Pharmacokinetics

Question 1

Define half life:

Answer 1

Time taken for the concentration of a drug to reduce to half the concentration at administration (i.e time taken for 50% of the drug to be metabolised)

Question 2

Define volume of distribution

Answer 2

The volume required to contain the drug in the body at the same concentration as the plasma

Question 3

When does plasma concentration equilibriate?

Answer 3

When the rate of injection and elimination are equal

Question 4

When is a steady-state plasma concentration acheieved?

Answer 4

After 3 or 4 half lives, hence why loading doses of drugs are often given to speed this up.

Question 5

Clinically, why is the half life of a drug important?

Answer 5

It determines the interval/ frequency of drug administration

Question 6

Define bioavailability

Answer 6

The amount of drug that enters systemic circulation and is available at the drugs site of action

Question 7

What factors can affect bioavailability?

Answer 7

First pass metabolism

Incomplete absorption

Question 8

Do ocular topical drugs undergo first pass metabolism?

Answer 8

No, they are absorbed by the nasal and nasopharyngeal mucosa directly into the systemic circulation, so they avoid the first pass metabolism in the liver. Hence topically applied ocular drugs can have marked systemic side effects.

Question 9

What are the two types of kinetics that drugs can exhibit?

Answer 9

First order kinetics

Zero order kinetics

Question 10

What is first order kinetics?

Answer 10

This is when the rate of a drug is directly proportional to the dose (amount of drug present)

Question 11

What is zero order kinetics?

Answer 11

Drug dynamics show saturation at higher concentration of the drug i.e. at higher concentrations the rate cannot be increased any further with further increase in the drug because there are no more receptors/enzymes etc

Question 12

How is drug absorption related to lipid solubility?

Answer 12

Lipid solubility increase the rate of absorption because the drug can diffuse directly through the cell lipid membrane

Question 13

Do Polar or non-poalr substances diffuse easily?

Answer 13

Non-polar substances

Question 14

What factors affect the rate of diffusion through a cell lipid membrane?

Answer 14

Ionised state (ie. polar vs non-polar)
Lipid solubility
Size of molecule
pH
Route of administration
Bound to proteins

Question 15

How does food in the gut affect absorption of tetracyclines?

Answer 15

Presence of food in the gut will form insoluble salts with magnesium and calcium

Question 16

If a drug is bound to protein (eg albumin) in the plasma, will the absoprtion be affected by changes in protein level?

Answer 16

No, unless >90% of the drug is carried by binding to protein/albumin, changing protein levels will not have an effect on the distribution of the drug

Question 17

Are protein-bound drugs freely available to act on tissues?

Answer 17

no

Question 18

Are acidic on alkalitic drugs more likely to bind with albumin?

Answer 18

Acidic

Question 19

What is a1 acidic glycoprotein?

Answer 19

A protein that can bind drugs such as propanolol

Question 20

How does a1 acidic glycoprotein affect propanolol concentrations?

Answer 20

A1 acidic glycoprotein concentrations can be increased in certain conditions such as inflammation, which means that it binds more propanolol therefore less of the free drug is available (AKA reduced action of propanolol)

Question 21

What factors are known to alter protein binding levels?

Answer 21

Hypoalbuminaemia (Albumin <25g/l)
Increase of other high affinity binding proteins
Last trimester of pregnancy (increased circulating volume dilutes albumin)
Renal failure

Question 22

Where does drug excretion usually occur?

Answer 22

Mostly in urine, sometimes bile

Question 23

What are the two phases of drug metabolism?

Answer 23

1. Oxidation (cytochrome P450)

2. Conjugation

Question 24

Where is Cytochrome p450 located?

Answer 24

Liver and some in eye

Question 25

Which drugs can induce Ctyochrome P450?

Answer 25

Phenytoin and carbamazepine

Question 26

What factors affect oxidative metabolism (Ctyochrome P450)?

Answer 26

1. Age: premature babies metabolise poorly and elderly individuals due to smaller livers
2. Liver failure reduces oxidative metabolism
3. Alcohol: inhibits cytochrome P450
4. poor nutrition reduces oxidative metabolism
5. Smoking induces oxidative metabolism
6. Genetic differences

Question 27

What factors allow a drug to be filtered in the glomerulus of kidney?

Answer 27

1. Small size irregardless of charge (<20,000 Da)

2. Free (not bound to proteins)

Question 28

What percentage of drug delivered to the kidney is cleared by the glomerulus?

Answer 28

20%, the rest is carried through to tubules where it is cleared

Question 29

What are the three ways a drug can be excreted by the kidney/

Answer 29

1. Through glomerular filtration
2. Active secretion in tubules
3. reabsorption in tubules

Question 30

How are drugs actively secreted in the nephron tubules?

Answer 30

Active systems are present, they are non-selective and will transport the drug into the glomerular filtrate
However, competion for active sites does occur, hence the drug secretion can be blocked by other drugs (secretion of penicillins at this site is blocked by probenecid)

Question 31

How are drugs excreted by reabsorption in the kidney?

Answer 31

The large reabsoprtion of water in the tubules creates a drug [gradient] whereby the drug passively diffuses into the surrounding plasma and is reabsorbed. Weak acids and bases are more readily absorbed. Hence, altering the urinary pH can affect the excretion of the drug i.e. forced alkalinesis of urine will drive acidic drugs out e.g. in aspirin overdoses

Question 32

What is competitive inhibition?

Answer 32

When a antagonist is displaced by increased concentration of the agonist

Question 33

What is non-competitive antagonism?

Answer 33

When an antagonist blocks the action of the agonist (not at the receptor) and therefore its action cannot be overcome by increased concentration of a drug

Question 34

In which direction is the %response/dose concentration curve shifted in non-competitive antagonism?

Answer 34

Down and to the right (i.e. limits the maximum action of the agonist)

Question 35

What is a graded dose response?

Answer 35

Often drugs show a graded dose response, which means that the increasing the drug concentration increases the drug effect. This is seen with drugs that do not ‘permanently’ bind with the receptor

Question 36

What is the difference between efficacy and potency?

Answer 36

Efficacy describes the maximum response that a drug can give, whereas potency describes the amount of drug required to give the desired response.

Question 37

What is tolerance?

Answer 37

When the efficacy of a drug diminishes (i.e. the maximum response is no longer achieved with the same dose).

This is due to down-regulation of receptors