pharmacology

Question 1

what are major routes for drug administration

Answer 1

Topical
Transdermal
Subcutaneous

Question 2

what is the brick and mortar model of the stratum corneum

Answer 2

Bricks = corneocytes containing keratin microfilaments embedded in a filaggrin matrix surrounded by a cornfield cell envelope. Corneocytes are highly cross linked by protein ‘rivets’ providing tensile strength

Mortar = multiple lamelluluar structures of intracellular lipids. A largely hydrophobic ‘intracellular glue’ that can also act as a reservoir for lipid soluble drugs

Question 3

how is drug delivery across the stratum corneum when applied topically

Answer 3

It is a passive process mediated by diffusion. Local and systemic effects of drugs requires movement into and through the stratum corner - mainly the intercellular route allowing diffusion of small hydrophobic drug

Question 4

what is the choice of vehicle dictated by

Answer 4

• physiochemical properties of the drug

- the clinical condition

Question 5

what is a vehicle

Answer 5

base in which the drug is dissolved

Question 6

what are important factors in the rate and extent of absorption of a topically applied drug

Answer 6

• dissolved concentration of the drug in vehicle

- the movement (or partitioning) of the drug from vehicle into the stratum corneum and deeper

Question 7

where do hydrophilic drugs and lipophilic drugs move

Answer 7

hydrophilic drugs move into aqueous environment

lipophilic drugs would accumulate in lipid environment

Question 8

what provides the driving force for skin penetration for drugs applied topically

Answer 8

the fraction within the vehicle solubilised (Cv)

Question 9

what can improve partitioning

Answer 9

• hydration of the skin by occlusion (prevention of water loss by evaporation)
• inclusion of excipients that also increase the solubility of hydrophobic drugs

Question 10

what factors influence absorption of topically applied drugs

Answer 10

• nature of the skin ie site of application, hydration of the skin and integrity of the epidermis
• drug and pharmaceutical preparation ie drug conc and properties, the drug salt, the vehicle

Question 11

what is subcutaneous route of adminstration

Answer 11

drug delivered by a needle into the fatty tissue just beneath the skin surface

Question 12

how does the drug reach systemic circulation by the subcutaneous administration

Answer 12

by diffusion into either capillaries or lymphatic vessels

Question 13

what are advantages and disadvantages of the subcutaneous route of administration

Answer 13

advantages

• absorption is relatively slow due to poor vascular supply
• route of administration for many protein drugs and suitable for administration of oil based drugs
• can be used to introduce a depot of drug and drug under the skin that is very slowly released into the circulation
• relatively simple and fairly painless

disadvantages
- injection volume limited

Question 14

what is transdermal drug delivery

Answer 14

drug is usually incorporated into an adhesive patch applied to the epidermis

drug absorption is controlled by a drug release membrane - occurs by diffusion across a cuteness barrier

Question 15

what are advantages and disadvantages of transdermal drug delivery

Answer 15

advantages

• steady rate of drug delivery, decreased dosing frequency, avoidance of first pass metabolism, rapid termination of action
• user friendly

disadvantages
- relatively few drugs suitable for TDD, allergies, cost

Question 16

what are strategies to enhance transdermal drug delivery

Answer 16

• chemical enhancement - enhancers interact with the lipid matriculates of the stratum corneum to increase permeability, mainly to drugs that already cross the skin reasonably well

advantage - low cost, can be incorporated into vehicles or conventional patches

disadvantage - skin irritation, not effective for highly water soluble drugs