Acne, cystic

Isotretinoin COOH Topical 0.05% cream Oral 0.251.0 mg/kg/ d Cystic acne, recalcitrant nodular acne Rosacea gram-negative folliculitis pyoderma faciale hidradenitis suppurativa cancer prevention... 

Severe nodulo-cystic acne Pyruvic acid 40-60%... 

Severe nodulo-cystic acne Superficial post-acneic scars Medium-deep post-acneic scars... 

All of these metabolites possess retinoid activity that is in some in vitro models more than that of the parent isotretinoin. However, the clinical significance of these models is unknown. After multiple oral dose administration of isotretinoin to adult cystic acne patients (18 years of age and older), the exposure of patients to 4-oxo-isotretinoin at steady state under fasted and fed conditions was approximately 3.4 times higher than that of isotretinoin. In vitro studies indicated that the primary P450 isoforms involved in isotretinoin metabolism are 2C8, 2C9, 3A4, and 2B6. Isotretinoin and its metabolites are further metabolized into conjugates, which are then excreted in urine and feces. 

Excretion - Following oral administration of an 80 mg dose of C-isotretinoin as a liquid suspension, C-activity in blood declined with a half-life of 90 hours. The metabolites of isotretinoin and any conjugates are ultimately excreted in the feces and urine in relatively equal amounts (total of 65% to 83%). After a single 80 mg oral dose of isotretinoin to 74 healthy adult subjects underfed conditions, the mean elimination half-lives of isotretinoin and 4-oxo-isotretinoin were approximately 21 and 24 hours, respectively. After single and multiple doses, the observed accumulation ratios of isotretinoin ranged from 0.9 to 5.43 in patients with cystic acne. 

Isotretinoin, or 13-cis-retinoic acid, and etretinate are available for oral administration. Isotretinoin is a synthetic retinoid that is used for sever cystic acne, recalcitrant to standard therapies. Its mechanism of action is not well understood but involves the inhibition of sebaceous gland size and function. 

Pseudotumor cerebri is another potential complication of chronic use of these agents, particularly in individuals treated for severe cystic acne with simultaneous use of isotretinoin. This complication can be induced within several days of initiation of therapy and usually resolves with cessation of treatment. 

Extreme clinical examples of androgen excess include central precocious puberty, the adrenogenital syndromes, and androgen-secreting adrenal, ovarian, or testicular tumors. Less severe problems include idiopathic hirsutism, premenstrual syndrome, and severe cystic acne. 

Isotretinoin (Accutane) is a synthetic retinoid currently restricted to the oral treatment of severe cystic acne that is recalcitrant to standard therapies. The precise mechanism of action of isotretinoin in cystic acne is not known, although it appears to act by inhibiting sebaceous gland size and function. The drug is well absorbed, extensively bound to plasma albumin, and has an elimination half-life of 10-20 hours. 

Most patients with cystic acne respond to 1-2 mg/kg, given in two divided doses daily for 4-5 months. If severe cystic acne persists following this initial treatment, after a period of 2 months, a second course of therapy may be initiated. Common adverse effects resemble hypervitaminosis A and include dryness and itching of the skin and mucous membranes. Less common side effects are headache, corneal opacities, pseudotumor cerebri, inflammatory bowel disease, anorexia, alopecia, and muscle and joint pains. These effects are all reversible on discontinuance of therapy. Skeletal hyperostosis has been observed in patients receiving isotretinoin with premature closure of epiphyses noted in children... 

Much recent interest has been aroused by the fact that retinoid compounds, including both retinol and retinoic acid, reduce the incidence of experimentally induced cancer. In addition, 13-czs-retinoic acid taken orally is remarkably effective in treatment of severe cystic acne. s However, both vitamin A and retinoic acid in large doses are teratogenic, i.e., they cause fetal abnormalities. The use of 13-cis-retinoic acid during early phases of pregnancy led to a high incidence of major malformations in infants born.1 11 1... 

A change in dreaming pattern has been reported in two patients, occurring within 2-3 weeks after the start of treatment with isotretinoin 40 mg/day for cystic acne (684). One patient also reported increased irritability and bouts of depression. In both patients all the symptoms abated after 4-5 weeks without a change in isotretinoin dosage. 

Retinoids in Dermatology 13-Qs-retinoic acid (isotretinoin, Accutane ) is used orally, and all-trans-retinoic acid (Tretinoin ) topically, for treatment of severely disfiguring cystic acne. Etretinate (the trimethoxyphenyl analog of retinoic acid) and tazarotene (a receptor-specific retinoid) are used topically for the treatment of psoriasis. They are effective in cases in which other therapy has failed, and at lower levels than are required for the control of tumor development in experimental animals, although they have heen associated with hirth defects (Section 2.5.1.1 fohnson and Chandrarama, 1999). 

An analogue of vitamin A, isotretinoin (Accutane), or 13-cfs-retinoic acid, is used for control of severe recalcitrant cystic acne and other keratinizing dermatoses. Oral administration of 1 to 2 mg/kg body weight daily temporarily suppresses sebaceous gland activity, changes surfece lipid composition of the skin, and inhibits kera-tinization. The therapeutic effect is resolution of lesions and, in most patients, prolonged remission of the disease. 

Isotretinoin, or 13-cw-retinoic acid, is widely used for the treatment of recalcitrant cystic acne. Although this drug more commonly affects the external tissues of the eye, causing ocular surface dryness, there is sufficient evidence to designate that this agent has a certain retinotoxic effect, causing nyctalopia. It also has a probably/likely designation for reversible decreases in color vision. 

Excessive use of vitamin A can result in ocular dryness, loss of lashes, night blindness, and even intracranial hypertension, the latter of which is similar to that occurring with the other forms of vitamin A such as isotretinoin, approved for the treatment of cystic acne. With large doses, increased intracranial pressure is considered certain. ... 

Isotretinoin is indicated for the treatment of severe recalcitrant cystic acne. Because of the risks of adverse effects, its use should be reserved for patients who are unresponsive to conventional acne therapies. Treatment should be individu-alixed and modilled depending on the course of the di.sease. The mechanism is believed to involve inhibition of sebaceous gland function and follicular keratinixation. Isotretinoin reduces sebum production, the size of the glantfs. and gland differentiation. 

Use Treatment of severe, recalcitrant cystic acne that is unresponsive to conventional acne therapies. Treatment of g-negative folliculitis, severe rosacea, correcting severe keratinization disorders Half-life 10-20 hours Onset UK Peaks Duration UK 5.3 hours... 

Trade names Accutane (Roche) Amnesteem (Genpharm) Isotrex Roaccutan Roaccutane Roacutan Roacuttan Indications Cystic acne Category Retinoid Half-life 10-20 hours... 

Using Saw Palmetto for Other Health Conditions Male Pattern Baldness Polycystic Ovary Disease Deep Cystic Acne... 

Possible uses Male pattern baldness, prostate cancer, mate and female infertility, cystic acne, "male menopause."... 

In the case of saw palmetto, the standardized extract may have a greater activity in conditions such as benign prostatic hyperplasia/hypertrophy (BPH), cystic acne, male pattern baldness, and female hirsutism. At the same time, this type of product has little or no activity as an immune potentiator, adaptogen, lung tonic, or reproductive amphoteric. 

Deep cystic acne is a complex condition that involves an interaction between hormones (testosterone), sebum, and bacteria. It starts at puberty when the increase in androgen levels causes greater activity of the sebaceous glands. This leads to increased growth of epidermal tissue, which blocks the follicle and creates a comedo (cyst) composed of sebum, keratin, and bacteria. Irritation of the follicular wall follows, with rupture of the follicle and then an acute inflammatory reaction. This leads to an abscess and finally healing with scar tissue. 

---