Wk 2 - Pharmacology: Antifungal Drugs Flashcards
List the different types of fungi that cause fungal infections in humans.
- True yeast – single-celled eukaryotic organisms e.g. Cryptococcus
- Yeast like fungi – non-branching filaments e.g. Candida albicans
- Filamentous fungi – branching filaments (mycelium) e.g. Aspergillus, dermatophytes (ringworm)
Fungal infections are generally superficial and affect ____ and ____.
Fungal infections are generally superficial and affect skin and mucous membranes.
Among immunocompromised individuals, fungal infections present after _____ as _____ infections.
Among immunocompromised individuals, fungal infections present after broad-spectrum antibiotic as opportunistic infections.
What are the main types of antifungal drugs?
- Polyenes
- Imidazoles / Triazoles
- Others: Flucytosine, Griseofulvin, Terbinafine
Avoidance and good hygiene are a component of…
effective treatment of fungal infections
What are the mechanisms of action of antifungal drugs? List three.
- Cell wall synthesis inhibitors
- Nucleic acid synthesis inhibitors
- Mitotic spindle
Give examples of antifungal drugs that inhibit cell wall synthesis.
- Polyenes
- Imidazole
- Triazoles
- Terbinafine
Give an example of an antifungal drug that inhibits nucleic acid synthesis.
Flucytosine
Give an example of an antifungal drug that acts in the mitotic spindle.
Griseofulvin
Most antifungal drugs act as…
cell wall synthesis inhibitors
Describe how a fungus makes its cell wall.
- Squalene (part of cholesterol formation)
- Converted into lanosterol (becomes cholesterol) - via squalene epoxidase
- In fungi, also made into ergosterol (via lanosterol demethylase)
- Ergosterol is incorporated into cell wall of fungi
How do polyenes antifungals work?
- Bind to ergosterol (which makes up fungi cell wall) and compete with it
- They cause pore generation in fungi membrane
- Which prevents fungi’s ability in maintaining its environment (loss of K ions mainly)
- Leading to its death eventually
List some side effects of antifungal polyenes.
Side effects:
- Few because most are used topically
- Some cause GI upset internally if need to taken orally and also nephrotoxicity
Give examples of polyene antifungals.
- Amphotericin – IV used for systemic fungal infection, most fungi and yeasts – C.albicans
- Nystatin – C.albicans infection of skin and mucous membranes, oesophageal and intestinal candidiasis
What are imidazoles?
Antifungal drugs that inhibit cell wall synthesis
How do imidazoles work?
- Block lanosterol demethylase
- Removing ergosterol completely
- Lead to growth arrest
- Fluidity of cell wall increases, cell permeability increases
What is one side effect of blocking lanosterol demethylase?
Enzyme (lanosterol 14a-demethylase) is P450 like, Ketoconazole (antifungal) can also block adrenal gland hormone and steroid formation
What is imidazole used to to treat?
Local treatment of vaginal candidiasis, dermatophyte infections
List the three different imidazoles used as antifungals.
- Clotrimazole
- Miconazole
- Ketoconazole
Clotrimazole (antifungal imidazole) is used to treat…
- Vaginal candidiasis
- Ring worm
Miconazole (antifungal imidazole) is used…
- Locally to treat oral infections
- For intestinal infections (possible drug interactions)
Ketoconazole (antifungal imidazole) is used to treat…
- Systemic mycoses
- Vulval candiasis
Ketoconazole has the best ____ (oral/buccal) absorption.
Ketoconazole has the best oral absorption.
What are triazoles?
Antifungal drugs that inhibit cell wall synthesis via inhibiting lanosterol demethylase from concerting lanosterol to ergosterol (ergosterol is what makes up fungal cell wall)
Give three examples of triazoles (antifungal cell wall inhibitors).
- Fluconazole
- Itraconazole
- Voriconazole
Fluconazole (triazole antifungal) is used for…
- Candida
- Cryptococcus
Fluconazole (triazole antifungal) has the ability to penetrate the…
Cerebrospinal fluid
Itraconazole (triazole antifungal) is used for…
- Mucocutaneous candidiasis
- Dermatophytes
Voriconazole (triazole antifungal) is used for…
Life-threatening aspergillosis
What drug is used for life-threatening aspergillosis?
Voriconazole
Itraconazole is contraindicated in…
individuals who take calcium channel blockers (due to increased negative ionotropic effect).
What is terbinafine?
Antifungal cell wall synthesis inhibitor
What is the mechanism of action of terbinafine?
- Blocks squalene epoxidase
- Stops formation of lansosterol from squalene
- Leads to membrane disruptions and death
Terbinafine is used in treatment of…
dermatophyte (ringworm) of the nail
What is flucytosine?
Antifungal drug
How does flucytosine work?
Penetrates the fungal cell wall and is converted to 5-fluorouracil which competes with uracil, thus interfering with fungal RNA and protein synthesis.
Generally, flucytosine is only used in combination with…
Only used in combination with amphotericin (polyene) or fluconazole (triazole)
What is griseofulvin?
Antifungal that acts on the mitotic spindle
What is griseofulvin’s mechanism of action?
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.
What is griseofulvin used to treat?
Mainly prescribed for infections occurring on the skin or scalp
What are the three antifungals that are most used?
- Amphotericin (polyene)
- Itraconazole (Triazole)
- Fluconazole (Triazole)
Name an OTC antifungal.
Clotrimazole (imidazole)
What is the site of action of most antifungal drugs?
Cell wall synthesis inhibitors
Triazole blocks the formation of what cell component?
Ergosterol via lanosterol demethylase inhibition
Griseofulvin is used against which infection?
Dermatophytes - ringworms
