Antifungals are medicines that kill or stop the growth of fungi (the plural of fungus) that cause infections. They are also called antimycotic agents.

1. Antifungal drugs

2. • Fungi cells are eukaryotic and possess nuclei,
mitochondria and cell membranes.
• The membranes contain distinctive sterols,
ergosterol and lanesterol.

3. POLYENES
• AMPHOTERICIN B
• Its spectrum is broad and includes Aspergillus
and Candida species
• Histoplasma capsulatum (which causes
histoplasmosis),
• Cryptococcus neoformans (which causes
cryptococcosis),

4. • Amphotericin is insoluble in water
• Amphotericin B is given as an intravenous
infusion over four to six hours.
• Topical amphotericin or suspension are used
for oral or pharyngeal candidiasis

5. uses
• Amphotericin is used in treating life-
threatening systemic fungal infections,
• but has considerable toxicity.

6. Mechanism of action
• Amphotericin is a polyene macrolide
• It has higher affinity for fungal sterols than for
cholesterol in mammalian cell membranes
• it increases membrane permeability by
creating a ‘membrane pore’which causes
leakage of small molecules, e.g. glucose and
potassium ions.

7. Pharmacokinetics
• Poor gastro-intestinal absorption necessitates
intravenous administration for systemic
infections.
• Amphotericin distributes very unevenly
throughout the body.
• Cerebrospinal fluid (CSF) concentrations are
1/40 of the plasma concentration,
• The t1/2 is 18–24 hours.

8. Adverse effects
• fever, chills, headache, nausea, vomiting, and
hypotension during intravenous infusion.
• nephrotoxicity; this is dose dependent and
almost invariable.
• tubular cationic losses, causing hypokalaemia and
hypomagnesaemia.
• anaemia due to temporary marrow suppression
is common.

9. • Dose: Oral; intestinal candidiasis, 100 – 200mg
every 6 hours.
• By intravenous infusion; systemic fungal
infection, (0.25mg/kg) 250mcg/kg body
weight daily, gradually increased if tolerated
to 1mg/kg daily.
• The maximum dose for severe infection,
1.5mg/kg daily or on alternate days

10. NYSTATIN
• Nystatin works in the same way as amphotericin B.
• its greater toxicity hence not used systemically.
• Its indications are limited to cutaneous/mucocutaneous
and intestinal infections caused by Candida species.
• nystatin is not absorbed systemically from the
oropharynx or gastrointestinal tract.
• resistance does not develop during therapy.
• Preparations of nystatin include tablets and suspension.
• Adverse effects Nystatin can cause nausea and diarrhoea
when large doses are administered orally.

11. • Dose: Oral: intestinal candidiasis 500,000 units
every 6 hours doubled in severe infections.
Child; 100,000 units every 6 hours.
• Neonate; 100,000 units as a single dose.
• For use in oral infections
• . Vaginal candidiasis; insert 1 – 2 pessaries at
night for at least 14 nights.

12. AZOLES
• Imidazoles are fungistatic at low concentrations
and fungicidal at higher concentrations.
• Mechanism of action of azoles competitively
inhibit lanostero.
• This disrupts fungal membrane phospholipids
increasing membrane fluidity and causing
membrane leakage and dysfunction of
membrane-bound enzymes.

13. • They are used topically and are active both
against yeasts (e.g. Candida).
• Some imidazoles are also used systemically,
although they have limited efficacy and
significant toxicity.

14. • Clotrimazole
• Presentation: Pessaries containing 100mg,
500mg Clotrimazole. Lozenges 1%, Cream 1%,
Topical 505, vaginal cream 1 %, Lotions1 % and
Solutions 1%.
• Indications: Vaginal and vulval candidiasis
• Dose: insert 2 pessaries at night for 3 nights or 1
pessary for 6 nights.
• For oral 20 drops after meals 3 times and for
fungal dermatosis apply twice a day.

15. • Side effects: Occasional local irritation
Caution: Antibiotic therapy, oral
contraceptives, pregnancy and diabetes
mellitus may affect the clinical effectiveness of
clotrimazole.
• Contra-indications: Hypersensitivity to
imidazole and other antifungal Medicines

16. TRIAZOLES
• This group of drugs such fluconazole, itraconazole and
voriconazole is derived from the imidazoles.
• Triazole drugs work by the same mechanism as
imidazoles but have a wider antifungal spectrum .
• FLUCONAZOLE Uses
• Fluconazole is a potent and broad-spectrum antifungal
agent.
• It is active against many Candida species, Cryptococcus
neoformans and Histoplasma capsulatum.
• Aspergillus species are resistant and resistant Candida
species are problematic in immunocompromised
patients.

17. • Fluconazole is used clinically to treat
superficial Candida infections and
oesophageal Candid.
• acute therapy of disseminated Candida,.
• It is administered orally or intravenously as a
once daily dose.

18. Adverse effects
• nausea,
• abdominal
• distension
• diarrhoea
• flatulence
• rashes
• hepatitis (rarely, hepatic failure).

19. Contraindications
• Fluconazole is contraindicated in pregnancy
because of fetal defects in rodents and
humans.
• Breast milk concentrations are similar to those
in plasma and fluconazoles hould not be used
by nursing mothers.

20. Pharmacokinetics
• Fluconazole is well absorbed after oral
administration
• widely distributed throughout the body. CSF
concentrations reach 50–80% of those in the
plasma.
• About 80% is excreted by the kidney and dose
reduction is required in renal failure.
• The fluconazole mean elimination t1/2 is 30
hours in patients with normal renal function.

21. Drug interactions
• Fluconazole reduces the metabolism of several
drugs by inhibiting CYP3A.
• benzodiazepines, calcium channel blockers,
ciclosporin, importantly, warfarin.
• The plasma concentrations and toxicity of these
drugs will increase during concomitant
treatment with fluconazole.
• Rifampicin enhances the metabolism of
fluconazole

22. Side effects
• abdominal discomfort
• anorexia,
• diarrhoea
• rashes .

23. • Dose: Acute or recurrent vaginal candidiasis; an oral single dose of
150mg.
• Mucosal candidiasis; oral, 50 – 100mg daily for 7 – 14 days.
• Tinea pedis, corporis, cruris, Versicolor and dermal candidiasis; oral,
50mg daily for 2 – 4 weeks (up to 6 weeks for tinea pedis).
• Systemic candidiasis; oral or i.v. infusion, 400mg initially then
200mg daily and continued according to patient response.
• Cryptococcal meningitis, by i.v. infusion; 800mg daily. Child, over 1
year; oral or i.v. infusion 1-2mg/kg body weight daily.
• Systemic and life-threatening infections; 3 – 6mg/kg body weight
daily.
• Can be increased up to 12mg/kg body weight daily in a child aged 5
- 13 years

24. GRISEOFULVIN
• Griseofulvin is orally active, but its spectrum is
limited to dermatophytes. It is concentrated in
keratinized cells. It is given orally with meals
and treatment is recommended for six weeks
for skin infections and up to 12 months for nail
infections.

25. Mechanism of action
• Griseofulvin is concentrated in fungi and binds
to tubulin, blocking polymerization of the
microtubule, disrupting the mitotic spindle.

26. Pharmacokinetics
• Griseofulvin is metabolized by the liver
• which is excreted in the urine.
• Less than 1% of the parent drug is excreted in
the urine.

27. Adverse effects
• These include:
• headaches and
• mental dullness or inattention
• diarrhoea
• nausea.
• rashes
• photosensitivity;

28. • Dose: adult; 500mg daily in divided doses or
as a single dose, in severe infection dose may
be doubled reducing when the response
occurs.
• Child; 10mg/kg body weight daily in divided
doses or as a single dose.