Derm Pharmacology Flashcards
Retinoids
Retinoids are Vitamin A derivatives
Oral
First-generation – Tretinoin, Isotretinoin (Accutane)
Second-generation – Acitretin (Soriatane)
Third-generation – Bexarotene
Topical
Topical Tretinoin (Retin-A)
Adapalene (Differin)
Tazarotene (Tazorac)
Indications for Retinoids
● Acne, photoaged skin
○ Isotretinoin (PO)
○ Topical Tretinoin
○ Adapalene
○ Tazarotene
● Psoriasis, keratinizing disorders
○ Acitretin (PO)
● Cutaneous T-cell lymphoma
○ Bexarotene (PO)
Contraindications to using retinoids
● PREGNANCY
● Coadministration with tetracyclines
Mechanism of Action of retinoids
● A retinoid is a molecule that binds to and activates RARs (retinoic acid
receptors)
● Retinoid receptors act as transcription factors; they activate gene transcription
○ Increased growth factors are released → results in epidermal hyperplasia and thickened skin (caused by the increased proliferation
of basal keratinocytes)
○ As a consequence of the hyperplasia, subsequent desquamation and peeling of the skin occur
Acne – Isotretinoin MOA
○ Decreases sebum secretion and sebaceous
gland size
○ Reduces the abnormal follicular epithelial
differentiation and desquamation
○ Reduces inflammation
○ Reduces comedogenesis
○ Reduces colonization with
Cutibacterium acnes
Retinoid MOA for photoaged skin
○ Partial restoration of reduced
collagen levels in sun-exposed skin
Cutaneous T-cell Lymphoma - Retinoid MOA
○ Bexarotene is 100x more potent for retinoid X receptors
■ Blocks cell cycle progression
■ Induction of apoptosis and differentiation
■ Prevention of multidrug resistance
■ Inhibition of angiogenesis and metastasis
Retinoids pharmacokinetics
● Metabolized by the liver
● Oral retinoids are lipophilic; absorption is increased with fatty foods
● Topical retinoids have limited systemic absorption, however, it is recommended
to delay treatment until after the pregnancy
Source: Epocrates
● Acitretin converts to etretinate when taken with alcohol
Retinoids side effects
● Mucocutaneous – cheilitis (chapped lips),
xeroderma (dry skin), skin peeling,
epistaxis (nose bleeds)
○ Cheilitis appears in almost all patients
taking isotretinoin
● Myalgias – back pain and joint pain
○ Occurs in up to 50% of patients
● Hyperostosis – excessive bone growth
○ Usually occurs after 5 years of treatment; is generally asymptomatic
● Photosensitivity
Less Common Side Effect of Retinoids
Reversible increase in liver enzymes
Benzoyl Peroxide MOA
May also be combined with topical antibiotics
Available in many OTC products
● Antiseptic effects against
Cutibacterium acnes
● Opens pores
Indications for Benzoyl Peroxide
Considered first-line for mild to
moderate acne with no inflammation
Side Effects (Common) of benzoyl peroxide
● Dry skin, peeling, and irritation
● Contact dermatitis
● Xerosis
● Erythema
● Skin peeling
Topical Steroids indications
● Many…
● Common and responsive conditions
○ Psoriasis
○ Atopic dermatitis
○ Eczema
○ Seborrheic dermatitis
○ Contact or irritant dermatitis
Contraindications to topical steroid use
Active infection in the skin
Topical Steroids MOA
● Anti-inflammatory properties → benefits
● Immunosuppression → benefits inflammatory skin lesions
● Antimitotic, or antiproliferative → benefits highly proliferative conditions (scaling lesions)
● Vasoconstrictor → benefit is cosmetic (decreases redness and swelling)
Pharmacokinetics of topical steroids
● Absorption
○ Minimal absorption with application to normal skin
○ Occlusion of drug (i.e. covering it with a plastic film) increases absorption by a
factor of 10
○ Increased absorption in inflamed skin
Potency grading of topical steroids
○ Graded on a scale of 1-7 (1 = most potent)
○ Depends on delivery vehicle, concentration and the salt (ester derivative) to which the steroid is
bound
Potency order based on form of topical steroids
Ointments > creams > gels > lotions > foams > solutions
Side effects of topical steroids
● More prevalent with higher-potency
steroids, larger surface area covered,
and longer durations
● Skin atrophy
○ Shiny, thin skin; telangiectasia,
ecchymoses, striae, redness,
pigmentation changes
Adverse reactions of topical steroids
● Systemic absorption → systemic
side effects – adrenal suppression, Cushing’s syndrome, hypertension, mood changes
● Glaucoma (rare, associated with periorbital application)
Imiquimod
Imiquimod modifieds the immune response in the skin
Imiquimod indications
● Genital and perianal warts resistant to
conventional therapy
● Actinic keratoses
● Basal cell carcinoma
Imiquimod Mechanism of Action
● It enhances the innate and acquired immune systems which stimulates a
response against abnormal skin cells
○ Binds to Toll-like receptors on B cells
○ Increases release of inflammatory mediators (interferon, TNF, interleukins)
○ Increases immune cell activity
○ Has direct apoptosis activity with tumor cells
○ Causes an increased inflammatory reaction in the dermis → abnormal cells are destroyed
