Antifungals for GIT Infections

Study Notes

Antifungals are used to treat fungal infections in the gastrointestinal tract.
Learning outcomes include identifying antifungal drugs, describing their mechanisms of action, pharmacokinetic considerations, and adverse effects/contraindications for azoles, amphotericin B, and echinocandins.
Introduction: Antifungal classes like amphotericin B, azoles (fluconazole, voriconazole, miconazole, clotrimazole), and echinocandins (anidulafungin, caspofungin, micafungin) are discussed.

Identify antifungal drugs used in treating gastrointestinal tract infections.
Describe the mechanism of action for azoles, amphotericin B, nystatin, and echinocandins.
Explain pharmacokinetic considerations for azoles, amphotericin B, and echinocandins.
Describe adverse effects and contraindications for azoles, amphotericin B, and echinocandins.

Amphotercin B: A crucial antifungal.
Azoles: Fluconazole, voriconazole, miconazole (oral gel), clotrimazole (topical) are examples.
Echinocandins: Anidulafungin, caspofungin, micafungin

Aspergillosis: Voriconazole is the first choice, with amphotericin B, caspofungin, itraconazole, and posaconazole as alternatives. Use of prophylactic antifungals can affect treatment choices.
Candidiasis (oropharyngeal/oesophageal): Fluconazole is the first choice, with echinocandins (anidulafungin, caspofungin, micafungin), itraconazole, posaconazole, voriconazole, and amphotericin B as alternatives.
Candidiasis (systemic): Echinocandins and fluconazole, along with voriconazole and amphotericin B are options.

Antifungals target fungal cell walls and membranes as well as other fungal components, leading to fungal death.
Azoles: Inhibit ergosterol synthesis.
Amphotericin B and Nystatin: Bind to ergosterol, changing membrane permeability.
Echinocandins: Inhibit synthesis of 1,3-β-D-glucan.

Two formulations: amphotericin B deoxycholate (available via intravenous route only) and liposomal amphotericin B (AmBisome), often preferable for better tolerability and reduced toxicity.
Poor oral bioavailability, hence intravenous route.
IV administration, lozenges for oral candidiasis.
High protein binding (up to 99%).
No dose adjustments needed for renal or hepatic impairment.

Fluconazole has the highest oral bioavailability.
Loading dose followed by a maintenance dose is common.
Long half-lives, which can influence the time it takes for concentrations to reach steady state.

Administered intravenously.
Variable half-lives.
Variable metabolism properties.
Poor CYP450 substrates..
High protein binding (up to 99%).
Dose reduction possible in moderate hepatic impairment. Avoidance of dose reduction normally for renal impairment.

Infusion-related reactions: Fever, chills, muscle spasms, vomiting, headache, and hypotension are possible.
Slowing infusion rate or pre-treatment with antihistamines and paracetamol is crucial.
Renal toxicity: Decreased perfusion and tubular injury may occur. Serum creatinine should be monitored.

Mild gastrointestinal disturbance, liver enzyme abnormalities, prolonged QT interval, which can lead to arrhythmia.
Visual side effects and photosensitivity are also potential issues.
Fluconazole use in pregnancy is classified as Category D.
Drug-drug interactions due to cytochrome P450 enzyme (CYP) inhibition or induction.

Generally well-tolerated, with similar adverse effects (AEs) across all echinocandins.
Mild gastrointestinal upset, liver abnormalities are common.
Infusion reactions are rare.