Bangabandhu Sheikh Mujibur Rahman Science & Technology University, Gopalganj-8100

Department Of Pharmacy
Course Tittle: Pharmacology-2
Course Code: PHR 263
An Assignment On Antifungal Agents

Submitted By Submitted To
Students ID: 19PHR050, 19PHR051, 19PHR052, 19PHR053, Md. Solayman Hossain
19PHR054, 19PHR055, 19PHR056, 18PHR005, 18PHR017, Assistant Professor
18PHR021, 18PHR025, 18PHR026 Department of Pharmacy,
Year: 2nd Bangabandhu Sheikh Mujibur Rahman Science & Technology
Semester: 2nd University
Session: 2019-2020
Department of Pharmacy,
Bangabandhu Sheikh Mujibur Rahman Science & Technology
University

Submission Date: 25-06-2023

 Antifungal Agents

Definition: Antifungal agents are medications used to treat fungal infections. Fungal infections can affect
various parts of the body, including the skin, nails, mouth, throat, and internal organs. Antifungal agents work
by either killing the fungi or inhibiting their growth, thus helping to eliminate the infection.

Classifications: The major antifungal agents can be classified in five groups

Antifungal Agents

Azoles Polyenes Allylamine Echinocandins Others

• Itraconazole • Amphotericin B • Terbinafine • Caspofungin • Griseofulvin
• Fluconazole • Micafungin • Flucytosine
• Ketoconazole
• Voriconazole
 Azoles
Azoles are widely used antifungal agents. They act by inhibiting 14α-demethylase enzyme. Some common
azoles antifungal drugs are Itraconazole, fluconazole, ketoconazole, voriconazole.

Mechanism of action:
Azoles

Inhibits 14α-demethylase enzyme

Blocks the conversion of lanosterol to ergosterol

Inhibits production of ergosterol

Disruption of the fungal cell membrane

Some common azoles are Itraconazole, Fluconazole, Ketoconazole, Voriconazole.

Itraconazole

Therapeutic uses:
• Fungal infections
• Tinea cruris
• Tinea pedia
• Candidiasis

Adverse effects:
• Nausea
• Vomiting
• Headache
• Dizziness
• Impotence Skeletal formula of itraconazole
 Fluconazole

Fluconazole is also a common antifungal agent. It is used to treat many fungal infections.

Therapeutic uses:
• Vaginal candidiasis
• Oropharyngeal candidiasis
• Esopharyngeal candidiasis

Adverse effects:
• Dizziness
• Hair loss
• Wight loss
• Allergic reaction
Skeletal formula of fluconazole 
 Ketoconazole

Ketoconazole is a azole derivative and it is used to treat fungal infections.

Therapeutic uses:
• Candidiasis
• Pityriasis
• Seborrheic dermatitis

Adverse effects:
• Alopecia
• Headache
• Dizziness
• Fever Chemical structure of Ketoconazole 
 Polyenes

The polyene compounds are so named because of the alternating conjugated double bonds that constitute a
part of their macrolide ring structure. The polyene antibiotics are all products of Streptomyces species. These
drugs interact with sterols in cell membranes (ergosterol in fungal cells; cholesterol in human cells) to form
channels through the membrane, causing the cells to become leaky.

Mechanism of action:
Polyenes

Binds ergosterol in fungal cell membrane

Form pores in cell membrane

Cell contents leak out

Cell death
The polyene antifungal agents include nystatin, amphotericin B, and pimaricin.

Nystatin

Nystatin was the first successful antifungal antibiotic to be developed, and it is still in general use.

Therapeutic Uses:
• ‌Superficial mycotic infections of the eye.
• ‌Fungal infection.
• ‌Candidiasis.
• ‌Fungal infections of the inside of the mouth
& lining of the stomach and intestines.

Adverse effects:
• ‌Diarrhea.
• ‌Feeling or being sick.
• ‌Nausea. Chemical structure of Nystatin
• ‌Vomiting.
• ‌Impotence.
 Amphotericin B

Amphotericin B is an antifungal medication that is primarily used to treat severe systemic fungal
infections. It is considered a broad-spectrum antifungal agent and is particularly effective against invasive
fungal infections caused by species such as Candida and Aspergillus.
 

Therapeutic Uses:
• Systemic Fungal Infections
• Leishmaniasis

Adverse Effects:
• Nephrotoxicity
• Infusion-Related Reactions
• Electrolyte Imbalances
• Anemia
• Hepatotoxicity Chemical structure of Amphotericin B
 Allylamines

Allylamines are also an antifungal agent commonly used to treat many fungal infections. They act by
inhibiting squalene epoxidase.

Mechanism of action:
Allylamines

Inhibition of squalene epoxidase

Accumulation of squalene

Inhibition of ergosterol synthesis

Disruption of fungal cell membrane

 Terbinafine

A commonly used Allylamine drug is Terbinafine. It is used to treat many fungal infections.

Medicinal Uses:
• Tinea pedis
• Tinea cruris
• Dermatophytosis
• Nail infections

Adverse effects:

• Headache
• Rash
• Nausea Skeletal formula of terbinafine (original brand
• Diarrhoea name Lamisil) - an antifungal drug.
 Echinocandins
Echinocandins are a novel class of antifungal drugs that act by a unique and completely fungal-specific
mechanism-inhibition of the synthesis of β-1,3-D-glucan, an essential component of the fungal cell wall.

Mechanism of action:
Echinocandins

Inhibit synthesis of beta-(1,3)-D-glucan

Inhibits synthesis of essential cellular components

Disruption of cell wall

Fungicidal effect
Some common Echinocandins are caspofungin and micafungin. These two are commonly used antifungal
agents to treat fungal infections.

Caspofungin
Therapeutic uses:
• Febrile neutropenia
• Candida infections
• Invasive candidiasis
• Esophageal candidiasis
• Invasive aspergillosis

Adverse effects:
• Fever
• Phlebitis/thrombophlebitis
• Tachycardia
• Nausea, vomiting
• Rash
• Abdominal pain Skeletal formula of Caspofungin 
• Headache & Diarrhea
 Micafungin

Therapeutic uses:
To overcome serious fungus infections, such as-
• Candidemia.
• Acute disseminated candidiasis.
• Candida peritonitis and abscess
without meningoencephalitis or ocular dissemination.
• Esophageal candidiasis.

Adverse effects:
• Abdominal pain.
• Agitation.
• Allergic reactions like skin rash or itching.
• Hives. Skeletal formula of Micafungin
• Swelling of the lips, mouth, tongue or throat.
After all types of antifungal agents some drugs also use as antifungal agent. We enlist here 2 drugs in this
category.
• Griseofulvin
• Flucytosine
This two drugs also use as antifungal.

Griseofulvin

Griseofulvin is an antifungal agent used to treat a variety of superficial tinea infections and fungal
infections of the fingernails and toes.

The chemical Structure of Griseofulvin

Mechanism of action of Griseofulvin:
It is a fungistatic drug,  exact mechanism by which it inhibits the growth of dermatophytes. It is thought
to inhibit fungal cell mitosis and nuclear acid synthesis. It also binds to and interferes with the function
of spindle and cytoplasmic microtubules by binding to alpha and beta tubulin.

Griseofulvin
Binds to

Tubulins
Inhibiting

Miotic spinal formation

Resulting in

Inhibition of separation of daughter nuclei

Fungistatic effect
Therapeutic uses of Griseofulvin:

• Used to treat fungal infections of the skin, hair, and nails.

• Inhibiting the growth of fungi and preventing them from reproducing.
• Ringworm, athlete's foot, and fungal nail infections.
• Taken orally in the form of tablets or capsules.
• Griseofulvin may interact with other medications, so it is important to inform your healthcare
provider about any other drugs you are taking.

Adverse effect of  Griseofulvin:

• Gastrointestinal disturbances, such as nausea, vomiting, and diarrhea.

• Allergic reactions, including skin rash, itching, and hives.
• Headaches and dizziness.
• Photosensitivity, making the skin more sensitive to sunlight.
• Liver toxicity, which may manifest as jaundice, abdominal pain, and dark urine.
• Blood disorders, such as leukopenia (reduced white blood cell count) and thrombocytopenia
(reduced platelet count).
 Flucytosine

Flucytosine is an antifungal indicated only to treat severe infections throughout the body caused by
susceptible strains of Candida or Cryptococcus.

The chemical Structure of Flucytosine

Mechanism of action of Flucytosine:
Flucytosine has been proposed that flucytosine acts directly on fungal organisms by competitive inhibition
of purine and pyrimidine uptake and indirectly by intracellular metabolism to 5-fluorouracil. Flucytosine
enters the fungal cell via cytosine permease; thus, flucytosine is metabolized to 5-fluorouracil within fungal
organisms. The 5-fluorouracil is extensively incorporated into fungal RNA and inhibits synthesis of both DNA
and RNA. The result is unbalanced growth and death of the fungal organism. It also appears to be an
inhibitor of fungal thymidylate synthase.

Flucytosine
Converts

Converts to 5-fluorouracil
Interfere

Interfere with fungal DNA/RNA

Inhibit

Inhabit fungal cell growth

Fungicidal effect
Therapeutic uses of  Flucytosine:

• Used to treat certain types of fungal infections.

• Used in combination with other antifungal drugs for more effective treatment.
• Interfering with fungal DNA synthesis, preventing the growth and spread of the infection.
• Cryptococcal meningitis and severe systemic Candida infections.
• Administered orally or intravenously, depending on the severity of the infection.
• Used with caution in patients with renal impairment due to the risk of drug accumulation.

Adverse effect of  Flucytosine:

• Bone marrow suppression

• Gastrointestinal disturbances
• Hepatotoxicity:
• Renal toxicity
• Skin reactions
• Neurotoxicity
• Hematological disorders