Pharmacology

Question 1

What are the three major routes of drug administration?

Answer 1

Topical, Transdermal and Subcutaneous

Question 2

Answer 2

Question 3

What does the stratum corneum consist of?

Answer 3

Cornerocytes (hardened, dead keratinocytes), surrounded by intercellular lipids forming 10-30 sheets of tissue that are constantly shed (desquamated) and renewed

Question 4

Answer 4

Question 5

What is the differences between these routes and which is the principle route?

Answer 5

Principle route is intercellular

Question 6

Why can steriods be stored in the Stratum Coneneum?

Answer 6

The “mortar” is highly lipophillic, allowing highly lipophillic drugs such as steriods to be stored

Question 7

Describe the “brick and mortar” model

Answer 7

Brick: corneocytes suspended in aggegated keratin filaments embedded in a matrix of filagrin. Adjacent corneocytes are held together by corneodesmosomes

Mortar: Multiple bilayers of intercellular lipids (ceramides, cholesterol and free fatty acids). Highly hydrophobic and can act as a reservior for lipid soluble drugs (eg steriods).

Question 8

What is the most effective way for drugs to enter across the stratum corneum both locally and systemically?

Answer 8

Via intercellular route, and normally only allows the diffusion of small, hydrophobic drugs.

Question 9

What two factors dictate the choice of vehicle?

Answer 9

1) Physicochemical properties of the drug
2) The clincal condition

Question 10

What is Fick’s law of diffusion?

Answer 10

Question 11

What other factors does Kp, the permeability coefficient, take into account within Fick’s Law of Diffusion?

Answer 11

Question 12

What is the concentration of the drug and the partition coefficient of the drug highly dependant on?

Answer 12

The vehicle

Question 13

What are the important factors when considering the rate and extent of absorption of a topically applied drug?

Answer 13

• Solubility of the drug in vehicle (Cv)
• Maximising the movement (or partitioning) or the drug from vehicle to the stratum corneum (Km)

Question 14

Comment on each of these stages of drug absorption

Answer 14

1) Lipophilic drug is good for absorption. If in a lipophillic base, likes to dissolve, therefore vehicle retains drug
2) Can expect good partitioning
3) Hydrophillic cannot diffuse rapidly through strateum corneum

Question 15

What is the driving force for percutaneous absorption?

Answer 15

The concentration of soluble drug in the vehicle

Question 16

How can percutaneous absorption be enhanced?

Answer 16

By increasing the concentration of soluble drug in the vehicle. To do this, an inclusion of excipients such as propylene glycol can enhance solubility.

Question 17

Why are topically applied drugs generally poorly absorbed?

Answer 17

Because only a small fraction partitions into the stratum corneum

Question 18

What are the physical and chemical conditions which can improve partitioning?

Answer 18

• Hydration of the skin by occlusion (prevention of water loss) by using ointments, creams or even cling film!
• Increase the solubilty of hydrophobic drugs by inclusion of excipients such as propylene glycol

Question 19

Why should non specific prescribing be avoided, in particular reference to hydrocortisone?

Answer 19

Hydrocortisone comes in many forms and the salt can can vastly influence potency

Question 20

What must be considered when prescribing?

Answer 20

Where is the drug being applied, skin thickness, hydration of the skin, intergrity of the epidermis, drug concentration, vehicle, the drug salt

Question 21

What can glucocorticosteriod features vary with?

Answer 21

-Body site, state of skin, occlusion, vehicle, concentration of drug and form of drug

Question 22

Explain the mechanism of glucocorticosteriods in relation to this diagram

Answer 22

Question 23

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

Answer 23

Question 24

When is Transdermal drug delivery suitable and what are the advantages and disadvantages?

Answer 24