Retinoids Flashcards
Name 2nd generation of retinoids
- Etretinate
- Acitretin
Name 1 st generation of retinoids
- Tretinoin
- Isotretinoin
Name 3rd generation?
- Adapelene
- Tazarotene
- Bexarotene
Indications for usage of isotretinoin ?
- schnauzers comedo syndrome
- SA
- Ichtiosis
- ACne
- MF
- Keratinizing acanthoma
- Seb gl hyperplasia, adenomas
- BISC
- SCC
- Actinic keratosis
Vitamin A in body is oxydized to ?
Retinal acid
Retinoid acid
What does vitamin A do
-Normal growth and differentiation of KC (normal desquamation)
-Acts antiinflammatory
-Reduces proliferation
Bexarotene (Targretin) (third generation)
-activates RXR (selective)
-reduces KZ proliferation (block cell cycle in G phase), down regulation of K6, K16
caspase 3 - > induces apoptosis
-reduces IL-2, TNF alfa
reduces TGM14 (from cornification process)
-modulates epidermal differentiation
-reduces inflammation
for MF
increases wound healing - > stimulates fibroblasts
Etretinate/Acitrein
-Etretinate no longer available (had very long half life (3 months)- >
-new drug Acitretin (second generation)
-higher bioavailability
-shorter half life (few days)
less teratogenic
+ all above:
BISC
Seborrhea
AE of retinoids
- GI- vomiting, diarreha
- PU
- Dry foot pads
- Pruritus
- KCS
- Behaviour changes
- Hepatotoxicity
- Impact on bone metabolism, stiffness
- conjunctivitis D;C
- hyperactivity
- pedal and mucocutaneous junction erythema
- anorexia
- incerased chol, trig , ALT, AST, SAP
- terayogenesis
- ETRETINATE- exfoliative dermatits, reluctance to eat hard food
What means „retinoid dermatitis“ or „retinoid reaction“?
Topical retinoid therapy can lead to local skin irritation including dryness, peeling, erythema and pruritus. This is known as retinoid dermatitis or the “retinoid reaction”
2 pathways of MOA?
RAR is more usual
MOA
-in plasam they bound to albumin and lipoproteins- enter cell (no need of receptor)
-> bind to cellular retinol acid binding protein (CRABP) in cytoplasma - > then metabolized to retinoic acid- > bind to retinoic acid receptor in nucleus/ RAR & RXR-> gene transcription (up regulation or suppression of nucelar transcriptions factors)
Name 2 families of retinoid nuclear receptors ( RNR)
- RA receptors (RAR), which natural ligand is retinoic acid (all known synthetic retinoids bind that except Bexarotene)
- Retinoid X Receptors (RXR), which´s natural ligand is 9-cis-retinoic acid. Binds Bexarotene
Metabolism of retinoids?
- Metabolized by C P450
- Hepatic system
- Eliminated by biliary or renal tracts
What retinoids in general do?
- Altering expression of growth factors, keratins and transglutaminases: antiproliferative, regulation of growth and differentiation of epithelial tissues, inhibition of cholesterol sulfate production → cell membrane stabilization
- Downregulation of nitrites and TNF-α: anti-inflammatory, immunomodulatory
