Antifungal drugs

Drug Amphotericin B Characteristic -Broad spectrum -Inhibit cell membrane -Initial treatment, then replaced by other less toxic drugs -Poorly absorbed through GIT Amphotericin B complex and liposomal amphotericin B -Less infusion associated side effects -Decrease in nephrotoxicity (highly protein bound) Route of Administration Systemic (IV), topical Adverse Effects Systemic -Infusion related side effects -Chill, fever, muscle spasm, vomit, hypotension -Encountered by slow infusion rate and premedication of antihistamine, antipyretics -Nephrotoxicity, anaemia (decreased production of erythropoietin by kidney) Topical -Local irritation -Hypersensitive (rare) -Bone marrow toxicity -Elevated hepatic enzymes -Alopecia Treatment of Diseases Systemic -Some pulmonary fungal infection Topical -Candida infection Drug Interaction

Flucytosin

Azoles

-Narrow spectrum -Inhibit nucleic acid -Pro drug - need to be activated to form 5-fluorouracil (5-FU) -Specific to fungi as converted to 5-FU less in mammalian cells -Weak drug (used in combination to avoid resistance and for synergism) -Broad spectrum -Inhibit cell membrane through inhibition of cytochrome P450 dependant enzymes to synthesize sterols -Classified into: -Imidazoles (ketoconazole, clotrimazole) -Triazoles (1st generation: itraconazole and fluconazole;

Systemic (oral)

Systemic (oral/IV), systemic mucocutaneous, topical

Systemic -Triazoles (generally safe): -Hepatotoxicity -Idiosyncratic (no cross sensitivity occurs) -Imidazoles: -Endocrine disturbance (inhibition of gonadal and adrenal steroids due to P450 inhibition)

Systemic -Amphotericin-resistant fungi Systemic mucocutaneous -Dermatophytes -Candidiasis Topical -Dermatophytes -Candidiasis

-Inhibit cytochrome P450 -Greater for itraconazole and voriconazole, lower for fluconazole

Created by Qosru Iskandariah

Echinocandins

Griseofulvin

Terbinafine

Nystatin

2nd generation: voriconazole) -Triazoles differ from imidazole: -Broader spectrum -Better distribution -Less effect on human steroid synthesis as less affinity -2nd generation differs from 1st generation: -Extended spectrum -Active against fluconazoleresistant fungi -Narrow spectrum -Inhibit cell wall -Poor oral absorption -Specific to fungal glucan cell wall, so toxicity is infrequent -Inhibit microtubular -Taken up selectively by newlyformed skin and concentrated in keratin -Triazoles and terbinafine are used alternatively due to less problems with tolerability and adverse effects -Inhibit cell membrane -Accumulates in skin, nail, subcutaneous -More effective than azoles and griseofulvin -Inhibit cell membrane -Not absorbed through GIT, so no systemic effect -Never given parenterally due to serious systemic toxicity

Systemic (IV)

-Hepatotoxicity -Hypersensitivity -Fever

-Not metabolized in liver minimal drug interaction EXCEPT cyclosporin raised liver transaminase Systemic mucocutaneous -Dermatophyte - P450 inducer which may reduce efficacy of concomitant drug

Systemic mucocutaneous

-Hepatotoxicity -Hypersensitivity -Bone marrow suppression

Systemic mucocutaneous, topical

-GIT disturbance -Headache

Systemic mucocutaneous -Dermatophyte Topical -Dermatophyte

Topical

Created by Qosru Iskandariah