Antivirals, Antifungals, and Antiparasitics

Antivirals, Antifungals, and Antiparasitics

Overview

  • The focus is on a limited selection of antivirals, antifungals, and antiparasitics critical for clinical knowledge.

  • Antivirals especially include a wide range with hundreds available, particularly for HIV treatment.

  • The specific drugs to remember:   - Antivirals: Oseltamivir, Valacyclovir   - Antifungals: Fluconazole, Amphotericin B, Echinocandins (Caspofungin, Micafungin)   - Antiparasitics: Ivermectin, Permethrin

Antivirals

Oseltamivir (Tamiflu)

  • Class: Neuraminidase Inhibitor

  • Mechanism:   - Prodrug that is hydrolyzed to Oseltamivir carboxylate, inhibiting the enzyme neuraminidase, which cleaves sialic acid glycans and facilitates the release of viral progeny.   - Results in prevention of the release of new virions from infected cells.

  • Indications: Treatment of influenza, seasonal prophylaxis; effective within the first 24 hours of symptom onset, shortens duration of illness.

  • Formulation: Available in oral suspension and capsules, approved for children over 1 year old.

  • Adverse Reactions:   - Most common: transient nausea and vomiting.   - Rare: confusion, delirium, hallucinations (causality not firmly established).

  • Contraindications: Hypersensitivity reactions.

Valacyclovir (Valtrex)

  • Class: Antiviral (anti-herpes agent)

  • Mechanism:   - Converted to Acyclovir in the intestine and liver (prodrug).   - Acyclovir acts by competing with deoxyguanosine triphosphate for incorporation into viral DNA after phosphorylation by viral thymidine kinase.

  • Indications: Herpes zoster (shingles), genital herpes, herpes labialis (cold sores), and chickenpox in children.

  • Types of HSV:   - HSV-1: typically affects the oral region.   - HSV-2: typically affects the genital region.   - HSV-3: varicella zoster virus (chickenpox, shingles).

  • Adverse Reactions:   - Mostly gastrointestinal side effects; neurotoxicity is uncommon.

Antifungals

Amphotericin B

  • Class: Polyene antifungal

  • Mechanism:   - Binds to ergosterol in fungal cell membranes, altering permeability and causing leakage of cell contents.

  • Common Nickname: "Amphoterrible" due to its severe side effects including infusion-related toxicity (rigors, fever).

  • Premedication: Diphenhydramine, acetaminophen, and potentially corticosteroids to mitigate reactions.

  • Adverse Effects: Nephrotoxicity, infusion-related reactions; multiple formulations (conventional, lipid complex, liposomal); the latter two have a safer profile.

Fluconazole

  • Class: Triazole antifungal

  • Mechanism:   - Inhibits fungal cytochrome P450 enzyme lanosterol 14 alpha-demethylase, disrupting ergosterol synthesis.

  • Indications: Treatment of candidiasis, systemic fungal infections (urinary tract, vaginal infections).

  • Common Adverse Effects: Nervous system effects; headache.

  • Drug Interactions: Strong CYP2C19 inhibitor; also inhibits CYP2C9 and CYP3A4, necessitating monitoring for interactions with concomitant medications.

Echinocandins

  • Examples: Caspofungin, Micafungin

  • Mechanism: Inhibit 1,3-beta-glucan synthase, impacting the synthesis of crucial components of Candida cell walls.

  • Characteristics: Generally, second-line agents, parenteral (IV) only, more expensive than others.

Antiparasitics

Ivermectin

  • Class: Antiparasitic

  • Mechanism:   - Derived from soil bacteria, opens glutamate-sensitive chloride channels in helminth nerve and muscle cells, leading to hyperpolarization and death of parasites.

  • Indications: Choice for oncocerciasis, strongyloidiasis; off-label for scabies and lice.

  • Adverse Effects: Neurotoxicity, potential for post-treatment reactions with inflammation.

Permethrin

  • Class: Neurotoxic antiparasitic

  • Mechanism:   - Blocks sodium channels in parasites preventing repolarization of membranes, which leads to paralysis and death.

  • Indications: Effective treatment for head lice, scabies, pubic lice; preferred treatment in scabies during pregnancy.

  • Formulation: Topical application, not oral; local skin reactions may occur (rash, pruritus).

Clinical Implications and Exam Review

  • It is essential for a thorough understanding of drug mechanisms, indications, and side effects. Here are some notable examination aspects:   - Remember specific use cases for antivirals and how timing affects their efficacy (Oseltamivir should be given within 24 hours).   - Understand adverse reaction management for infusions of Amphotericin B due to its severe side effects.   - Recognize drug interactions for Fluconazole, especially affecting CYP enzyme metabolism which could lead to complications with other concurrent medications.

  • Practice questions provided included scenarios highlighting clinical applications and drug interactions among the discussed drugs.