Pharmacokinetics

Question 1

what is the journey of a drug?

Answer 1

Administration
Absorption
Distribution
Metabolism
Excretion
Removal

Question 2

In administration, what are the 2 types drugs can be?

Answer 2

• systemic (across entire organism)

- local (restricted to one area)

Question 3

what are the sites used for admin?

Answer 3

• enteral - GI admin

- parenteral - outside GI tract

Question 4

in absorption, what are the 2 pathways drugs move via?

Answer 4

• bulk flow transfer: in blood

- diffusional transfer: molecule by molecule over short distances

Question 5

what are compartments? what are barriers?

Answer 5

compartments = aqueous (blood, lymph, ECF)
barriers = lipids (cell membranes)

Question 6

to cross the barriers, what methods are used?

Answer 6

• diffusing through lipid
• carrier molecules
• diffusing through aqueous pores in lipid
• pinocytosis

Question 7

what are most drugs?

Answer 7

weak acids or weak bases

so drugs exist in ionised or unionised forms

Question 8

what are the levels of the ionised and non-ionised?

Answer 8

in dynamic eqm

ratio of ionised to unionsied will depend on pH of environment and pKa of molecules

Question 9

what is the pH partition hypothesis?

Answer 9

• passive diffusion: drug best diffuses when unionised

- when pH of environment is below pKa of drug, most drug is unionised and so readily passively diffuses

Question 10

what is ion trapping?

Answer 10

if pH of environment is too far above drug’s pKa, drug may become ion-trapped
mainly in ionised form so isn’t passively diffused as much
e.g. aspirin in neutral blood

Question 11

what are the factors that influence drug distribution?

Answer 11

• regional blood flow
• EC binding
• capillary permeability
• localisation in tissues

Question 12

what are the 2 major routes of excretion?

Answer 12

• liver: some drugs are concentrated into bile (usually large molecular weighted drugs that can’t be filtered in kidneys)
• kidneys - MOST excretion

Question 13

describe kidney excretion

Answer 13

1. glomerulus - drug-protein complexes not filtered, but bioactive drug is
2. proximal tubule: active secretion of acids and bases occur, some lipi-soluble drugs reabsorbed
3. proximal and DTs: some lipid-soluble drugs reabsorbed

Question 14

describe the enterohepatic cycling of drugs

Answer 14

• larger molecular weighted drugs are excreted here (conc. into bile in liver bile canaliculi)
• drug/metabolites are excreted into gut, reabsorbed ad then taken back to liver to be excreted again
• DRUG PERSISTANCE

Question 15

name some other routes of excretion

Answer 15

• lungs
• skin
• GI secretions
• saliva
• sweat
• milk
• genital secretions

Question 16

why might treatment with IV sodium bicarbonate inc. aspirin excretion?

Answer 16

• inc. urine pH ionises the aspirin making it less lipid soluble
• less reabsorbed from tubules
• inc. its rate of excretion

Question 17

define bioavaliability

Answer 17

proportion of administered drug that is available in the body to exert a pharmacological effect

Question 18

define apparent volume of distribution

Answer 18

volume in which a drug appears to be distributed (i.e. blood volume)

Question 19

define biological half life

Answer 19

time it takes for the conc of a drug to half

Question 20

define clearance

Answer 20

volume of blood plasma completely cleared of a drug per unit time

Question 21

what is first order kinetics?

Answer 21

• rate of elimination of a drug where the amount of drug dec. at a rate proportional to conc of drug remaining in body
• slower removal at lower conc

Question 22

what is zero order kinetics?

Answer 22

e. g. alcohol
- describes a linear rate of elimination of a drug
- implies a sturated enzymatic process
- same amount of drug is always removed regardless of the concentration in volume of distribution