Retinoidsin Skin Disease and Care- Class of natural and synthetic compounds chemically related to vitamin A
- Vitamin A exists in three interconvertible forms: retinol (vitamin A alcohol), retinal (aldehyde), retinoic acid (acid)
- Function
- Normalizes keratinization (allowing for decrease in follicular occlusion): inhibits ornithine decarboxylase, inhibits collagenase, downregulates proliferative keratins (K6 and K16), increases filaggrin production/keratin filaments/ KHGs, antagonizes function of AP-1 and IL-6, downregulates TLR2
- Binds two types of nuclear receptors: retinoic acid receptors (RARs) and retinoid X receptors (RXRs)
- RARs: all-trans RA ligand, RARγ is the most ubiquitous RAR in human skin and likely main mediator of retinoid effects on keratinocytes, nuclear receptors activated and gene transcription affected
- RXRs: cis RA ligand, receptors activated in bexarotene
- Retinoids classified into three generations (see Table 7-7)
- Isotretinoin
- 13-cis retinoic acid; increased absorption with fatty meal; half-life 18–20 h; goal cumulative dose 120–150 mg/kg (0.5–2 mg/kg/day for 16–20 weeks); start with lower dose in markedly inflammatory acne
- Results in atrophy of sebaceous glands, reduction in sebum (up to 90%) so P. acnes unable to thrive, normalization of follicular keratinization
- Treatment for nodulocystic acne, recalcitrant inflammatory acne, pyoderma faciale, acne fulminans, and gramnegative folliculitis
- Females must avoid pregnancy for at least 1 month after discontinuing drug
- Side effects: cheilitis, xerosis, alopecia, skin fragility, eczematous dermatitis, photophobia, keratitis, myalgias (associated with ↑ creatine phosphokinase levels), headache, pseudotumor cerebri (with concomitant TCN use), skeletal hyperostosis, premature closure of epiphyseal plates, teratogenicity, elevated triglycerides (25–45%, most common lab abnormality), elevated liver transaminases, reduced night vision, pyogenic granulomas, staph colonization
- Retinoid teratogenicity: craniofacial, cardiac, thymic, and CNS malformations
- Acitretin:
- Metabolite of etretinate; half-life 2 days
- Females must avoid pregnancy for at least 3 years after discontinuing acitretin (since drug can re-esterify to etretrinate, which is highly lipophilic with 120 day half-life)
- Side effects: teratogenicity, hyperlipidemia, alopecia, arthralgias, abnormal liver function tests, reduced night vision, bone and joint pain, pseudotumor cerebri, xerosis of mucous membranes
| | | | | | Gemfibrozil may increase plasma
level of bexarotene | | | | | |
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- RXR-specific retinoid; approved for treatment of cutaneous T-cell lymphoma (CTCL); half-life 7–9 h; metabolized by cytochrome p450 enzymes and elimination via hepatobiliary system
- SE: similar to other retinoids with addition of
drug-induced hypothyroidism
| | | | | | | Table 7-7 Retinoids | | | Generation of Retinoid | | Name | | Half-life | | | First generation | | Tretinoin (all-trans RA)
Isotretinoin (13-cis RA) | | Half-life: 48 min
Half-life: 20 h | | | Second generation | | Etretinate
Acitretin | | Half-life: 120 days (highly lipophilic)
Half-life: 50 h | | | Third generation | | Tazarotene, Adapalene
Bexarotene | | Half-life: 7 h | | | | | | | |
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