pharmacokinetics

Question 1

what is pharmacokinetics?

Answer 1

the movement and bio-transformation of drugs

Question 2

ADME

Answer 2

-Absorption-rate depends upon route of administration
-Distribution-depends upon lipid/water solubility
-Metabolism-depends upon volume of distribution, site of metabolism, enzyme activity
-Elimination-depends upon urinary pH (pKa of drug) presence of transporters,GFR

Question 3

how is the plasma concentration of the oral administration route?

Answer 3

-there is a delay in the maximum drug concentration
-its approx 10-30mins
-absorption rate is greater than rate of distribution,metabolism and elimination

Question 4

how is the plasma concentration of the intravenous administration route?

Answer 4

-there is instantaneous maximum plasma concentration achieved
-there is a decline in plasma conc due to distribution,metabolism and elimination

Question 5

what are the effects of repeated oral administration?

Answer 5

-results in oscillations in plasma conc,influenced by rate of drug absorption and rate of drug elimination (inactivation/excretion)

Question 6

what are the main routes of drug administration?

Answer 6

-oral or rectal-gut
-percutaneous-skin
-intravenous
-intramuscular-muscle
-intrathecal-CSF
-inhalation-lung

Question 7

what are the main routes of elimination?

Answer 7

-urine
-faeces-gut
-milk,sweat
-expired air

Question 8

how do drugs cross cell membranes?

Answer 8

-diffusion through lipid
-diffusion through aqueous channel
-carrier

Question 9

what are factors affecting drug movement?

Answer 9

-lipid solubility-partition coefficient
-extent of ionisation
-size of molecule
-presence of carrier mediated transporters
-plasma protein binding
-partition into body fat and other tissues

Question 10

how does lipid solubility and membrane permeation affect drug movement?

Answer 10

-a lipid-soluble drug [A] is subject to a much larger transmembrane concentration gradient (ΔCm) than a lipid-insoluble drug [B].
-It therefore diffuses more rapidly, even though the aqueous concentration gradient is the same in both cases.

Question 11

how can you measure lipid solubility (partition coefficient)?

Answer 11

• a solution of the sample is titrated in a two phase system (water + octanol)
  -the sample can ionise in water (pKa), or it can partition into octanol)

Question 11

what does the presence of octanol do to the pKa equilibrium?

Answer 11

-it disturbs it
-the pKa shifts to a new value to minimise this disturbance.We calculate logP from this shift in pKa

Question 12

how is the partition coefficient of barbiturates

Answer 12

-the greater the partition coefficient, the greater the amount of drug absorbed

Question 13

how does the structure of barbiturates and how this influences lipid solubility?

Answer 13

-R1 and R2 are variable functional side groups
-The longer the carbon chain at R1 and R2 the more delocalised the electron cloud and less polar the barbiturate