Pharmacology

Question 1

Major routes of drug administration?

Answer 1

topical
transdermal
subcutaneous/depot

Question 2

what are the other epithelial routes?

Answer 2

airways 
bladder 
conjuctival sac
nasal mucosa
rectum 
vagina

Question 3

what effects are transdermal & subcutaneous used for?

Answer 3

systemic effects (often prolonged)

Question 4

what is intravesical mitomycin?

Answer 4

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

Question 5

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

Answer 5

the stratum corneum

Question 6

what does the stratum corneum consist of?

Answer 6

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

Question 7

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

Answer 7

the corneocytes

Question 8

what do corneocytes contain?

Answer 8

aggregated keratin filamnts

Question 9

what are the keratin filaments in corneocytes embedded in?

Answer 9

a matrix of filaggrin surrounded by a cornfied cell envelope

Question 10

describe the cornfield cell envelope

Answer 10

highly crosslinked

Question 11

who are adjacent corneocytes held together?

Answer 11

by corneodesmosomes

Question 12

what are corneodesmosomes?

Answer 12

intracellular junctions

Question 13

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

Answer 13

depends on the corneodesmosomes being stable & not damaged

Question 14

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

Answer 14

the multiple bilayers of lamellar structures of intracellular lipids

Question 15

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

Answer 15

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

Question 16

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

Answer 16

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

Question 17

what is the intracellular rome?

Answer 17

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

Question 18

what is the trancellular route?

Answer 18

short & direct route through the corneocytes, short diffusion path

Question 19

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

Answer 19

1:1:1

change effects the barrier function of the skin

Question 20

what is the topical route of absorption of drugs?

Answer 20

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

Question 21

what is a pharmacologically inactive substance called?

Answer 21

a vehicle

Question 22

when is topical administration usually used?

Answer 22

• superficial skin disorders
• skin infections
• itching
• dry skin
• warts

Question 23

what vehicles are usually used for topical administration?

Answer 23

ointments 
creams 
gels 
lotions 
pastes 
powders

Question 24

what is the choice of vehicle dictated by?

Answer 24

• the physiochemical properties of the drug

- the clinical condition

Question 25

what are warts?

Answer 25

the abnormal division of keratinocytes

Question 26

is conventional transdermal drug delivery passive or active?

Answer 26

a passive process, driven by diffusion

Question 27

what is Fick's law?

Answer 27

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

Question 28

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

Answer 28

- the solubility of the drug in the vehicle | - maximising the movement of the drug from the vehicle to the stratum corneum

Question 29

what is an excipient?

Answer 29

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

Question 30

what are excipients used for?

Answer 30

they can enhance the solubility & absorption of drugs in vehicles

Question 31

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

Answer 31

it increases & provides a constant rate of delivery

Question 32

why are topically applied drugs generally poorly absorbed?

Answer 32

only a small fraction partitions into the stratum corneum

Question 33

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

Answer 33

- hydration of the skin by occlusion (prevention of water loss) - inclusion of excipients which also increase the solubility of hydrophobic drugs

Question 34

how can hydration of the skin by occlusion be achieved?

Answer 34

- choice of vehicle | - cling film

Question 35

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

Answer 35

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

Question 36

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

Answer 36

- site of application - hydration of the skin - integrity of the epidermis

Question 37

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

Answer 37

- drug concentration/physiochemical properties - the drug salt - the vehicle

Question 38

what are glucocorticosteroids widely used topically in?

Answer 38

atopic eczema

Question 39

what properties do topical glucocorticosteroids posses?

Answer 39

- anti-inflammatory - immunosuppressant - vasoconstricting - anti-proliferating action on keratinocytes & fibroblasts

Question 40

how are glucocorticosteroids categorised?

Answer 40

mild moderate potent very potent

Question 41

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

Answer 41

- 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

Question 42

what is the subcutaneous route of administration?

Answer 42

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

Question 43

how does subcutaneously administered drug reach the systemic circulation?

Answer 43

by diffusion into capillaries of lymphatic vessels

Question 44

what are the advantages of subcutaneous administration?

Answer 44

- 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

Question 45

what is the disadvantage of subcutaneous administration?

Answer 45

the injection volume is limited

Question 46

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

Answer 46

- 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

Question 47

what is first pass metabolism?

Answer 47

metabolism by the intestine & liver (avoidance avoids toxicity)

Question 48

what is transdermal drug delivery (TDD)?

Answer 48

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

Question 49

how is the drug absorption from a TDD controlled?

Answer 49

partially by a drug release membrane

Question 50

how does drug absorption occur from a TDD?

Answer 50

by diffusion across the cutaneous barrier

Question 51

what drugs is TDD most suitable for?

Answer 51

drugs that are: - low molecular weight - moderatley lipophilic - potent - of relatively short half-life

Question 52

what are the advantages of TDD?

Answer 52

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

Question 53

what are the disadvantages of TDD?

Answer 53

- relatively few drugs are suitable - costly - allergies

Question 54

how can TDD be chemically enhanced?

Answer 54

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

Question 55

what are the advantages of chemical enhancement of TDD?

Answer 55

low cost | can be incorporated into vehicles/conventional patches

Question 56

what are the disadvantages of chemical enhancement of TDD?

Answer 56

skin irritation/toxicity | not effective for highly water soluble drugs of macromolecules

Question 57

what agents can be used to chemically enhance TDD?

Answer 57

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

Question 58

how can TDD be physically enhanced?

Answer 58

- iontophoresis - electroporation - sonophoresis - microneedles

Question 59

what is iontophoresis?

Answer 59

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

Question 60

what is electroporation?

Answer 60

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

Question 61

what is sonophoresis?

Answer 61

the use of ultrasound to increase skin permeability

Question 62

how are microneedles used to enhance TDD?

Answer 62

punch microscopic holes in the skin - largely experimental