Chapter 185 - Retinoids Flashcards
Predominant retinoid receptors in human skin are
RAR alpha
RAR gamma
RXR alpha
RXR beta
Approved of topical steroids (6)
Acne Psoriasis Cutaneous T cell lymphoma Kaposi sarcoma Melasma Photoaged skin
Approved use of oral steroids (4)
Acne
Cutaneous T cell lymphoma
Chronic hand eczema
Psoriasis
Most concerning side effect
Teratogenicity
Molecular storage form of retinol
Retinyl esters
First generation retinoids (3)
All-trans-retinoic acid (tretinoin)
13-cis-retinoic acid (isotretinoin)
9-cis-retinoic acid (alitretinoin)
Second generation retinoids (2)
Etretinate
Acitretin
Third generation retinoids (3)
Adapalene
Tazarotene
Bexarotene
Known as synthetic retinoids
2nd and third gen retinoids
Predominant retinol-esterifying activity
Lecithin/retinol acyltransferase
Class of drugs that target CYP26 activity
Retinoic acid metabolism blocking agents (RAMBAs)
For isotreinoin, a ____ posttherapy period of contraception provides an adequate safety margin
1 month
Etretinate is ___ times more lipophilic than acitretin
50
Etretinate has a half life of ___ and acitretin has a half life of ____
120 days; 2 days
Major metabolite of acitretin via isomerization
13-cis-isomer
Compulsory contraception in patients taking acitretin is ____ years
2
Approved for the treatment of acne, photoaged skin, and melasma in the United States
Tretinoin
Approved for acne
Topical adapalene and tazarotene
Approved for psoriasis and photoaging
Tazarotene
For management of cutaneous T cell lymphoma
Bexarotene
For treatment of patients with Kaposi sarcoma
Alitretinoin
2 features improved by application of tazarotene or tretinoin
Fine wrinkles
Dyspigmentation
Antiviral role against HHV8
Alitretinoin
Retinoid of choice in psoriasis
Acitretin
Approved in Europe and Canada for treatment resistant chronic hand eczema
Alitretinoin 10-30mg/day for 6 months
FDA approved for CTCL that is refractory to at least one systemic therapy
Bexarotene 300mg/m2 with 60% response rate in first two months
Topical combination approved for the treatment of melasma
Tretinoin 0.05%/
hydroquinone4%/
Fluocinolone 0.1%
Posttherapy relapse is minimized by administering cumulative dose of at least ___
120 mg/kg
The most common adverse effect
Skin irritation, peaks within first month
Central hypothyroidism is observed with topical bexarotene gel
True or False
False, not observed
No evidence exists for teratogenicity of topical tretinoin in humans
True or False
True
Retinoid therapy does not appear to produce abnormalities in spermatogenesis, sperm morphology, or sperm motility.
True or False
True
Most common cutaneous side effect of bexarotene
Localized or extensive exfoliative dermatitis
___ appears to induce fewer mucocutaneous and ocular side effects than other classes of retinoids
Bexarotene
___ colonization tends to correlate with isotretinoin -induced reduction in sebum production and may lead to overt cutaneous infections
Staphylococcus aureus
Diffuse or localized hair loss is more severe during treatment with
Acitretin
Muscle effects like cramps are more frequent with
Isotretinoin
Major risk factor for development of pseudotumor cerebri
Concomitant use of isotretinoin with tetracycline
Central hypothyroidism is irreversible even with DC of systemic bexarotene therapy.
True or False
False, reversible
Most frequent abnormalities in lab test results
Serum lipid changes
50-80% triglyceride levels
30-50% cholesterol levels
Disturbance of blood lipid levels is higher with acitretin than isotretinoin and bexarotene.
True or False
False, higher with isotretinoin and bexarotene
Therapy should be discontinued if TGL reaches ____ mg/dl
800
Transient abnormal elevations in serum transaminases has been reported in approximately __%of patients treated with __
20%
Acitretin and etretinate
Transaminase levels more than ___x should lead to discontinuation of retinoid therapy
3
28% who use bexarotene therapy presents with
Dose-related neutropenia 2-4 weeks form initiation of treatment
Concurrent use of ___ increase half life of tretinoin; use of _____, bexarotene
Ketoconazole and liarozole
Gemfibrozil
Use of ff should be avoided with use of retinoids
Tetracyclines
Alcohol
Methotrexate
VitA supplements
___ therapy is not recommended for women with childbearing potential due to long term treatment of more chronic diseases and slow elimination of aromatic retinoids
Acitretin or etretinate
Woman with childbearing potential must have ___ negative results on pregnancy test spaced ___ days apart and practice effective contraception during treatment and after ___
2, 30 days, 1 month
Unapproved indications with clinical studies supporting benefit
Pityriasis rubra pilaris Premalignancies Photoaging Ichythyosis Darier White disease
Characteristic common to retinoids is that they bind to regulatory regions in DNA called
Hormone response elements or target sequences
Treatment of human skin with all-trans-retinol or retinaldehyde increases retinyl ester levels in epidermal layer by more than ___ fold
10
CYP26 activity inhibitor
Ketoconazole
Liarozole
Metabolism of retinoids involve 2 steps
- Esterification and oxidation of retinol
2. Hydroxylation of all-trans-retinoic acid
Major metabolite of isotretinoin
4-oxo-isotretinoin
All women taking acitretin should avoid taking alcohol during treatment and for __ months thereafter
2
Bexarotene is __ fold more potent in activating RXR than RAR
100
Bexarotene is metabolized by ___
CYP 3A4
Alitretinoin and tretinoin have been reported to inhibit herpes simplex virus replication.
True or False
True
Most significant response of alitretinoin occurred __ weeks of therapy
14
Topical retinoids can be used in all age groups, except
Neonates
Teratogenicity is not caused by topical retinoids.
True or False
True
Best results for acitretin have been obtained in
Pustular psoriasis of palmoplantar or generalized (von Zumbusch) type
ARCI, esp. lamellar type
Rebound occurs after cessation of treatment of acitretin.
True or False
False, does not occur
Acitretin causes decrease of __% in PASI score depending on the dosage
60 to 70%
Effective in the treatment of premalignancies, including HPV-induced tumors and actinic keratosis, malignant skin lesions in renal transplant recipients, basal cell nevus syndrome, and xeroderma pigmentosum patients
Acitretin 30 mg/ day for 6 months
Treatment for Darier White Disease
10mg/ day acitretin
The most important element in topical retinoid therapy
Patient education
Matching type
- Tagretin
- Avita
- Differin
- Triluma
- Panretin
- Avage
A. Tretinoin B. Adapalene C. Tazarotene D. Bexarotene E. Alitretinoin
D A B A C
0.025% tretinoin and 0.01% tretinoin are equally efficacious
True or False
True
Length of therapy for
- Isotretinoin
- Acitretin
- Bexarotene
- Alitretinoin
- 4-6 months
- > 3 months
- > 2 months
- > 6 months
__ of acne patients require second course of isotretinoin therapy for either persistent disease or relapse
1/3
If CTCL does not respond after 8 weeks, dose may be increased to __
400 mg/m2/day
Local irritation is observed as the most common side effect in the ff
Bexarotene
Alitretinoin
All retinoids does not produce neutropenia, except
Bexarotene
Hypothyroidism has been associated with
Alitretinoin
Bexarotene
Most common retinoid associated with ocular side effects
Isotretinoin
Most common retinoid associated with alopecia side effects
Isotretinoin
Most common retinoid associated with headache as side effect
Alitretinoin
Most common retinoid associated with musculoskeletal side effects
Isotretinoin
Most common retinoid associated with hepatotoxic side effects
Isotretinoin
Alitretinoin
Most common retinoid associated with hyperlipidemia side effects
Isotretinoin
Bexarotene
Blepharoconjunctivitis occurs in __ of patients treated with isotretinoin due to its effects on Meibomian glands
1/3
Bone pain without objective evidence and without sequelae are frequent in retinoid treated patients.
True or False
True
DISH syndrome stands for
Diffuse idiopathic skeletal hyperostosis
Increased muscle tone, axial rigidity, myopathy were related to treatment with
Etretinate and acitretin
Bleeding complications has been reported with isotretinoin induced fibrinolysis.
True or False
True
Program used to minimize risk of isotretinoin teratogenicity
IPLEDGE
Labs requested before oral retinoid therapy
Serum lipid levels
CBC
Thyroid function tests
Liver enzyme levels
Retinoid induced hyperlipidemia is not associated with accelerated atherosclerosis or increased risk of CV disease.
True or False
True