06 - Drug Absorption and Distribution

Question 1

1) Pharmacokinetics involves…

Answer 1

1. Absorption
2. Distribution
3. Metabolism
4. Excretion

Question 2

2) Drugs effects are determined by..

Answer 2

1. Route of administration.
2. Dose and frequency
3. Delivery to site of action
4. Time to onset of effect
5. Duration of effect
6. Elimination from the body
7. Accumulation on repeat dosing
8. Inter- and intra-patient differences
9. Drug interactions

Question 3

3) Membrane permeability of drugs:

Answer 3

1. NON POLAR > polar

2. LIPOPHILIC > hydrophilic

Question 4

4) Diffusion of drugs across plasma membrane depends on..

Answer 4

1. Concentration gradient

2. Surface area of membrane available for diffusion

Question 5

5) Dissociation constant formula for acids (AH)

Answer 5

pKa = pH + log10 ( [AH] / [A-] )

AH is the unionised drug

Question 6

6) Dissociation constant formula for bases (B)

Answer 6

pKa = pH + log10 ( [BH+] / [B] )

B is the unionised drug

Question 7

7) What is the relationship between pKa value and the drugs affinity for proton?

Answer 7

Low pKa (Less than -2):
   -  Weak affinity for proton.

High pKa (more than 12):
   -  Strong affinity for proton.

Question 8

8) How is the pKa determines the ionisation of weak acid at different pH?

Answer 8

1. if pH > pKa… less [H+]
   so, more (AH) –> (A-) + (H+)
   [ionised] > [unionised]
   LESS DRUGS ABSORBED BY CELL

2 if pH < pKa… more [H+]
so, more (AH) [ionised]
MORE DRUGS ABSORBED BY CELLS

Question 9

9) How is the pKa determines the ionisation of weak bases at different pH?

Answer 9

1 if pH > pKa… less [H+]
so, (BH+) –> (B) + (H+)
[unionised] > [ionised]
MORE DRUGS ABSORBED BY CELLS

2 if pH < pKa… more [H+]
so, (BH+) [unionised]
LESS DRUGS ABSORBED BY CELLS

Question 10

10) Main sites for carrier-mediated transportations:

Answer 10

1. Renal tubule
2. Biliary tract
3. Blood brain barrier
4. GIT

Question 11

11) Main proteins involved in drug-plasma protein bindings..

Answer 11

1. Albumin binds to acidic drugs (some basic drugs ie. TCA, chlorpromazine)
2. Beta-globulin and acid glycoprotein bind to basic drugs.

Question 12

12) Factor affecting absorption:

Answer 12

1. Gastrointestinal motility
   
   • Gastric stasis -> slow absorption
   • Muscarinic antagonist -> reduce GI motility
   • Metoclopramide -> increase GI motility
2. Food/splanchnic blood flow
   
   • Drugs taken after meal often slower absorption
   • But for some drugs, increase absorption due to increase splanchnic blood flow
3. Formulation
   
   • Particle size ( larger -> reduce absorption)
   • Coating of tablet/capsule
4. Physicochemical factors
   
   • Complexation (tetracycline and calcium)