Retinoids

retinol = vitamin A alcohol the primary dietary source, transport, and storage form

retinal = vitamin A aldehyde

retinoic acid = vitamin A acid = the biologically active form

•	retinol in the human skin cells must be oxidated to retinoic acid

•	metabolism of retinoids occurs mainly in the liver

•	beta carotene is converted (in the intestine) to 2 molecules of retinal

nuclear receptors for retinoids:

•	belong to a superfamily of receptors that act as DNA transcription factors and include steroid, vitamin D, and thyroid hormone receptors

•	retinoid action = “physiologic instead of cytotoxic” i.e. induce differentiation to dysplastic epithelium

retinoids treat disorders of cornification:

•	the ichthyoses (hyperproliferative vs. retention hyperkeratosis)

•	Darier’s disease

•

PRP

•	psoriasis (hyperproliferative epidermis)

•	acne (excessive desquamation of follicular epithelium in sebaceous follicles)

SIDE EFFECTS:

acute toxicity:

•	arthralgia and myalgia

•	reversible hair loss

•	pseudotumor cerebri (rare)

•	persistent headaches with visual changes, nausea, and vomiting

•	d/c and examine for papilledema

lab abnormalities:

•	increase triglycerides – dose dependent and reversible

•	d/c if levels reach 800mg/dL or higher

•	increased transaminases

•	occur in 15% of patients, but usually return to normal within 2 to 4 weeks

•	acute hepatotoxic reactions may occur with fever and eosinophilia, possibly indicating hypersensitivity

chronic toxicity (after long term use; > 2 years)

•	may result in demineralization of bones, premature closure of epiphysis resulting in shorter stature, and calcification of tendons and ligaments

SPECIFIC RETINOIDS:

Panretin (alitretinoin) - topical treatment for Kaposi's Sarcoma

Targretin (baxarotene) - oral treatment for Mycoses Fungoides

Guy Webster:

•	for patient with truncal acne, will start Accutane with PO prednisone (20-40mg/day X first month) to avoid flare with keloids

•	rarely re-treats after less than 4 months

•	unknown how many times one can retreat (he has treated as often as 6 times)

•

labs

•

baseline

•	2-4 weeks repeat triglycerides, monitor until they plateau

•	4-6 weeks repeat liver profile (again at end of treatment, or after 4 months)

•	contact lenses (extra lubricant, try not to wear overnight)

adverse effects:

•	acute – increased triglycerides, LFT’s, dryness, hair loss, pseudotumor cerebri

•	chronic (>2 years) – demineralization of bones, premature closure of the epiphyses (short stature), calcification of tendons and ligaments

total dose goal = 120 to 150 mg/kg (typically takes 6 months to achieve this total dose)

acitretin:

•	= the free acid metabolite of etretinate

•	shorter half-life

•	decreased potential for post treatment teratogenicity