What is the Chemical Structure of Accutane
Isotretinoin, also known as 13-cis retinoic acid, is a cis isomer of tretinoin and belongs to the first generation of retinoids (non-aromatic retinoids). Isotretinoin was introduced in 1982 by Roche under the name Accutane brought on the market.
Isotretinoin has been approved as a medicinal substance in Germany for the treatment of acne. It can also be used for rosacea, psoriasis (psoriasis) and actinic keratosis. It hardly works against acne inversa.
Isotretinoin is used both topically (externally) and systemically (internally). Because of the considerable risks and side effects, only severe and therapy-resistant disease courses are usually treated systemically. The active ingredient is approved in Europe and North America.
Mechanisms of Action
Systemic isotretinoin therapy reduces the size of the sebum glands. The amount and composition of the sebum lipids normalize. The acne is supposed to be healed in this way. However, recurrences (relapses) are possible. A study from 1998 put the recurrence rate three years after the first therapy at 61% of the treated cases. 
An immunomodulating effect occurs through inhibition of granulocyte migration and stimulation of Langerhans cells. Isotretinoin also has a direct impact on lymphocytes.
Isotretinoin improves the maturation of the keratinocytes. This also applies to cells that show signs of malignant degeneration (“tumor-protective effect”). These anti-tumor effects are also observed after UV radiation.
With systemic intake, various parts of the body can be affected by undesirable effects. The side effects of topical application remain limited to the treated skin area.
skin and hair
Dry skin, especially lips, peeling of the skin, inflammation of the mucous membranes, and nosebleeds are common. The skin's sensitivity to light is increased. Isotretinoin is not stable when exposed to sunlight and can therefore cause phototoxic reactions when applied topically. With systemic intake, hair loss occurs in some cases. At the beginning of isotretinoin therapy, there may be a temporary deterioration in the appearance of the skin due to additional inflammation. The immunomodulatory properties of the active ingredient are suspected to be the cause.
With systemic intake, there is a risk of liver dysfunction and lipid metabolism disorders, which makes it necessary to monitor liver values closely. Increases in transaminases are very common. Inflammation of the liver (hepatitis) occurs very rarely.
Nervous system and psyche
Headaches are common with systemic therapy. Very rarely there is an increase in pressure in the skull (intracranial pressure in the brain), cramps and drowsiness. An influence on the brain metabolism could be demonstrated . Depression and increased suicidality are under discussion.
Blood and lymphatic system
Increased erythrocyte sedimentation rate and anemia are very frequently observed with systemic therapy. Likewise thrombocytopenia and thrombocytosis. Neutropenia (lack of white blood cells) is common. Lymph nodes very rarely become diseased (lymphadenopathy).
Inflammation of the eyelid margins and conjunctiva, dry and irritated eyes are very common. Very rarely, blurred vision, cataracts, color blindness, corneal opacity, night blindness, corneal inflammation, changes in the fundus with swelling (papillary edema) as a sign of one Cerebral pseudotumor and photophobia.
Support and musculoskeletal system
Reversible muscle and joint pain are very common. Joint inflammation, premature closure of the bone growth plates, excessive formation of bone substance (hyperostosis and exostosis) and the calcification of ligaments and tendons (calcinosis) occur very rarely.
The simultaneous use of isotretinoin and tetracyclines can result in a pseudotumor cerebri, since isotretinoin as well as the tetracyclines increase the intracranial pressure. The combination of isotretinoin with other keratolytic agents can increase local irritation. To avoid a vitamin A overdose, isotretinoin must not be taken together with high-dose vitamin A-containing drugs and food supplements. Liver and liver products can also contain high doses of vitamin A, which must be taken into account when determining the amount consumed.
Isotretinoin must not be administered systemically to persons suffering from a lipid metabolism disorder (hyperlipoproteinemia) or hypervitaminosis A. . With topical application, diseases such as acute eczema, rosacea or perioral dermatitis on the surface of the skin to be treated are an obstacle. Regardless of the form of administration, increased sensitivity to the active ingredient or other preparation components is also a clear contraindication.
pregnancy and breast feeding period
Isotretinoin must not be used in women of childbearing potential or only after pregnancy has been excluded (including four weeks beyond treatment). Otherwise there is a risk of severe malformations in the fetus. The safety of topical application during pregnancy and breastfeeding has not been adequately investigated, so that it is also not recommended.
- ↑ White GM et al .: Recurrence rates after the first course of isotretinoin. In: Archives of Dermatology 1998; 134:376-378
- ↑ Bremner et al .: Functional Brain Imaging Alterations in Acne Patients Treated With Isotretinoin. In: At J Psychiatry 162: 983-991; May 2005. Full text
- ↑ Package insert from Ciscutan® [Isotretinoin system preparation, note], para. Contraindications. Status: September 2002. online
- ↑ Package insert Isotrexin® Gel [isotretinoin topical, note]: Par. Contraindications. Status February 1999. online
Categories: Drugs | Retinoid
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