lec 14-15. pharmacokinetics

Question 1

bioavailability

Answer 1

free concentration of drug in plasma compared to the amount first taken

Question 2

absorption

Answer 2

how the drug enters the body

Question 3

factors affecting absorption

Answer 3

• site of administration
• molecular weight
• lipid solubility
• pH and ionization
• if it uses carriers (which can get saturated, and blocked by competitive inhibitors)

Question 4

the effect of a drug depends on

Answer 4

1) mechanism of action
2) physiological properties (affinity, efficacy)
3) pharmacokinetics (ADME)

Question 5

routes of absorption

Answer 5

intravenous (plasma)
oral
rectal
percutaneous
intramuscular
intrathecal
inhalation

Question 6

how do drugs cross barriers

Answer 6

pinocytosis
channels/carriers
diffusion

Question 7

diffusion of a drug depends on

Answer 7

molecular weight (smaller - better) -> diffusion coefficient
lipid solubility (higher better) -> partition coefficient
be polar/uncharged

Question 8

diffusion coefficient

Answer 8

= 1/ √molecular weight

Question 9

partition coefficient

Answer 9

= drug dissolved in water / drug dissolved in lipid

Question 10

henderson-hasselbach equation

Answer 10

pKa = pH + log ([HA] / [A-])

enter pH of compartment the drug is being dissolved in and pKa of the drug to get ratio of lipophilic/uncharge molecule and hydrophilic charged molecule

Question 11

aspirin absorption and metabolism

Answer 11

it has a pKa of 3.5 and [HA]/[A-] of 3.3 in stomach (where pH=3) so it is very well absorbed in the stomach. But as it goes through the plasma, kidneys and urine where the pH is increased, it becomes more in the charged form, which allows it to be excreted.

hydroxylated by cytochrome P450 to create salicylic acid to become reactive, then OH is conjugated to glucuronide

Question 12

distribution

Answer 12

how drugs move around the body

Question 13

factors affecting distribution

Answer 13

• lipid solubility
• permeability
• pH
• other protein competitors

Question 14

factors that limit distribution

Answer 14

1) blood brain barrier - has tight junction which can become leaky during infection, so meningitis can be treated with penicillin
2) plasma proteins - albumin can bind to (mostly acidic) drugs
3) fat can act as reservoir for lipophilic drugs, causing prolonged action

Question 15

factors affecting metabolism

Answer 15

• administration
• drugs may bind to bile reducing bioavailability
• some drugs may be metabolised before making it to target

Question 16

metabolism

Answer 16

occurs in liver through catabolic phase (creates reactive intermediate) and then anabolic phase (conjugation to produce inactive product)

Question 17

pro-drugs

Answer 17

become active only after metabolism

Question 18

microsomal enzymes

Answer 18

stimulate metabolism

1) MAO
2) cytochrome P450
3) alcohol dehydrogenase

Question 19

Cytochrome P450

Answer 19

a microsomal enzyme

metabolises:
aspirin into salicylic acid
paracetomal into NAPQI (lethal)

inhibited by grapefruit juice
induced by brussel sprouts and smoking

Question 20

factors affecting excretion

Answer 20

drugs need to be in the kidneys

• lipophilic drugs slow in getting there and getting excreted
• weak acid and bases are faster

need to have been made polar to stay in kidneys

Question 21

renal excretion

Answer 21

1) glomerular filtration - for small drugs
2) active tubular secretion - for weak acids/bases
3) passive diffusion - for lipophilic/nonpolar drugs

Question 22

organic anion transporter/ organic cation transporter

Answer 22

OAT used in active tubular secretion for weak acids, and OCT used for weak bases.

Question 23

GI excretion

Answer 23

cleared through feces (eg. bound to bile)

Question 24

Lung excretion

Answer 24

exhaled out (eg. asthma meds)