Skin Pharmacology (Lect 9)

Question 1

Functions of skin

Answer 1

• A barrier
• Thermoregulation
• Vitamin D synthesis
• Sensory organ

Question 2

Acne occurs due to

Answer 2

• Changes in circulating androgens stimulate sebaceous glands
  (hair follicles become blocked with sebum and debris)

Question 3

What is rosacea?

Answer 3

– 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

Question 4

What is eczema?

Answer 4

– 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.)

Question 5

What is pruritus?

Answer 5

– Refers to itch
– Common with eczema, urticaria and psoriasis, and largely due
to release of inflammatory mediators from mast cells

Question 6

What is Urticaria?

Answer 6

– Skin inflammation characterized by raised wheals/bumps
– Many causes (e.g. sun exposure, heat, cold, insect bites, food,
certain drugs, etc.)

Question 7

What is Psoriasis?

Answer 7

– Autoimmune condition characterized by inflammation and
hyperproliferation of keratinocytes
– Life-long condition (can reappear and disappear)

Question 8

What are warts?

Answer 8

– Infection with human papilloma virus
– Characterized by small raised lesions with an irregular shape
(hyperkeratinisation)

Question 9

What are Glucocorticoids?

Answer 9

• Transcription factors used to treat psoriasis, eczema, and pruritus

Question 10

What is the MOA of glucocorticoids?

Answer 10

– 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)

Question 11

Adverse Effects of Glucocorticoids

Answer 11

– 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

Question 12

Example of mildly potent glucocorticoid

Answer 12

hydrocortisone

Question 13

Examples of moderately potent glucocorticoids

Answer 13

• alclomethasone diproprionate
• clobetasone butyrate
• fludroxycortide,
• fluocortolone

Question 14

Examples of potent glucocorticoids

Answer 14

• beclomethasone diproprionate
• betamethasone
• fluocinolone
• acetonide
• flucocinonide
• fluticasone proprionate
• mometasone fuorate
• triamcinolone acetonide

Question 15

Examples of VERY potent glucocorticoids

Answer 15

• Clobetasol proprionate

- diflucortolone valerate

Question 16

What are retinoids?

Answer 16

• Are derivatives of retinoic acid (metabolites of vitamin
  A [retinol])

Used to treat
– Acne
– Eczema
– Psoriasis

Question 17

Examples of retinoids

Answer 17

– Tretinoin
– Isotretinoin (Accutane)
– Alitretinoin
– Tazarotene
– Bexarotene

Question 18

MOA of retinoids

Answer 18

– 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

Question 19

Adverse effects of retinoids

Answer 19

– Teratogenic (women should be using suitable contraception)
– Skin peeling

(NOT AS IMPORTANT)
– Dry/flaky skin
– Stinging/burning sensations
– Joint pain (oral administration)

Question 20

What is Bexarotene?

Answer 20

– A retinoid used to treat cutaneous T-cell lymphoma

– 100x more potent for RXR than RAR

Question 21

What is Bexarotene’s MOA?

Answer 21

– Blocks cell cycle progression
– Induces apoptosis and differentiation
– Inhibits angiogenesis and metastasis

Question 22

Primary Vitamin D analogues

Answer 22

– Calcitriol
– Calcipotriol
– Tacalcitol

Question 23

What are Vitamin D analogues used to treat ?

Answer 23

– Psoriasis

– Vitamin D is a mixture of several substances and plays an essential role in calcium/phosphate metabolism and in bone formation

Question 24

What is the MOA for Vitamin D analogues?

Answer 24

– Are agonists of the Vitamin D receptor (nuclear receptor)
– Reduce proliferation and increase apoptosis of keratinocytes
– Inhibit T cell activation

Question 25

Adverse Effects of Vitamin D analogues

Answer 25

– 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

Question 26

What are Keratolytics and what are they used to treat?

Answer 26

– Keratolytics break down keratin in the skin – Used to treat warts

Question 27

Examples of keratolytics

Answer 27

• α-hydroxy acids – Salicylic acid – Glycolic acid

Question 28

MOA of Keratolytics

Answer 28

– 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

Question 29

Adverse Effects of Keratolytics

Answer 29

– Local skin irritation (redness, itching) | – Salicylic acid toxicity (children at increased risk for systemic toxicity)

Question 30

Mechanism of action of Cryotherapy

Answer 30

– Removal of the wart by freezing | – Can involve liquid nitrogen, carbon dioxide, or dimethyl ether

Question 31

What is Imiquimod?

Answer 31

An immune modifier used to treat anogenital warts

Question 32

What is the MOA of Imiquimod?

Answer 32

– 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)

Question 33

Adverse effects of Imiquimod

Answer 33

– Local skin reactions (e.g. burning, itching, swelling) – Long-term skin reactions (e.g. pigmentation changes) – Systemic reactions (fatigue, diarrhea, flu-like symptoms, headache)

Question 34

What can immunosuppressants be used for?

Answer 34

For more serious cases of eczema or | psoriasis (or if glucocorticoids prove ineffective)

Question 35

What is ciclosporin and what is its MOA?

Answer 35

– An immunosuppressant MOA: – Cyclic peptide that binds to cyclophilin and inhibits calcineurin, which decrease IL-2 synthesis and the proliferation of T cells

Question 36

Adverse Effects of Ciclosporin

Answer 36

``` (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 ```

Question 37

What are Tacrolimus/Pimecrolimus and what are their MOA?

Answer 37

– (Immunosuppressant like ciclosporin) Macrolide compounds that also inhibit calcineurin to decrease IL-2 synthesis and the proliferation of T cells

Question 38

Adverse Effects of Tacrolimus/Pimecrolimus

Answer 38

– 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 ```

Question 39

What is Infliximab?

Answer 39

– 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)

Question 40

What is Adalimumab?

Answer 40

– A biologic for psoriasis – Humanized monoclonal antibody against TNFα – Reduces inflammation by neutralizing activity of TNFα (which is a pro-inflammatory cytokine)

Question 41

Secukinumab is a

Answer 41

monoclonal antibody against IL-17 (newer antibody for treatment of psoriasis)

Question 42

Ixekizumab is a

Answer 42

monoclonal antibody against homodimers of IL- | 17A (newer antibody for treatment of psoriasis)

Question 43

Ustekinumab is a

Answer 43

monoclonal antibody against IL-12 and IL-23 (newer antibody for treatment of psoriasis)

Question 44

Interleukin are key mediators of

Answer 44

INFLAMMATION