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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
Q

What else do Topical Retinoids also do?

A
  • 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
Q

What are adverse effects of Topical Retinoids?

A
  • Skin desquamation (peeling), erythema (redness)
  • Can cause skin irritation (dermatitis)
  • Usually localized to the epidermis without inflammation
  • Subsides after a few weeks
27
Q

What are Oral Acne Tx’s?

A

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
Q

What is the summary of acne tx’s?

A
  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
Q

What is Eczema?

A
  • 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
Q

How does Eczema occur?

A
  • 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
Q

What are Calcineurin inhibitors?

A

Tacrolimus and Pimecrolimus

Very low systemic absorption after topical application

32
Q

What are the adverse effects of Calcineurin Inhibitors?

A
  • Burning sensation, irritation, redness
  • Possible increased risk of skin cancer or lymphoma
  • Generally, very well tolerated
33
Q

What is Psoriasis?

A
  • 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
Q

What is Psoriasis Pathogenesis?

A
  • Defective inflammatory response (overactive Th17 T-cells)
  • Stimuli= stress, environment, medications, smoking, etc.
35
Q

What are Psoriasis tx’s?

A

Coal tar ointment
* Also works for eczema
* Relieves itching, irritation and scaling of the skin

36
Q

What is the mech of action of Coal Tar Ointment for Psoriasis tx’s?

A
  • Keratolytic (break down keratin)
  • Reduces DNA synthesis and mitosis of keratinocytes
  • Slows bacteria growth
  • Looses and softens scales and crust
37
Q

What are the drawbacks of Psoriasis tx’s?

A
  • Smelly (like tar)
  • Stains clothing or skin
38
Q

What is the Psoriasis Tx:
Topical Vitamin D Derivatives

A

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
Q

What are the adverse effects of Psoriasis Treatment:
Topical Vitamin D Derivatives
- Calcipotriol

A
  • 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
Q

What is Rosacea?

A
  • Redness and visible blood
    vessels on the face
  • Pustules
  • Burning, itching rash
  • Enlarged nose (increase cartilage in nose to make it larger)
41
Q

Where is Rosacea influenced by?

A

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
Q

What are the tx’s for Rosacea?

A

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
Q

What are the adverse effects of Brimonidine gel for Rosacea?

A
  • include facial flushing, erythema (including
    rebound erythema)
  • opposite effect
  • vasodil instead of vasocon
  • and a burning sensation upon application.
44
Q

What are the adverse effects of Ivermectin cream for Rosacea?

A
  • Skin irritation
  • Burning sensation
45
Q

What is the drug for Acne?

A

Topical retinoids

(+ sometimes corticosteroids in addition)

46
Q

What is the drug for Eczema?

A

Calcineurin inhibitors

(+ sometimes corticosteroids in addition)

47
Q

What is the drug for Psoriasis?

A

Vitamin D derivatives

(+ sometimes corticosteroids in addition)

48
Q

What is the drug for Rosacea?

A

Brimonidine, Ivermectin

(+ sometimes corticosteroids in addition)

Pharmacology (Winter) (23 decks)

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