Pharmacokinetics: Metabolism, Excretion, Absorption, Distribution

Question 1

Phase 1 of metabolism of drugs?

Answer 1

Drugs become more polar and water-soluble → more prone to renal elimination
Oxidation, hydrolysis, reduction

Question 2

Phase 2 of metabolism of drugs? what forms?

Answer 2

Drugs are conjugated and are usually inactivated or become more water-soluble → more prone to renal elimination

• Formation of glucuronides, acetates, sulfates
• Transferase enzymes

Question 3

Difference between ionized and unionized medication?

Answer 3

ionized made by two phases stay in blood to be excreted, unionized diffuse more readily though membrane.

Question 4

what Enzyme system involved in phase I metabolism?

Answer 4

CPY system

-can be affected by other drugs, genotype and disease.

Question 5

what is Induction enzyme change?

Answer 5

Drug or substance increases enzyme expression (e.g., caffeine)
Results in faster metabolism

Question 6

job of Plasma Esterases?

Answer 6

Catalyze hydrolysis of ester groups
Ubiquitous, independent of organ function
Usually leave drugs inactive
May activate/inactivate some drugs

Question 7

what two things of urine can affect the excretion of drug secondary to pKa?

Answer 7

Alkalization and acidification

Question 8

1st order pharmacokinetics

Answer 8

Serum concentration changes are proportional to drug dosing changes
Elimination rate is dependent on drug concentration
Constant proportion is eliminated from body
Body is able to keep up with dose increases & prevent accumulation in normal course of therapy

Question 9

Zero order kinetics

Answer 9

Zero order kinetics
Elimination is a constant X mg/hr (amount)

Independent of the drug concentration in the body

Can lead to accumulation

Question 10

Michaelis-Menten Kinetics

Answer 10

Below a given serum concentration, elimination follows 1st order kinetics

Above the given serum concentration, elimination follows zero order kinetics

Steady-state concentrations increase greater than expected with dose increases

Question 11

Enteral Route?

Answer 11

Oral (PO) – by mouth
Sublingual (SL) – under the tongue
Rectal (PR) – per rectum

Question 12

Factors Affecting Drug Absorption

Answer 12

Diffusion:
-Concentration gradient of the drug 
(Fick’s Law of Diffusion)
-Lipid solubility of the drug 
(Henderson-Hasselbalch Equation)
-pH levels on both sides of the membrane 
(pH trapping)

Question 13

pKa is when

Answer 13

the pH at which 50% of the drug is non-ionized

Question 14

when pH = pKa

Answer 14

the drug is at equilibrium

Question 15

when pH < pKa

Answer 15

protonated (non-ionized) form dominates

Question 16

when pH > pKa

Answer 16

non-protonated (ionized) form dominates

Question 17

Vd is a proportionality constant defined as:

Answer 17

Amount of drug in the body/plasma concentration

Question 18

Factors Affecting Vd

Answer 18

Drug pKa 
Extent of drug-plasma protein binding 
Partition coefficient of the drug in fat (lipid solubility) 
Vd may be affected by: 
Gender 
Age 
Disease 
Body composition (muscle mass, body fat

Question 19

For drugs of equal potency, a drug with a high Vd typically requires?

Answer 19

a higher initial dose to establish therapeutic plasma levels (“loading dose”)

Question 20

what (6) factors affect drug distribution

Answer 20

Blood flow to the tissue
Solubility of the drug
Capillary permeability
Binding
Volume of distribution
All the above