ANTIFUNGAL DRUGS

BY: ALEEZA AHMED

ABASYN UNIVERSITY
ANTIFUNGAL DRUGS
• Medication used to treat Mycoses or fungal infections.
• Work through fungistatic action means inhibit fungal growth.
• Or work through fungicidal action means killing fungi.
 ANTFUNGAL TARGET SITES & DRUG CLASSIFICATION

ALTER CELL WALL & DISRUPT

BLOCK NUCEIC ACID
MEMBERANE MICROTUBULE
PERMEABILITY
SYNTHESIS
FUNCTIONS Cell wall
• Azoles • Flucytosine • Griseofulvin
Ketoconazole Nucleus
Fluconazole
Itraconazole
Voriconazole Cell membrane
• Polyenes
• Terbinafine
• Glucan synthesis
inhibitors
 Echinocandins
• Caspofungin
• Micafungin
MOA
• Fungal cell is made up of tough outer cell wall & inner cell membrane .
• Target: CELL MEMBRANE
• Cell membrane is mostly made up of phospholipids & with some sterol molecules called
Ergosterol (Most common target for antifungal drugs).
• Ergosterol is similar to mammalian sterol that is found in fungal cell membrane which acts to
maintain cell membrane stability or integrity.
• Without ergosterol structure of cell membrane is going to disrupt & this will cause membrane
bound proteins, called ion channels to stop working properly & will also make cell membrane so
fragile which eventually leads to inhibition of fungal growth.
• The precursor for both mammalian sterol & fungal sterol is Lanosterol & precursor of lanosterol
is Squalene.
• The conversion of squalene into lanosterol is going to happen via the formation of squalene
epoxide, catalyzed by an enzyme called squalene epoxidase.
• Fungi have a cytochrome p450 enzyme called 14-α-demthylase enzyme in the mitochondria as
well as in the endoplasmic reticulum. This enzyme going to convert lanosterol into ergosterol.
MOA
• Target: CELL WALL
• What makes the cell wall to be so strong???
• Presence of carbohydrates & beta glucans; which are polysaccharides
polymers that are cross linked with carbohydrate molecules which
make a strong cell wall.
• Beta glucans are produced by an enzyme called β-1-3-glucansynthase
& this enzyme is not found in human cells which makes it a good
target for antifungal medications.
Polyenes
MOA
• Target: NUCLEUS
• Microtubule function inhibitors
• Nucleic acid synthesis inhibitors i.e. DNA & RNA synthesis inhibitors
as well as mitosis inhibitors
DRUG CLASS EXAMPLES MOA
Polyenes Amphotericin B • Polyenes are designed in such a manner that these drugs
Nystatin are going to bind with ergosterol.
• Forming “artificial pores” in cell membrane thereby
making the cell membrane of fungi very permeable or
very leaky
• This cause significant changes in ion balance including
the loss of intracellular potassium
• This leads to death of fungal cell.

Azoles Ketoconazole • Inhibit the p450-dependent enzyme called 14-α-

Fluconazole demethylase
Itraconazole • Blocking conversion of lanosterol into ergosterol
Voriconazole
Polyenes Terbinafine • Inhibits epoxidation of squalene, by inhibiting an enzyme
called squalene epoxidase.
• Eventually stopping the production of ergosterol.

Echinocandins Caspofungin • Inhibit synthesis of cell wall component called beta

Micafungin glucan thereby going to prevent formation of beta glucan;
Anidulafungin • Preventing the cross linking of carbohydrate molecules
• Cell wall become so fragile

Microtubule function Inhibitor Griseofulvin • Prevents the replication of fungus

• By attacking microtubules.
DNA & RNA Synthesis Inhibitor Flucytosine Inhibit DNA & RNA Polymerases
DRUGS CLINICAL USES SIDE EFFECTS

Amphotericin B – • Fungicidal spectrum • Highly toxic

First antifungal drug • Treat fungal infections such as cryptococcal meningitis and visceral • Infusion related S/E(Pretreat with
leishmaniasis antihistamine and steroids)
• Nephrotoxicity
• QT prolongation
• Anemia
• Impaired Hepatic function
• Intrathecal administration may cause
seizures & neurotoxicity

Nystatin • Used to treat fungal infections of the inside of the mouth and lining • Steven Johnson syndrome
of the stomach and intestines. • GI disturbances
• Vaginal candidiasis
• Diaper rash
Azoles • Can be used to treat fungal infections of the body and skin, • Inhibition of p450 decrease synthesis of
including athlete's foot, onychomycosis (fungal nail infections), steroids including cortisol & testosterone
ringworm, and vaginal candidiasis. ultimately decreasing libido,
• Only fluconazole penetrates into the CSF and can be used in gynecomastia & irregular menstruation.
meningeal infection • GI Upset
• Shorten QT intervals
• Hallucinations
• Transient vision disturbances
Terbinafine • Treating athlete's foot, jock itch and pityriasis versicolor. • GI upset
• Headache
DDRUGS CLINICAL USES SIDE EFFECTS
Echinocandins Echinocandins are widely used for • Infusion reactions
the treatment of invasive candidiasis, • May elevate liver enzymes
especially in critically ill and
neutropenic patients
DNA & RNA synthesis inhibitors It is often used with other • Bone marrow suppression
medications i.e. Amphotericin B • Liver toxicity
• GI upset
Mitosis inhibitors Dermatophytosis • Hypersensitivity reactions
• Hepatic toxicity
• Neurological effects
• May reduce efficacy of oral
contraceptives
ANTIFUNGAL RESISTANCE

Increased efflux of the drug from the fungal cell

Modifications to the sterol biosynthesis pathway caused by

point mutations and promoter insertions
THANKS