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Anti fungal

Pharma

QuestionAnswer
Amphotericin B Binds to Ergosterol And form large pores in the cell wall causing disturbances in electrolytes inside the cell.
Amphotericin B -insoluble in water + sodium deoxycholate or in artificial lipids to form liposomes.
Amphotericin B -narrow therapeutic index -broad spectrum antifungal -derived from Streptomyces
Amphotericin B Resistance -low formation of Ergosterol
Amphotericin B Contra: - Those who have -electrolyte imbalance (hypokalemia, hypomagnesemia) -renal dysfunction -pregnancy
Amphotericin B Systemic infection that requires rapid response -candida albicans and aspergillus
Amphotericin B Slow IV
Amphotericin B SE:- Nephrotoxicity -Renal vasculature and epithelium are damaged Hypotension Thrombophlebitis Anemia
Caspofungin from Echinocandin B found naturally in Aspergillus nidulans IV
Caspofungin Fungicidal -> candida Fungistatic -> Aspergillus
Caspofungin Inhibit the synthesis of 1,3-β-glucan, a glucose polymer, and found in the cell wall. .’. lose integrity of cell wall -> death
Caspofungin Uses:- Invasive candida and aspergillus
Caspofungin SE:- Hepatotoxicity Flushing (Histamine) GI upset Hypotension Phlebitis Fever shivering
Griseofulvin -fromPenicillium Griseofulvin -plasma T1/2= 24h , and stays in the skin for much longer. -induces cytochrome p450-> drug interactions. Oral
Griseofulvin 1- interferes with mitosis by binding to microtubules 2-binds to keratin cells producing -> accumulation in keratin rich cells -> goes into fungal cells -> interfere with microtubule.-> no replication and cell death
Griseofulvin Dermatophytes skin and nail (disease = Tinea pedis) Ringworm Jock itch Scalp fungal infections Largely superseded by other drugs. ->Replaced by oral terbinafine for the treatment of onychomycosis
Griseofulvin Contra :- Porphyria Hepatic failure Pregnancy Breastfeeding
Griseofulvin SE:- Photosensitivity Allergy = fever and rash Headache GI upset
IMIDAZOLE= Clotrimazole and Ketoconazole
IMIDAZOLE= -Dangerous for immunocompromised pt HIV infected & bone marrow
IMIDAZOLE + 1)Inhibit the fungal C-14 alpha demethylase, and lanosine14 alpha demethylase So, X-> lanosterol -> Ergosterol .’. 1-membrane fluidity is altered 2-Those enzymes that are associated with membrane will be not work ->.’. no replication
IMIDAZOLE + 2) inhibits the transformation of candida yeast to hyphae
TRIAZOLES Fluconazole
IMIDAZOLE + TRIAZOLES Resistance: 1-Mutation of C-14 alpha demethylase So, azoles will not bind. 2-Efflux of the drug out of the fungi cell
IMIDAZOLE + TRIAZOLES FOR: Skin infection Athlete’s foot Onychomycosis = nail infection Ringworm Vaginal candidiasis Topical: - 1-vaginal yeast 2-oral thrust 3-Daipers rash 4-atheletes foot
IMIDAZOLE Ketoconazole = Orally: - Systemic infection (Toxicity to liver)
TRIAZOLES Fluconazole orally and IV: - Fungal Meningitis
IMIDAZOLE SE;- ketoconazole = hepatotoxicity
Flucytosine and can be found in CSF
Flucytosine -Converted inside the cell into active form 5-Fluorouracil Flucytosine -> 5-Fluorouracil By cytosine deaminase Inhibits thymidylate synthase .’. DNA and RNA synthesis .’. death
Flucytosine Resistance:- 1-Decrease the enzymes the converts the Flucytosine -> 5 – Fluorouracil 2- increase the synthesis of cytosine
Flucytosine Combination therapy: - + Amphotericin -> systemic infection =candidiasis and cryptococcal Meningitis Mono-therapy: - Genitourinary candida not used as monotherapy due to high chances of resistance
Flucytosine SE:- Bone marrow suppression Neutropenia Thrombocytopenia Alopecia Hepatitis Enterocolitis
Terbinafine Naftifine Fungicidal
Terbinafine Naftifine Inhibits squalene epoxidase .’. no synthesis of Ergosterol from the precursor Squalene .’. accumulation of Squalene = toxicity
Terbinafine Naftifine USES: Dermatophytes skin and naiL
Terbinafine Naftifine Topical Terbinafine = + oraL
Created by: Heba666
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