Chapter 2 - Pharm Flashcards
What are the three interconvertible forms of retinoids?
RetinOL (alcohol based), RetinAL (aldehyde form) and Retinoic Acid (acid form)
How do we get retinoids through our diet?
Meat, fish, eggs, leafy greens, dairy, orange/yellow veggies
How are retinoids stored in the body?
Stored in the liver as retinol
What families of nuclear receptors do retinoids influence?
Retinoic Acid Receptors (RAR) and Retinoid X Receptors (RXR). Each receptor has 3 isotypes: alpha, beta, and gamma
Which retinoid receptors are most abundant in the skin?
Retinoic Acid Receptor gamma (RAR-y) is #1, Retinoid X receptor alpha (RXR-a) is #2 in keratinocytes
What happens to retinoid receptors in photoaging?
Decreased RAR-y and RXR-a
What do topical retinoids do for the skin?
Increased stratum corneum thickness. Epidermal hyperplasia. Correction of atypia. Increased Dermal Collagen I. Increased Dermal Elastic Fibers. Increased Hyaluronic Acid. Decreased Matrix Metalloproteinases. Decreased Angiogenesis.
What does binding RAR/RXR lead to?
Inhibition of IL-6, AP-1 (proinflammatory), Inhibition of TLR-2, Downregulation of K6 and K16, Inhibition of Ornithine Decarboxylase, Increased TH1 cytokines and Decreased TH2 cytokines.
How exactly are topical retinoids helpful in CTCL?
Retinoids lead to increased TH1 cytokines and Decreased TH2 cytokines. Sezary actually promotes the opposite.
What level of Triglycerides do you discontinue Isotretinoin?
> 800
What retinoid commonly affects the thyroid?
Bexarotene (80% of patients) thus recommend low dose levothyroxine in all patients on this
What retinoid commonly affects the lymphocyte count?
Bexarotene, associated with neutropenia and agranulocytosis
What can pregnant patients exposed to isotretinoin expect for “healthy appearing” births?
Most have “healthy appearing” births, though 30% have gross mental retardation and 60% moderate mental deficits.
What are the most common adverse events for pregnant patients exposed to isotretinoin?
20% have Spontaneous abortion. Approximately 18-28% have babies with Retinoid Embryopathy
What are the specific features of retinoid embryopathy?
Craniofacial, CNS, Thymic abnormalities
What interactions should you know about while taking systemic retinoids?
Fatty foots increase absorption and bio-availability. No MTX, avoid alcohol (specifically with acitretin). Avoid Vitamin A supplementation. Avoid Tetracyclines. Avoid simvastatin. Avoid Gemfibrozil.
Why do you avoid alcohol specifically with Acetretin
Conversion of acitretin to etretinate, causing hepatotoxicity
Why do you avoid simvastatin specifically with systemic Bexarotene?
Simvastatin interacts with cytochrome p450 3A4 which metabolizes Bexarotene
Why do you avoid gemfibrozil specifically with systemic Bexarotene?
Gemfibrozil INHIBITS cytochrome p450 3A4 which metabolizes Bexarotene
How do you treat increased LDL from retinoid therapy?
Statin
How do you treat increased Triglycerides from retinoid therapy?
Fenofibrate and/or omega 3
