, diarrhea, xerostomia, furry tongue, change in taste, ataxia, vaginal candidiasis, pancreatitis, neutropenia
Contraindications: 1st trimester pregnancy

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Pentamidine: route, indications, ADE

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R: parenterally only!
I: Leishmaniasis, Pneumocystis, and Trypanosomiasis
ADE: Highly toxic (renal, pancreatic), hypoglycemia, severe hypotension, tachycardia, dizziness, dyspnea

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Malaria: 4 species of plasmodium

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-P falciparum: highest morbidity and mortality
-P vivax
-P malariae
-P ovale

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Malaria DOCs for all plasmodium except Chloroquine-resistant P falciparium and P vivax

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Chloroquine phosphate

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Extraluminal amebiasis DOC

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Metronidazole (must be use with a luminal agent)

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Malaria Treatment categories

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Chemoprophylaxis
Clinical Cure- eliminates parasites from erythrocytes
Radical Cure- for pts with P vivax and P ovale malaria; follows clinical cure to eradicate exoerythrocytes and prevent recurrence

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DOC all Plasmodium (malaria)

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Quinidine gluconate
or
Quinine dihydrocholoride

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Alternative tx for all plasmodium

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Alternative Arthemether

Prevention of relapses (P vivax and P ovale only)- Primaquine phosphate

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Malaria DOC for Chloroquine-resistant P falciparum

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Quinine sulfate
plus
Doxycycline
or
Tetracycline
or
Pyrimethamine-sulfadoxine
or
Clindamycin
or
Atovaquine/proguanil (Malarone)

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Malaria alternative tx for Chloroquine-resistant P falciparum

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Mefloquine
Halofantrine
Artesunate plus Mefloquine

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Malaria DOC for Chloroquine-resistant P vivax

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Quinine sulfate
plus
Doxycycline
or
Mefloquine

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Malaria alternative tx for Chloroquine-resistant P vivax

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Halofantrine
plus
Primaquine

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Malaria prophylaxis chloroquine-sensitive areas

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Chloroquine phosphate

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Malaria prophylaxis DOC Chloroquine-resistant areas

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Mefloquine
or
Doxycycline
or
Atovaquone/Proguanil (Malarone)

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Malaria prophylaxis alternatives Chloroquine-resistant areas

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Primaquine
or
Chloroquine phosphate plus Proguanil
or
Pyrimethamine-sulfadoxine

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Chloroquine (Aralen): Indications, MOA, Contraindications, ADE

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I: DOC for all but chloroquine-resistant plasmodium strains (malaria)
MOA: interferes with metabolism and hemoglobin utilization, inhibits growth by raising pH
Contraindications: retinal or visual field changes; patients with psoriasis and porphyria
ADE: Nausea, diarrhea, anorexia, fatigue, hypotension, ekg changes, blood dyscrasias, ocular toxicity, blurred vision, skin rxns, peripheral neuropathy, psychosis and seizures
!Bitter Tasting!!

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Quinine and Quinidine: Indications, MOA, ADE, Contraindications

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I: DOC for all plasmodium spp.; (quinine) and in combination against reistant spp.
MOA: effective blood schizonticide against all 4 species; gametocidal against P vivax and P ovale; NOT active against liver stage parasite
ADE: Tinnitus, nausea, visual disturbances, headache, dizziness, flushing (cinchonism), blood dyscrasias, hepatitis, cardiovascular toxicity, severe hypotension with IV admin, hypoglycemia; use in pregnancy can cause ototoxicity and deafness in neonates
C: avoid in pts with visual, auditory, or cardiac abnormalities; renal impairment; discontinue in severe cinchonism or hemolysis

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Mefloquine: indications, MOA, ADE, Contraindications

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I: DOC for Chloroquine-resistant P vivax in combination with quinine sulfate; alternative for Chloroquine-resistant P falciparum
MOA: structurally similar to quinine, destroys asexual blood forms; not active against hepatic stages or gametocytes
ADE: Toxic psychosis, seizures, prolonged QT, dysrhythmias, n/v, diarrhea, dizziness, weakness, nightmares, dysphoria, visual disturbances, post-malaria neurologic syndrome,
Contraindications: recent hx of depression, GAD, psychosis, schizophrenia, or other major psychotic disorders; hx of epilepsy, arrhythmia, cardiac conduction defects

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Primaquine: indications, MOA, ADE, Contraindications

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I: alternative drug for Chloroquine-resistant P vivax with halofantrine, prevention of relapses in P vivax and P ovale
MOA: hepatic stages of all human malaria parasites; ONLY agaent active against dormant stages of P vivax and P ovale; gametocidal against all 4 human species
ADE: Bone marrow suppression (monitor CBC) - Hemolytic anemia in G-6-PD deficiency, Methemoglobinemia, Arrhythmias, headache, pruritus, leukopenia, agranulocytosis, leukocytosis, interference with visual accommodation; abdominal pain, n/v
Contraindications: Rheumatoid arthritis, SLE, drugs that can depress bone marrow

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Pyrimethamine: Indications, MOA, ADE, Contraindications

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I: drug resistant uncomplicated malaria
MOA: inhibits parasitic dihydrofolate reductase
ADE: Anorexia, abdominal cramps, vomiting, megaloblastic anemia, leukopenia, thrombocytopenia, agranulocytosis, stevens-johnson syndrome
Contraindications: megaloblastic anemia secondary to folate deficiency

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Malarone (atovaquone and proguanil): Indications, MOA, ADE, Contra

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I: a DOC for Chloroquine-resistant P falciparum including prophylaxis
MOA: Atovaquone – inhibitor of parasite mitochondrial electron transport; Proguanil – inhibits parasitic dihydrofolate reductase
ADE: Proguanil- gastric intolerance, ulcerations, hair loss, scaling of palms andsoles, urticaria, hematuria, vomiting, abdominal pain, diarrhea, thrombocytopenia; Atovaquone- rash, n/v, diarrhea, headache, fever, insomnia, asthenia, pruritus, anemia and neutropenia (rare), hyponatremia, elevated hepatic enzymes

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Doxycycline (Vibramycin): Indications, MOA, ADE, Contra

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I: Chloroquine-resistant P falciparum in combination with quinine sulfate
MOA:
ADE: phototoxicity, GI disturbances, discoloration of teeth
Contra: Pregnancy, lactation, or small children

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Clindamycin (Cleocin): indications, MOA, ADE, Contra

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I: Chloroquine-resistant P falciparum in combination with quinine sulfate
MOA:
ADE: pseudomembranous colitis, vomiting, leukopenia, anemia, hepatotoxicity
Contra: Previous pseudomembranous colitis, hepatic impairment

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Halofantrine: Indications, MOA, ADE, Contra

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NOT AVAILABLE IN THE US!!
I: alternative tx of drug-resistant uncomplicated malaria when other drugs cannot be used
ADE: QT and PR prolongation, GI effects, headache, rash
Contra: preexisting cardiac conduction defects, avoid in pregnancy

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Safe Malarial drugs with pregnancy

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Chloroquine
Clindamycin
Pyrimethamine-sulfadoxine (except in 3rd trimester)
Proguanil
Chlorproguanil
Azithromycin

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Malarial drugs to avoid with pregnancy

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Mefloquine (may be safe in 2nd and 3rd trimesters)
Halofantrine
Arteminisinin compounds?

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Malarial drugs contraindicated with pregnancy

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Tetracycline
Doxycycline
Primaquine
Quinine
Quinidine

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Antihelminthic therapies

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Benzimidazoles: Albendazole, Thiabendazole
Praziquantel
Pyrantel

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Albendazoles (Albenza): Indication, MOA, ADE,

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I: antihelminthic
MOA: inhibits microtubule synthesis in nematodes, irreversibly impairs glucose uptake; intestinal parasites are immobilized or die slowly; also larvicidal and ovicidal
ADE: Diarrhea, abdominal pain, migration of round worms through nose or mouth, leukopenia (check cbc q 2wks), alopecia, increased transaminases (monitor hepatic markers)

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Praziquantel (Biltricide): Indications, MOA, ADE

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I: Helminths
MOA: loss of intracellular Ca++, results in paralysis and dislodgement of worms; higher doses damage worm's surface membrane making it more susceptible to immune response, and boosts host immune response
ADE: structure is similar to benzos, can cause dizziness, headache, malaise; abdominal discomfort, fever, sweating, and occasionally eosinophilia

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Pyrantel Pamoate (Antiminth): indications, MOA, ADE

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I: roundworms and pinworms
MOA: depolarizing neuromuscular blocker, spastic paralysis, also inhibits cholinesterases
ADE: n/v, headaches, dizziness, rash, and transient AST elevations

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4 classes of Helminthes

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Intestinal Nematodes (roundworms)
Tissue Nematodes (flatworms)
Trematodes (flukes)
Cestodes (tapeworms)