Pharmacokinetics 2

Question 1

the larger the therapeutic range…

Answer 1

depends on how well the drug has been absorbed

Question 2

For drugs reaching target via blood/plasma (systemic circulation):

Answer 2

“the magnitude of drug effect is associated to [drug] available in the plasma/blood)”

Question 3

first order kinetics

Answer 3

concentration and rate in proportion

Question 4

zero order kinetics

Answer 4

conc and rate NOT in proportion

Question 5

Such kinetics may not be TRUE, if

Answer 5

the drug effect is mediated through a metabolite
the drug effect is irreversible
follow different kinetics in the target compartment (different from blood)

Question 6

Passive diffusion

Answer 6

Major mechanism of drug delivery
Depends on the ability of drug (physiochemical characteristics) crossing lipid bilayer membrane

[most drugs gets absorbed by passive diffusion]

Question 7

Active diffusion

Answer 7

Require transporter/carrier for the uptake of drug across cell membrane

Question 8

Rate of diffusion
(PD)

Answer 8

surface area
-thickness of membrane
-molecular size & lipid solubility
(diffusion constant)

Question 9

[D] amount transfer
(PD)

Answer 9

Transfer rate
Residence time at membrane

Question 10

Low lipid soluble (hydrophilic) drugs use transporters
(AD)

Answer 10

Organic anion transporters (OATs)
Organic cation transporters (OCTs)
(also covered in urinary system lectures)

Question 11

what kind of drugs will ONLy pass through lipid bi-layers?

Answer 11

un-ionised

Question 12

Weak acids or weak bases

Answer 12

Equilibria between
AH A- + H+ [Acid]
B + H+ BH+ [Base]
(un-ionized) (ionized)

Question 13

What are the Factors affecting ionisation?

Answer 13

pH (i.e. concentration of H+ ions)

pKa of drug

(pH at which 50% of molecules are in each state)

pH mouth 7.4
stomach 1.5
Intestine 5.3

Question 14

Factors influencing G. I. absorption (physiological)

Answer 14

G.I. motility
- G.I. secretions & enzymes
- drug-food/supplement interactions

Question 15

Advantages of G. I absorption (physiological)

Answer 15

Large surface area for passive diffusion

Range of pH environments promote uptake of weak acids/bases

Richly vascularised (high blood supply)
Long tract and long dwell time

Some active transport (e.g. Levodopa taken up by phenylalanine transporter)

Small intestine is a major site for drug absorption

Question 16

How well a drug absorbed in the body?

(efficiency of drug absorption)

Answer 16

Bioavailability (F): measure of proportion of dose absorbed, compared to I. V. (same) dose

F= AUC of oral/AUC of I.V (for oral drug)

Time to peak (tmax): time required to reach maximum drug concentration in plasma (is a measure of rate of absorption)

	 tmax (oral)= 25 min

Question 17

when acid gets put in drug it will become IONISED WHICH MEANS…..

Answer 17

it WILL NOT pass through lipid bilayer membrane

Question 18

weakly acidic

Answer 18

unionised drug - effective absorption

Question 19

Administration & Absorption: Summary

Answer 19

Most common route of administration is through oral

Major site of drug absorption is small intestine.
Drug absorption from sites, muscle, skin, lungs and others can bypass GI tract

The rate of absorption depend on the
- Vascularisation of site of absorption
- Characteristics of formulation/dosage forms
lipid solubility of the drug
- pH of the site of absorption

Question 20

AUC

Answer 20

area under curve