Dermatopharmacology Flashcards
MOA of Antihistamines?
H1 and H2 antihistamines are inverse agonists (downregulate constitutively activated state of receptor ) or antagonists at histamine receptors
Which Histamine receptor mediates itch in the skin?
H1
What antihistamines are safe in pregnancy? What pregnancy category?
Chlorpheniramine or Diphenhydramine have the longest safety record. Category B. Also safe in lactation.
First generation H1 antihistamine SE?
sedation and anticholinergic (dry mouth, constipation, dysuria, blurred vision)
Name 4 first generation H1 blockers.
hydroxyzine, diphenhydramine, chlorpheniramine, cyproheptadine (interferes with hypothalmic function–> increased appetitie and growth retardation in children)
Fexofenadine is an active metabolite of what drug that was withdrawn?
metabolite of terfenadine (which was withdrawn for QT elongation and torsades de pointes)
Loratadine dosage needs to be adjusted for
People with hepatic or renal impairment
Cetirizine (zyrtec) dosage needs to be adjusted for
People with hepatic or renal impairment
What is the most sedating of 2nd generation antihistamines?
Cetirizine (zyrtec). Metabolite of hydroxyzine
how are desloratadine and loratadine different?
Desloratadine is 5x more potent than loratadine
Doxepin side effects include
orthostatic hypotension, anticholinergic
Do not give doxepin to patients with
bipolar (induce manic episodes in patients with manic depressive disorder), severe heart disease (risk of heart block), severe depression (black box warning for suicides), seizure (decreases seizure threshold)
Retinoids have 3 interconvertable forms
Retinol, retinal, retinoic acid
Retinoids bind to two families of nuclear receptors
retinoic acid receptors (RAR) and retinoid X receptors (RXR). Each class has an alpha, beta and gamma
What are the most abundant retinoid receptors in skin?
RAR-gamma > RXR-alpha RARG» RXRA
What are the downstream effects of retinoids?
Inhibits AP1, NF-IL6
Inhibits TLR2
Antikeratinization (inhibits ornithine decarboxylase)
Down regulated K6, K16
Increases Th1 cytokines, Decreases TH2 cytokines
SE of systemic retinoids: mucocutaneous. name 5
cheilitis, photosensitivity, staph aureus colonization, pyogenic granuloma, sticky sensation
SE of systemic retinoids: systemic. Name one rare one.
pseudotumor cerebri, pancreatitis 2/2 hypertriglyceridemia, diffuse idiopathic skeletal hyperostosis (DISH), calcification of tendons/ligaments, premature epiphyseal closure
What triglyceride level should you discontinue isotretinoin? Highest risk retinoid?
TG> 800 because of risk of pancreatitis. Highest risk retinoid is bexarotene
What LFT value should you discontinue isotretinoin? Highest risk retinoid?
LFT> 3x ULN. Highest risk retinoid is acitretin.
What teratogenicity does isotretinoin have?
Spontaneous abortion in 20%. No defects at birth, but will have decreased mental function (30% have gross mental retardation, 60% have mild mental deficits)
What patients have the highest risk of DISH? (diffuse idiopathic skeletal hyperostosis (DISH)
People who have been on low dose isotreitnoin for many years. And people who have had multiple courses of isotretinoin.
What are specific features of retinoid embyropathy?
Craniofacial, CNS, CV, Thymic. Microtia (small ears), cleft palate, microophthalmia, hypertelorism, microcephaly, cardiac septal defects, tetralogy of Fallot, thymic aplasia
Bexarotene cannot be given with which lipid/cholesterol lowering agent?
- Gemfibrozil (inhibits CYP 3A4), causing high levels of bexarotene –> causes severe hypertriglyceridemia
- Simvastatin (CYP 3A4)