8.4 Antiparasitic Drugs
Antiparasitic drugs target protozoa (malaria, toxoplasmosis, giardiasis) and helminths (worms). These agents exploit biochemical differences between parasites and human hosts, though toxicity remains a significant concern.
Classification of Parasites
Protozoa (Single-celled)
- • Plasmodium: Malaria
- • Toxoplasma gondii: Toxoplasmosis
- • Giardia lamblia: Giardiasis
- • Entamoeba histolytica: Amebiasis
- • Trypanosoma: African sleeping sickness, Chagas disease
- • Leishmania: Leishmaniasis
Helminths (Worms)
- • Nematodes (roundworms): Ascaris, hookworm, pinworm
- • Cestodes (tapeworms): Taenia, Echinococcus
- • Trematodes (flukes): Schistosoma
Antimalarial Drugs
Malaria Life Cycle & Drug Targets
Tissue Schizonticid es
Target liver stage (primaquine)
Blood Schizonticides
Target RBC stage (chloroquine, artemisinin)
Gametocytocides
Prevent transmission (primaquine)
Chloroquine & Related 4-Aminoquinolines
Mechanism of Action:
Concentrates in parasite food vacuole, inhibiting heme polymerase. Prevents detoxification of toxic heme (from hemoglobin digestion) into hemozoin, leading to parasite death.
Clinical Use:
- • Chloroquine: Drug of choice for chloroquine-sensitive P. falciparum/vivax
- • Also used for amebiasis, lupus, rheumatoid arthritis
- • Prophylaxis in chloroquine-sensitive areas
- ⚠️ Widespread resistance limits use
Adverse Effects:
- • GI distress, headache, pruritus (especially in dark-skinned patients)
- • Retinopathy with chronic use (monitor eye exams)
- • QT prolongation, cardiotoxicity
- • Hemolysis in G6PD deficiency
Resistance: Mutations in PfCRT transporter pump chloroquine out of food vacuole. Prevalent in Southeast Asia, Africa, South America.
Artemisinin & Derivatives
Mechanism:
Endoperoxide bridge generates free radicals when activated by heme iron, causing oxidative damage to parasite proteins and membranes. Rapid action.
Agents:
- • Artemether: IM formulation
- • Artesunate: IV (severe malaria); water-soluble
- • Dihydroartemisinin: Active metabolite
Clinical Use:
- • First-line for severe P. falciparum malaria
- • Always used in combination therapy (ACT)
- • Artesunate + amodiaquine/mefloquine/lumefantrine
- • Rapid parasite clearance, low toxicity
- ✓ Most effective antimalarials available
Primaquine
8-aminoquinoline active against dormant liver forms (hypnozoites) of P. vivax and P. ovale. Also kills gametocytes, preventing transmission.
- • Radical cure of P. vivax/ovale (prevents relapse)
- • Terminal prophylaxis after exposure
- • 14-day course after chloroquine
⚠️ Critical Warning:
- • Hemolytic anemia in G6PD deficiency
- • Screen for G6PD before use (required)
- • Methemoglobinemia
- • GI upset
Other Antimalarials
Mefloquine
- • Prophylaxis and treatment
- • Neuropsychiatric side effects (nightmares, psychosis)
- • Resistance in Southeast Asia
Atovaquone-Proguanil (Malarone)
- • Prophylaxis, treatment of uncomplicated malaria
- • Atovaquone: Inhibits mitochondrial electron transport
- • Proguanil: Inhibits DHFR (folate synthesis)
Quinine
- • Severe malaria (if artesunate unavailable)
- • Cinchonism: Tinnitus, headache, nausea
- • Hypoglycemia (stimulates insulin release)
Doxycycline
- • Prophylaxis (daily dosing)
- • Inhibits parasite protein synthesis
- • Photosensitivity; avoid in pregnancy/children
Antihelminthic Drugs
Benzimidazoles
Mechanism:
Bind to β-tubulin, inhibiting microtubule polymerization. Disrupts glucose uptake and depletes ATP in worms, causing immobilization and death.
Agents:
- Mebendazole:
- • Broad-spectrum (roundworms, hookworms, whipworms, pinworms)
- • Poorly absorbed (acts locally in GI tract)
- • Single dose for pinworm; 3 days for others
- Albendazole:
- • Better absorbed than mebendazole
- • Also for tissue nematodes (Strongyloides), hydatid cyst (Echinococcus)
- • Neurocysticercosis (with steroids)
Adverse Effects:
- • Generally well-tolerated
- • GI upset, headache
- • Hepatotoxicity (rare)
- • Teratogenic (avoid in pregnancy)
- • Bone marrow suppression with prolonged use
Pyrantel Pamoate
Mechanism:
Depolarizing neuromuscular blocker (nicotinic agonist). Causes spastic paralysis of worms, which are then expelled.
Clinical Use:
- • Pinworm (Enterobius)
- • Hookworm, roundworm (Ascaris)
- • Single oral dose; repeat in 2 weeks
Adverse: GI upset, headache. Generally safe.
Do not combine with piperazine (antagonistic effects)
Ivermectin
Mechanism:
Enhances GABA-mediated transmission in parasite nerve/muscle cells, causing paralysis. Humans lack glutamate-gated Cl- channels in CNS (BBB protection).
Clinical Use:
- • Onchocerciasis (river blindness)
- • Strongyloidiasis
- • Scabies, head lice
- • Single oral dose annually (onchocerciasis)
Special Considerations:
- • Mazzotti reaction in onchocerciasis (pruritus, fever from dying microfilariae)
- • Avoid in pregnancy, children <15 kg
- • Safe in G6PD deficiency (unlike primaquine)
Praziquantel
Mechanism:
Increases cell membrane permeability to Ca2+, causing contraction and paralysis of worms. Also disrupts tegument (surface).
Clinical Use:
- • Drug of choice for flukes (trematodes)
- • Schistosomiasis (all species)
- • Tapeworms (cestodes): Taenia, Diphyllobothrium
- • Neurocysticercosis (with albendazole + steroids)
Adverse: Generally well-tolerated. GI upset, headache, dizziness. Transient elevation of liver enzymes.
Other Antiparasitic Agents
Metronidazole
- • Giardiasis: G. lamblia (backpacker's diarrhea)
- • Amebiasis: E. histolytica (intestinal/hepatic)
- • Trichomoniasis: T. vaginalis
- • Anaerobic bacteria (C. difficile, Bacteroides)
- ⚠️ Disulfiram reaction with alcohol; metallic taste
Pyrimethamine + Sulfadiazine
- • Toxoplasmosis: T. gondii (HIV/AIDS, congenital)
- • Synergistic inhibition of folate synthesis (DHFR + DHPS)
- • Add leucovorin (folinic acid) to reduce bone marrow toxicity
- Sulfa allergy: Use clindamycin instead
Nitazoxanide
- • Giardia, Cryptosporidium
- • Inhibits pyruvate:ferredoxin oxidoreductase (PFOR)
- • Broad antiparasitic activity
Nifurtimox & Benznidazole
- • Chagas disease: T. cruzi
- • Most effective in acute phase
- • Peripheral neuropathy, GI toxicity
Summary: Antiparasitic Therapy by Organism
| Organism | Disease | Treatment |
|---|---|---|
| Plasmodium falciparum | Malaria | Artemisinin-based combination therapy (ACT) |
| Plasmodium vivax | Malaria (relapsing) | Chloroquine + primaquine (after G6PD screen) |
| Toxoplasma gondii | Toxoplasmosis | Pyrimethamine + sulfadiazine + leucovorin |
| Giardia lamblia | Giardiasis | Metronidazole or nitazoxanide |
| Entamoeba histolytica | Amebiasis | Metronidazole + paromomycin (luminal agent) |
| Schistosoma spp. | Schistosomiasis | Praziquantel |
| Ascaris, hookworm | Intestinal nematodes | Albendazole or mebendazole |
| Onchocerca volvulus | River blindness | Ivermectin (annual) |