Pharmacokinetics

Question 1

Absorption

Answer 1

process of drug entering the systemic circulation

drug begins to be absorbed from the minute it is ingested, up to the peak of plasma concentration

Question 2

Graph of a single oral dose

Answer 2

Increase to peak and then slow decline
Plasma conc/ time
Window within plasma conc, that is therapeutic window, toxic/non efficacious dose is above and below

Question 3

Factors affecting absorption

Answer 3

Chemical nature - charge, lipophilicity, size
route of administration
formulation (fast/slow acting, coating)

Question 4

Chemical features - charge

Answer 4

charged is difficult to cross bilayer, uncharged can cross freely - effect of pH differences across the epithelia on distribution go ionisable drugs
eg. aspirin is neutral acid, however in alkali becomes charged and cannot cross
Estimate the % of drug that will be ionised to estimate amount that will enter cells, use Henderson-hasselbach
For acids: pH = pKa + log[A]/[HA]
For bases: pH = pKb + log[B]/[BH+]

Question 5

Chemical features - size

Answer 5

bigger molecules have decreased bioavailability

Question 6

Chemical features - lipophilicity

Answer 6

how hydrophobic/ greasy the molecule is
Greasier molecule = greater bioavailability
LogP measures lipophilicity

Question 7

Route of administration

Answer 7

intravenous, inhalation, sublingual, oral, intramuscular, transcutaneous
fastest acting -> slowest
also have to consider physical barriers, BBB/ blood placental

Question 8

Drug formulation

Answer 8

Fast or slow release formulation

Liquids absorb faster than capsules, can coat tablets to slow absorption (will reduce plasma conc. peak)

Question 9

Drug distribution

Answer 9

peak of distribution takes place when the concentration of drug reaches its peak
not just plasma conc, can be distributed in lots of tissues

Question 10

Distribution affected by

Answer 10

• natural barriers (BBB/ b-plasma)
• accumulation in cells (pass through transporters and get stuck in cells)
• no distribution for drugs that bind to plasma proteins
• distribution to fat (lipophilic drugs, slows distribution and clearance)

Question 11

Implications in changed distribution

Answer 11

• decreases initial free concentration
• slows distribution and clearance
• prolonged duration of action

Question 12

quantifying distribution

Answer 12

volume of distribution of a drug
measure concentration in blood over time
measure the volume the drug appears to be dissolved in
Vd = dose/ C (C=-blood plasma conc.)

Question 13

why metabolism is needed

Answer 13

most drugs filtered freely at glomerulus

need to ensure they remain in the nephron and are excreted rather than diffusing back in

Question 14

excretory organs

Answer 14

renal = major
hepatic/ billiard = faecal
other = sweat, milk, lungs

Question 15

quantify elimination

Answer 15

zero order = concentration wont change elimination

first order = concentration will change elimination (so get half life to reach 50% original conc.)