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Pharmacology (Winter) > Dermatological Drugs > Flashcards

Dermatological Drugs Flashcards

1
Q

What are the functions of the skin?

A
  1. Thermoregulation
  2. Sensation
  3. Storage & Synthesis
  4. Protection
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2
Q

How does the skin thermoregulate?

A
  • Blood flow in the dermis helps the body adjust to cold (BV contract) and heat (BV relax).
  • In cold weather, the dermal blood vessels constrict,
    warm blood flow bypasses the skin.
  • Sweat glands- ~500 ml of sweat a day; up to 12 L a day
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3
Q

How does the skin have a sensation function?

A

Nerve endings for touch, pressure, temperature and
pain

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4
Q

How does the skin have a storage & synthesis function?

A
  • Stores lipids and water
  • Vitamin D synthesis
  • Collagenases (needed for turnover of collagen)
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5
Q

How does the skin have a protection function?

A
  • Physical barrier
  • Chemical barriers:
  • Acid secretions and dermcidin in sweat
  • Bactericidal substances in sebum
  • Melanin preventing ultraviolet damage
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6
Q

Topical vs. Transdermal Medications:

A

Topical
* Directly treat disorders of the skin
* Ideally the drug will stay in the skin (acting locally)

Transdermal
* Deliver drugs to other tissues
* Drug needs to make it to the blood stream (pen, through all layers of skin & then act systemically)

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7
Q

What is skin absorption?

A

Drugs have to make it across the stratum corneum
a) Across appendages (ex: hair follicle, sweat duct)
b) Transcellular
c) Intercellular (if small molecule, can squeeze b/t these cells)

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8
Q

What is a reservoir in terms of skin absorption?

A

Drugs can get stuck in the stratum corneum and can be
released later (causes a slow release b/c trapped in skin)

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9
Q

Chemical penetration enhancers:

A
  • Decrease barrier properties of skin
  • Often included in transdermal drug formulations (for systemic levels)
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10
Q

Topical therapies penetration influenced by:

A
  • Concentration of the drug (increase [ ], more able to get into skin layers)
  • Content of vehicle or base (ointment/cream)
  • Degree of hydration of the skin (if skin is dry, the drugs don’t pen the same way)
  • Patient age (thin as age increases)
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11
Q

For topical therapies, why is the area of application imp.?

A

Absorption is greater at flexural sites (elbows), so less potent drugs should be used

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12
Q

What are Emollients?

A
  • Diverse array of products
  • Creams, ointments, bath products, sprays
  • Increase skin hydration- soften and soothe rough, dry skin
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13
Q

What could the use of emollients do?

A

Use of emollients can increase topical drug penetration five fold

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14
Q

What is the topical tx in the elderly?

A

Substances enter aged skin more easily, but clearance into the circulation is slower because of changes in the dermal matrix and reduced vasculature

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15
Q

What is the drug metabolism in the skin?

A
  • Skin is a biochemical barrier

Dermis contains:
* Metabolizing enzymes
- CYP26A1, Phase I (oxidases, etc.), Phase II (glucuronidation, etc.)

Drug transporters
* Influx and efflux transporters
- P-glycoprotein etc.

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16
Q

What are Topical Corticosteroids?

A

Anti-inflammatory & Anti-pruritic (Anti-itch)

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17
Q

How do corticosteroids have anti-inflammatory properties in skin?

A

Anti-inflammatory and immunosuppressive action

  • REDUCE inflammatory cytokines
    – less cytokines means decreased T-cell activation, less inflammatory cell migration, etc.
  • indirect inhibition of phospholipase A2 & arachidonic acid synthesis which is needed for prostaglandin production
  • COX-2 synthesis is reduced
  • interferes w/ mast cell histamine release
  • vasoconstriction & decreased BV permeability
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18
Q

What are some adverse effects of topical steroid use?

A
  • Skin atrophy (thinning of skin)
  • Skin striae (stretch marks)
  • Infections may spread
  • Local hirsutism (increase hair growth @ that area)
  • Depigmentation
  • Use on eyelids can cause glaucoma
  • Abrupt cessation can cause disease rebound
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19
Q

Topical Corticosteroids for
Dermatologic Use Adverse Effects:

A
  • Higher potency formulations can cause systemic side
    effects if used on large areas and/or for prolonged
    periods
  • Vehicle can increase or decrease potency level
  • Delicate skin (flexure points at joints, face, etc.) use
    mild potency
  • Thick skin (palms of hands or soles of feet) use higher
    potency
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20
Q

What are the commonly prescribed topical corticosteroids?

A

Low - Hydrocortisone

Med - Triamcinolone

High - Betamethasone, Mometasone

Ultra-High - Clobetasol proprionate

21
Q

Noninflammatory vs. Inflammatory Acne:

A

Noninflammatory:
- open & closed comedones, papules, few pustules

Inflammatory:
- erythematous papules, pustules, possible scarring

22
Q

What are the causes of acne?

A
  • Excess keratin
  • Excess sebum
  • Clogged pores
  • P. acnes overgrowth
23
Q

What are Topical Retinoids?

A

Derivatives of vitamin A
* Adapalene, tazarotene,
tretinoin and isotretinoin

24
Q

What are Topical Retinoids mech of action?

A
  • Bind retinoic acid nuclear hormone receptors to alter DNA
    transcription
  • Decreases the size and the output of the sebaceous glands.
  • Decreases desquamation in
    follicles
  • Reduces the number of bacteria in the sebaceous glands and on the skin surface
  • Result: fewer blackheads and
    whiteheads (comedones)
25
What else do Topical Retinoids also do?
* Also improve acne scars and lighten hyperpigmented areas * 12-15 weeks to show a benefit * Often given in combo with topical antimicrobial therapy - Benzoyl peroxide (limits antimicrobial resistance)
26
What are adverse effects of Topical Retinoids?
* Skin desquamation (peeling), erythema (redness) * Can cause skin irritation (dermatitis) - Usually localized to the epidermis without inflammation - Subsides after a few weeks
27
What are Oral Acne Tx's?
Isotretinoin (Accutane) * Stronger reduction in sebum production and sebaceous glad size * Strong side effects when given systemically * Must monitor liver function and possible pregnancy * Hepatoxic and teratogenic * Generally taken for 3-6 months * For women- Oral contraceptives (particularly with anti-androgenic progestins)
28
What is the summary of acne tx's?
1. Excess Keratin: - Goal: decrease keratin shedding - Topical adapalene, tretinoin (Vitamin A derivatives) stop it 2. Excess Sebum: - Goal: decrease sebum production --> shut it down - Oral isotretinoin & anti-androgenic hormones - cyproterone acetate 3. Clogged pores: - Goal: prevent/remove blockage - Soaps, Benzyl peroxides, etc. 4. P. acnes overgrowth: - Goal: kill the bacteria - Benzyl peroxides, topical erythromycin, oral tetracycline
29
What is Eczema?
* Atopic dermatitis * Itchy, red, DRY, raised skin * Sometimes weeping blisters * Often in sensitive areas: inside elbows, back of knees, etc. * Often occurs in kids
30
How does Eczema occur?
* Not an allergic reaction; but more common in people with food allergies * Th2 T-cells are overactive producing IL-4 and IL-13 * Overactive immune system shortens lipids in the skin * This creates dry, cracked conditions that allow inflammation, irritants to enter and lesions to develop
31
What are Calcineurin inhibitors?
Tacrolimus and Pimecrolimus Very low systemic absorption after topical application
32
What are the adverse effects of Calcineurin Inhibitors?
* Burning sensation, irritation, redness * Possible increased risk of skin cancer or lymphoma * Generally, very well tolerated
33
What is Psoriasis?
* Chronic, inflammatory autoimmune skin disease * Causes itchy, scaly-white, raised red skin * Often on elbows, knees, scalp * Dry flakes of silvery-white skin scales result from the excessively rapid proliferation of skin cells (like Eczema, but raised & scaly - white flaky)
34
What is Psoriasis Pathogenesis?
* Defective inflammatory response (overactive Th17 T-cells) * Stimuli= stress, environment, medications, smoking, etc.
35
What are Psoriasis tx's?
Coal tar ointment * Also works for eczema * Relieves itching, irritation and scaling of the skin
36
What is the mech of action of Coal Tar Ointment for Psoriasis tx's?
* Keratolytic (break down keratin) * Reduces DNA synthesis and mitosis of keratinocytes * Slows bacteria growth * Looses and softens scales and crust
37
What are the drawbacks of Psoriasis tx's?
* Smelly (like tar) * Stains clothing or skin
38
What is the Psoriasis Tx: Topical Vitamin D Derivatives
Calcipotriol * Binds Vitamin D receptor with the same affinity as calcitriol (active metabolite of Vitamin D), but with only 1% of the calcium activity * Modulates T-cell gene expression, suppressing keratinocyte proliferation and inducing epidermal differentiation * Takes 8-12 weeks for max benefits
39
What are the adverse effects of Psoriasis Treatment: Topical Vitamin D Derivatives - Calcipotriol
* Hypercalcaemia may occur if used too much (b/c has ~ effects of Ca2+) * Skin irritation * Contraindicated in pregnancy (b/c vitamin D syn. is needed for pregnancy) * Should not be used on the face (b/c thinner skin on face)
40
What is Rosacea?
* Redness and visible blood vessels on the face * Pustules * Burning, itching rash * Enlarged nose (increase cartilage in nose to make it larger)
41
Where is Rosacea influenced by?
Influenced by genetics and triggered by environmental factors (cold weather, sun exposure, etc.) Pathophysiology not completely understood * Neurogenic component- burning and stinging suggests overactive nerves * Vascular component- vasodilation * Innate immune dysregulation and chronic inflammation- increased toll-like receptor 2 signalling on dermal macrophages
42
What are the tx's for Rosacea?
Brimonidine gel * Selective α2-adrenergic agonist * Causes vasoconstriction of the superficial dilated blood vessels, which leads to a reduction in facial erythema. Ivermectin cream * Known anti-parasitic drug with anti-inflammatory properties * Precise action in rosacea is unknown
43
What are the adverse effects of Brimonidine gel for Rosacea?
* include facial flushing, erythema (including rebound erythema) - opposite effect - vasodil instead of vasocon * and a burning sensation upon application.
44
What are the adverse effects of Ivermectin cream for Rosacea?
* Skin irritation * Burning sensation
45
What is the drug for Acne?
Topical retinoids (+ sometimes corticosteroids in addition)
46
What is the drug for Eczema?
Calcineurin inhibitors (+ sometimes corticosteroids in addition)
47
What is the drug for Psoriasis?
Vitamin D derivatives (+ sometimes corticosteroids in addition)
48
What is the drug for Rosacea?
Brimonidine, Ivermectin (+ sometimes corticosteroids in addition)

Pharmacology (Winter) (23 decks)

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