Ketoconazole

nonsedating antihistamine, apparently lacks  the  QT  prolongation effect  and  no  drug  interactions  with  either

erythromycin or the antifungal agents listed have been established. Diphenhydramine, clemastine, and chlorpheniramine

are also free of these drug interactions. However, many antihistamines have some potential to cause tachycardia and

palpitations because of their antimuscarinic activity.

Ketoconazole [Ref. K.D.T. 6^th/c p 762, 760, 760]

Dermatophytoses

• Dermatophytes are a category of cutaneous fungal infections.
• The dermatophytic fungi live in the dead, horny layer of skin, hair and nails (cutaneous layers).
• These fungi secrete an enzyme called keratinase which digests keratin.
• Since keratin is the primary structural protein of skins, nail and hair the digestion of keratin manifests as scaling of the skin, loss of hair and crumbling of the pails.
• The common dermatophytes are Microsporum, Trichophyton, Epidermophyton.
• Candida is a fungal which causes both deep systemic infections and also cutaneous infections.

Antifungal spectrum of the drugs given in the option:-

Ketoconazole 6th/e p 762)

“It is the first orally effective broad-spectrum antifungal drug useful in both dennatophytosis and deep mycosis”

Griseofulvin (K.D.I 6^th/e p 760)

“Griseofulvin in active against most dermatophytes but not against candida and other _.fungi causing deep mycoses”

Nystatin (K.D.T. 6^th/e p 760)

“Nystatin is ineffective dermatophytosis. Because of higher systemic toxicity it is used only in superficial candidiases”

Tolnofate 61h/e p 766)

“It is a topical antifungal agent used only for dennatophytesis”

Griseofulvin has been approved by U.S. Food and Drug Administration for several dermatophyte infections.

However, because of its limited spectrum of coverage compared to other agents and the lengthy courses required,

Griseofulvin is not used as a first-line therapy for fungal infections other than tinea capitis.

Important microsomal enzyme inhibitors are:

• Valproate
• Ketoconazole
• Cimetidine
• Ciprofloxacin
• Erythromycin
• Isoniazid

Ans. is ‘a’ i.e., Ketoconazole

Ans. is ‘a’ i.e., Cardiac arrhythmia

• Terfenadine causes blockade of delayed rectifier K⁺ channels in the heart at higher concentration and can cause Torsades De Pointes (Polvmorph ventricular tachcardia) —> Prolonged QT interval.
• Drugs inhibiting the metabolism of terfenadine by inhibiting CYP3AY enzyme, can precipitate ventricular arrythmia Erythromycin, clarithromycin, itraconazole, ketoconazole.

Ans. is ‘a’ i.e., Ketoconazole

A i.e. Ketoconazole

– Pityriasis versicolor is superficial mycosis caused by mycelial phase of yeast Malassezia (furfur, globosa, sympodialis)Q. It presents with multiple, small, hypopigmented (usually or pink-salmon or hyperpigmented) scaly macules that develop insidiously over the trunk, chest, back and shoulders in young adultsQ. Macules start around the hair follicle and then merge with each other to form large areasQ. The characteristic scale is futfuraceous or dust like (fine, branny scaling)Q. Microscopic examination (in 10% KOH) show bananas and grapes (or spaghetti and meat balls) appearance and Wood’s lamp examination show apple (yellow) green fluoresce.

– Griseofulvin is used systemically for dermatophytosis (tinea infections) but it is ineffective topicallyQ and has no role in treatment of tinea versicolor and candidaQ.

Answer is A (Cisapride)

Co-administration of ketoconazole with cisapride is contraindicated secondary to an increased risk of cardiovascular adverse effects such as lorsades-de-pointes’, ventricular tachycardia or ventricular fibrillation’.

Drugs with High Risk of Generating Pharmakokinetic Interactions 

Ans. D: All of the above

Medical care for Cushing syndrome can be summarized as follows:

• Agents that inhibit steroidogenesis, such as mitotane, ketoconazole, metyrapone, aminoglutethimide, trilostane, and etomidate, have been used to cause medical adrenalectomy. These medications are used rarely and often are toxic at the doses required to reduce cortisol secretion. Efficacy of these medical interventions can be assessed with serial measurements of 24-hour urinary free cortisol.

–        Patients receiving these medications may require glucocorticoid replacement to avoid adrenal insufficiency.

–        Metyrapone and trilostane are agents that competitively inhibit a single steroidogenic enzyme. Ketoconazole and aminoglutethimide act at several sites.

• Because ACTH production may persist or increase in patients with Cushing disease, radiation therapy of the pituitary is often required after unsuccessful initial therapy, either surgical or medical. These agents have higher efficacy when used in combination because they may act synergistically.
• Ketoconazole is probably the most popular and effective of these agents for long-term use and usually is the agent of choice

Ans. is ‘b’ i.e., Ketoconazole

Ans. is ‘a’ i.e., Ketoconazole

Pityriasis versicolor (Tinea versicolor)

• Tinea versicolor is a misnomer as it is not caused by dermatophyte; Pityriasis versicolor is more appropriate term. It is caused by a nondermatophyte fungus called Pityrosporum ovale (Malasezia furfur). It usually affects young adults.

Clinical features

• There are multiple small scaly hypopigmented macules (macules may be hyperpigmented also). Scaling is furfuraceous or rice powder like. Macules start around the hair follicles and then merge with each other to form large areas. Affects trunk and shoulders (mainly chest and back). There may be loosening of scales with finger nails -4 Coupled onle or stroke of nail. Lesions are recurrent in nature (may reappear after treatment).

Diagnosis of P.versicolor

• Examination of scales in 10% KOH shows short hyphae and round spores (Sphagetti and meat ball appearance). Wood’s lamp shows apple green fluorescence (blue-green fluorescence). Skin surface biopsy —) A cyanoacrylate adhesive (crazy glue) is used to remove the layer of stratum corneum on glass slide and then stained with PAS reagent.

Treatment of P.versicolor

1. Systemic agents : – Systemic azoles provide a convenient therapeutic option. Drugs used are ketoconazole, Fluconazole or intraconazole.
2. Topical antifungals :- Topical antifungals used are : –

i.  Azoles —> Clotrimazole, econazole, Miconazole, Ketoconazole.

ii.  Others —> Selenium Sulfide, Sodium thiosulphate, whield’s ointment (3% salicylic acid + 6% Benzoic acid).