Pharmacokinetics 5

Question 1

Drug action - targets?

Answer 1

• enzyme
• receptors

Question 2

routes of administration examples

Answer 2

IV - blood
Oral - gut
IM - Muscle

Question 3

The drug hits the site of absorption > diffuses through (normally passive) >

Answer 3

drug binds to PLASMA PROTEIN

Reversible binding to plasma proteins

Acidic (& neutral) drugs bind to albumin (warfarin)
Basic drugs bind to β-globulins (quinine)

Question 4

Drug binding with plasma proteins

Answer 4

[Free] or [bound] drug is in dynamic equilibrium

High binding to plasma proteins- less available for target action

One drug can displace other drug binding of other drug

(Thermodynamic motion, collision; thermal energy dominate the electrostatic forces)

Question 5

Distribution of Drugs (influencing factors)

Answer 5

Barriers
- cell arrangements
-active transporters
- size and lipid solubility
Blood flow (how well the tissue perfused)
-High: heart, brain, lungs, kidney, glands
-low: skin, muscle
-negligible- bone, teeth, hairs, cartilage

Question 6

Tissue accumulation (fat depots)

Answer 6

Highly lipid soluble drugs accumulate
acute- thiopental
chronic- xenobiotics, benzodiazepines

Question 7

Blood Brain Barrier (Tight junctions, restricted access to biomolecules)

Answer 7

Diffusion only possible for lipid soluble drugs

The integrity compromised during meningitis (allowing access for antibiotics)

Active transport possible (e.g. methylDOPA)

Question 8

Blood Placental Barrier (Tight junctions, restricted access to biomolecules)

Answer 8

Lipid solubility and size of the drug determine the distribution to foetus.

Drug use in pregnancy: Risk adverse/toxic teratogenic effects during pregnancy and neonatal toxicity during labour

Question 9

Pharmacokinetics- Volume of Distribution

Answer 9

A. Drug bound to plasma proteins
B. Fat Deopts
C. Fluid Compartments

Question 10

40 liters total body fluids
=
components?

Answer 10

• 15 liters Extracellular
• 3 litres Plasma (fluid)
• 12 litres Interstitial
  Includes cerebrospinal / matrix
  >90% as a gel

Question 11

Pharmacokinetics- Volume of Distribution (Vd)

Answer 11

Theoretical volume of plasma that would accommodate total drug amount at the measured plasma concentration

Vd = total amount of drug (Q) / plasma concentration (Cp)

The total amount of drug (Q) will vary with time due to the elimination

Question 12

How many litres gets accumulated and restricted?

Answer 12

Vd > 40 litres: drug accumulation in tissues

Vd < 10 litres drug restricted to plasma and interstitial fluid (largely)

Question 13

Pharmacokinetics- Volume of Distribution

Answer 13

Drug A
Q (amount of drug)= 200 gms
Plasma concentration, Cp= 10 gms/L (mass/volume)
Volume of distribution = Q/Cp = 200 gms/ 10 gm/L = 20 L
Vol. of distribution (for an average human)= 20 L/60 Kg = 0.33 L/Kg

Drug B
Q (amount of drug)= 200 gms; Plasma concentration, Cp= 1 gm/L