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Dermatology > Pharmacology > Flashcards

Pharmacology Flashcards

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Dermatology Board Prep flashcards
1
Q

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

A

Topical, transdermal, subcutaneous/depot

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2
Q

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

A

Transdermal and subcutaneous/depot injections

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3
Q

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

A

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

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4
Q

What is the main advantage of epithelial drug administration?

A

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

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5
Q

What is the structure of the keratin layer?

A

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

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6
Q

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

A

Keratin layer

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7
Q

How are corneocytes held together?

A

Intercellular corneodesmosomes

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8
Q

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

A

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

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9
Q

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

A

Intercellular (most common) and transcellular.

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10
Q

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

A

True

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11
Q

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

A

Breaking down corneodesmosomes

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12
Q

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

A

True

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13
Q

What are the topical treatments for superficial skin disorders?

A

Glucocorticoids and retinoids

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14
Q

What are the topical treatments for skin infections?

A

Antivirals, antibacterials, antifungals and antiparasitics

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15
Q

What is the topical treatment for pruritis?

A

Antihistamines

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16
Q

What is the topical treatment for dry skin?

A

Moisturising agents

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17
Q

What is the topical treatment for warts?

A

Keratinolytics

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18
Q

What are the vesicles used for topical drugs?

A

Ointments, creams, gels, lotions, pastes and powder

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19
Q

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

A

Physiochemical properties and clinical condition

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20
Q

What is Fick’s law?

A

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

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21
Q

What does Kp consist of?

A

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

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22
Q

Why is Fick’s law clinically important?

A

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

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23
Q

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

A

Lipophilic and hydrophilic

24
Q

What can increase absorption of a topical drug?

A

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

25
Q

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

A

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

26
Q

Which physical and chemical factors can improve drug partitioning?

A

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

27
Q

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

A

True

28
Q

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

A

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

29
Q

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

A

Skin thickness, skin hydration and integrity of the epidermis

30
Q

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

A

Vehicle choice and occlusive dressings

31
Q

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

A

True

32
Q

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

A

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

33
Q

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

A

True

34
Q

What are the effects of topical glucocorticoids?

A

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

35
Q

What are the UK catagories of topical glucocorticoids?

A

Mild, moderate, potent and very potent

36
Q

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

A

Oral

37
Q

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

A

Hydrocortosone butyrate is potent (the other is mild)

38
Q

Describe the molecular mechanism of action of glucocorticoids

A

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

39
Q

What is the process subcutaneous drug delivery?

A

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

40
Q

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

A

Diffusion into capillaries or lymphatics (if high molecular weight)

41
Q

What are the advantages and disadvantages of subcutaneous drug delivery?

A 
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
42
Q

Why is subcutaneous drug absorption relatively slow?

A

Poor vascular supply

43
Q

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

A
  • 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
44
Q

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

A

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

45
Q

What is transdermal drug delivery?

A

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

46
Q

What features do drugs delivered by transdermal patches usually possess?

A

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

47
Q

What are the advantages and disadvantages of transdermal drug delivery?

A 
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
48
Q

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

A

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

49
Q

What are the advantages and disadvantages of chemical enhancers?

A

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

50
Q

What are some examples of chemical enhancers?

A

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

51
Q

Why is water a good chemical enhancer?

A

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

52
Q

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

A

Iontophoresis, electroporation, sonophoresis and microneedles

53
Q

What is iontophoresis? What drugs is it used for?

A

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

54
Q

What is electroporation?

A

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

55
Q

What is sonophoresis?

A

The use of ultrasound to increase skin permeability

56
Q

What are microneedles?

A

Very small needles which punch microscopic holes in the skin

Dermatology (26 decks)

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