Medicine for acne: Tretinoin

Tretinoin
Tretinoin (Retin-A), also known as retinoic acid, is the agent of choice for noninflammatory acne consisting of open and closed comedones. It is available in various preparations: Retin-A solution (0.05%) is the strongest and most irritating. Retin-A gel (0.025% and 0.01%) is drying and is for oily skin. Retin-A cream (0.1%, 0.05%, and 0.025%) is lubricating and is for dry skin

Mechanism of action
Tretinoin, an oxidation product of vitamin A, initiates increased cell turnover in both normal follicles and comedones and reduces the cohesion between keratinized cells. It acts specifically on microcomedones (the precursor lesion of all forms of acne), causing fragmentation and expulsion of the microplug, expulsion of comedones, and conversion of closed comedones to open comedones. New comedone formation is prevented by continued use. Inflammation may occur during this process, temporarily making acne worse. Continual topical application leads to thinning of the stratum corneum, making the skin more susceptible to sunburn; sun damage; and irritation from wind, cold, or dryness. Irritants such as astringents, alcohol, and acne soaps will not be tolerated as they were previously. The incidence of contact allergy is very low. Because of the direct action of tretinoin on the microcomedone, many clinicians believe tretinoin is appropriate for all forms of acne

Combination therapy: synergism
Tretinoin enhances the penetration of other topical agents such as topical antibiotics and benzoyl peroxide. The enhanced penetration results in a synergistic effect with greater overall drug efficacy and a faster response to treatment

Application techniques
The skin should be washed gently with a mild soap (e.g., Purpose, Basis) no more than two to three times each day, using the hands rather than a washcloth. Special acne or abrasive soaps should be avoided. To minimize possible irritation, the skin should be allowed to dry completely by waiting 20 to 30 minutes before applying tretinoin. Tretinoin is applied in a thin layer once daily. Medication is applied to the entire area, not just to individual lesions. An amount the size of a pea is enough for a full facial application. Patients with sensitive skin or those living in cold, dry climates may start with an application every other or every third day. The frequency of application can be gradually increased to as often as twice each day if tolerated. The corners of the nose, the mouth, and the eyes should be avoided; these areas are the most sensitive and the most easily irritated. Tretinoin is applied to the chin less frequently during the initial stages of therapy; the chin is sensitive and is usually the first area to become red and scaly. Sunscreens should be worn during the summer months if exposure is anticipated.

Response to treatment

One to four weeks
During the first few weeks, patients may experience redness, burning, or peeling. Those with excessive irritation should use less frequent applications (i.e., every other or every third day.) Most patients adapt to treatment within 4 weeks and return to daily applications. Those tolerating daily applications may be advanced to a higher dosage or to the more potent solution.

Three to six weeks
New papules and pustules may appear because comedones become irritated during the process of being dislodged. Patients unaware of this phenomenon may discontinue treatment. Some patients never get worse and sometimes begin to improve dramatically by the fifth or sixth week

After six weeks
Most patients improve by the ninth to twelfth week and exhibit continuous improvement thereafter. Some patients never adapt to tretinoin and experience continuous irritation or continue to worsen. An alternate treatment should be selected if adaptation has not occurred by 6 to 8 weeks. Some patients adapt but never improve. Tretinoin may be continued for months to prevent appearance of new lesions

Medicine for acne: Oral antibiotics: Minocycline

Minocycline.
Minocycline (50-mg and 100-mg capsules and scored tablets) is a tetracycline derivative that has proved valuable in cases of pustular acne that have not responded to conventional oral antibiotic therapy. Minocycline is very expensive; generic forms are now available. One study comparing minocycline (50 mg three times a day) with tetracycline (250 mg four times a day) revealed that minocycline resulted in significant improvement in patients who did not respond to tetracycline. Patients who responded to tetracycline had significantly advanced improvement when switched to minocycline. The inhibitory effect on gastrointestinal absorption with food and milk is significantly greater for tetracycline than for minocycline. Food causes a 13% inhibition of absorption with minocycline and a 46% inhibition with tetracycline, milk a 27% inhibition with minocycline and a 65% inhibition with tetracycline. The simpler regime and early onset of clinical improvement are likely to result in better patient compliance. There is therefore justification for the use of minocycline as first-line oral therapy.
DOSING.
The usual initial dosage is 50 to 100 mg twice each day. The dosage is tapered when a significant decrease in the number of lesions is observed, usually in 3 to 6 weeks.
ADVERSE EFFECTS.
Minocycline is highly lipid-soluble and readily penetrates the cerebrospinal fluid, causing dose-related ataxia, vertigo, nausea, and vomiting in some patients. In susceptible individuals, central nervous system (CNS) side effects occur with the first few doses of medication. If CNS adverse reactions persist after the dosage is decreased or after the capsules are taken with food, alternative therapy is indicated. A blue-gray pigmentation of the skin, oral mucosa, nails, and thyroid gland has been found in some patients, usually those taking high dosages of minocycline for extended periods. Skin pigmentation has been reported in depressed acne scars, at sites of cutaneous inflammation, as macules resembling bruises on the lower legs, and as a generalized discoloration suggesting an off-color suntan. Pigmentation may persist for long periods after minocycline has been discontinued. The consequences of these deposits are unknown. Tooth staining (lasting for years) located on the incisal one half to three fourths of the crown has been reported in adults, usually after years of minocycline therapy. In contrast, tooth staining produced by tetracycline occurs on the gingival third of the teeth in children treated before age 7.

Medicine for acne: Oral antibiotics: Tetracycline

Tetracycline.
Tetracycline is the most widely prescribed oral antibiotic for acne. One major disadvantage is the requirement that tetracycline not be taken with food (particularly dairy products), certain antacids, and iron, all of which interfere with the intestinal absorption of the drug. Failure to adhere to these restrictions accounts for many of the reported therapeutic failures of tetracycline.
DOSING.
Efficacy and compliance are obtained by starting tetracycline administration at 500 mg twice each day and continuing this dosage until a significant decrease in the number of inflamed lesions occurs, usually in 3 to 6 weeks. Thereafter the dosage may be decreased to 250 mg twice each day or oral therapy may be discontinued in favor of topical antibiotics. Patients with severe pustular and cystic acne or those who do not respond to 1 gm/day might respond to a higher dosage of tetracycline (1.5 to 3.0 gm/day). These higher dosages may not be tolerated by some patients. Patients who do not respond after 6 weeks of adequate dosages of oral tetracycline should be introduced to an alternative treatment. For unknown reasons a significant number of patients who take tetracycline exactly as directed do not respond to high dosages, whereas others respond very favorably to 250 mg once a day or once every other day and flare when attempts are made to discontinue treatment.
ADVERSE EFFECTS.
The incidence of photosensitivity to tetracycline is low, but it increases when higher dosages are used. All females should be warned about the increased incidence of Candida albicans vaginitis that occurs while taking antibiotics. The package labeling of oral contraceptives warns that reduced efficacy and increased incidence of breakthrough bleeding may occur with tetracycline and other antibiotics. Although this association has not been proven, it is prudent to inform patients of this potential risk. Pseudotumor cerebri, a self-limited disorder in which the regulation of intracranial pressure is impaired, is a rare complication of tetracycline treatment. Increased intracranial pressure causes papilledema and severe headaches. Increased intraocular pressure can lead to progressive visual impairment and eventually blindness.

Medicine for acne : Benzoyl peroxide

Benzoyl peroxide

The primary effect of benzoyl peroxide is antibacterial, therefore it is most effective for inflammatory acne consisting of papules, pustules, and cysts, although many patients with comedone acne respond to it. Benzoyl peroxide is less effective than vitamin A acid at disrupting the microcomedo. Benzoyl peroxide and isotretinoin significantly reduce noninflamed lesions in 4 weeks. In one study, benzoyl peroxide had a more rapid effect on inflamed lesions with significant reductions at 4 weeks, whereas the use of isotretinoin showed a significant improvement at 12 weeks.

Preparations.

Benzoyl peroxide is available over the counter and by prescription. Some examples of benzoyl peroxide preparations are water-based gel (Benzac AC 2.5%, 5%, and 10%), alcohol-based gel (Benzagel 5% and 10%), and acetone-based gel (Persa-gel 5% and 10%) (see the Formulary). Water-based gels are less irritating, but alcohol-based gels, if tolerated, might be more effective. Benzoyl peroxide is also available in a soap base in strengths from 2.5% to 10%.

Mechanism of action.

Benzoyl peroxide produces a drying effect that varies from mild desquamation to scaliness, peeling, and cracking. Patients should be reassured that drying does not cause wrinkles. It causes a significant reduction in the concentration of free fatty acids via its antibacterial effect on P. acnes. This activity is presumably caused by the release of free radical oxygen, which is capable of oxidizing bacterial proteins. Benzoyl peroxide seems to reduce the size of the sebaceous gland, but whether sebum secretion is suppressed is still unknown. Patients should be warned that benzoyl peroxide is a bleaching agent that can ruin clothing.

Principles of treatment.

Benzoyl peroxide should be applied in a thin layer to the entire affected area. Most patients experience mild erythema and scaling during the first few days of treatment, even with the lowest concentrations, but adapt in a week or two. It was previously held that vigorous peeling was necessary for maximum therapeutic effect; although many patients improved with this technique, others became worse. Recent studies show that an adequate therapeutic result can be obtained by starting with daily applications of the 2.5% or 5% gel and gradually increasing or decreasing the frequency of applications and strength until mild dryness and peeling occur.

Allergic reaction.

Approximately 2% of patients develop allergic contact dermatitis to benzoyl peroxide and must discontinue its use. The sudden appearance of diffuse erythema and vesiculation suggests contact allergy to benzoyl peroxide.

Medicine for acne : Corticosteroids

Corticosteroids.
Corticosteroids can be considered in recalcitrant cases of acne not responsive to oral contraceptives or spironolactone and for patients with elevated DHEAS. Corticosteroids can be used alone or in combination with oral contraceptives and antiandrogens. Elevated DHEAS indicates adrenal androgen overproduction. Either dexamethasone (0.125 to 0.5 mg at bedtime) or prednisone (2.5 to 7.5 mg at bedtime and 2.5 mg on waking) is prescribed. Low-dose steroids administered at bedtime prevent the pituitary from producing extra ACTH and thereby reduce the production of adrenal androgens. Dexamethasone may be the more rational choice for adrenal suppression with its longer duration of action. The drug is given at bedtime so that effective levels will be present during the early morning hours when ACTH secretion is most active. Initial dosage should be dexamethasone 0.25 mg or prednisone 2.5 mg, and the dosage should be increased to dexamethasone 0.5 mg or prednisone 5.0 to 7.5 mg if the DHEAS level has not been lowered after 3 to 4 weeks of treatment. Therapy is continued for 6 to 12 months, but the benefits may persist beyond that. This low dosage produces a clinical improvement and suppresses DHEAS levels. At these dosages, few patients experience shutdown of the adrenal-pituitary axis or other adverse effects of the drug. ACTH stimulation tests or early morning cortisol levels may be performed every few months to make sure that there is no adrenal suppression. Not all patients respond.