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Dermatology > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

Major routes of drug administration?

A

topical
transdermal
subcutaneous/depot

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2
Q

what are the other epithelial routes?

A 
airways 
bladder 
conjuctival sac
nasal mucosa
rectum 
vagina
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3
Q

what effects are transdermal & subcutaneous used for?

A

systemic effects (often prolonged)

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4
Q

what is intravesical mitomycin?

A

when a cannula is directed into the bladder via the urethra & the drug affects the bladder lining

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5
Q

which layer of the skin is the single most important barrier to drug penetration?

A

the stratum corneum

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6
Q

what does the stratum corneum consist of?

A

corneocytes (hardened, dead, keratinocytes) surrounded by intracellular lipids forming sheets of tissue that are constantly shed & renewed

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7
Q

what are the bricks in the “brick & mortar” model

A

the corneocytes

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8
Q

what do corneocytes contain?

A

aggregated keratin filamnts

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9
Q

what are the keratin filaments in corneocytes embedded in?

A

a matrix of filaggrin surrounded by a cornfied cell envelope

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10
Q

describe the cornfield cell envelope

A

highly crosslinked

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11
Q

who are adjacent corneocytes held together?

A

by corneodesmosomes

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12
Q

what are corneodesmosomes?

A

intracellular junctions

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13
Q

what does the functional integrity of the stratum corneum depend on?

A

depends on the corneodesmosomes being stable & not damaged

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14
Q

what is the mortar in the the “brick & mortar” model?

A

the multiple bilayers of lamellar structures of intracellular lipids

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15
Q

what can the bilayers of lamellar structures of lipid act as?

A

they are highly hydrophobic & can act as a reservoir for lipid-soluble drugs

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16
Q

what do both local & systemic effects of drug require penetration of?

A

the stratum corneum - occurs largely via the intracellular route & normally allows only diffusion of small, hydrophobic, drugs

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17
Q

what is the intracellular rome?

A

highly convoluted & toturous route through the intracellular lipids, long diffusion path

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18
Q

what is the trancellular route?

A

short & direct route through the corneocytes, short diffusion path

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19
Q

what is the molar ratio of ceramides:cholestrol:free fatty acid in the intracellular lipid bilayers?

A

1:1:1

change effects the barrier function of the skin

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20
Q

what is the topical route of absorption of drugs?

A

drug in a pharmacologically inactive substance is applied directly to the surface of the skin

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21
Q

what is a pharmacologically inactive substance called?

A

a vehicle

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22
Q

when is topical administration usually used?

A
  • superficial skin disorders
  • skin infections
  • itching
  • dry skin
  • warts
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23
Q

what vehicles are usually used for topical administration?

A 
ointments 
creams 
gels 
lotions 
pastes 
powders
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24
Q

what is the choice of vehicle dictated by?

A
  • the physiochemical properties of the drug

- the clinical condition

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25
Q

what are warts?

A

the abnormal division of keratinocytes

26
Q

is conventional transdermal drug delivery passive or active?

A

a passive process, driven by diffusion

27
Q

what is Fick’s law?

A

J = KpCv

rate of absorption = the permeability coefficient x the concentration of drug in the vehicle

28
Q

what factors affect the absorption of a drug from a vehicle?

A
  • the solubility of the drug in the vehicle

- maximising the movement of the drug from the vehicle to the stratum corneum

29
Q

what is an excipient?

A

a natural or synthetic substance formulated alongside the active ingredient of a medication

30
Q

what are excipients used for?

A

they can enhance the solubility & absorption of drugs in vehicles

31
Q

what happens to the duration of effectiveness of a drug when excess, non-dissolved drug is included in a transdermal patch?

A

it increases & provides a constant rate of delivery

32
Q

why are topically applied drugs generally poorly absorbed?

A

only a small fraction partitions into the stratum corneum

33
Q

what are the physical & chemical factors that can improve partitioning of a drug into the stratum corneum?

A
  • hydration of the skin by occlusion (prevention of water loss)
  • inclusion of excipients which also increase the solubility of hydrophobic drugs
34
Q

how can hydration of the skin by occlusion be achieved?

A
  • choice of vehicle

- cling film

35
Q

how is increased partitioning of a drug done in relation to the barrier function of the stratum corneum?

A

results from a reduction in the barrier function of the stratum corneum

36
Q

what factors to do with the skin influence the absorption of topically applied drugs?

A
  • site of application
  • hydration of the skin
  • integrity of the epidermis
37
Q

what factors to do with the drug/pharmaceutical preparation influence the absorption of topically applied drugs?

A
  • drug concentration/physiochemical properties
  • the drug salt
  • the vehicle
38
Q

what are glucocorticosteroids widely used topically in?

A

atopic eczema

39
Q

what properties do topical glucocorticosteroids posses?

A
  • anti-inflammatory
  • immunosuppressant
  • vasoconstricting
  • anti-proliferating action on keratinocytes & fibroblasts
40
Q

how are glucocorticosteroids categorised?

A

mild
moderate
potent
very potent

41
Q

what do glucocorticosteroid penetration, potency & clinical effect vary with?

A
  • body site: thickness of stratum corneum
  • state of skin: lower potency in children/certain body sites
  • occlusion
  • vehicle: affects potency & compliance
  • concentration of drug
  • form of drug
42
Q

what is the subcutaneous route of administration?

A

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

43
Q

how does subcutaneously administered drug reach the systemic circulation?

A

by diffusion into capillaries of lymphatic vessels

44
Q

what are the advantages of subcutaneous administration?

A
  • absorption is relatively slow
  • suitable for oil-based drugs
  • can be used to introduce a depot of drug under the skin for slow release into circulation
  • simple & painless
45
Q

what is the disadvantage of subcutaneous administration?

A

the injection volume is limited

46
Q

why is the skin an attractive route of drug adminisitration for a systemic effect?

A
  • simple & non-sterile
  • can allow for a steady stare plasma concentration to be achieved over a prolonged period of time
  • avoids first pass metabolism
  • drug absorption can be terminated rapidly
47
Q

what is first pass metabolism?

A

metabolism by the intestine & liver (avoidance avoids toxicity)

48
Q

what is transdermal drug delivery (TDD)?

A

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

49
Q

how is the drug absorption from a TDD controlled?

A

partially by a drug release membrane

50
Q

how does drug absorption occur from a TDD?

A

by diffusion across the cutaneous barrier

51
Q

what drugs is TDD most suitable for?

A

drugs that are:

  • low molecular weight
  • moderatley lipophilic
  • potent
  • of relatively short half-life
52
Q

what are the advantages of TDD?

A
  • steady state of drug delivery
  • decreased dosing frequency
  • avoidance of first-pass metabolism
  • rapid termination of action
  • user friendly, convenient & painless
53
Q

what are the disadvantages of TDD?

A
  • relatively few drugs are suitable
  • costly
  • allergies
54
Q

how can TDD be chemically enhanced?

A

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

55
Q

what are the advantages of chemical enhancement of TDD?

A

low cost

can be incorporated into vehicles/conventional patches

56
Q

what are the disadvantages of chemical enhancement of TDD?

A

skin irritation/toxicity

not effective for highly water soluble drugs of macromolecules

57
Q

what agents can be used to chemically enhance TDD?

A

water (prolonged occlusion)
variety of solvents (e.g. ethanol)
variety of surfactants (e.g.sodium dodecyl sulphate)

58
Q

how can TDD be physically enhanced?

A
  • iontophoresis
  • electroporation
  • sonophoresis
  • microneedles
59
Q

what is iontophoresis?

A

the application of low voltage electrical pulses to the skin via a surface electrode over a long period of tie can drive low molecular mass molecules (of the same charge) through the skin

60
Q

what is electroporation?

A

very brief high voltage pulses lead to “pore” formation, has the potential for the delivery go hydrophilic & changed molecules into the skin

61
Q

what is sonophoresis?

A

the use of ultrasound to increase skin permeability

62
Q

how are microneedles used to enhance TDD?

A

punch microscopic holes in the skin - largely experimental

Dermatology (16 decks)

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