Pharmokinetics

Question 1

What do drug effects depend on?

Answer 1

mechanism of action and effects of cellular protein and physiological properties

Question 2

Physiochemical properties of a drug that effect diffusion through lipids

Answer 2

diffusion coefficient- how quickly it moves, lipid solubility- measured by partition coefficient, polarity

Question 3

Being non-polar increases what rates?

Answer 3

Rate of absorption from gut, penetration into brain and other tissues, renal elimination

Question 4

Types of drugs given intravenously

Answer 4

biological and small molecule drugs

Question 5

What do intravenous drugs avoid?

Answer 5

Gut and portal system

Question 6

Rate into plasma of oral or rectal drugs depends on what?

Answer 6

Contents of gut, gut motility, size of drug

Question 7

Bioavailability of a drug

Answer 7

Fraction of ingested drug/ fraction in plasma- ie. how much drug actually ends up in plasma

Question 8

Factors that affect absorption of a drug

Answer 8

Site/method of admin, molecular weight, lipid solubility, pH and ionisation

Question 9

At what pH will weak acids be unionised?

Answer 9

Low pH

Question 10

henderson Hasselbacks equation

Answer 10

pKa= pH+ log10(HA/A-)

Question 11

What is pKa?

Answer 11

acid dissociation constant - pH at which 50% of the molecules are the dissociated form

Question 12

Asprins pKa

Answer 12

3.5

Question 13

pH of the gut

Answer 13

3

Question 14

Plasmas pH

Answer 14

7.4

Question 15

pH in Kidneys

Answer 15

8

Question 16

What do you do if neurotoxicity from aspirin poisoning?

Answer 16

Increase pH by adding sodium bicarbonate- causing drug to be extracted from CNS into plasma where they get trapped

Question 17

Percentage of fluid in extracellular fluid compartment?

Answer 17

Plasma-4.5%, interstitial- 65%, lymph-1-2%

Question 18

Percentage of fluid intracellular fluid compartment

Answer 18

30-40%

Question 19

Percentage of fluid that is transcellular

Answer 19

2.5%

Question 20

Percentage of fluid in fat

Answer 20

20%

Question 21

Structure of the blood brain barrier

Answer 21

Endothelial cells lining blood vessels in CNS form tight junctions

Question 22

Factors that influence drug distribution

Answer 22

Binding to plasma proteins, partition into specific tissue

Question 23

Why are Parkinson’s drugs complicated?

Answer 23

Dopamine drugs trigger CTZ as it has many DA receptors so have to administer other drugs that block CTZ DA receptors (i.e. large drug that won’t cross BBB)

Question 24

2 biochemical reactions of drug metabolism

Answer 24

Catabolic and then synthetic/ anabolic to make conjugate

Question 25

Examples of microsomal enzymes in liver for drug metabolism

Answer 25

Cytochrome p450, MAO, alcohol dehydrogenase

Question 26

Aspirin metabolism

Answer 26

Phase 1- oxidation, hydroxylation, dealkylation, deamination, hydrolysis. Phase 2- conjugate

Question 27

Different isoforms of p450 do what?

Answer 27

React with different drugs

Question 28

What is pharmacokinetics?

Answer 28

Time course of drug concentration attained in the body during and after dosing

Question 29

What is saturation kinetics?

Answer 29

Metabolism and excretion become overwhelmed so can’t go any faster

Question 30

What does saturation kinetics result in?

Answer 30

Disproportionate increase in steady-state plasma concentration - clinical side effects