Download Free Medical Chemotherapy of Fungal Infections - ANTIFUNGAL DRUGS PowerPoint Presentation

Chemotherapy of Fungal Infections - ANTIFUNGAL DRUGS PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Chemotherapy of Fungal Infections - ANTIFUNGAL DRUGS

Tags : Chemotherapy,Fungal Infections,ANTIFUNGAL DRUGS,DRUGS

Published on : Nov 06, 2020 | Views : 4133 | Downloads : 23

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

Chemotherapy of Fungal Infections ANTIFUNGAL DRUGS Dr. Mohammed Samir Hussein BCs of Pharmaceutical Science MDs of Clinical Pharmacology
Slide 2-

Learning Outcomes Classification of Anti-fungal drugs (Systemic & Topical) Mechanism of action Toxicity Clinical uses Contraindications & Drug Interactions Drug Resistance
Slide 3-

Targets of antifungal drugs
Slide 4-

SYSTEMIC ANTIFUNGAL DRUGS FOR SYSTEMIC INFECTIONS AMPHOTERICIN B FLUCYTOSINE TERBINAFINE AZOLES
Slide 5-

AMPHOTERICIN B It is nearly insoluble in water and prepared as a colloidal suspension sodium deoxycholate for IV injection Poor oral absorption and thus effective only on fungi within the lumen of the tract Resistance develops, if ergosterol binding is impaired Broad-spectrum antifungal activity MOA: It binds to ergosterol and alters the permeability of the cell by forming amphotericin B–associated pores in the cell membrane It combines avidly with lipids (ergosterol) along the double bond–rich side of its structure and associates with water molecules along the hydroxyl-rich side This amphipathic characteristic facilitates pore formation The pore allows the leakage of intracellular contents, leading to cell death.
Slide 6-

AMPHOTERICIN B -MOA
Slide 7-

AMPHOTERICIN B Clinical Uses Used for initial induction therapy for immunosuppressed patients and those with Severe fungal pneumonia, Severe cryptococcal meningitis Histoplasmosis or coccidioidomycosis Fungal infections of CNS -Intrathecal therapy (not responded to other agents) Mycotic corneal ulcers and keratitis (direct subconjunctival injection) Fungal arthritis (adjunctive local injection directly into the joint) Candiduria (Bladder irrigation with amphotericin B)
Slide 8-

AMPHOTERICIN B Adverse Effects (Cumulative Toxicity) Renal damage (the most significant) - >4 g cumulative dose causes irreversible toxicity Reduced erythropoietin production and anaemia due to renal damage Azotaemia Chemical arachnoiditis & Seizures (Intrathecal therapy)
Slide 9-

FLUCYTOSINE Limited monotherapy It is taken up by fungal cells via the enzyme cytosine permease. It is converted intracellularly first to 5-FU and then to 5-fluorodeoxyuridine monophosphate (FdUMP) and fluorouridine triphosphate (FUTP), which inhibit DNA and RNA synthesis, respectively It has synergy with amphotericin B Enhanced penetration through amphotericin-damaged fungal cell membranes Resistance develops through altered metabolism of flucytosine
Slide 10-

FLUCYTOSINE Combination therapy with Amphotericin B for cryptococcal meningitis, or with itraconazole for chromoblastomycosis. Adverse Reactions: Narrow therapeutic window Bone marrow toxicity with anaemia, leukopenia, and thrombocytopenia Enterocolitis Derangement of liver enzymes
Slide 11-

Azoles They reduce the ergosterol synthesis by inhibition of fungal cytochrome P450 enzymes It has selective (greater affinity) toxicity to fungal CYP450 (CYP3A4) Examples: Ketoconazole Itraconazole Fluconazole Voriconazole Posaconazole Isavuconazole (Prodrug)
Slide 12-

Azoles Indications Useful in the treatment of intrinsically amphotericin-resistant Candida infections (candidemia, candidiasis.) C neoformans Blastomycosis, coccidioidomycosis, histoplasmosis Dermatophytes Aspergillus infections Onychomycosis
Slide 13-

Azoles Indications: Specific Secondary prophylaxis of cryptococcal meningitis (Fluconazole) Reduce fungal disease in bone marrow transplant recipients and AIDS patients –Prophylactic Fluconazole Serious invasive fungal infections (especially mold infections) – Posaconazole Prophylaxis of fungal infections during induction chemotherapy for leukemia, and for allogeneic bone marrow transplant patients with graft-versus host disease– Posaconazole
Slide 14-

Azoles ADRS: Abnormalities in liver enzymes, and, very rarely, clinical hepatitis Potential drug-drug interactions by inhibition of cytochrome P450 (CYP450) Rifamycins (CYP Inducers)- reduced bioavailability of itraconazole VORICONAZOLE (CYP3A4 inhibitor) - cyclosporine, tacrolimus, and HMG-CoA reductase inhibitors (Increased bioavailability) CYP3A4 inhibitors (ritonavir) or inducers (eg, rifampin) avoided with ISAVUCONAZOLE Visual disturbances (30%) - changes in colour vision or brightness - voriconazole Photosensitivity dermatitis caused by chronic oral therapy - voriconazole
Slide 15-

ORAL SYSTEMIC ANTIFUNGAL DRUGS FOR MUCOCUTANEOUS INFECTIONS GRISEOFULVIN ECHINOCANDINS
Slide 16-

Griseofulvin MOA: It is deposited in newly forming skin where it binds to keratin, protecting the skin from new infection. It must be administered for 2–6 weeks for skin and hair infections to allow the replacement of infected keratin, Nail infections (requires month therapy) Pharmacokinetics Insoluble fungistatic drug, Improved Absorption with fatty foods Use: Dermatophytosis ADR: Allergic reactions - lupus-like syndrome Hepatotoxicity Drug interactions with warfarin and phenobarbital
Slide 17-

Terbinafine MOA: Keratophilic medication and fungicidal. it interferes with ergosterol biosynthesis It inhibits the fungal enzyme squalene epoxidase This leads to the accumulation of the sterol squalene, which is toxic to the organism Use: Onychomycosis (Dermatophytosis) ADR: GIT upset and headache (Primary) Serious hepatotoxicity No drug-drug interactions
Slide 18-

TOPICAL ANTIFUNGAL THERAPY Nystatin Azoles Terbinafine and Naftifine
Slide 19-

Nystatin Polyene macrolide Too toxic for parenteral and only used topically Available as creams, ointments, suppositories, and other forms for application to skin and mucous membranes. Suppression of local candida infections (Candida sp) Oropharyngeal thrush, Vaginal candidiasis, and Intertriginous candidal infections.
Slide 20-

Topical Azoles Clotrimazole, Ketoconazole and Miconazole (MOA similar to oral) Oral clotrimazole troches are available for treatment of oral thrush and are a pleasant-tasting, alternative to nystatin (unpleasant taste). Topical and shampoo (ketoconazole) - treatment of seborrheic dermatitis and pityriasis versicolor. Indicated for dermatophytic infections, including Tinea corporis, Tinea pedis, and Tinea cruris
Slide 21-

Topical allylamine Terbinafine and Naftifine MOA: Similar to oral formulation Both are effective for treatment of Tinea cruris and Tinea corporis.
Slide 22-

THANK YOU FOR YOUR ATTENTION