Antifungal drugs are used to treat and prevent fungal infections. There are several classes of antifungal drugs including polyenes, echinocandins, azoles, and others. Azole resistance can develop through mechanisms such as decreased drug concentration due to efflux pumps, target site alterations of the ERG11 gene, and bypassing of the ergosterol pathway. Amphotericin B works by binding to ergosterol in the fungal cell membrane. Ketoconazole inhibits the enzyme lanosterol 14α-demethylase. Antifungal drugs can cause side effects and are also used to treat specific fungal infections.

1. PRESENTER: SAIYAD ARSH ZIA
M.PHARM 2ND SEMESTER
PHARMACOLOGY
Antifungal Drugs

2. Antifungal Drugs
An antifungal medication, also known as an antimycotic medication, is
a pharmaceutical fungicide or fungistatic used to treat and prevent mycoses such
as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such
as cryptococcal meningitis, and others. Such drugs are usually obtained by a
doctor's prescription, but a few are available OTC (over-the-counter).

3. CLASSIFICATION
1. Antibiotics
A. Polyenes: Amphotericin B (AMB),
B. Echinocandins:Caspofungin, Micafungin,
C. Heterocyclic benzofuran: Griseofulvin
2. Antimetabolite Flucytosine (5-FC)
3. Azoles
A. Imidazoles
Topical: Clotrimazole, Econazole, Miconazole, Oxiconazole
Systemic: Ketoconazole
B. Triazoles: Fluconazole,
5. Other topical agents
Tolnaftate, Benzoic acid, Quiniodochlor, Ciclopirox olamine, Butenafine, Sod.
thiosulfate.

4. Mechanism of Resistance
Mechanisms of Azole Resistance
Decreased drug concentration.The development of active efflux pumps
results in decreased drug concentrations at the site of action. Efflux pumps
are encoded in Candida species by 2 gene families of transporters:
the CDR genes of the ATP-binding cassette super family, and the MDR genes
of the major facilitators class. Up regulation of CDR1, CDR2, and MDR1 has
been demonstrated in azole-resistant C. albicans [60, 61]. Other transporter
genes have been detected in other Candida species, such
as CgCDR1 and PDH1 in C. glabrata and CdCDR1 and CdMDR1 in Candida
dubliniensis. Whereas CDR gene up-regulation confers resistance to almost
azoles, MDR-encoded efflux pumps have a narrower spectrum specific for
fluconazole.

5.  Target site alteration.It has been demonstrated that mutations in ERG11, the
gene encoding for the target enzyme lanosterol C14α-demethylase, prevents
binding of azoles to the enzymatic site.
 Development of bypass pathways.Exposure to azole compounds results in
depletion of ergosterol from the fungal membrane and accumulation of the
toxic product 14α-methyl-3,6-diol, leading to growth arrest. Mutation of
the ERG3 gene prevents the formation of 14α-methyl-3,6-diol from 14α-
methylfecosterol. Replacement of ergosterol with the latter product leads to
functional membranes and negates the action of azoles on the ergosterol
biosynthetic pathway.

6. MECHANISM OF AMPHOTERICIN B

7. MECHANISM OF KETOCONAZOLE

8. Pharmacokinetics
• Poorly absorbed orally , is effective for fungal infection of
gastrointestinal tract.
• Highly bound to plasma protein .
• Poorly crossing BBB.
• Metabolized in liver
• Excreted slowly in urine over a period of several days.
• Half-life 15 days.

9. Side effects of antifungal medicines
Your antifungal medicine may cause side effectsThey can include:
• itching or burning
• redness
• feeling sick
• tummy (abdominal) pain
• diarrhoea
• a rash
Occasionally, your antifungal medicine may cause a more severe reaction, such
as:
• an allergic reaction – your face, neck or tongue may swell and you may have
difficulty breathing
• a severe skin reaction – such as peeling or blistering skin
• liver damage (occurs very rarely) – you may experience loss of appetite,
vomiting, nausea, jaundice, dark urine or pale faeces, tiredness or weakness
Stop using the medicine if you have these severe side effects, and see your GP
or pharmacist to find an alternative.

10. Clinical uses
Drug Uses
AmphotericinB : Most fungal infections (Not for Pseudallescheria
Anidulafungin: Candidiasis, including candidemia
Caspofungin: Aspergillosis Candidiasis, including candidemia
Fluconazole: Mucosal and systemic candidiasis, Cryptococcal meningitis Coccidioidal meningitis

11. THANK YOU