Pharmacology

Question 1

What are the main routes of drug administration in the skin?

Answer 1

Topical
Transdermal
Subcutaneous

Question 2

Other than the skin, what other epithelial routes can be used for drug administration?

Answer 2

Airways 
Bladder
Conjunctival sac 
Nasal mucosa
Rectum
Vagina

Question 3

What is the single most important barrier to drug penetration?

Answer 3

The stratum corneum (keratin layer)

Question 4

What makes up the stratum corneum?

Answer 4

corneocytes (hardened, dead, keratinocytes)

surrounded by intercellular lipids forming 10 - 30 sheets of tissue (these are constantly shed and renewed)

Question 5

What are the two routes by which drugs can travel through the stratum corneum?

Answer 5

Transcellular

Intercellular

Question 6

What holds adjacent corneocytes together?

Answer 6

corneodesmosomes

Question 7

describe the structure of the intercellular route

Answer 7

multiple bilayers of lamellar structures of intercellular lipids

Highly hydrophobic and can act as a reservoir for lipid-soluble drugs (e.g. topical corticosteroids)

Question 8

In what conditions are topical agents most likely to be used?

Answer 8

superficial skin disorders 
skin infections
itching (pruritus) 
dry skin 
warts

Question 9

What formula describes the factors which influence absorption of a topical drug?

Answer 9

Fick’s Law of Diffusion

                                 J = KpCv

J = Rate of absorption 
Kp = permeability coefficient 
Cv = concentration of drug in the topical medication

Question 10

What part of topical drugs provides the driving force for absorption?

Answer 10

soluble fraction

Question 11

What substances can be added to topical drugs to aid solubility?

Answer 11

excipients (e.g. propylene glycol)

Question 12

What factors can affect the absorption of topical drugs?

Answer 12

• Site of application (thickness of stratum corneum)
• hydration of the skin
• Integrity of the epidermis
• drug concentration / physicochemical properties
• drug salt (hydrocortisone butyrate far more potent than hydrocortisone acetate)
• vehicle (betamethasone valerate more active as an ointment than as a cream, or lotion)

Question 13

How are subcutaneous drugs delivered to the body?

Answer 13

needle inserted into the fatty (adipose) tissue just beneath the surface of the skin

Drug reaches systemic circulation by diffusion into either:

• capillaries
• lymphatic vessels (particularly high molecular weight compounds)

Question 14

What are the advantages of subcutaneous drugs?

Answer 14

Absorption = slow

Relatively simple and painless

Route of administration for many protein drugs (e.g. insulin)

Suitable for administration of oil-based drugs (e.g. steroids)

Used to introduce depot of drug under skin that is slowly released into the circulation:

• certain contraceptive steroids (medroxyprogesterone)
• antipsychotic drugs (fluphenazine decanoate)

Question 15

What disadvantage do subcutaneous drugs have?

Answer 15

Injection volume is limited

Question 16

Why is the skin an attractive route of drug administration for a systemic effect?

Answer 16

Application = simple and non-sterile

Allows steady-state plasma concentration (Cpss) of drug to be achieved over a prolonged period of time

Avoids first pass metabolism

Drug absorption can be terminated rapidly

Question 17

What drugs are most suitable for transdermal delivery?

Answer 17

(i) low molecular weight
(ii) moderately lipophilic
(iii) potent
(iv) of relatively brief half-life (t½)

Question 18

What are the advantages of transdermal drug delivery?

Answer 18

• Steady rate of drug delivery
• decreased dosing frequency,
• avoidance of first-pass metabolism
• rapid termination of action (if t½ is short)
• User friendly, convenient, painless

Question 19

What are the disadvantages of transdermal drug delivery?

Answer 19

• Relatively few drugs suitable
• allergies
• cost

Question 20

Give examples of drugs that can be administered transdermally?

Answer 20

nicotine
GTN
Fentanyl
estradiol

Question 21

What do chemical enhancers do to improve transdermal drug delivery?

Answer 21

interact with the lipid matrix of the stratum corneum to increase permeability

(mainly to drugs that already cross the skin reasonably well)

Question 22

What agents can be used to chemically enhance a transdermal patch?

Answer 22

Water – increased hydration of the stratum corneum and the formation of a ‘pore’ pathway

Variety of solvents (e.g. ethanol) and surfactants (e.g. sodium dodecyl sulphate)