Drugs For Alopecia

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Alopecia Pathophys

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An autoimmune disease; associated with other autoimmune diseases (e.g., Hashimoto's thyroiditis, vitiligo, myasthenia gravis)

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Alopecia Drug Therapy

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Treatment is directed at inflammation and growth inhibitor factors produced by inflammation. Drug treatment is not curative. Cyclosporine and glucocorticoids can induce regrowth of hair but alopecia areata recurs upon discontinuation of the drugs.

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Cyclosporine-- Admin/ Mechanism of action (mentioned before)

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Oral admin (capsules and solution)
Cyclosporine crosses the plasma membrane and binds to the cytoplasmic immunophilin cyclophilin (right side of figure). The cyclosporine-cyclophilin complex binds to calcineurin, preventing the activation of calcineurin phosphatase activity by Ca2+/calmodulin. This suppresses IL-2 production and T cell proliferation.

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Cyclosporine--Adverse Effects

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i. Hypertension (monitor BP)
ii. Renal dysfunction (monitor serum creatinine)
iii. Increased risk of cutaneous, solid organ, and lymphoproliferative malignancies

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Glucocorticoids--Mechanism

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i. The glucocorticoid receptor resides in the cytoplasm in an inactive form
ii. Glucocorticoid binding results in receptor activation and translocation to the nucleus.
iii. In the nucleus, the activated complex interacts with glucocorticoid response elements of affected genes to alter transcription and hence protein synthesis.
iv. Changes in gene activity result in antiinflammatory and immunosuppressive effects of glucocorticoids

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Glucocorticoid--Admin

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i. Topically: Super high potency agents (e.g., clobetasol) may be effective.
ii. Intralesional Injections of triamcinolone can be used if there are few or small spots of alopecia areata
iii. Systemic glucocorticoids can induce regrowth, but alopecia areata recurs on discontinuation. Moreover, there are serious adverse effects associated with long-term use of glucocorticoids

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Glucocorticoids--Adverse Effects

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i. Localized side effects including epidermal and dermal atrophy, telangiectasia, fine hair growth, bruising, hypopigmentation, striae, and acne
ii. Systemic side effects include adrenal suppression

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Androgenetic alopecia-- Relevant pathophysiology

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1. Androgenetic alopecia, commonly known as male and female pattern baldness, is the most common cause of hair loss in adults older than age 40.
2. It is a genetically inherited trait with variable expression
3. In susceptible hair follicles, testosterone is converted to dihydrotestosterone by type II 5α-reductase. Dihydrotestosterone binds to the androgen receptor, and the hormone-receptor complex activates the genes responsible for the gradual transformation of large terminal follicles into miniaturized vellus follicles.
4. Treatment of androgenetic alopecia is aimed at reducing hair loss and maintaining existing hair.

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Finasteride--Mech

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The drug inhibits type II 5α-reductase

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Finasteride--Admin

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i. Orally administered finasteride increases hair growth in men over a 2-year period.
ii. It is approved for use only in men.
iii. Treatment with finasteride must be continued or any new hair growth
will be lost.

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Finasteride--Adverse Effects

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i. Decreased libido, erectile dysfunction, ejaculation disorder, and decreased ejaculate volume.
ii. Pregnant women should not be exposed to the drug because of the potential for inducing genital abnormalities in male fetuses.

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Minoxidil--Mechanism of action

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i. Minoxidil was first developed as an antihypertensive agent and was noted to be associated with hypertrichosis in some patients.
ii. A topical formulation of minoxidil then was developed to exploit this side effect.
iii. Minoxidil enhances follicular size, resulting in thicker hair shafts, and stimulates and prolongs the anagen phase of the hair cycle, resulting in longer and increased numbers of hairs.

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Minoxidil--Admin

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i. Topically
ii. Treatment must be continued, or any drug-induced hair growth will be lost.

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Minoxidil--Adverse effects

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i. Allergic and irritant contact dermatitis can occur
ii. Hair growth in undesirable locations
(a) This is reversible on stopping the drug.
(b) Patients should wash their hands after applying minoxidil