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Retinoids

Natural and synthetic chemicals which are structurally related to vitamin A.

May not have vitamin A like activities.

Topical retinoids, either as monotherapy or in topical combinationare the first line therapies of acne.

Retinoids are vitamin A derivatives that bind  to retinoic acid receptors and retinoid X receptors in the keratinocyte cytoplasm and translocate to the nucleus to initiate transcription changes.

Retinoids are vitamin A derivatives that bind to retinoic acid receptors (RARs) and retinoid X receptors (RXRs).

Binding to these receptors induces a cascade of cellular processes that ultimately lead to increased collagen production and epidermal thickening, reducing the appearance of skin sagging and wrinkling. 

Tretinoin is also efficacious for the treatment of acne. 

Retinoids stimulate epidermal cell liberation, loosing connections among cells in the stratum corneum, accelerate elimination of sebum in sebaceous ducts, and promote micro comedone clearance.

Play a critical role in cellular growth, division, differentiation, and apoptosis activation.

Retinoids reduce the amount of sebum produced by the sebaceous glands.

 

A class of chemicals that are vitamers of vitamin A or are chemically related to it. 

Retinoids regulate epithelial cell growth.

 

Retinoids work by increasing cell turnover and can take a few months before a change. 

 

Retinoid functions: roles in vision,regulation of cell proliferation and differentiation, growth of bone tissue, immune function, and activation of tumor suppressor genes.

 

Alitretinoin (9-cis-retinoic acid) may be used topically to help treat skin lesions from Kaposi’s sarcoma.

 

ATRA (all-trans- retinoic acid) is used to treat acute promyelocytic leukemia.

 

Three generations of retinoids exist: 

First generation include retinol, retinal, tretinoin (retinoic acid), isotretinoin, and alitretinoin

 

Second generation include etretinate and its metabolite acitretin

 

Third generation include adapalene, bexarotene, and tazarotene

 

First- and second-generation retinoids are able to bind with several retinoid receptors due to their alternating single and double bonds.

 

Retinoids in the diet are plant pigments such as carotenes and retinyl esters derived from animal sources. 

 

Retinyl esters are hydrolyzed in the intestinal lumen, resulting in free retinol its corresponding fatty acid.

 

Bile salts are required for retinyl ester hydrolysis by solubilizing them and activating hydrolyzing enzymes.

 

 

After hydrolysis, retinol is taken up by the enterocyte cells of the GI tract.

 

Several enzymes that are present in the intestinal lumen may be involved in the hydrolysis of dietary retinyl esters. 

 

Cholesterol esterase is secreted into the intestinal lumen from the pancreas and has retinyl ester hydrolase activity. 

 

Hydrolyzing enzymes are activated by different types of bile salts.

 

Retinoids used in the treatment of many diverse diseases: inflammatory skin disorders, skin cancers, disorders of increased cell turnover such as psoriasis, photoaging, prommyelocytic leukemia and acne.

 

In the presence of retinoids embryonic stem cells also more readily differentiate into cortical stem cells

 

They reduce the risk of head and neck cancers.

 

Toxicity occurs with prolonged high intake. 

 

Toxicities are related to exposure time and concentration. 

 

Chronic retinoid poisoning: painful tender swellings on the long bones, anorexia, skin lesions, hair loss, hepatosplenomegaly, papilloedema, bleeding, general malaise, pseudotumor cerebri, and death may also occur

 

Chronic overdose causes increased lability of biological membranes.

 

 Chronic overdose causes the outer layer of the skin to peel.

 

Systemic retinoids are contraindicated during pregnancy as they may cause CNS, cranio-facial, cardiovascular and other defects.

Four topical retinoids are approved to treat acne: tretinoin, adapalene,  yazarotine and  trifarotene.

Approximately 30% of patients with topical retinoids treatment experience cutaneous  irritation with burning, stinging, dyrness and, scaling.

Topical retinoids skin adverse effects can be reduced by initiating treatment with low with strength medication, applying moisturizers, applying every other day therapy, slowly increasing the dose as tolerated, are using short contact therapy.

Adapalene .1% that’s been approved for over-the-counter use to treat acne.

Fetal malformations have been reported with systemic retinoids and topical retinoids use is not recommended during pregnancy.

 

 

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