Pharmacokinetics (Wolff)

Question 1

What are the 4 basic pharmacokinetic processes?

Answer 1

ADME

Absorption, Distribution, Metabolism, Excretion

Question 2

What are the factors affecting drug Absorption

Answer 2

rate of dissolution (eg. of tablet)
surface area
blood flow (to surface area)
lipid solubility
pH partitioning

Question 3

What are the enteral routes of drug administration?

Answer 3

Oral
Rectal
Sublingual/buccal (in mouth but not swallowed)

Question 4

What are the parenteral routes of drug administration?

Answer 4

Intravenous
Intramuscular
Subcutaneous
Inhalation
Topical
Transdermal

Question 5

What is a major transporter of drugs OUT of cells?

Answer 5

P-glycoprotein

Question 6

What is the typical way for drugs to cross the cell membrane?

Answer 6

Direct penetration of the membrane

aka simple diffusion

Question 7

Weak acids and bases can only cross membranes when in their _______ form

Answer 7

unionized

Question 8

What is ka?

Answer 8

ka = rate constant for absorption

Question 9

What is S?

Answer 9

S = salt factor; less than or equal to 1

drugs are often administered as their salt, but only parent compound is measured

Question 10

What is F?

Answer 10

F = bioavailability, fraction of drug that reaches the bloodstream; less than or equal to 1

Question 11

Amount of drug absorbed formula

Answer 11

amount absorbed = SFDose

Question 12

Formula for Concentration in Plasma (Cp)

Answer 12

Cp = (SFDose)/Vd

Question 13

Formula for Volume of distribution (Vd)

Answer 13

Vd = (amount of drug in body)/(Plasma concentration)

Question 14

What are the factors affecting drug Distribution

Answer 14

Ability of drugs to enter cells
Blood flow to tissues
Ability of drugs to exit the vascular system

Question 15

A drug is only bioactive if ____

Answer 15

free

Question 16

What is the primary site of biotransformation/drug metabolism?

Answer 16

The liver

Question 17

Drug metabolism is crucial for the renal elimination of _______ drugs?

Answer 17

Lipophilic drugs. They must be made more polar so they can be trapped in the renal tubular fluid

Question 18

Phases of drug metabolism/biotransformation

Answer 18

Phase I: oxidation, reduction, hydrolysis

Phase II: conjugation

Question 19

Phase I biotransformation

Answer 19

products are usually more polar metabolites

Oxidative processes often involve the cytochrome P450 system in the sER

Question 20

Cytochrome p450 INDUCERS do what

Answer 20

Speeds up metabolism and leads to quicker lowering of plasma levels below minimal effective concentration

Question 21

Cytochrome p450 INHIBITORS do what

Answer 21

slow the metabolism and can lead to toxic levels of a drug

Question 22

Which enzyme does grapefruit juice inhibit

Answer 22

grapefruit juice is an inhibitor of CYP3A4 enzyme (the major cyt p450 enzyme)

Inhibition of this enzyme in the intestinal epithelial cells increases the bioavailability of other drugs

Question 23

What is the goal of conjugation in phase II of biotransformation

Answer 23

Conjugation usually makes drugs more water soluble and more excretable since the molecule added is highly polar

Question 24

What is the goal of acetylation and methylation in phase II of biotransformation

Answer 24

Typically makes drugs less water soluble

Usually inactivates the drug

Question 25

What is the major route of drug excretion?

Answer 25

The renal route

Question 26

What are the steps of renal drug excretion?

Answer 26

Glomerular filtration (small mol drugs)

Passive tubular reabsorption (lipid soluble drugs and unionized weak acids and bases)

Active tubular secretion (protein-bound drugs)

Question 27

What are factors that modify renal drug excretion

Answer 27

pH dependent ionization
Competition for active tubular transport
Age (GFR falls as we age)

Question 28

What are the consequences of drug-drug interacitons

Answer 28

intensification of effects (synergy, potentiation)

Reduction of effects (antagonism)

Creation of a unique response

Question 29

What is zero order kinetics

Answer 29

A constant amount eliminated per unit

Drug elimination is saturated

The amount of drug eliminated is independent of the drug concentration

Question 30

What is first order kinetics

Answer 30

Constant fraction is eliminated per unit time

drug elimination is not saturated

The mass of drug eliminated is directly related to the drug concentration

The more typical form of drug elimination