Term
| What are the forms of Vit A and retinoids? |
|
Definition
- Retinol - any chemical with vit A activity
- RetinAL - in vision
- Retinoic acid - biologically active
- Retinyl esters - ingested from animals, highest source from fish liver oils
**Carotenoids - beta carotene, from plants. must be converted to active |
|
|
Term
| What are the functions of retinoids? |
|
Definition
- Vision - RetinAL
- Growth/development of tissue
- Immune defense
- Retinoic acid is the active form, except for vision which uses retinal |
|
|
Term
| What are characteristics of Vit A deficiency? |
|
Definition
- Mucous membrane degeneration
- Excessive dryness of the eyes, night blindness
- Advanced - dry/scaly skin, infection, skin lesions, bones/teeth underdeveloped |
|
|
Term
| What are hypervitaminosis A symptoms? |
|
Definition
- CNS - incr pressure and HA, seizures
- GI - short term - N/V
- Dermatology - desquamation, itching, dryness
- eye - blind spots
- Short term liver dmg is reversible, long term is permanent |
|
|
Term
| Are retinoids teratogenic? |
|
Definition
| Large amounts lead to birth defects: neural tube, etc. Beta carotene is nontoxic. |
|
|
Term
| What is the metabolism of Vit A? |
|
Definition
| Retinyl ester is gained from an animal source --> encorporated into chylomycrons/CRBP is a chaperone --> storage in the liver, 90% by Stellate cells. Small amounts in the eye --> Liver cells can release via mobilization, convert to retinoic acid |
|
|
Term
|
Definition
The form of vit A that can be absorbed by Stellate cells, converted from retinyl esters.CRBPs transport and protect retinol
**Once back inside liver, converted back into retinyl ester --> chylmicrons. TTR transports to site of action. |
|
|
Term
| What is the storage site for retinol? |
|
Definition
| Stellate cells in the liver - Stored as retinyl esters, converted to retinol as needed. |
|
|
Term
| What are the active forms of Vit A? |
|
Definition
| - Retinol converted by retinol dehydrogenase to retinAL --> retinaldehyde dehydrogenase to retinoic acid --> enters nucleus and binds to receptors. |
|
|
Term
| What are the types of retinoic acid? |
|
Definition
- All-trans-retinoic acid - the ligand for RAR. RARgamma predominant
- 9-cis-retinoic acid - the ligand for RXR. RXRalpha predominant |
|
|
Term
| What are the first generation retinoid drugs? |
|
Definition
- retinol
- tretinoin - reduces hyperkeratinization, increases shedding, prevents blockage
- isotretinoin - systemic. Tx of pathogenic factors. AE: typical of hypervitaminosis A, teratogenic
- alitretinoin |
|
|
Term
| What are 2nd generation retinoids? |
|
Definition
- Etretinate - no longer available
- Acitretin/Soriatane - milk/lipids incr absorption. A metabolite of Etretinate, interacts w/ alcohol. |
|
|
Term
| What are the 3rd generation retinoids? |
|
Definition
- Tazarotene/Tazorac - only RAR
- Bexarotene
- Adapalene/Differin - only RAR
**Comedolytic, keratolytic, and anti-inflammatory |
|
|
Term
| What are the 4 pathogenic factors of acne? |
|
Definition
- Follicular hyperkeratinization
- Sebum production
- Inflammation - Retinoids decrease the migration of neutrophils
- Propionibacterium acnes
**Comedo - a large plugged hair follicle |
|
|
Term
| What are non-retinoid keratolytics? |
|
Definition
- Salicylic - desquamation, keratolytic
- Benzoyl peroxide - generates free radicals, antimicrobial. Higher str = increased irritation
- Propylene glycol - Converted to lactic/pyruvic acid, removes debris and increases water in the corneum |
|
|
Term
| What T-cell modulators are used to treat psoriasis? |
|
Definition
- Alefacept/Amevive
- Etanercept/Enbrel
- Infliximab/Remicade
- Adalimumab/Humira
- Ustekinumab/Stelara |
|
|
Term
|
Definition
- Psoriasis - hyperkeratinization and decreased squamation causes plaques to form.
- T cells produce TNFalpha --> keratin and epithelial proliferation
- Thicker epidermis, increased vasculature. Bleeds when scraped off. |
|
|
Term
| What is the MoA of Alefacept/Amevive? |
|
Definition
- Antigen presenting cells have LFA3 - try to bind to CD2 on T cells.
- Alefacept binds to LFA3, preventing activation of T cells --> cytokines cannot form. An IM injection. |
|
|
Term
| What psoriasis agents are TNF blockers? |
|
Definition
- Etanercept/Enbrel
- Infliximab/Remicade - IV
- Adalimumab/Humira
**Prevent binding of TNFalpha to its receptor by binding TNFalpha |
|
|
Term
| What is the MoA of Ustekinumab/Stelara? |
|
Definition
- Prevents binding of IL-12 and IL-23 to their receptors, decreasing helper T cells.
- Binds p40 subunit = no cytokines |
|
|
Term
| What determines potency of topical steroids? |
|
Definition
- intrinsic - from structure
- Concentration in formula
- Vehicle - ointment vs. cream |
|
|
