Pharmacology-4 PHL 425

Seventh Lecture

By

Abdelkader Ashour, Ph.D. Phone: 4677212 Email: aeashour@ksu.edu.sa

Anti-Acne Vulgaris Drugs

Acne Vulgaris (Acne), Overview & Pathogenesis

Acne is derived from the Greek word “Akme” which means the highest point Acne is the formation of comedones, papules, pustules, nodules, and/or cysts as a result of

obstruction and inflammation of pilosebaceous units (hair follicles and their accompanying sebaceous gland)

Acne Vulgaris (Acne), Overview & Pathogenesis Acne is derived from the Greek word “Akme” which means the highest point Acne is the formation of comedones, papules, pustules, nodules, and/or cysts as a result of

obstruction and inflammation of pilosebaceous units (hair follicles and their accompanying sebaceous gland)

closed comedo open comedo

sebaceous follicle Micro comedo

Acne, Pathogenesis

Manifestations differ depending on whether P. acnes stimulates inflammation in the follicle

Comedones are termed closed (whiteheads) or open (blackheads) depending on whether the follicle is closed or dilated at the skin surface

Noninflammatory acne is characterized by comedones; uninfected sebaceous plugs “a plug of keratin and sebum” impacted within follicles

Thus, acne can be inflammatory or noninflammatory, depending on whether P. acnes stimulates inflammation in the follicle or not

Acne occurs when pilosebaceous units become obstructed with plugs of sebum and desquamated keratinocytes, then sometimes infected with the normal skin anaerobe P. acnes

Acne, Pathogenesis

Inflammatory acne comprises papules, pustules, nodules and cysts

Papules appear when lipases from P. acnes metabolize triglycerides into free fatty acids (FFA), which irritate the follicular wall

Acne, Pathogenesis

Inflammatory acne comprises papules, pustules, nodules and cysts

Pustules occur when active P. acnes infection causes inflammation within the follicle

Pustule

Acne Vulgaris (Acne), Pathogenesis

Inflammatory acne comprises papules, pustules, nodules and cysts

Nodules and cysts occur when rupture of follicles due to inflammation, physical manipulation, or harsh scrubbing releases FFAs, bacteria and keratin into tissues, triggering soft-tissue inflammation

Acne, Epidemiology & Etiology Acne vulgaris is the most common of all cutaneous disorders and occurs in more

than 85% of adolescents. It is more severe in males than in females. Genetic background plays a role in the incidence of this disorder

Commonly involved areas are those with the highest concentration of sebaceous glands, that is the face, neck, chest, shoulders, and upper back.

The most common trigger is puberty, when surges in androgen stimulate sebum production and hyperproliferation of keratinocytes

Other triggers include hormonal changes that occur with pregnancy or throughout the menstrual cycle; occlusive cosmetics, cleansing agents, and clothing; and humidity and sweating

Acne may improve in summer months because of sunlight's anti-inflammatory effects

Drugs such as lithium, hydantoin, isoniazid, glucocorticoids, oral contraceptives, androgens (e.g., testosterone), iodides, bromides and danazol are contributory factors

Others: Emotional stress can definitely cause exacerbations Occlusion and pressure on the skin, such as by leaning face on hands, very important

and often unrecognized exacerbating factor (acne mechanica) Acne is not caused by chocolate or fatty foods or, in fact, by any kind of food

Type 1: Comedones only, fewer than 10 lesions on the face, no lesions on the trunk and no scarring

Type 2: Papules, 10 to 25 lesions on the face and trunk, mild scarring

Type 3: Pustules, more than 25 lesions, moderate scarring

Type 4: nodules or cysts, extensive scarring

Severity rating for acne

Management of Acne The withdrawal of aggravating factors such as cosmetics and drugs is paramount where

they appear to be involved in the etiology of acne. Trauma, such as picking and vigorously squeezing acne lesions, can aggravate the condition

Affected areas should be cleansed dailyExtra washing, use of antibacterial soaps, and scrubbing confer no added benefitChanges in diet are also unnecessary and ineffective

Treatments are directed at reducing sebum production, comedones formation, inflammation and infection

Mild and mild to moderate acne: Single-agent therapy is generally sufficient for comedonal acne (a mainstay of treatment for

comedones is daily topical tretinoin in escalating concentrations as tolerated). Azelaic acid has comedolytic and antibacterial properties and may be synergistic with retinoids

Papulopustular acne generally requires dual therapy (e.g., the combination of tretinoin with benzoyl peroxide or topical antibiotics)

Daily adapalene gel and tazarotene cream or gel are alternatives for patients who cannot tolerate topical tretinoin

Treatment should be continued for 6 wk or until lesions respond. Maintenance treatment may be necessary to maintain control

Mild inflammatory acne should be treated with topical benzoyl peroxide, topical antibiotics (e.g., erythromycin, clindamycin) and/or glycolic acid

Oral antibiotics (e.g., tetracycline, minocycline, doxycycline, erythromycin) can be used when wide distribution of lesions makes topical therapy impractical

Selection of treatment is generally based on severity

Management of Acne Moderate acne:

Moderate acne responds best to oral systemic therapy with antibiotics. Antibiotics effective for acne include tetracycline, minocycline, doxycycline and erythromycin. Full benefit takes ≥ 12 wk

Tetracycline is usually a good first choice: 250 or 500 mg bid (between meals and at bedtime) for 4 wk or until lesions respond, after which it may be reduced to the lowest effective dose

Because relapse ordinarily follows short-term treatment, therapy must be continued for months to years, although for maintenance tetracycline 250 or 500 mg once/day is often sufficient

Minocycline 50 or 100 mg bid causes fewer GI adverse effects, is easier to take, is less likely to cause photosensitization

Erythromycin and doxycycline are considered 2nd-line agents because both can cause GI adverse effects, and doxycycline is a frequent photosensitizer

In women, prolonged antibiotic use can cause candidal vaginitis; if local and systemic therapy does not eradicate this problem, antibiotic therapy for acne must be stopped

Severe acne: Oral Isotretinoin is nearly always effective. It is also the best treatment for patients with

moderate acne in whom antibiotics are unsuccessful and for those with severe inflammatory acne

It is limited by adverse effects, including dryness of conjunctiva and genital mucosa, chapped lips, arthralgias, depression, elevated lipids and birth defects. Petrolatum usually alleviates mucosal and cutaneous dryness

CBC, liver function, and fasting glucose, triglyceride, and cholesterol levels should be determined before treatment. Each should be reassessed at 4 wk and, unless abnormalities are noted, need not be repeated until the end of treatment

Inhibitors of bacterial protein synthesis, Overview

These agents are bacteriostatic, protein-synthesis inhibitors that target the ribosome

Examples: Chloramphenicol, tetracyclines, macrolides, clindamycin

(A-site)

(P-site)

ChloramphenicolΘ

Macrolides, clindamycin

Θ

Θ

Tetracyclines