Med2042 Week 10 - Pharmacology (Antifungal Drugs)

Front 1

What are some common superficial fungal infections?

Back 1

Oral thrush (Candida) in babies
Candidal nappy rash in babies
vaginal thrush (Candida)
Athelete's foot (tinea pedis)
Other fungal skin infections
Onychomycosis (fungal infection of nails, often involving the big toe nail)

Front 2

Predisposing factors for fungal infections.

Back 2

- Broad spectrum antibiotics that kill off protective bacteria that normally compete with fungi
- Diabetes
- Immunodeficiency (e.g. due to HIV/AIDS, immunosuppressant or anticancer drugs)
- Moisture and warmth (fungal infections can be more prevalent in the tropis)

Front 3

What are some examples of fungal infetions

Back 3

Serious systemic infections (i.e. affecting deep tissues and organs) e.g.
- Systemic candidiasis
- Cryptococcal meningitis or endocarditis
- Pulmonary aspergillosis

Superficial, affecting skin, nails and mocous membranes:
- dermatomycoses (cauase various types of 'ringworm' or tinea, e.g. tinea pedis (foot), tinea cruris (groin), tinea capitis (scalp), tinea corporis (body)
- Candidal infections e.g. oral, vaginal, nappy area

Front 4

Amphotericin

Back 4

- Polyene with complex ring structure
- Binds to fungal cell membranes (which contain ergosterol rather than cholesterol
- Creates a membrane pore
- Get loss of intracellular K+
- not absorbed orally
- Lozenges used for oral thrust
- Intravenous use for systemic fungal infections
- Renal toxicity and other serious effects (i.v)

Front 5

Nystatin

Back 5

- Polyene, similar in structure and mechanism of action to amphotericin
- No absorption orally
- Only used topically e.g. for infections fo skin, vagina, mouth, gastrointestinal tract

Front 6

Griseofulvin

Back 6

- Narrow spectrum antifungal isolated from cultures of Penicillium griseofulvum
- Fungistatic - interacts with microtubules and prevents mitosis
- Used orally to treat nail infections (usually need to give for several months)
- induces liver enzymes an dinteracts with other drugs including alcohol
- can cause gastrointestinal upset, headache and photosensitivity rashs

Front 7

Azoles

Back 7

- synthetic compounds with broad antifungal spectrum
- Interfere with formation of fungal cell membranes by inhibiting ergosterol synthesis
- Ketoconazole, fluconazole, and itraconazole can all be given orally
- Clotrimazole ("canesten") and econazole are only used for topical application e.g. to skin

Front 8

Orally active azoles

Back 8

e.g. ketoconazole, fluconazole, itraconazole

- can cause liver toxicity (particularly ketoconazole)
- may get hepatic drug interactions
- fluconazole penetrates well into brain
- can be used for treatment of chronic mucocutaneous candidiasis and other ufngal infections

Front 9

Flucytosine

Back 9

- synthetic, orally active, mainly against yeasts
- In fungal (but not human) cells it is converted to the antimetabolite 5-fluorouracil (5-FU) that inhibits htymidylate synthetase & DNA synthesis
- Adverse effects uncommon
- often combined with amphotericin to reduce emergence of resistant fungal strains

Front 10

Terbinafine ("Lamisil")

Back 10

- lipophilic, keratinophilic fungicidal
- Inhibits synthesis of ergosterol from squalene and therefore affects the fungal cell membrane
- often used orally to treat fungal infections of the nails (need prolonged treament)
- also used topically
- adverse effects usually mild, including gastrointestinal upset, rashes, headache

Front 11

Amorolfine

Back 11

- interferes with fungal sterol synthesis
- used in lacquer to paint on nails to treat onychomycoses (fungal nail infections)