Skin Pharmacology (Lect 9) Flashcards
Functions of skin
- A barrier
- Thermoregulation
- Vitamin D synthesis
- Sensory organ
Acne occurs due to
- Changes in circulating androgens stimulate sebaceous glands
(hair follicles become blocked with sebum and debris)
What is rosacea?
– Chronic hyperaemia of the facial skin
– Erythema spread across the nose, cheeks & forehead
– Erythema is due to vasodilation of blood vessels close to the
surface of the skin
What is eczema?
– A generic term referring to dry, itchy & inflamed skin
– Distributes usually on flexor surfaces (e.g. elbows, knees)
– Different types (e.g. atopic eczema, contact dermatitis, xerotic
eczema, etc.)
What is pruritus?
– Refers to itch
– Common with eczema, urticaria and psoriasis, and largely due
to release of inflammatory mediators from mast cells
What is Urticaria?
– Skin inflammation characterized by raised wheals/bumps
– Many causes (e.g. sun exposure, heat, cold, insect bites, food,
certain drugs, etc.)
What is Psoriasis?
– Autoimmune condition characterized by inflammation and
hyperproliferation of keratinocytes
– Life-long condition (can reappear and disappear)
What are warts?
– Infection with human papilloma virus
– Characterized by small raised lesions with an irregular shape
(hyperkeratinisation)
What are Glucocorticoids?
- Transcription factors used to treat psoriasis, eczema, and pruritus
What is the MOA of glucocorticoids?
– Inhibit release of inflammatory mediators from mast cells
– Inhibit neutrophil activation and emigration
– Inhibit immune cell activation
– Upregulate lipocortin expression (inhibits phospholipase A2, reducing formation of arachidonic acid-based inflammatory mediators)
– Inhibition of DNA synthesis and mitosis, reducing proliferation of epidermal cells
– Topical application produces vasoconstriction of the skin (‘blanching’ reaction)
Adverse Effects of Glucocorticoids
– Steroid rebound
– Skin atrophy (skin thinning)
(NOT AS IMPORTANT) – Systemic effects (not common with topical application) – Spread of infection – Steroid rosacea – Production of stretch marks
Example of mildly potent glucocorticoid
hydrocortisone
Examples of moderately potent glucocorticoids
- alclomethasone diproprionate
- clobetasone butyrate
- fludroxycortide,
- fluocortolone
Examples of potent glucocorticoids
- beclomethasone diproprionate
- betamethasone
- fluocinolone
- acetonide
- flucocinonide
- fluticasone proprionate
- mometasone fuorate
- triamcinolone acetonide
Examples of VERY potent glucocorticoids
- Clobetasol proprionate
- diflucortolone valerate
What are retinoids?
- Are derivatives of retinoic acid (metabolites of vitamin
A [retinol])
Used to treat
– Acne
– Eczema
– Psoriasis
Examples of retinoids
– Tretinoin – Isotretinoin (Accutane) – Alitretinoin – Tazarotene – Bexarotene
MOA of retinoids
– Are agonists of the retinoic acid receptor
(RAR) and retinoid X receptor (RXR)
– Are transcription factors that induce/repress gene transcription
– Reduce sebaceous gland activity & sebum production
– Have some anti-inflammatory actions
Adverse effects of retinoids
– Teratogenic (women should be using suitable contraception)
– Skin peeling
(NOT AS IMPORTANT)
– Dry/flaky skin
– Stinging/burning sensations
– Joint pain (oral administration)
What is Bexarotene?
– A retinoid used to treat cutaneous T-cell lymphoma
– 100x more potent for RXR than RAR
What is Bexarotene’s MOA?
– Blocks cell cycle progression
– Induces apoptosis and differentiation
– Inhibits angiogenesis and metastasis
Primary Vitamin D analogues
– Calcitriol
– Calcipotriol
– Tacalcitol
What are Vitamin D analogues used to treat ?
– Psoriasis
– Vitamin D is a mixture of several substances and plays an essential role in calcium/phosphate metabolism and in bone formation
What is the MOA for Vitamin D analogues?
– Are agonists of the Vitamin D receptor (nuclear receptor)
– Reduce proliferation and increase apoptosis of keratinocytes
– Inhibit T cell activation
Adverse Effects of Vitamin D analogues
– Systemic (oral) administration
▪ Hypercalcemia
▪ GI pain
▪ Renal stones
(NOT AS IMPORTANT)
– Skin irritation (topical administration)
– Avoid in people with problems related to calcium or bone
metabolism
What are Keratolytics and what are they used to treat?
– Keratolytics break down keratin in the skin
– Used to treat warts
Examples of keratolytics
• α-hydroxy acids
– Salicylic acid
– Glycolic acid
MOA of Keratolytics
– By breaking down keratin, these agents reduce thickness of the stratum corneum
- Solubilize the protein components of desmosomes
- Activate endogenous hydrolytic enzymes within the stratum corneum
- Diffuse into the stratum corneum and increase water content making the tissue easier to physically debride
Adverse Effects of Keratolytics
– Local skin irritation (redness, itching)
– Salicylic acid toxicity (children at increased risk for systemic toxicity)
Mechanism of action of Cryotherapy
– Removal of the wart by freezing
– Can involve liquid nitrogen, carbon dioxide, or dimethyl ether
What is Imiquimod?
An immune modifier used to treat anogenital warts
What is the MOA of Imiquimod?
– Enhances both the innate and acquired immune response
▪ Binds toll-like receptors on B cells
▪ Increases release of inflammatory mediators (e.g. TNFα and interleukins)
Adverse effects of Imiquimod
– Local skin reactions (e.g. burning, itching, swelling)
– Long-term skin reactions (e.g. pigmentation changes)
– Systemic reactions (fatigue, diarrhea, flu-like symptoms, headache)
What can immunosuppressants be used for?
For more serious cases of eczema or
psoriasis (or if glucocorticoids prove ineffective)
What is ciclosporin and what is its MOA?
– An immunosuppressant
MOA:
– Cyclic peptide that binds to cyclophilin and inhibits calcineurin, which decrease IL-2 synthesis and the proliferation of T cells
Adverse Effects of Ciclosporin
(MAIN) – Nephrotoxicity (not related to calcineurin inhibition) – Hepatotoxicity – Hypertension
(LESS SERIOUS) – anorexia – lethargy – hirsutism – tremor – Paresthesia (tingling, prickling sensations in hands and toes) – GI disturbances
What are Tacrolimus/Pimecrolimus and what are their MOA?
– (Immunosuppressant like ciclosporin) Macrolide compounds that also inhibit calcineurin to decrease IL-2 synthesis and the proliferation of T cells
Adverse Effects of Tacrolimus/Pimecrolimus
– Similar adverse effects to ciclosporin, but also
• hyperglycemia
• alopecia (tacrolimus only)
(MAIN) – Nephrotoxicity (not related to calcineurin inhibition) – Hepatotoxicity – Hypertension
(LESS SERIOUS) – anorexia – lethargy – hirsutism – tremor – Paresthesia (tingling, prickling sensations in hands and toes) – GI disturbances
What is Infliximab?
– A biologic for psoriasis
– Chimeric neutralizing antibody against tumor necrosis factor α (TNFα)
– Reduces inflammation by neutralizing activity of TNFα (which is a pro-inflammatory cytokine)
What is Adalimumab?
– A biologic for psoriasis
– Humanized monoclonal antibody against TNFα
– Reduces inflammation by neutralizing activity of TNFα (which is a pro-inflammatory cytokine)
Secukinumab is a
monoclonal antibody against IL-17 (newer antibody for treatment of psoriasis)
Ixekizumab is a
monoclonal antibody against homodimers of IL-
17A (newer antibody for treatment of psoriasis)
Ustekinumab is a
monoclonal antibody against IL-12 and IL-23 (newer antibody for treatment of psoriasis)
Interleukin are key mediators of
INFLAMMATION
