Pharmacology

Question 1

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

Answer 1

Topical, transdermal, subcutaneous/depot

Question 2

Which methods of drug administration via the skin are useful for systemic drug effects?

Answer 2

Transdermal and subcutaneous/depot injections

Question 3

What epithelial routes of drug administration exist? (excluding those involving the skin)

Answer 3

Airways, bladder/intravesicle, conjunctival sac, nasal mucosa, rectum and vagina

Question 4

What is the main advantage of epithelial drug administration?

Answer 4

High local concentration of the drug giving a strong local effect but minimal systemic effect

Question 5

What is the structure of the keratin layer?

Answer 5

Corneocytes surrounded by intercellular lipids in lamellar structures (brick and mortar model)

Question 6

What is the most pharmacologically relevant layer of the skin in terms of drug delivery?

Answer 6

Keratin layer

Question 7

How are corneocytes held together?

Answer 7

Intercellular corneodesmosomes

Question 8

What are intercellular lipids composed of? What ratio is this in?

Answer 8

Ceramides, cholesterol, free fatty acids. 1:1:1

Question 9

What are the different routes of drug transport through the keratin layer of the skin? What is the most common route?

Answer 9

Intercellular (most common) and transcellular.

Question 10

Normally only small, hydrophobic drugs may pass through the skin. T/F

Answer 10

True

Question 11

How can you increase the permeability of the skin to drugs?

Answer 11

Breaking down corneodesmosomes

Question 12

Intercellular lipids can act as a reservoir for the storage and slow release of lipophilic drugs. T/F

Answer 12

True

Question 13

What are the topical treatments for superficial skin disorders?

Answer 13

Glucocorticoids and retinoids

Question 14

What are the topical treatments for skin infections?

Answer 14

Antivirals, antibacterials, antifungals and antiparasitics

Question 15

What is the topical treatment for pruritis?

Answer 15

Antihistamines

Question 16

What is the topical treatment for dry skin?

Answer 16

Moisturising agents

Question 17

What is the topical treatment for warts?

Answer 17

Keratinolytics

Question 18

What are the vesicles used for topical drugs?

Answer 18

Ointments, creams, gels, lotions, pastes and powder

Question 19

What factors are important for deciding the vesicle of a topical drug?

Answer 19

Physiochemical properties and clinical condition

Question 20

What is Fick’s law?

Answer 20

J (the rate of absorption) = Kp (the permeability coefficient) x Cv (concentration of drug in the vehicle/concentration gradient)

Question 21

What does Kp consist of?

Answer 21

[Km (the partition coefficient) x D (the diffusion coefficient)]/ L (length of the diffusion pathway)

Question 22

Why is Fick’s law clinically important?

Answer 22

Km (the partition coefficient) and Cv (concentration of drug in the vehicle) are dependent on the choice of vehicle

Question 23

The best drugs for topical absorption are lipophilic/hydrophilic and dissolved in a hydrophilic/lipophilic base

Answer 23

Lipophilic and hydrophilic

Question 24

What can increase absorption of a topical drug?

Answer 24

Inclusion of excipients in the drug vehicle can increase drug solubility and so absorption

Question 25

The inclusion of excess, non-dissolved drug in topical applications (e.g transdermal patches) can be useful for what reason?

Answer 25

As the dissolved drug is absorbed by the skin the undissolved drug can migrate into the vehicle, therefore providing a fairly constant delivery rate

Question 26

Which physical and chemical factors can improve drug partitioning?

Answer 26

Hydration of the skin (occlusion - vehicle choice or clingfilm) Excipients which increase solubility

Question 27

Reducing the barrier function of the keratin layer increases drug partitioning. T/F

Answer 27

True

Question 28

Rank the thickness (and so lack of permeability) of different areas of the skin

Answer 28

Nails > palm/sole > trunk/extremities > face/scalp > scrotum

Question 29

What factors relating to the skin influence the absorption of topically applied drugs?

Answer 29

Skin thickness, skin hydration and integrity of the epidermis

Question 30

What factors improve the hydration of the skin in relation to drug absorption?

Answer 30

Vehicle choice and occlusive dressings

Question 31

Moist/weeping skin, dry skin and hairy skin will all have different vehicle choices respectively. T/F

Answer 31

True

Question 32

What factors relating to the drug influence the absorption of topically applied drugs?

Answer 32

Drug concentration, physiochemical properties of the drug, the drug salt, the vehicle

Question 33

Glucocorticoids are used in the treatment of atopic eczema. T/F

Answer 33

True

Question 34

What are the effects of topical glucocorticoids?

Answer 34

Anti-inflammatory, immunosuppressant, vasoconstricting & anti-proliferative against keratinocytes & fibroblasts

Question 35

What are the UK catagories of topical glucocorticoids?

Answer 35

Mild, moderate, potent and very potent

Question 36

Are adverse affects of glucocorticoids more likely with topical or oral administration?

Answer 36

Oral

Question 37

Is hydrocortosone acetate or butyrate the more potent of the two?

Answer 37

Hydrocortosone butyrate is potent (the other is mild)

Question 38

Describe the molecular mechanism of action of glucocorticoids

Answer 38

Glucocorticoids are lipophilic and so diffuse across the cell membrane > in the cytoplasm they combine with GR-alpha receptors > inhibitory heat shock proteins then dissociate > the receptors, now activated, translocates to the nucleus with the help of importins > monomeric receptors join into homodimers > homodimers bind to glucocorticoid response elements in the promotor regions of genes > specific genes are either transactivated or transrepressed > the rate of protein synthesis is altered

Question 39

What is the process subcutaneous drug delivery?

Answer 39

A needle is inserted into the skin to the depth of the adipose tissue

Question 40

How do drugs delivered by subcutaneous injection reach the systemic circulation?

Answer 40

Diffusion into capillaries or lymphatics (if high molecular weight)

Question 41

What are the advantages and disadvantages of subcutaneous drug delivery?

Answer 41

``` Advantages: -slow absorption -useful for protein drugs (e.g insulin) -useful for oil-based drugs (e.g steroids) -useful for introducing depot of drugs -simple procedure -painless Disadvantages: -limited injection volume ```

Question 42

Why is subcutaneous drug absorption relatively slow?

Answer 42

Poor vascular supply

Question 43

What are the reasons that the cutaneous route of drug administration may be desirable for systemic drug delivery?

Answer 43

- Easy & non-sterile application (topical only) - Steady-state plasma concentration can be achieved relatively easily - Avoidance of first pass metabolism - Drug absorption can be terminated easily

Question 44

What is the difficulty with subcutaneous drug administration when there is a desired systemic effect?

Answer 44

The skin is a tight barrier that only a few drugs can diffuse through at a reasonable concentration

Question 45

What is transdermal drug delivery?

Answer 45

Drug is incorporated into a patch applied to the skin allowing drug to diffuse across the epidermis at a rate controlled by the drug release membrane

Question 46

What features do drugs delivered by transdermal patches usually possess?

Answer 46

Low molecular weight, lipophilic, potent & possessing a short half life

Question 47

What are the advantages and disadvantages of transdermal drug delivery?

Answer 47

``` Advantages: -steady drug delivery rate -decreased dosing frequency -avoids first pass metabolism -can terminate drug delivery rapidly -easy & painless to apply -patients very compliant Disadvantages: -tendency for allergic reaction -few drugs suitable -expensive ```

Question 48

What chemical strategy can be used to increase transdermal drug delivery?

Answer 48

Inclusion of chemical enhancers which increase the permeability of the lipid matrix of the keratin layer

Question 49

What are the advantages and disadvantages of chemical enhancers?

Answer 49

Advantages: -low cost -easily incorporated into vehicles or patches Disadvantages: -may irritate skin -not useful for highly water soluble drugs/macromolecules

Question 50

What are some examples of chemical enhancers?

Answer 50

Water, solvents (e.g ethanol) and surfactants (e.g sodium dodecyl sulphate)

Question 51

Why is water a good chemical enhancer?

Answer 51

Prolonged occlusion causes increased hydration of the keratin layer and the formation of a pore pathway

Question 52

What are some physical strategies that can increase transdermal drug delivery?

Answer 52

Iontophoresis, electroporation, sonophoresis and microneedles

Question 53

What is iontophoresis? What drugs is it used for?

Answer 53

Low voltage electrical pulses are applied to the skin over a long period of time driving low molecular weight drugs of the same charge through the skin. Lidocaine and fentanyl

Question 54

What is electroporation?

Answer 54

Short lasting high voltage pulses being applied to the skin causing the formation of pores. Delivers hydrophilic and charged drugs to the skin

Question 55

What is sonophoresis?

Answer 55

The use of ultrasound to increase skin permeability

Question 56

What are microneedles?

Answer 56

Very small needles which punch microscopic holes in the skin