Dermatology Pharma

Question 1

Most important barrier to drug penetration?

Answer 1

Stratum corneum

Question 2

Stratum corneum composed of?

Answer 2

CORNEOCYTES (dead ketatinocytes) + lipids

Question 3

Lipids of stratum corneum act as?

Answer 3

Reservoir for lipophillic drugs (e.g. topical steroids)

Question 4

Drug transport through skin? (2)

Answer 4

Intercellular (majority) = in between corneocytes

Transcellular = through conreocytes

Question 5

Vehicles for topical drugs? (6)

Answer 5

Ointments, creams, gels, lotions, pastes, powders

Question 6

What affects choice of vehicle? (2)

Answer 6

The drug + the condition of the skin itself

Question 7

What process is transdermal drug delivery?

Answer 7

Passive process driven by diffusion

Question 8

Equation for rate of absorption?

Answer 8

J = KpCy

• J = rate of absorption
• Kp = permeability
• Cy = concentration of drug in vehicle

Question 9

What factors affect the rate of absorption of applied drug? (2)

Answer 9

• Dissolved concentration of drug in vehicle

* Partition of drug from vehicle to stratum corneum

Question 10

Rules for applied drug partition? (4)

Answer 10

• Lipophillic drug in lipophillic base = partitions well
• Lipophillic drug in hydrophillic base = partitions extremely well
• Hydrophillic drug in lipophillic base = poor partition
• Hydrophillic drug in hydrophillic base = remains on surface on skin

Question 11

What provides driving force for absorption in topical drugs?

Answer 11

The fraction of drug that is dissolved in the vehicle

Question 12

What are excipients?

Answer 12

Added to vehicle to enhance solubility + absorption

Question 13

How is steady rate of delivery maintained in transdermal patch?

Answer 13

When dissolved drug is absorbed undissolved drug dissolves + replaces it

Question 14

How can partitioning of topical drugs be improved? (2)

Answer 14

• Hydration of skin by occlusion (prevention of water loss)

* excipients

Question 15

Rank permeability of skin

Answer 15

Nail < palm/sole < trunk/limbs < face/scalp < scrotum

Question 16

Glucocorticoids used to treat? (3)

Answer 16

Eczema, psoriasis, pruritus

Question 17

Effects of glucocorticoids? (4)

Answer 17

Anti-inflam, immunosuppressant, vasoconstricting, anti-proliferating effects on keratinocytes + fibroblasts

Question 18

Vehicle for glucocorticoids?

Answer 18

Ointment > cream/lotion

Question 19

Types of glucocorticoid + potency? (2)

Answer 19

• Hydrocortisone acetate = mild

* Hydrocortisone butyrate = potent

Question 20

Long term use of higher potency steroids? (6)

Answer 20

• Steroid rebound
• Skin atrophy
• Systemic effects
• Infection
• Steroid rosacea
• Stretch marks + telangiectasia

Question 21

Molecular mechanism of action of glucocoerticoids?

Answer 21

Signal via nuclear receptors, specifically GRa

• Glucocorticoids are lipophillic and enter cells via diffusion
• Combine with GRa in cytoplasm causing it to dissociate from heat shock proteins
• Activated receptor enters nucleus and binds to GRE
• Transactivation/transrepression of specific genes

Question 22

Subcutaneous delivery of drug?

Answer 22

Drug delivered by needle into adipose tissue

Question 23

Advantage of SC route?

Disadvantage?

Answer 23

• Absorption is slow

* Injection volume limited

Question 24

Transdermal drug delivery most suitable for what drugs? (4)

Answer 24

• Low molecular weight
• Lipophilic
• Potent
• Brief half-life

Question 25

Advantages of TDD? (4)

Answer 25

* Steady drug delivery * Decreased dosing frequency * Avoidance of first pass * Rapid termination (short 1/2 life)

Question 26

Examples of TDD drugs?

Answer 26

Nicotine, GTN

Question 27

Physical enhancement of TDD? (4)

Answer 27

Iontophoresis, electroporation, sonophoresis, microneedles