Antiparasitic & Antimicrobial Pharmacology
Protozoal & Helminthic Infections
Drug mechanisms, clinical use, and high-yield facts for USMLE preparation
Protozoal Infections Β· Overview
- Protozoa are single-celled eukaryotic organisms that cause significant global morbidity
- Transmission routes:
- Fecalβoral (contaminated water/food) β Giardia, Entamoeba
- Vector-borne (mosquito, sandfly, reduviid bug) β Plasmodium, Leishmania, Trypanosoma
- Congenital / blood-borne β Toxoplasma
- Clinical syndromes depend on the parasite's tissue tropism:
- Intestinal lumen β diarrhea, malabsorption
- Blood / reticuloendothelial system β fever, hepatosplenomegaly
- CNS β encephalitis, meningoencephalitis
| Infection | Pathogen | Key Clinical Feature |
|---|---|---|
| Amebiasis | Entamoeba histolytica | Bloody diarrhea, liver abscess |
| Giardiasis | Giardia lamblia | Foul-smelling diarrhea, bloating |
| Trichomoniasis | Trichomonas vaginalis | Vaginal discharge, urethritis |
| Toxoplasmosis | Toxoplasma gondii | Congenital infection, CNS mass |
| Leishmaniasis | Leishmania spp. | Skin ulcers, visceral organomegaly |
| Trypanosomiasis | Trypanosoma spp. | Chagas (cardiac/GI), African (sleeping sickness) |
High-yield: Most protozoal infections are diagnosed via microscopy (stool, blood smear, tissue biopsy) or serology.
Antiprotozoal Drugs Β· Amebiasis, Giardiasis, Trichomoniasis
Metronidazole
- Mechanism:
- Prodrug activated by reduction of its nitro group in anaerobic environments
- Reduced intermediates generate reactive radicals that damage DNA and inhibit nucleic acid synthesis
- Selective toxicity due to low redox potential in susceptible organisms
- Clinical uses:
- Amebiasis (invasive intestinal and extraintestinal)
- Giardiasis β first-line therapy
- Trichomoniasis β treat both sexual partners
- Bacterial vaginosis, Clostridioides difficile infection
- Adverse effects:
- Metallic taste, nausea, headache
- Disulfiram-like reaction with alcohol (inhibits aldehyde dehydrogenase)
- Peripheral neuropathy with prolonged use
- Darkening of urine (harmless metabolite)
Exam trap: Metronidazole is ineffective against noninvasive intestinal amebiasis (luminal cysts) β requires a luminal agent such as diloxanide furoate or paromomycin.
Drugs by Infection
| Infection | Drug of Choice | Alternative / Adjunct |
|---|---|---|
| Amebiasis (invasive) | Metronidazole | Tinidazole |
| Amebiasis (luminal) | Diloxanide furoate | Paromomycin, iodoquinol |
| Giardiasis | Metronidazole | Tinidazole, nitazoxanide |
| Trichomoniasis | Metronidazole | Tinidazole |
- Giardiasis commonly acquired from contaminated water β "backpacker's diarrhea"
- Trichomoniasis treatment requires concurrent treatment of all sexual partners to prevent reinfection
Toxoplasmosis Β· Leishmaniasis Β· Trypanosomiasis
Toxoplasmosis
- Pathogen: Toxoplasma gondii β obligate intracellular parasite
- Transmission:
- Ingestion of oocysts from cat feces or undercooked meat
- Congenital (primary infection during pregnancy)
- Clinical syndromes:
- Immunocompetent: usually asymptomatic or mononucleosis-like illness
- Immunocompromised: CNS toxoplasmosis (brain abscess, encephalitis)
- Congenital: chorioretinitis, intracranial calcifications, hydrocephalus
- Treatment:
- First-line: Pyrimethamine + sulfadiazine (synergistic inhibition of folate synthesis)
- Add leucovorin (folinic acid) to prevent bone marrow suppression
- Alternatives: clindamycin + pyrimethamine, atovaquone, trimethoprim-sulfamethoxazole
Clinical pearl: In HIV/AIDS patients with CD4 < 100 cells/Β΅L, toxoplasmosis is a common cause of ring-enhancing brain lesions.
Leishmaniasis
- Pathogen: Leishmania species transmitted by sandflies
- Forms:
- Cutaneous β skin ulcers, self-healing in some cases
- Mucocutaneous β destructive mucosal lesions
- Visceral (Kala-azar) β fever, hepatosplenomegaly, pancytopenia
- Drug of choice: Sodium stibogluconate (pentavalent antimonial)
- Alternatives: amphotericin B, miltefosine, paromomycin
Trypanosomiasis
- Chagas disease (American trypanosomiasis):
- Pathogen: Trypanosoma cruzi β transmitted by reduviid bugs
- Acute phase: fever, chagoma (inoculation site)
- Chronic phase: cardiomyopathy, megacolon, megaesophagus
- Treatment: Nifurtimox or benznidazole
- African trypanosomiasis (sleeping sickness):
- Pathogen: Trypanosoma brucei β transmitted by tsetse flies
- Stage 1: hemolymphatic β fever, lymphadenopathy
- Stage 2: CNS involvement β sleep disturbance, neurologic decline
- Treatment: Arsenicals (melarsoprol) for late-stage; pentamidine or suramin for early-stage
Antimalarial Drugs
- Malaria caused by five Plasmodium species:
- P. falciparum β most severe, high mortality
- P. vivax and P. ovale β have hypnozoite (liver) stage, require primaquine
- P. malariae β nephrotic syndrome complication
- P. knowlesi β zoonotic, rapidly progressive
Mosquito bite
β
Sporozoites β liver
β
Hepatic schizogony
β
Merozoites β RBCs
β
Erythrocytic cycle
Chloroquine-Sensitive Malaria
| Species | Treatment |
|---|---|
| P. falciparum | Chloroquine |
| P. malariae | Chloroquine |
| P. vivax | Chloroquine + primaquine |
| P. ovale | Chloroquine + primaquine |
- Primaquine eradicates hypnozoites in the liver β prevents relapse
- Prophylaxis in sensitive regions: chloroquine Β± primaquine
Chloroquine-Resistant Malaria
- Resistance mediated by PfCRT and PfMDR1 mutations in P. falciparum
- Prophylaxis options:
- Atovaquone-proguanil
- Mefloquine
- Doxycycline
- Treatment options:
- Artemisinin-based combination therapy (ACT) β first-line
- Atovaquone-proguanil
- Quinine + doxycycline or clindamycin
Key Drug Mechanisms & Side Effects
| Drug | Mechanism | Key Adverse Effect |
|---|---|---|
| Chloroquine | Inhibits heme polymerase β toxic heme accumulation | Retinopathy, pruritus, QTc prolongation |
| Primaquine | Generates reactive oxygen species | Hemolytic anemia in G6PD deficiency |
| Quinine | Inhibits heme polymerase; increases pH of digestive vacuole | Cinchonism (tinnitus, headache, nausea) |
| Atovaquone-proguanil | Mitochondrial electron transport inhibition; dihydrofolate reductase inhibition | GI upset, rash |
| Artemisinin derivatives | Endoperoxide β free radical generation | Hemolysis, delayed hemolytic anemia |
| Mefloquine | Similar to quinine | Neuropsychiatric effects, vivid dreams |
USMLE alert: Always test for G6PD deficiency before prescribing primaquine or quinine β hemolysis can be life-threatening.
Clinical pearl: Cinchonism from quinine is dose-related and reversible; early symptoms include tinnitus and headache.
Helminthic Infections Β· Nematodes, Cestodes, Trematodes
Intestinal Nematodes (Roundworms)
- Common pathogens: Ascaris, Enterobius, Trichuris, Ancylostoma, Necator
- Drugs:
- Albendazole:
- Mechanism: inhibits glucose uptake (decreases ATP) and disrupts microtubular structure
- Broad-spectrum: ascariasis, hookworm, trichuriasis, strongyloidiasis, neurocysticercosis
- Side effects: hepatotoxicity, bone marrow suppression (rare)
- Mebendazole:
- Mechanism: similar to albendazole (microtubule inhibition)
- Poorly absorbed β acts locally in GI tract
- Less effective systemically than albendazole
- Pyrantel pamoate:
- Mechanism: nicotinic acetylcholine receptor agonist β spastic paralysis of worms
- Used for pinworm, roundworm, hookworm
- Contraindicated in hepatic dysfunction
- Albendazole:
Cestodes (Tapeworms) & Trematodes (Flukes)
- Cestodes: Taenia solium, Taenia saginata, Diphyllobothrium, Echinococcus
- Trematodes: Schistosoma, Fasciola, Clonorchis, Paragonimus
- Drug of choice: Praziquantel
- Mechanism: increases calcium influx into parasite cells β vacuolization and tegument disruption
- Rapidly kills adult worms; efficacy against most cestodes and trematodes
- Side effects: headache, dizziness, GI upset (usually transient)
- Contraindicated in ocular cysticercosis (inflammatory reaction can cause blindness)
| Helminth Class | Example Pathogens | Drug of Choice | Mechanism |
|---|---|---|---|
| Nematodes | Ascaris, Trichuris, hookworm | Albendazole / Mebendazole | Microtubule inhibition, glucose uptake block |
| Nematodes | Enterobius (pinworm) | Pyrantel pamoate | Nicotinic agonist β spastic paralysis |
| Cestodes / Trematodes | Taenia, Schistosoma | Praziquantel | Ca2+ influx β vacuolization |
High-yield: Albendazole is the drug of choice for neurocysticercosis (Taenia solium larvae in the brain) and echinococcosis.
Exam trap: Praziquantel is not used for Fasciola hepatica (liver fluke) β triclabendazole is preferred.
Antimicrobial Drug Classes Β· Key Agents
| Class | Representative Drugs | Mechanism / Key Use |
|---|---|---|
| Penicillins | Penicillin G, nafcillin, amoxicillin, ampicillin, piperacillin, ticarcillin | Inhibit cell wall synthesis (transpeptidase) |
| Cephalosporins | 1st: cefazolin; 2nd: cefaclor; 3rd: ceftriaxone | Ξ²-lactam β cell wall inhibition; generational spectrum varies |
| Carbapenems | Imipenem, meropenem | Broad-spectrum Ξ²-lactam; resistant to most Ξ²-lactamases |
| Glycopeptides | Vancomycin | Cell wall synthesis inhibition (binds D-Ala-D-Ala) |
| Macrolides | Erythromycin, azithromycin, clarithromycin | 50S ribosomal subunit β protein synthesis inhibition |
| Aminoglycosides | Gentamicin, tobramycin, streptomycin | 30S ribosomal subunit β misreading, bactericidal |
| Tetracyclines | Tetracycline, doxycycline | 30S ribosomal subunit β protein synthesis inhibition |
| Fluoroquinolones | Ciprofloxacin, levofloxacin | DNA gyrase / topoisomerase IV inhibition |
| Antifolates | Sulfamethoxazole, trimethoprim | Inhibit folate synthesis (SMX) and dihydrofolate reductase (TMP) |
| Antimycobacterials | Isoniazid, rifampin, ethambutol, pyrazinamide | Multiple targets in mycobacterial cell wall / metabolism |
| Antifungals | Amphotericin B, ketoconazole, fluconazole | Ergosterol binding (amphotericin) or synthesis inhibition (azoles) |
| Anti-Herpes | Acyclovir, ganciclovir, foscarnet | DNA polymerase inhibition (HSV, VZV, CMV) |
| Anti-HIV | Zidovudine, lamivudine (NRTIs); indinavir, ritonavir (PIs); enfuvirtide, maraviroc | Reverse transcriptase inhibition, protease inhibition, entry/fusion inhibition |
- Ξ²-lactam antibiotics (penicillins, cephalosporins, carbapenems) share a core Ξ²-lactam ring and are bactericidal
- Macrolides, aminoglycosides, and tetracyclines target bacterial ribosomes but at different subunits
- Fluoroquinolones are concentration-dependent killers with broad gram-negative coverage
- Antifolates (TMP-SMX) are synergistic β sequential blockade of folate synthesis
Clinical pearl: Vancomycin, though a cell-wall inhibitor, does not contain a Ξ²-lactam ring and is reserved for MRSA and serious gram-positive infections.
High-yield: Amphotericin B is the "gold standard" for severe invasive fungal infections but has significant nephrotoxicity and infusion-related reactions.