28 - 185 - RETINOIDS Flashcards
US FDA approved as oral therapy for CTCL
A. Tretinoin
B. Alitretinoin
C. Tazarotene
D. Bexarotene
D
Example of second generation retinoid
A. Alitretinoin
B. Adapalene
C. Acitretin
D. Tazarotene
C
Discontinuation of isotretinoin is warranted in which situation/s
A. Elevation of transaminases three times from the normal range
B. Triglyceride levels reaches 800mg/dl
C. A and B
D. None of the above
C
These medications can prolong the half-life of tretinoin locallt on the skin
A. Ketoconazole
B. Alcohol
C. Liazole
D. A and C
D
High incidence of neutropenia has been identified with this retinoid
A. Alitretinoin
B. Bexarotene
C. Acitretin
D. Etretinate
B
Most frequent laboratory abnormality seen with retinoid therapy
A. Serum lipid changes
B. Elevated transaminases
C. Elevated kidney function test
D. Increased FBS
A
any molecule that by itself or through metabolic conversion binds to and activates retinoic acid receptors
Retinoid
predominant retinoid receptors in human skin
retinoic acid receptor α (RAR-α),
RAR-γ,
retinoid X receptor α (RXR-α),
RXR-β
bind to retinoic acid–responsive elements and are responsible for retinoid signaling
RAR-γ/RXR-α heterodimers
Approved indications of topical retinoids
acne, psoriasis, cutaneous T-cell lymphoma, Kaposi sarcoma, melasma, photoaged skin
Approved indications of oral retinoids
acne, chronic hand eczema, psoriasis, and cutaneous T-cell lymphoma
Most concerning side effect of retinoids
Teratogenicity
First-generation retinoids
- all-trans-retinoic acid (tretinoin),
- 13-cis-retinoic acid (isotretinoin),
- 9-cis-retinoic acid (alitretinoin)
Second-generation retinoids
Etretinate
Acitretin
Third Generation Retinoids
Adapalene
Tazarotene
Bexarotene
Also known as synthetic retinoids
2nd and 3rd gen retinoids
Until how long should you give contraception after discontinuation of isotretinoin?
1 month
“After the end of treatment, endogenous concentrations of isotretinoin and its major metabolite are reached within 2 weeks. Therefore, a 1-month posttherapy period of contraception provides an adequate safety margin.”
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Prodrug of acitretin
Etretinate
Until how long should a patient take contraception after discontinuation of acitretin?
Patients should avoid alcohol for how how many months after discontinuation?
2 years (contraception)
2 months (alcohol)
“Whereas etretinate is approximately 50 times more lipophilic than acitretin and binds strongly to plasma lipoproteins, acitretin binds to albumin. Thus, after etretinate is taken, it is stored in adipose tissue from which it is released slowly; it has a half-life of up to 120 days. In contrast, acitretin has a half-life of only 2 days. 15 However, small amounts of etretinate can be formed in patients receiving acitretin if it is taken simultaneously with alcohol. 16 This has prompted the manufacturer to extend the time of compulsory contraception in patients taking acitretin to 2 years (3 years in the United States). Acitretin still has a pharmacokinetic advantage over etretinate; however, all women must strictly avoid alcohol consumption during treatment and for 2 months thereafter. “
Retinoid approved for management of cutaneous T-cell lymphoma
Bexarotene
Retinoid approved for patients with Kaposi sarcoma (KS)
Alitretinoin
Out of all the acne medications, this is thought to be the best, if not the only, agents to normalize the abnormal follicular epithelial differentiation and desquamation that occur in acne
Retinoid
approved in Europe and Canada for treatment-resistant chronic hand eczema
Alitretinoin
Between 3 and 6 months of therapy is usually required to fully appreciate the effect
effective in the treatment of premalignancies, including human papillomavirus–induced tumors and actinic keratoses. In basal cell nevus syndrome and xeroderma pigmentosum, these drugs dramatically reduce the incidence of malignant degeneration of the precancers.
Acitretin
For photoaging, which topical retinoid are approved
Tretinoin and Tazarotene
most important element in topical retinoid therapy
patient education
optimal benefit in acne would be achieved with a daily dose of isotretinoin, approximately _____
0.5 to 1 mg/kg of body weight per day
For patients taking isotretinoin, Posttherapy relapse is minimized by administering a cumulative dose of at least ________
120 mg/kg
This implies 6 to 8 months of therapy.
A lag period of 1 to 3 months may occur before the onset of the therapeutic effect, and a flare-up of disease during the first few weeks may be observed.
The recommended alitretinoin dose in treatment of chronic hand eczema
10 to 30 mg/day
Treatment periods of up to 6 months are often needed before a full evaluation of the therapeutic effects can be made.
The recommended initial dosage of bexarotene
300 mg/m2 /day, administered as a single oral dose with meals
The most common adverse effect associated with topical retinoid use
Local skin irritation
most common cutaneous side effect with bexarotene
localized or extensive exfoliative dermatitis
Concomitant use of isotretinoin and tetracyclines, which rarely produce increased intracranial hypertension, is the major risk factor for development of _____________
pseudotumor cerebri
Discontinuation of therapy is required if the triglyceride level reaches what level
800 mg/dL
Transaminase elevations of more than ______ warrant discontinuation of retinoid therapy
3x the upper normal range
With isotretinoin, women with childbearing potential must have how many negative pregnancy tests
two negative results on a pregnancy test spaced 30 days apart and must practice effective contraception during treatment and for 1 month (2 months in some countries) after the completion of therapy.
Hypothyroidism may occur in patients taking these retinoids
Bexarotene and alitretinoin
both drugs bind to RXR that dimerizes with the nuclear thyroid receptor
concurrent use of these azoles and topical tretinoin can prolong the half-life of tretinoin locally in the skin, thereby aggravating local side effect
Ketoconazole and liarozole
The major avenue of tretinoin inactivation is through CYP26. Ketoconazole and liarozole are effective inhibitors of CYP26
Molecular storage form of retinol
Retinyl esters
Tazarotene is approved for what indications?
Acne, psoriasis, photoaging
