Cass 23 Pornpan Suksawadnumchok sec. c Phramacology A

Case Giovanni, 23 y/o, male single, came in to the skin clinic because of itchy lesion in both of the inguinal areas. Lesions are wet, irregular, locatized with some rounded erythematous rashes. No other s/s were noted. Laboratory exam done were negative except for fungal testing. Final diagnosis: Tinea Cruris.

Tinea Cruris Occure most frequently in the inguinal areas of obese men during warm weather. Heat, friction and maceration all predispose to its developement. The infection usually first appears on the upper inner thigh, with gradual extension of moist, red patches that have raised, scaling borders.

Tinea cruris.

Tinea cruris (hematoxylin and eosin stain). Tinea cruris (periodic acid-Schiff stain, magnification X 20).

1. Give at least 3 topical antifungal agent

The 2 classes of antifungal medications used most commonly to treat tinea cruris are the azoles and the allylamines. Topical azoles Clotrimazole (Lotrimin, Mycelex) Miconazole (Micatin, Monistat-Derm) Topical allylamines Terbinafine (Lamisil) Naftifine (Naftin) Topical antifungal agent

2. Explain the mechanism of action of each drug

2.1 Mechanism of action of topical azoles Azoles inhibit the enzyme lanosterol 14-alpha- demethylase, an enzyme that converts lanosterol to ergosterol, which is an important component of the fungal cell wall. Membrane damage results in permeability problems and renders the fungus unable to reproduce. Examples - Clotrimazole (Lotrimin, Mycelex) - Miconazole (Micatin, Monistat-Derm)

Clotrimazole Clotrimazole (Lotrimin, Mycelex) -- Often, first-line drug used in the treatment of tinea cruris. Broad-spectrum antifungal agent that inhibits yeast growth by altering cell membrane permeability, causing death of fungal cells. Reevaluate diagnosis if no clinical improvement after 4 wk. Available without a prescription. 1% cream, solution/spray, and lotion available. Not for treatment of systemic fungal infections; avoid contact with the eyes; if irritation or sensitivity develops, discontinue use and institute appropriate therapy

Adult Dose: Gently massage into affected area and surrounding skin areas bid for 4 wk Pediatric Dose: Administer as in adults Contraindications: Documented hypersensitivity Interactions: None reported Clotrimazole (cont.)

Miconazole Miconazole (Micatin, Monistat-Derm) -- Damages fungal cell wall membrane by inhibiting biosynthesis of ergosterol. Membrane permeability is increased causing nutrients to leak, resulting in fungal cell death. Available without a prescription. 2% cream, solution/spray, lotion, and powder forms available. Lotion is preferred in intertriginous areas. If cream is used, apply sparingly to avoid maceration effects.

Adult Dose: Cream and lotion: Cover affected areas bid for 4 wk Powder: Spray or sprinkle liberally over affected area bid for 4 wk Pediatric Dose: Administer as in adults Contraindications: Documented hypersensitivity Interactions: None reported Pregnancy: Safety for use during pregnancy has not been established. Precautions: Discontinue if sensitivity or chemical irritation occurs; for external use only; avoid contact with eyes Miconazole (cont.)

2.2 Mechanism of action of topical Allylamines Allylamines inhibit squalene epoxidase, which is an enzyme that converts squalene to ergosterol, resulting in the accumulation of toxic levels of squalene in the cell and in cell death. Examples - Terbinafine (Lamisil) - Naftifine (Naftin)

Terbinafine Terbinafine (Lamisil) -- Synthetic allylamine derivative, which inhibits squalene epoxidase, a key enzyme in sterol biosynthesis in fungi that results in a deficiency of ergosterol, causing fungal cell death. Widely studied and effective topical or oral antifungal.Topical form available without prescription. Some clinicians reserve this drug for more widespread/resistant infections because of its broad coverage and increased cost. Studies have found this medication to be effective and well tolerated in children.

Adult Dose: Topical: Apply to affected area qd for 1-4 wk Oral: 250 mg/d for 2 wk Pediatric Dose Topical: Administer as in adults Oral treatment based on body weight: kg: 62.5 mg/d for 6-12 wk kg: 125 mg/d for 6-12 wk >40 kg: 250 mg/d for 6-12 wk as in adults Contraindications: Documented hypersensitivity Interactions: When administered concurrently with cyclosporine, oral administration of terbinafine may increase cyclosporine clearance; conversely, rifampin may decrease terbinafine clearance; cimetidine may decrease terbinafine clearance Terbinafine(cont.)

Pregnancy: Safety for use during pregnancy has not been established. Precautions: Discontinue if symptoms or signs of hepatobiliary dysfunction or cholestatic hepatitis develop or if chemical irritation occurs; topical dosage form is for external use only; avoid contact with eyes Terbinafine(cont.)

Naftifine Naftifine (Naftin) -- Broad-spectrum antifungal agent and synthetic allylamine derivative; may decrease the synthesis of ergosterol, which in turn inhibits fungal cell growth Available in 1% cream or solution. If no clinical improvement after 4 wk, reevaluate patient.

Adult Dose: Cream/gel: Gently massage sparingly into affected area and surrounding skin for 2-4 wk Pediatric Dose : Administer as in adults Contraindications: Documented hypersensitivity Interactions: None reported Pregnancy: Usually safe but benefits must outweigh the risks. Precautions: Pediatric Dose Discontinue use if sensitivity or chemical irritation occurs; for external use only; avoid contact with eyes Naftifine (cont.)

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