Module 4: Retinoids Flashcards
What are retinoids?
A class of chemical compounds that are natural derivatives of vitamin A or are chemically related to it. Synthetic retinoids are utilized in cosmetic formulations, clinical dermatology, and the tx of some forms of Ca.
What is the indication for tazarotene?
For mod to severe acne in combination regiman.
Topical used for psoriasis.
What is the pharmacologic category for tazarotene?
Acne products; keratolytic agent; reinoic acid derivative; topical skin product, acne
What is the MOA for tazarotene?
Synthetic, acetylenic retinoid which modulates differentiation and proliferation of epithelial tissue and exerts some degree of anti-inflammatory and immunological activity.
What are pharmacokinetic considerations for tazarotene?
A: Minimal following cutaneous application.
D: Retained in skin for prolonged periods after topical application
M: Prodrug, rapidly meatoblized via esterase hydrolysis to an active metabolite floowing topical application. The metabolite undergoes further hepatic metabolism.
E: Urine and feces (metabolites)
Onset: 1 week
Duration: Up to 3 months after a 3 month course
Half-life: 18 hours
What are pregnancy and lactation considerations for tazarotene?
Reproductive: pregnancy status before starting. Adequate birth control during use.
Pregnancy - contraindicated
Breastfeeding - Not known if present. Stick with topical use for breastfeeding.
What are common side effects of tazartone?
Derm: burning sensation of skin, desquamation, erythema of skin, exacerbation of psoriasis, pruritus, skin irritation, skin pain, stinging of the skin, xeroderma
Local: application-site irrication
What are drug reaction considerations for tazarotene?
None known.
What are contraindications and cautions with tazarotene?
Contraindications:
Pregnancy
Presence of seborrheic dermatitis
Cautions:
Photosensitivity
Skin irritation
For external use only
What are monitoring parameters with Tazarotene?
Disease severity in plaque psoriasis during therapy (reduction in erythema, scaling, induration)
Clinical response and skin tolerance
Evaluate pregnancy status prior to starting
What pharmacological category is Acitretin?
Retinoid-like compound.
What are common indications for acitretin?
Tx of severe psoriasis in adults.
What is the MOA for acitretin?
Binds to and activates all nuclear subtypes (alpha, beta and gamma) of retinoid X receptors (RXR) and retinoic acid receptors (RAR) to inhibit the expression of the proinflammatory cytokines IL-6, migration inhibitory factor-related protein-8 (MRP-8) and interferon-gamma. Resulting actions are anti-inflammatory and antiproliferative, and keratinocyte differentiation is normalized in the epithelium.
What are pharmacokinetic considerations for acitretin?
A: 72% when taken with food.
D: >99% protein bound, mainly albumin.
M: Metaoblized to cis-acitretin; both compounds further mtabolized. Concomitant ethanol use leads to the formation of etretinate (active)
E: feces (34-54%); urine (16-53%)
Onset: 3-6 months for full response; improvement may be seen in 8 weeks
Peak: 2-5 hours
Half-life: Acitretin = 49 hours; cis-acitretin = 63 hours; etretinate = 120 days
What are special prescribing considerations for acitretin?
Altered kidney function = plasma concentrations are lower in end-stage renal failure. Contraindicated in severe.
Contraindicated in severe liver impairment
Older adult = higher plasma concentrations are seen; however, no changes to half-life.
Safety in pediatrics not confirmed.
What are pregnancy and lactation considerations for acitretin?
Must not be used by patients who intend to become pregnant during or any time for at least 3 years following d/c.
Major birth defects have been reported.
Do not use during lactation.
What are common adverse effects of acitretin?
CNS: hyperesthesia, paresthesia, rigors
DERM: Chelitis, alopecia, exfoliation of skin, xeroderma, paronchyica, skin atrophy, acquired cutaneous adherence
Endocrine and metabolic: hypertriglyceridema, increase serum glucose, decreased HDL etc.
GI: Xerostomia
GU: Erythrocyturia, hematuria
Hematologic and oncologic: Leukocyuria, reticulocytosis etc.
Hepatic: increased liver enzymes
Neuromuscular and skeletal: increased creatine phosphokinase
Optho: Xerophthalmia
Resp: Rhinitis
What are significant adverse effects with acitretin?
hepatoxicity
pancreatitis
rhabdomyolysis
Angioedema
Urticaria
What are significant drug interactions with acitretin?
Methotrexate = increased risk for hepatotoxicity
Tetracyclines
May decrease effectiveness of hormonal contraceptive
May increase hypoglycemic effects of sulfonylureas
Alcohol increases conversion to long-acting compound
concurrent use with high doses of Vit A increases risk of hypervitaminosis A
What are contraindications and cautions with acitretin?
Contraindicated:
- concurrent use of alcohol
- concurrent methotrexate or tetracycline therapy
- Chronically elevated blood lipids
- Severe hepatic or renal impairment
- Pregnancy
- Lactation
- Pediatrics
Cautions:
- concurrent phototherapy (intensity of tx may need to be altered)
- Extreme caution in women of reproductive potential
What are monitoring parameters for acitretin?
- Lipid profile and LFT’s, CBC, renal function tests = baseline and subsequent
- blood glucose in patients with diabetes
- evaluate for bone abnormalities with long-term use
- Pregnancy test in pt’s of reproductive potential. (Require two negative urine or serum tests). Then repeated every 3 months for approx 3 years after discontinuation.
