Pharmacology

Question 1

benefits of using topical drug admin?

Answer 1

for local effect and to treat underlying tissue etc.

Question 2

benefits of using transdermal/subcutaenous deposit admin?

Answer 2

good for prolonged systemic effects

Question 3

name a few epithelial routes of drug admin other than topical or transdermal/subcutaenous

Answer 3

• airways
• bladder
• conjunctival sac
• nasal mucosa
• rectum
• vagina

all good for local effects that minimise systemic absorption

Question 4

name the most important layer in skin for skin defence?

Answer 4

stratum corneum

Question 5

what is the stratum corneum?

Answer 5

• consists of layers of hard dead keratinocytes
• forms 10-30 sheets of tissue that consistently shed

Question 6

describe the brick and mortar model reference in the stratnum corneum

Answer 6

• Bricks = corneocytes
• Mortar = intercellular lipids in lamellar structures

Question 7

what are corneocytes?

Answer 7

hardened dead keratinocytes

Question 8

where is the stratnum corneum located in the epidermis?

Answer 8

outermost layer of the epidermis

Question 9

where are the keratin filaments of the corneocytes embedded into?

Answer 9

embedded in filarggrin matris surrounded by a conrified cell envelope

Question 10

what holds the corneocytes together?

Answer 10

corneo-desmosomes

Question 11

what is the mortar in the stratnum conreum?

Answer 11

• liquid layer
• has multiple bilayers of lamellar intracellular lipids
• can act as a resovoir for drugs
• incredibly hydrophobic
• liquid itself contains ceramides, cholesterol, free fatty acids etc.

Question 12

what do drugs need for both local and systemic effects to work effectively?

Answer 12

be able to move through the stratnum corneum

Question 13

how do most drugs move through the stratnum corneum?

Answer 13

• via intercellular route
• rely on molecules being small and hydrophobic

Question 14

what law calculates how easily a drug is absorbed?

Answer 14

FIck’s law

Question 15

Give the drug absorption equation

Answer 15

J (for john peters) = permability coefficient (K) X concetration of drug in medicine

Question 16

what is the permeability coeffcient (K)?

Answer 16

basically involves what the drug is like and what the barrier contains

Question 17

what is J in the drug absorption equation?

Answer 17

rate of absorption

Question 18

give the rate of absorption equation

Answer 18

• J = rate of absoprtion
• Km = partition coefficient
• D = diffusion coefficient
• L = length of diffusion pathway
• Cv = concentration of drug in the vehicle

Question 19

what is the best combination of frug solubility for absorption?

Answer 19

• hydrophobic (lipophilic) drug in a hydrophilic base
• best for absorption as it moves preferntially in to the skin

Question 20

what is the distribution of a hydrophobic (lipophilic) drug in a lipophilic base?

Answer 20

• drug can move through the skin but will equal out between the skin and the blood vessels

Question 21

what occurs when you have a hydrophilic drug in a hydrophobic (lipophilic) base?

Answer 21

the two dont dissolve into eachother

• so the drug partions only into the stratum corneum (weakly)
• as the drug has limited solubility in both the vehicle AND the skin

Question 22

why is a lipophilic (hydrophobic) drug in a hydrophilic base beneficial?

Answer 22

drug is more soluble in the skin and preferentially partitions into it

Question 23

describe the solubility of a lipophilic (hydrophobic) drug in a lipophilic (hydrophobic) base?

Answer 23

drug is soluble in both vehicle (blood vessels) and skin so partitions between the two

Question 24

describe what happens to a hyrophilic drug in a hydrophilic base on the skin?

Answer 24

• soluble in vehicle but not skin so remains on the surface of it

Question 25

why does a hydrophobic drug work so well in a hydrophilic base?

Answer 25

because a hydrophobic drug can make its way through the hyrophobic stratum corneum but wont bind to the base itself

Question 26

why are **excipients** added to drugs?

Answer 26

so the drug correctly dissolves into the liquid vehicle to make it through the skin

Question 27

give examples of vehicles for drugs?

Answer 27

* lotions * creams * ointments * gels * pastes * powders

Question 28

what is the function of an excipient?

Answer 28

* enhance the solubility of the drug in the vehicle * therefore enhance absorption * the excipients are compounds that will sit in patches and convert undissolved into soluble drug to move across skin * allow a constant drug flow to occur

Question 29

give an exmple of an excipient

Answer 29

propylene glycol

Question 30

what is the partiton coefficient?

Answer 30

* concept for drugs to move in well they need to partition into the stratum conreum and enter the deeper layers of the skin * physical and chemical barriers of the skin help with this

Question 31

what is one factor that increases the partition coefficient?

Answer 31

Hydrated skin * allows hydrophilic base to settle into the skin better * can be done through addition of a good hydrating vehicle e.g. ointment * cling film will also help as it prevents water loss through exaporation

Question 32

how can increased partition be achieved by the skin itself?

Answer 32

reduction in the barrier function of the stratum corneum

Question 33

does location of application affect drug potency?

Answer 33

yes * e.g. steroid on sctorum will be far more potent than on the nail bed

Question 34

list some factors that may affect absorption of topically applied drugs?

Answer 34

* hydration of skin * integrity of epidermis (moist/weeping vs. normal) * hair vs dry vs damages moist skin etc. * drug salt matters (some are more powerful than others) * some drugs more soluble in ointment than a cream (drug vehicle matters)

Question 35

what can long term use of high potency steroids result in?

Answer 35

* steroid rebound * skin atrophy * systemic effects * spread of infection * steroid roasacea * production of stretch marks * superficial blood vessels

Question 36

what is transdermal drug delivery?

Answer 36

* drugs penetrate through stratum corneum, epideris and dermis into systemic circulation * then delivered throughout the body to the site of action

Question 37

name the 4 features of a suitable drug for transdermal drug delivery?

Answer 37

1. low molecular weight 2. lipophilic/hydrophobic 3. potent 4. relatively brief half life

Question 38

give advantages of transdermal drug delivery

Answer 38

* steady state of drug delivery * decreased dosing frequency * avoidance of first-pass metabolism * rapid termination of action

Question 39

disadvantages of transdermal drug delivery (TDD)?

Answer 39

* relatively few drugs are suitable for this administration route

Question 40

give examples of TDD drugs?

Answer 40

* nicotine * GTN * fnetanyl * oestradiol

Question 41

what can be incorporated into the TDD's?

Answer 41

* strain of chemicals that can be used to make the stratum conreum more permeable * makes it cheaper to administer some drugs * can be incorporated into TDD's * can also be toxic for the skin and not effectuve for some soluble drugs

Question 42

why is the skin good for drug administration?

Answer 42

* simple to apply * steady state plasma conc. * avoids first-pass metabolism * can be terminated rapidly because you can just wipe it off

Question 43

why is first-pass metabolism avoidance a good thing?

Answer 43

first-pass metabolism means that only a proportion of the drug reaches circulation due to it passing through portal vein into liver