Topical Agents

Question 1

Where does most cell division occur in the skin?

Answer 1

BASAL LAYER

Question 2

What layer synthesizes more epidermal proteins (keratins)?

Answer 2

SPINOUS LAYER

Question 3

4 layers of skin

Answer 3

stratum corneum
granulosum
spinosum
basale

Question 4

What layer is the major barrier to percutaneous absorption?

Otherwise known as the?

Answer 4

stratum corneum

rate limiting step to percutaneous absorption

Question 5

3 absorption pathways of intact skin

Answer 5

shunt route (through appendages)

transcellular route (through corneocytes)

through intercellular lipid domains

Question 6

General Properties of topicals

Answer 6

ointments --> wetting
creams
gels
lotions/solutions
aerosols
pastes
powders
tinctures --> drying

Question 7

Partition Coefficient

Answer 7

Partitioning of drug from the vehicle into the stratum corneum

Question 8

Drug-Diffusion coefficient

Answer 8

Molecular aspects of the drug allowing diffusion across the skin layers

Question 9

Percutaneous Absorption (drug variables)

Answer 9

concentration - directly related to concentration applied

lipophilicity - most topically effective at least somewhat lipophilic

molecular size - less than 600 Daltons

Question 10

Percutaneous Absorption (Innate skin variables)

Answer 10

Stratum corneum thickness - thickness inversely related

cutaneous vasculature - increased will increase local/systemic drug effects

area of absorptive surface - increase SA will increase absorption

mucosal surfaces - far less innate barrier function

Question 11

Most penetration to least penetration

Answer 11

Mucous membranes
Scrotum
Eyelids
Face
Chest/Back
Arms/Legs
Dorsal hands/feet
Palmar/Plantar skin
Nails

Question 12

Topical Antibiotics used to treat acne

Answer 12

erythromycin - 50S ribosome inhibitor
Clindamycin - 50S ribosome inhibitor
metronidazole - DNA damage through free rads
Sodium-sulfacetamide - folate synthesis disruption

Question 13

Azelaic acid

Answer 13

Reduces inflammation- postulated to be due to free radical scavenging effects

Reduces keratinization

Keratolytic effects (loosening and shedding of top layers of stratum corneum) which cause desquamation

Question 14

Benzoyl Peroxide

Answer 14

Anaerobic antibacterial activity by releasing oxygen

Potential antiinflammatory actions by inhibiting activity of neutrophils

Keratolytic activity, which produces drying and desquamative actions

Comedolytic

More effective when used in combination with erythromycin, clindamycin, or adapalene

Question 15

Salicylic acid

Answer 15

topical keratolytic

increases solubilization of stratum corneum

clears comedones by desquamation

Question 16

Tretinoin MOA

Answer 16

decrease cohesiveness of follicular epithelial cells responsible for producing microcomedones

increase mitotic activity of follicular cells

reduce keratinization

Question 17

Adapalene MOA

important characteristic

Answer 17

Reduces cellular proliferation and inflammation
Comedolytic

Theorized that high lipophilicity prevents significant systemic exposure by allowing it to be trapped in the sebum

Question 18

Isotretinoin MOA

significant risk of?

Answer 18

Suppresses sebum production by inducing apoptosis sebum producing cells of the sebaceous glands

teratogenesis

Question 19

Tazarotene MOA

Adverse effects and contraindications (3)

Answer 19

Decreases inflammation and epidermal hyperproliferation

Teratogenic
Pregnancy category X (contraceptives should be used)
Photosensitivity

Question 20

Drugs for acne that inhibit sebaceous gland function

Answer 20

anti-androgens

oral contraceptives

isotretinoin

Question 21

Acetretin MOA

clinical use

contraindication

important characteristic

Answer 21

Exact mechanism is unknown, but it probably is due to activation of multiple types of retinoic acid receptors

Orally administered for severe, recalcitrant psoriasis

Highly teratogenic

Prolonged elimination time

Question 22

Calcipotriene MOA (2)

Adverse reactions

Answer 22

Inhibits proliferation of keratinocytes

Reduces inflammation - Inhibits production of IL-2 and IL-6 by T cells

Slight risk of hypercalcemia and hypercalciuria