Retinoids PO

Question 1

List 2 first gen retinoids?

Answer 1

tretinoin (all-trans RAs, t1/2 48 mins), isotretinoin (13-cis RA, t1/2 20 hrs)

Question 2

List 2 second gen retinoinds?

Answer 2

etretinate (t1/2 120 days) acitretin (t1/2 2 days)

Question 3

List 3 third gen retinoids?

Answer 3

adapalene
tazarotene
Bexarotene
all t/2 = 7 hrs

Question 4

What is half life of:
  isotretion
 acitretinoin
 etretinate
 bexarotene

Answer 4

isotretinoin - 20 hrs
acitretinoin - 2 days (more, pSo drug - slower)
etretinate (converted from aci ) - 120 hrs
bexarotene - 7 hrs (think under 10)
20 hrs - > 2 days -> 120 days -> 7 hrs

Question 5

What are 3 forms of vitamin A?

Answer 5

retinol (alcohol)
retinal (aldehyde)
retinoic acid (acid)

Question 6

retinoids are transported into the nucleus by which protein?

Answer 6

CRABP (people on retinoids feel CRAB/P-Y)

cytosolic (in cytosol, not yet in nucleus) retinoic acid (dah) binding protein

Question 7

What are 2 receptors (and 3 of their subtypes) that bind retinoids (?in nucleus)?

Answer 7

RAR (retinoic acid receptor: alpha, beta, gamma (RAR gamma #1)
RXR = retinoid X receptor, specific to bexarotene (also alpha, beta, gamma)

Question 8

after retinoid gets transported to nucleus by CRABP and binds to RAR, what happens next ?

Answer 8

RAR needs to heterodimerize w/ RXR -> dimer becomes transcription factor of RARE - retinoic acid response element -> activates gene transcription

Question 9

after retinoid binds to CRABP -> transported into nucleus and binds to RXR, what happens?

Answer 9

RXR can:
- homodimerize with RXR
- heterodimerize with RAR
- heterodimerize with Vit D3
- heterodimerize with thyroid hormone receptor (THR - > hence hypothyroidism in bexarotene)
once it dimerizes, it attaches to RARE - Retinoic acid response element -> transcription occurs

Question 10

What does CRABP stand for in retinoids?

Answer 10

Cytosolic (in cytosol) retinoic acid binding protein (b/c retinoid binds to it to get into nucleus)

Question 11

What does RARE stand for in retinoids?

Answer 11

retinoic acid response element - > basically a promoter for transcription

Question 12

List 3 therapeutic goals of 13-cis retinoic acid aka isotretinoin?

Answer 12

• reduces sebum production (up to 90%) - > P.acnes unable to thrive,
• sebaceous gland atrophy
• normalization of follicular keratinization

Question 13

How long should pregnancy be avoided on isotret?
What is ideal cumulative dose of isotret?
Is it better with or without fatty meal?
Half life of isotret?

Answer 13

1 month of pregnancy avoidance post d/c
ideal cum. dose of 120-150 mg/kg
- best with fatty meal (Vit A is fat soluble) - > increased absorption
- t1/2 of 20 hrs

Question 14

List 7 isotretinoin side effects?

Answer 14

PPAASS Photosensitivity PG AD Alopecia Staph colonization Skin fragility

Skin 
 - xerosis
 - cheilitis
- photosensitivity
PPAASS if know this 
- * pyogenic granulomas*
- *staph colonization*
-* increased skin fragility*
-*alopecias*
- *eczematous dermatoses*
Metabolic
 - LFT elevation
 - elevated triglycerides (25-45% MC lab abn)
CNS
- pseudotumour cerebri
- reduced night vision
- headaches
- keratitis
MSK
- myalgias and arthralgias (increased Cr phosphokinalse levels)
- premature closure of epiphyseal plates
DISH
Repro
- teratogenicity

Question 15

List 5 cutaneous side effects of isotretinoin?

Answer 15

PPPAASS

• xerosis
• cheilitis
• alopecia
• eczematous dermatitis
• photosensitivy
• pyogenic granulomas (think pregnancy and retinoids)
• staph colonization
• skin fragility
• sticky palms

Question 16

MC isotretinoin lab abn?

Answer 16

elevated triglycerides 25-45% of all pts

Question 17

List 4 organ systems affected in retinoid teratogenicity?

Answer 17

• craniofacial malformations
• CNS malformations
• cardiac malformations
• thymic malformation (think right above heart)