Department of PharmacologyDepartment of Pharmacology

NEIGRIHMS, ShillongNEIGRIHMS, Shillong

Antifungal DrugsAntifungal Drugs

Introduction - Introduction - Also called antimycotic Also called antimycotic drugsdrugs

Used to treat two types of fungal infection:Used to treat two types of fungal infection:– Superficial fungal infections - skin or mucous membraneSuperficial fungal infections - skin or mucous membrane– Systemic fungal infections - lungs or central nervous Systemic fungal infections - lungs or central nervous

systemsystem Fungi causing mycosis live as commensally or are

present in the environment. Earlier superficial infections were uncommon and

systemic rather rare. Recently there is increase in local as well as

systemic fungal infections. Reason for this is opportunistic infections

Opportunistic infectionsOpportunistic infections

Immuno-suppression due to- Cancer chemotherapy

- AIDS– Corticosteroid overuse

Indiscriminate use of broad spectrum antibiotics

Fungal infections

Superficial– Skin– Hair– Nails– Mucous membrane

Deep– Tissues (muscle &

connective tissue)– Organs

Images of some superficial skin infectio

ns

Types of fungal infections - Types of fungal infections - MycosesMycoses

Superficial mycosesSuperficial mycoses– Affect the skin, hair and nails – ringworm/tinea or Affect the skin, hair and nails – ringworm/tinea or

onychomycosisonychomycosis Subcutaneous mycoses (tropical)Subcutaneous mycoses (tropical)

– Affect the muscle and connective tissue immediately Affect the muscle and connective tissue immediately below the skinbelow the skin

Systemic (invasive) mycosesSystemic (invasive) mycoses– Involve the internal organsInvolve the internal organs

Allergic mycosesAllergic mycoses– Affect lungs or sinuses Affect lungs or sinuses – Patients may have chronic asthma, cystic fibrosis or sinusitisPatients may have chronic asthma, cystic fibrosis or sinusitis

There is some overlap between these groups

MOST COMMON FUNGAL MOST COMMON FUNGAL PATHOGENSPATHOGENS

DermatophytesDermatophytes – – Microsporum, Microsporum, Epidermophyton and TrichophytonEpidermophyton and Trichophyton

CandidaCandida – – C.C. albicans, C. glabrata, C. albicans, C. glabrata, C. tropicalistropicalis

AspergillusAspergillus CryptococcusCryptococcus RhizopusRhizopus

Causative fungiCausative fungi

Superficial infections by– Dermatophytes (ring worms): athlete`s foot or tinea

pedis, jock itch or tinea cruris, tinea capitis etc.– Candida:Candida: oral thrush, vaginitis and diaper candidiasis

etc. Deep infections are

– Candidiasis: Chronic mucocutaneous candidiasis, systemic candidiasis etc.

– Aspergillosis: broncho-pulmonary aspergillosis– Coccidiomycosis: pulmonary and disseminated

(complications – pneumonia)– Histoplasmosis:Histoplasmosis: H. capsulatum (common in HIV) H. capsulatum (common in HIV)

What are the targets for antifungal What are the targets for antifungal therapy?therapy?

Cell membraneFungi use principally ergosterol instead of cholesterol

Cell WallUnlike mammalian cells, fungi have a cell wall

DNA SynthesisSome compounds may be selectively activated by fungi, arresting DNA synthesis.

Cell Membrane Active AntifungalCell Membrane Active Antifungal

Cell membrane1. Polyene antibiotics - Amphotericin B, lipid

formulations - Nystatin (topical)

2. Azole antifungals Imidazoles:

• Topical: Clotrimazole, econazole, miconazole

• Systemic: KetoconazoleTriazoles: Fluconazole,

itraconazole and voriconazole

Polyene antibiotics-Polyene antibiotics-Amphotericin BAmphotericin B

Fermentation product of Fermentation product of Streptomyces nodususStreptomyces nodusus High affinity for ergosterol present in fungal cell membraneHigh affinity for ergosterol present in fungal cell membrane Hydrophilic polyhydroxyl chain along one side and a lipophilic Hydrophilic polyhydroxyl chain along one side and a lipophilic

polyene hydrocarbon chain on the otherpolyene hydrocarbon chain on the other Binds sterols in fungal cell membrane – Binds sterols in fungal cell membrane –

– high affinity for ergosterol present in fungal cell membranehigh affinity for ergosterol present in fungal cell membrane– affinity is less for host cell membrane although closely resemblesaffinity is less for host cell membrane although closely resembles

Creates transmembrane channel and electrolyte leakage.Creates transmembrane channel and electrolyte leakage. Active against most fungi except Active against most fungi except Aspergillus terreusAspergillus terreus, ,

Scedosporium Scedosporium sppspp.. Bacteria lack sterols so insensitive to polyenesBacteria lack sterols so insensitive to polyenes

Antifungal spectrumAntifungal spectrum

Most Toxic antifungalMost Toxic antifungal Fungicide at high and static at low conc.Fungicide at high and static at low conc. Effective againstEffective against

– Candida albicansCandida albicans– Histoplasma capsulatumHistoplasma capsulatum– CryptococcusCryptococcus

PharmacokineticsPharmacokinetics

Insoluble in waterInsoluble in water Unstable at 37degreeUnstable at 37degree Poorly absorbed from GITPoorly absorbed from GIT Cannot cross BBBCannot cross BBB Highly bound to plasma proteinsHighly bound to plasma proteins Takes 2 months for complete clearance of drugTakes 2 months for complete clearance of drug Given as I/V infusionGiven as I/V infusion For fungal meningitis given intrathecallyFor fungal meningitis given intrathecally Has immuno-stimulant action alsoHas immuno-stimulant action also Given in immuno-compromised patients for fungal Given in immuno-compromised patients for fungal

infectionsinfections

UsesUses

Broad spectrum antifungalBroad spectrum antifungal Useful forUseful for1. Candida that causes1. Candida that causes

– oraloral– vaginalvaginal– cutaneous candidiasiscutaneous candidiasis

2. Cryptococcus2. Cryptococcus3. Histoplasma3. Histoplasma4. Aspergillosis4. Aspergillosis5. Also effective for Leishmaniasis(Reserve drug for resistant 5. Also effective for Leishmaniasis(Reserve drug for resistant

cases of Kala Azar)cases of Kala Azar)

ADRsADRs

1.1. Acute reactions -Acute reactions - occurs with each infusion occurs with each infusion– Chills, Nausea, Vomiting, Pain, Fever, Aches, DyspnoeaChills, Nausea, Vomiting, Pain, Fever, Aches, Dyspnoea– So corticosteroids are administered along with the drugSo corticosteroids are administered along with the drug

2.2. ThrombophlebitisThrombophlebitis3.3. Bone marrow depressionBone marrow depression - Reversible anemia - Reversible anemia4.4. On intrathecal injectionOn intrathecal injection – Headache, Vomiting, – Headache, Vomiting,

Nerve paralysisNerve paralysis5.5. Renal toxicity leading toRenal toxicity leading to – Azotemia, Decreased – Azotemia, Decreased

GFR, Acidosis, Hypokalemia, Inability to conc. GFR, Acidosis, Hypokalemia, Inability to conc. urineurine

Newer Amphotericin BNewer Amphotericin B

They are developed to overcomeThey are developed to overcome1. Side effects1. Side effects2. To improve tolerability2. To improve tolerability3. To get the drug at site of action3. To get the drug at site of action4. To reduce the toxicity i.e.. Less nephrotoxic and minimal 4. To reduce the toxicity i.e.. Less nephrotoxic and minimal

anemiaanemiaFormulations are:Formulations are:1. Amphotericin B lipid complex1. Amphotericin B lipid complex2. Amphotericin B colloidal dispersion2. Amphotericin B colloidal dispersion3. Liposomal Amphotericin B3. Liposomal Amphotericin B(Only drawback of these formulations is less efficacy)(Only drawback of these formulations is less efficacy)

Drug Interactions of Amphotericin BDrug Interactions of Amphotericin B

With Flucytocin-synergistic actionWith Flucytocin-synergistic action Rifampicin and Minocyclin – Rifampicin and Minocyclin –

– Both potentiate Amphotericin BBoth potentiate Amphotericin B Vancomycin and Aminoglycoside – Vancomycin and Aminoglycoside –

– Both increase risk of nephrotoxicityBoth increase risk of nephrotoxicity Preparation and doses:Preparation and doses:

– 50 – 100 mg four times a day orally50 – 100 mg four times a day orally– 3% ear drops3% ear drops– Systemic: 50 mg vial (one vial diluted in 500 ml of 5% Systemic: 50 mg vial (one vial diluted in 500 ml of 5%

glucose and initially 1 mg test dose followed by infusion glucose and initially 1 mg test dose followed by infusion for 4 – 8 Hrs)for 4 – 8 Hrs)

NystatinNystatin

Similar to Amphotericin B but more Similar to Amphotericin B but more toxictoxic than than Amphotericin BAmphotericin B

Used only for superficial candidiasis ofUsed only for superficial candidiasis of

Skin, Mouth, Vagina, IntestineSkin, Mouth, Vagina, Intestine As ointment ,oral tablets & suppositoriesAs ointment ,oral tablets & suppositories Available as tablets and ointments (1 to 5 lacs U) Available as tablets and ointments (1 to 5 lacs U)

– also vaginal tablets– also vaginal tablets Orally not absorbed but can be used in monilial Orally not absorbed but can be used in monilial

diarrhoeadiarrhoea

Other PolyenesOther Polyenes

Hamycin: Water soluble Absorption from GIT not reliable Not used for systemic fungal infections Used topically for Aspergillus, Candida, Monilial,

Trichomonas vaginalis infectionsNatamycin: Broad spectrum Used topically for – Keratitis, Monilial infections,

Trichomonas vaginalis

Imidazoles and TriazolesImidazoles and Triazoles

Azole antifungals Imidazoles:

– Topical: Clotrimazole, econazole, miconazole– Systemic: Ketoconazole

Triazoles: Fluconazole, itraconazole and voriconazole

Remember that among imidazoles, only Remember that among imidazoles, only ketocanazole is systemic, other 3 are topical onlyketocanazole is systemic, other 3 are topical only

While, Triazoles are used systemically and largely While, Triazoles are used systemically and largely replacing ketoconazolereplacing ketoconazole

Azole StructuresAzole Structures

Fluconazole Ketoconazole

Azoles Azoles – Common Mechanism– Common Mechanism

• In fungi, the cytochrome P450-enzyme lanosterol 14-alpha demethylase is responsible for the conversion of lanosterol to ergosterol

• Azoles bind to lanosterol 14α-demethylase inhibiting the production of ergosterol– Some cross-reactivity is seen with

mammalian cytochrome p450 enzymes leading to

• Drug Interactions• Impairment of steroidneogenesis

(ketoconazole, itraconazole)

Effect of azoles on C. albicansEffect of azoles on C. albicans

Before exposure

After exposure

Decreased budding from the parent cells

Individual AgentsIndividual Agents

Ketoconazole:Ketoconazole: Spectrum: yeasts and moulds - poor absorption Spectrum: yeasts and moulds - poor absorption

limits its role for severe infections, generally used limits its role for severe infections, generally used in mucosal infections only (dematophytosis)in mucosal infections only (dematophytosis)

PharmacokineticsPharmacokinetics– Variable oral absorption, dependent on pH (often given Variable oral absorption, dependent on pH (often given

with cola or fruit juice)with cola or fruit juice)– T1/2 = 7-10 hoursT1/2 = 7-10 hours– Protein binding > 99%Protein binding > 99%– Hepatic, bile and kidney eliminationHepatic, bile and kidney elimination

Ketoconazole – contd.Ketoconazole – contd.

Adverse effectsAdverse effects– N&V, worse with higher doses (800 mg/day)N&V, worse with higher doses (800 mg/day)– Hepatoxicity (2-8%), increase in transaminases, Hepatoxicity (2-8%), increase in transaminases,

hepatitishepatitis– Dose related inhibition of CYP P450 responsible Dose related inhibition of CYP P450 responsible

for testosterone synthesisfor testosterone synthesis Gynecomastia, oligosperma, decreased libidoGynecomastia, oligosperma, decreased libido

– Dose-related inhibition of CYP P450 Dose-related inhibition of CYP P450 responsible for adrenal cortisol synthesisresponsible for adrenal cortisol synthesis

Ketoconazole – contd.Ketoconazole – contd.

Drug Interaction:Drug Interaction: Potent inhibitor of cytochrome P450 3A4Potent inhibitor of cytochrome P450 3A4

– Rifampin and phenytoin decrease ketoconazole levelsRifampin and phenytoin decrease ketoconazole levels– Ketoconazole increases cyclosporin, waKetoconazole increases cyclosporin, warrfarin, astemizole, farin, astemizole,

corticosteroid, and theophylline levelscorticosteroid, and theophylline levels– Many of these drug interactions are severeMany of these drug interactions are severe

Drugs that increase gastric pH will decrease blood levels of Drugs that increase gastric pH will decrease blood levels of ketoconazoleketoconazole– Antacids, omeprazole, H2 blockersAntacids, omeprazole, H2 blockers

Doses: Doses: – Serious infections 800 mg/day POSerious infections 800 mg/day PO– Other: 200-400 mg/day POOther: 200-400 mg/day PO

FluconazoleFluconazole

Water soluble having wider range of activity than Water soluble having wider range of activity than KetoconazoleKetoconazole

Good activity against C. albicans and Cryptococcus Good activity against C. albicans and Cryptococcus neoformansneoformans

Non-albicans Candida species more likely to exhibit Non-albicans Candida species more likely to exhibit primary resistanceprimary resistance

Always resistant Sometimes resistant

C. krusei > C. glabrata > C. parapsilosis

C. tropicalis

C. kefyr

ResistanceResistance

Primary resistancePrimary resistance (seen in severely ill or (seen in severely ill or immunocompromised patients)immunocompromised patients)– Selection of resistant species or subpopulationsSelection of resistant species or subpopulations– Replacement with more resistant strainReplacement with more resistant strain

Secondary resistanceSecondary resistance (seen in patients with (seen in patients with AIDS who experienced recurrent orophayrngeal AIDS who experienced recurrent orophayrngeal candidiasis and received long-term fluconazole candidiasis and received long-term fluconazole therapy)therapy)– Genetic mutationGenetic mutation– Upregulation of efflux pumpsUpregulation of efflux pumps

Mechanisms of antifungal resistanceMechanisms of antifungal resistance

Target enzyme Target enzyme modificationmodification

Ergosterol Ergosterol biosynthetic biosynthetic pathwaypathway

Efflux pumpsEfflux pumps Drug importDrug import

Fluconazole - KineticsFluconazole - Kinetics Available as both IV and POAvailable as both IV and PO

– Bioavailibility > 90%Bioavailibility > 90% PharmacokineticsPharmacokinetics

– t 1/2 = ~24 hourst 1/2 = ~24 hours– Protein binding < 12%Protein binding < 12%– Vd 0.85 L/kg (widely distributed)Vd 0.85 L/kg (widely distributed)– >90% excreted unchanged through the kidney>90% excreted unchanged through the kidney

DosingDosing1.1. Mucosal candidiasisMucosal candidiasis

100-200 mg/day (150 mg tablet vulvovaginal candidiasis)100-200 mg/day (150 mg tablet vulvovaginal candidiasis)2.2. Systemic fungal infectionsSystemic fungal infections

400-800 mg q24h400-800 mg q24h >> 800 mg q24h in unstable patient, S-DD isolate, or if non- 800 mg q24h in unstable patient, S-DD isolate, or if non-albicansalbicans spp. (except spp. (except

C. kruseiC. krusei))3.3. Maintenance for cryptococcal meningitisMaintenance for cryptococcal meningitis

400 mg q24h400 mg q24h

Fluconazole - ADRsFluconazole - ADRs

N&V, rash:N&V, rash:– More likely with high doses and in AIDS patientsMore likely with high doses and in AIDS patients– Asymptomatic increase in LFTs (7%)Asymptomatic increase in LFTs (7%)

Drug interactions:Drug interactions:– May increase phenytoin, cyclosporin, rifabutin, May increase phenytoin, cyclosporin, rifabutin,

warfarin, and zidovudine concentrationswarfarin, and zidovudine concentrations– Rifampin reduced fluconazole levels to halfRifampin reduced fluconazole levels to half

(even though FLU is not a major substrate)(even though FLU is not a major substrate)

ItraconazoleItraconazole

Some Features:Some Features: Newer orally active triazoleNewer orally active triazole Broader spectrun than KTZ and FCZ – Broader spectrun than KTZ and FCZ –

includes moulds like aspergillusincludes moulds like aspergillus Fungistatic action but very effective in Fungistatic action but very effective in

immunocompromizrd patientsimmunocompromizrd patients Steroid hormone synthesis inhibition is Steroid hormone synthesis inhibition is

absent and no serious hepatotoxicityabsent and no serious hepatotoxicity

KetoconazoleKetoconazole FluconazoleFluconazole ItraconazoleItraconazole

11 Broad spectrumBroad spectrum Still wider rangeStill wider range Fungi staticFungi static

22 DermatophyteDermatophyte

& deep mycosis& deep mycosis

Cryptococcal & coccidialCryptococcal & coccidial

meningitismeningitis

immunocompromisedimmunocompromised

patientspatients

33 Absorbed at low pHAbsorbed at low pH Good oral absorptionGood oral absorption Varies with food & pHVaries with food & pH

44 Highly bound to PPHighly bound to PP Not muchNot much Highly boundHighly bound

55 More S/E, headache, androgenMore S/E, headache, androgen

inhibitioninhibition

Less S/E, headache & rashLess S/E, headache & rash Hypokalemia, pruritis &Hypokalemia, pruritis &

dizzinessdizziness

66 Causes hepatic impairmentCauses hepatic impairment MildMild Not hepatotoxicNot hepatotoxic

77 Inhibit cytochrome P450Inhibit cytochrome P450 Inhibit only fungal P450Inhibit only fungal P450 No effectNo effect

88 Used for Monilial vaginitis. Used for Monilial vaginitis.

Cushing’s synCushing’s syn

Candidiasis, Keratitis, Candidiasis, Keratitis,

Cryptococcal meningitisCryptococcal meningitis

Mycosis, meningitis Mycosis, meningitis

Chromo & paracocciChromo & paracocci

Local azolesLocal azoles

Very popular local azoles are – Clotrimazole, Econazole and Miconazole

(For Tinea, Ring worm, Athlete’s foot, otomycosis, oral, cutaneous & vaginal candidiasis)

Mechanism of action is same as that of Ketoconazole i.e. ergosterol inhibition by inhibiting CYP450

Clotrimazole is favoured in vaginitis because of long lasting residual effect and once daily dosing

Miconazole causes frequently vaginal irritation & pelvic cramp.

Available s lotion, cream, powder, vaginal tablet etc. Available s lotion, cream, powder, vaginal tablet etc.

Heterocyclic Nitrofurans - Heterocyclic Nitrofurans - GriseofulvinGriseofulvin

Used for superficial fungal infections by Used for superficial fungal infections by dermatophytesdermatophytes

Derived from Penicillium griseofulvum but Derived from Penicillium griseofulvum but no antibacterial activityno antibacterial activity

Effective against most dermatophytes, but Effective against most dermatophytes, but not against candida causing deep mycosisnot against candida causing deep mycosis

Dermatophytes actively concentrate it – Dermatophytes actively concentrate it – accounts for selective toxicity against themaccounts for selective toxicity against them

Taken up by newly formed keratinTaken up by newly formed keratin

Griseofulvin - MOAGriseofulvin - MOA

Interferes with mitosis – results in Interferes with mitosis – results in multinucleated and stuntedmultinucleated and stunted hyphae hyphae

((In most fungi, hyphae are the main mode of vegetative growth, and are In most fungi, hyphae are the main mode of vegetative growth, and are collectively called a mycelium yeasts are unicellular fungi that do not collectively called a mycelium yeasts are unicellular fungi that do not grow as hyphae)grow as hyphae)

Abnormal metaphase configurations leading Abnormal metaphase configurations leading to failure of daughter nuclei to fall apartto failure of daughter nuclei to fall apart

(Colchicine and vinca alkloids also mitotic inhibitors but they cause (Colchicine and vinca alkloids also mitotic inhibitors but they cause arrest arrest of mitosis)of mitosis)

Disorientation of polymerized microtubules Disorientation of polymerized microtubules

Griseofulvin – contd.Griseofulvin – contd.

Pharmacokinetics:Pharmacokinetics: Given orally and fats improve absorptionGiven orally and fats improve absorption Absorption depends on the particle sizeAbsorption depends on the particle size Duration of treatment depends upon tissue turn overDuration of treatment depends upon tissue turn over 1. 3-6 wks for skin & hair1. 3-6 wks for skin & hair 2. 3-6 months for nails2. 3-6 months for nails Treatment should continue till whole infected tissue is shed Treatment should continue till whole infected tissue is shed

off.off.Doses:Doses: Used orally only for dermatophytosis (125 to 250 mg 4 Used orally only for dermatophytosis (125 to 250 mg 4

times daily, but depends on site of infection times daily, but depends on site of infection

Griseofulvin - ADRsGriseofulvin - ADRs

Safe with mild side effectsSafe with mild side effects 1. GIT upsets1. GIT upsets 2. CNS symptoms2. CNS symptoms 3. Hepatotoxicity3. Hepatotoxicity 4. Leucopenia4. Leucopenia 5. Photosensitivity5. Photosensitivity 6. Allergy etc.6. Allergy etc. Microsomal enzyme inducerMicrosomal enzyme inducer Causes decrease in activity of anticoagulantsCauses decrease in activity of anticoagulants Cause intolerance to alcoholCause intolerance to alcohol Phenobarbitone reduces its oral absorption so failure of Phenobarbitone reduces its oral absorption so failure of

therapytherapy

FlucytosinFlucytosin Fluorinated pyrimidine related to flurouracilFluorinated pyrimidine related to flurouracil Restricted spectrum of activity.Restricted spectrum of activity. Acquired Resistance due to > result of monotherapy Acquired Resistance due to > result of monotherapy Due to:Due to: 1) Decreased uptake (permease activity)1) Decreased uptake (permease activity) 2) Altered 5-FC metabolism (cytosine deaminase or UMP 2) Altered 5-FC metabolism (cytosine deaminase or UMP

pyrophosphorylase activity)pyrophosphorylase activity)

Kinetics:Kinetics: Orally absorbedOrally absorbed Widely distributed even in CSFWidely distributed even in CSF Exc. in urine.Exc. in urine. Converted in fungal cell to 5-FU which is antimetabolite.Converted in fungal cell to 5-FU which is antimetabolite. Mammalian cells remain unaffected except few bone marrow cellsMammalian cells remain unaffected except few bone marrow cells

FlucytosinFlucytosin

Monotherapy : NeverMonotherapy : Never

Candidiasis Candidiasis CryptococcosisCryptococcosis

?Aspergillosis?Aspergillosis } In combination with amphotericin B or

fluconazole.

Doses:1. Vaginal candidiasis: 200 mg OD for 3 days2. Dermatophytosis; 100-200 mg OD for 7-15 days3. Onychomycosis: 200 mg per day for 3 monthsADRs: 1.Mild BM depression 2. Loss of hair 3. Dose should be decreased in the presence of renal impairment

TerbinafineTerbinafine

Belongs to a newer allylamine class of antifungalsBelongs to a newer allylamine class of antifungals Given both orally & locallyGiven both orally & locally Lipophillic so widely distributedLipophillic so widely distributed Fungicidal in contrast to azoles (fungistatic)Fungicidal in contrast to azoles (fungistatic) Acts by non-competitive inhibition of Acts by non-competitive inhibition of “squalene epoxidase”“squalene epoxidase”

(early step enzyme in ergosterol synthesis (Image in Slide (early step enzyme in ergosterol synthesis (Image in Slide No. 22) – accumulation of squalene in fungal cells – cidal No. 22) – accumulation of squalene in fungal cells – cidal effecteffect

Used for dermatophytes & candidaUsed for dermatophytes & candida Dose is 250mg OD for 2-6 wksDose is 250mg OD for 2-6 wks Locally 1% ointmentLocally 1% ointment.

Terbinafine – contd.Terbinafine – contd.

ADRsADRs With oralWith oral

– GIT upsetGIT upset– Hepatic dysfunctionHepatic dysfunction– RashRash– Taste disturbanceTaste disturbance– No interaction with CYP450No interaction with CYP450

Preparations and doses: Preparations and doses: – 1% cream 125/250 mg tablets etc.1% cream 125/250 mg tablets etc.– Tinea pedis: 250 mg OD for 2-6 weeksTinea pedis: 250 mg OD for 2-6 weeks– Onychmycosis: 3-12 months (alternative to fluconazole) Onychmycosis: 3-12 months (alternative to fluconazole)

• On local application -On local application - ddryness, Erythemaryness, Erythema, , Rash, Rash, itching etc. itching etc.

Expected QuestionsExpected Questions Classify antifungals. Write MOA, ADRs and Uses of Amphotericin BClassify antifungals. Write MOA, ADRs and Uses of Amphotericin B Classify azoles. Write briefly on MOA and Uses of azolesClassify azoles. Write briefly on MOA and Uses of azoles Write briefly on MOA and mechanism of resistance of azolesWrite briefly on MOA and mechanism of resistance of azoles

MCQs:MCQs:1.1. Amphotericin B is: fungistatic, fungicidal etc. and other choicesAmphotericin B is: fungistatic, fungicidal etc. and other choices2.2. Azoles: inhibits ergosterol, inhibits nucleic acid, inhibits microtubule etc.Azoles: inhibits ergosterol, inhibits nucleic acid, inhibits microtubule etc.3.3. Ketoconazole may cause: cortisol deficiency, testosterone deficiency etc.Ketoconazole may cause: cortisol deficiency, testosterone deficiency etc.4.4. Griseofulvin causes: destruction of fungal microtubule, inhibits fungal cell Griseofulvin causes: destruction of fungal microtubule, inhibits fungal cell

membrane etc.membrane etc.5.5. Griseofuvin is best administered: with fatty diet, in empty stomach etc.Griseofuvin is best administered: with fatty diet, in empty stomach etc.

Short Notes: Short Notes: – Fluconazole, Griseofulvin, Ketoconazole, Clotrimazole, TerbinafineFluconazole, Griseofulvin, Ketoconazole, Clotrimazole, Terbinafine

Thank youThank you