Pharmacology

Question 1

Who needs monitoring while on a drug?

Answer 1

drug:
- narrow therapeutic window
- benefit = very important (eg. cancer treatment)
- serious drug complications

disease:
- close control required (eg. glucose levels in DM)

patient:
- renal impairment
- poor memory

Question 2

Define pharmacokinetics

Answer 2

how the body handles a drug

Question 3

Define pharmacodynamics

Answer 3

drug action in body

Question 4

What are some clinical reasons for monitoring a drug?

Answer 4

• no-one responds to drug in same way
• prescribing decision guided by monitoring (eg. dose adjustment, stop drug)
• aim = increase benefit and reduce harm

Question 5

How can you measure the effect of a drug?

Answer 5

signs + symptoms
clinical measurement (BP, HR etc.)
lab/radiological markers (cholesterol, CRP etc.)
directly sample drug conc.

Question 6

What is TDM?

Answer 6

therapeutic drug monitoring

Question 7

List 3 scenarios for use of TDM

Answer 7

narrow therapeutic index
loss of control is damaging
levels fluctuate/influenced by many factors (eg. diet, other drugs)

Question 8

When is TDM mainly used?

Answer 8

antibiotics (gentamicin, vancomycin)
digoxin
antiepileptics
lithium
aminophylline
immunosuppressants (eg. ciclosporin)

Question 9

What are 3 means of passage of how the drug gets to the target?

Answer 9

Lipid-soluble = passively diffuse through membrane phospholipid bilayer

Drug mimics natural protein = actively transported

Small water-soluble molecules = pass through ion channels

Question 10

Describe passive diffusion with respect to ionised state of drug

Answer 10

unionised = lipid-soluble = easy passage

ionised = water-soluble = difficult passage

Question 11

What is the function of the blood brain barrier (BBB)?

Answer 11

brain isolated from peripheral environment
function:
- protect brain from harmful substances
- allow nutrients through
- tight capillary endothelial junctions
- enzyme barriers

major rate-limiting factor for drugs

Question 12

Describe first order kinetics

Answer 12

(exponential)
most common scenario
rate at which body processes drug is related to concentration
as conc increases, rate of reaction (or breakdown of drug) increases
predictable half life

Question 13

Describe zero order kinetics

Answer 13

zero order = saturation = rate limited
limited capacity of body to process drug
as dose rises above certain level, metabolic process cannot cope, and saturates
drug level starts smoothly but then suddenly shoots up
dose increase - sudden toxicity

Question 14

Define bioavailability

Answer 14

proportion of parent drug that passes into systemic circulation after administration

Question 15

How can you improve bioavailability?

Answer 15

change in formulation:
- eg. enteric-coated tablets

route:
- sublingual GTN - avoids liver metabolism that breaks down oral nitrates

use of inhibitors to stop drug being broken down

Question 16

Define apparent volume of distribution

Answer 16

calculation of amount of drug in plasma after being taken up
- total amount of drug in body divided by plasma concentration

Question 17

What would a high apparent volume of distribution mean (eg. 10 litres)?

Answer 17

drug must have gone elsewhere such as fat, intracellular stores

Question 18

What would a low apparent volume of distribution mean (eg. 0.1 litres)?

Answer 18

drug strongly bound to plasma proteins + not in tissue

Question 19

What volume of distribution would lipid-soluble drugs have?

Answer 19

high
reach all compartments
may accumulate in fat

Question 20

What volume of distribution would lipid-insoluble drugs have?

Answer 20

lower
mainly in plasma + interstitial fluid
many don’t enter brain on acute dosing

Question 21

Define and describe clearance

Answer 21

elimination of drug from plasma
similar to renal creatinine clearance
amount of plasma totally cleared of drug
completely removed by renal filtration = 125 ml/min

Question 22

Define and describe clearance

Answer 22

elimination of drug from plasma
similar to renal creatinine clearance
amount of plasma totally cleared of drug
completely removed by renal filtration = 125 ml/minDe

Question 23

Define half-life

Answer 23

time take for drug concentration to fall to half its initial value
[constant for 1st order kinetics]

Question 24

What 2 main parameters affect half-life?

Answer 24

clearance
volume of distribution

high clearance = shorter half-life
high volume of distribution = longer half-life (difficult to remove drug that has gone elsewhere aside from plasma)

Question 25

How many half-lives until steady state is reached?

Answer 25

5
occurs when drug given at constant rate

Question 26

What are 2 types of modified release formulations?

Answer 26

sustained release tablets
- acts like slow, constant infusion

depot injectables
- useful with patients who have difficulty with compliance to daily tablets