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Anti Fungal drugs, Pharmacology III, Unit-3 Download Notes PDF BPharmacy 6th Semester 2022

Anti Fungal drugs, Pharmacology III, Unit-3 Download Notes PDF BPharmacy 6th Semester 2022

📑 BP602T Pharmacology III


Anti Fungal drugs, Pharmacology III, Unit-3

Course: BPharmacy
Semester/Year: 6th Semester
Subject: BP602T Pharmacology III
Session: 2022
Category: Notes
Pharmacology BPharmacy BPharm 6th Semester Important Exam Notes


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BP602T Pharmacology III BPharmacy 6th Semester
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ANTI-FUNGALAGENT• These are drugs used for superficial anddeep(systemic)fungal infections. • Fungal infections are mostly associatedwiththeuseofbroad-spectrum antibiotics, corticosteroids, anticancer/immunosuppressant drugs, catheters andimplantsandemergence of AIDS. • As a result of breakdown of host defencemechanismsbythe above agents, saprophytic (live andfeedondead)fungi easily invade living tissue.

Classification of drugs:
1. Antibiotics
A. Polyenes: Amphotericin B (AMB), NystatinB. Echinocandins: Caspofungin, MicafunginC. Heterocyclic benzofuran: Griseofulvin
2. Antimetabolite: Flucytosine (5-FC)
3. Azoles

A. Imidazoles
Topical: Clotrimazole, Econazole, Miconazole, OxiconazoleSystemic: Ketoconazole
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B. Triazoles: Fluconazole, Itraconazole, Voriconazole.4. Allylamine: Terbinafine
5. Other topical agents:
Tolnaftate, Undecylenic acid, Benzoicacid,Butenafine, Sodium thiosulfate. Amphotericin B (AMB)
• Obtained from Streptomyces nodosus. • Amphotericin has two parts:
A- lipophilic (non-polar) and B- hydrophilic(polar)• When amphotericin binds with the fungal cell membrane,it makes a special channel (micropore), andincreasethecell membrane permeability, so that thehydrophilicportion of drug can penetrate easily andresult inthecellcontents comes out (ions, amino acidsandotherwater-soluble substances). • When the lipid portion of AmphotericinBbindstofungalcell membrane, it is called ‘micropore’. • Given orally (50–100 mg QID) for intestinalmoniliasis; also topically for vaginitis, otomycosis,etc. • active against a wide range of yeastsandDownloaded from HK Technical PGIMS (pgims.hktechnical.com)
fungi—Candida albicans, Histoplasmacapsulatum,Cryptococcus neoformans, Leishmaniaetc. Adverse effects:
1. Acute reaction: on infusion causes chills, fever, aches,nausea, vomiting and dyspnoea (Shortnessof breath).2. Thrombophlebitis (inflammatory processintheveindue to clot formation) of the injectedvein. 3. Long-term toxicity: Nephrotoxicity
4. CNS toxicity: intrathecal (Spinal cord) injectioncausesheadache, vomiting, nerve palsies, etc. Uses: Amphotericin B can be appliedtopicallyfororal,vaginal and cutaneous candidiasis andotomycosis.• Used in Febrile neutropenia
• Used in Leishmaniasis (an infectioncausedbyleishmania parasite)
• Conventional formulation of AMB (C-AMB):
For systemic mycosis, C-AMB is availableasdrypowder along with deoxycholate(DOC)forextemporaneous dispersion before use. • Liposomal amphotericin B (L-AMB): • It has been produced to improve tolerabilityofi.v.infusion of AMB, reduce its toxicityandachievetargeted delivery. It consists of 10%AMBincorporatedin liposomes made up of lecithinandotherDownloaded from HK Technical PGIMS (pgims.hktechnical.com)
biodegradable phospholipids. Nystatin
• Obtained from S. noursei. • Similar to Amphotericin in antifungal action. • Due to high systemic toxicity, usedonlylocallyinsuperficial candidiasis. • AE: Nausea and bad taste in mouth. • Used in vaginitis, oral thrush, corneal, conjunctivalandcutaneous candidiasis, diarrhoea. • Dosage: MYCOSTATIN 5 lakh U tab (1mg=2000U).Caspofungin
• active mainly against Candida and Aspergillusstrains.• MOA: inhibits the synthesis of β-1, 3-glucan, whichisaunique component, responsible for toughnessoffungalcell wall. As a result cell wall disrupt. • It is not absorbed orally; has to be infusedi.v. • Uses: deep and invasive candidiasis, esophagealcandidiasis.
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• Dose: 70 mg loading dose infusedi.v. over1hour,followed by 50 mg i.v. daily. Griseofulvin
• Obtained from Penicilliumgriseofulvum. • It is fungistatic against Epidermophyton, Trichophyton,Microsporum, etc. • MOA: It interferes with mitosis—multinucleatedandstunted fungal hyphae are produced under itsaction.Italso causes abnormal metaphase configurations. • AE: Headache, g.i.t. disturbances, rashes, photoallergy.• Uses: used orally only for dermatophytosis. • Dose: 125–250 mg QID with meals, usedfor
Scalp 4 weeks
Palm, soles 6 to 8 weeks
Finger nails 6 to 8 months
Toe nails 10 to 12 months
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Imidazoles and Triazoles:
• They are broad spectrumantifungal drugscoveringdermatophytes, candida, other fungi involvedindeepmycosis, Nocardia and Leishmania. • They inhibit the fungal cytochromeP450enzyme‘lanosterol 14- demethylase’ whichisrequiredforergosterol synthesis. Thus leadingtomembraneabnormalities in the fungus. Clotrimazole:
• Effective in the topical treatment of tineainfectionslikeringworm, athletes’ foot, otomycosis andoral/cutaneous/vaginal candidiasis. • Dose: SURFAZ, CLODERM1% lotion, cream, powder.Econazole:
• Similar to clotrimazole; penetrates superficial layersofthe skin and is highly effective indermatophytosis,otomycosis, oral thrush.
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• Dose: ECONAZOLE 1% oint. Miconazole:
• Highly efficacious (>90% cure rate) drugfortinea,pityriasis versicolor (yeast infectionof theskin),otomycosis, cutaneous and vulvovaginal candidiasis.• AE: vaginal irritation, pelvic cramps. Ketoconazole (KTZ):
• First orally effective broad-spectrumantifungal drug,useful in both dermatophytosis and deepmycosis. • Dose is 200 mg OD or BD, used in shampoo. • AE: hormonal effects, gynaecomastia, lossofhair,menstrual irregularities.
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• Has a wider range of activity than KTZ. • Used in cryptococcal meningitis, systemicandmucosalcandidiasis. • AE: nausea, vomiting, abdominal pain, rashandheadache.• Uses: can be taken orally as well as i.v. (insevereinfections). • Used in vaginal candidiasis, oropharyngeal candidiasis,tinea infections and cutaneous candidiasis.
• Orally active triazole antifungal moreefficaciousthanKTZ or fluconazole. • Well tolerated in doses below 200 mg/day. • Dizziness, pruritus, headache and hypokalaemiaaretheother common side effects.
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Posaconazole :
• This recently introduced broad-spectrumtriazolehasmore potent antifungal activity andistheonlyazolewhich has shown efficacy in mucormycosis. Terbinafine
• Orally and topically active drug against dermatophytesand Candida. • Fungicidal in nature. • It acts as a non-competitive inhibitor of ‘squaleneepoxidase’
, an early step enzymeinergosterolbiosynthesis by fungi. • Side effects: gastric upset, rashes, tastedisturbance,hepatic dysfunction, haematological disorder andseverecutaneous reaction. • Uses: Terbinafine applied topically as 1%creamtwicedaily is indicated in localized tinea pedis/ cruris/corporis(infection between toes, rashes in groin) andpityriasisversicolor.
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