Chapter 2 - Pharm

Question 1

What are the three interconvertible forms of retinoids?

Answer 1

RetinOL (alcohol based), RetinAL (aldehyde form) and Retinoic Acid (acid form)

Question 2

How do we get retinoids through our diet?

Answer 2

Meat, fish, eggs, leafy greens, dairy, orange/yellow veggies

Question 3

How are retinoids stored in the body?

Answer 3

Stored in the liver as retinol

Question 4

What families of nuclear receptors do retinoids influence?

Answer 4

Retinoic Acid Receptors (RAR) and Retinoid X Receptors (RXR). Each receptor has 3 isotypes: alpha, beta, and gamma

Question 5

Which retinoid receptors are most abundant in the skin?

Answer 5

Retinoic Acid Receptor gamma (RAR-y) is #1, Retinoid X receptor alpha (RXR-a) is #2 in keratinocytes

Question 6

What happens to retinoid receptors in photoaging?

Answer 6

Decreased RAR-y and RXR-a

Question 7

What do topical retinoids do for the skin?

Answer 7

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.

Question 8

What does binding RAR/RXR lead to?

Answer 8

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.

Question 9

How exactly are topical retinoids helpful in CTCL?

Answer 9

Retinoids lead to increased TH1 cytokines and Decreased TH2 cytokines. Sezary actually promotes the opposite.

Question 10

What level of Triglycerides do you discontinue Isotretinoin?

Answer 10

> 800

Question 11

What retinoid commonly affects the thyroid?

Answer 11

Bexarotene (80% of patients) thus recommend low dose levothyroxine in all patients on this

Question 12

What retinoid commonly affects the lymphocyte count?

Answer 12

Bexarotene, associated with neutropenia and agranulocytosis

Question 13

What can pregnant patients exposed to isotretinoin expect for “healthy appearing” births?

Answer 13

Most have “healthy appearing” births, though 30% have gross mental retardation and 60% moderate mental deficits.

Question 14

What are the most common adverse events for pregnant patients exposed to isotretinoin?

Answer 14

20% have Spontaneous abortion. Approximately 18-28% have babies with Retinoid Embryopathy

Question 15

What are the specific features of retinoid embryopathy?

Answer 15

Craniofacial, CNS, Thymic abnormalities

Question 16

What interactions should you know about while taking systemic retinoids?

Answer 16

Fatty foots increase absorption and bio-availability. No MTX, avoid alcohol (specifically with acitretin). Avoid Vitamin A supplementation. Avoid Tetracyclines. Avoid simvastatin. Avoid Gemfibrozil.

Question 17

Why do you avoid alcohol specifically with Acetretin

Answer 17

Conversion of acitretin to etretinate, causing hepatotoxicity

Question 18

Why do you avoid simvastatin specifically with systemic Bexarotene?

Answer 18

Simvastatin interacts with cytochrome p450 3A4 which metabolizes Bexarotene

Question 19

Why do you avoid gemfibrozil specifically with systemic Bexarotene?

Answer 19

Gemfibrozil INHIBITS cytochrome p450 3A4 which metabolizes Bexarotene

Question 20

How do you treat increased LDL from retinoid therapy?

Answer 20

Statin

Question 21

How do you treat increased Triglycerides from retinoid therapy?

Answer 21

Fenofibrate and/or omega 3