Pharmacokinetics 1

Question 1

What determines a drug response?

Answer 1

Concentration at its site of action, which is in equilibrium with the concentration obtained in blood

Question 2

What is pharmacodyamics?

Answer 2

What the drug does to the body

Question 3

What is pharmacokinetics?

Answer 3

What the body does to the drug

Question 4

What two factors determine the route of drug administration?

Answer 4

1. Speed of onset

2. Convenience

Question 5

What does ADME stand for?

Answer 5

Absorption, distribution, metabolism, excretion

Question 6

What is drug absorption?

Answer 6

Movement of drug from site of administration to site of measurement

Question 7

What is drug distribution?

Answer 7

Reversible transfer of absorbed drug into and out of various tissues in the body from the bloodstream

Question 8

What is drug metabolism?

Answer 8

Conversion of a drug to a usually more water soluble compound

Question 9

What is drug excretion?

Answer 9

Loss of unchanged drug from the body in the urine or faeces including biliary excretion

Question 10

What is drug elimination?

Answer 10

Metabolism and excretion of a drug (everything after the distribution equilibrium)

Question 11

What is drug disposition?

Answer 11

Distribution and elimination of a drug (all process which occur after a drug has been absorbed)

Question 12

What is first pass metabolism?

Answer 12

The metabolism of a drug before it reaches the systemic circulation after oral administration

Question 13

What is bioavailability?

Answer 13

The amount of drug which reaches systemic circulation

Question 14

What happens to orally administered drugs once swallowed?

Answer 14

Transport proteins absorb the drugs through the gut wall to the liver, where the drugs are metabolised

Question 15

What occurs during the metabolism of a drug in the liver?

Answer 15

The liver usually adds a water soluble molecule to the drug as water soluble molecules are easier for the kidney to remove

Question 16

What happens to lipid soluble or small drugs which are hard for the kidney to excrete?

Answer 16

Usually travel to tissue reservoirs e.g. muscle

Question 17

What is the main reason a drug may not be orally administered?

Answer 17

Low oral bioavailability

Question 18

What are 4 reasons a drug may have low oral bioavailability?

Answer 18

1. Poorly absorbed due to low lipid solubility
2. Destroyed by acid or enzymes
3. Causes major gut adverse conditions
4. Has a large first pass effect

Question 19

What is a method of administration to avoid first pass effect?

Answer 19

Sublingual administration

Question 20

What 6 chemical properties determine the amount of drug in systemic circulation after oral administration?

Answer 20

1. Stability to acid
2. Stability to digestive enzymes
3. Solubility in aqueous solution
4. Lipid solubility
5. Molecular weight
6. pKₐ

Question 21

What 4 physiological variables determine the amount of drug in systemic circulation after oral administration?

Answer 21

1. Presence and type of food
2. Blood flow to GIT and liver
3. Gastric motility
4. pH of stomach and intestinal contents

Question 22

What is the greatest risk of pH on a drug?

Answer 22

Can cause the drug to become ionized, forming a charge on the drug making it harder to move through the phospholipid bilayer

Question 23

What is the volume of distribution of a drug?

Answer 23

A measure of how easily the drug leaves the bloodstream

Question 24

How does a drug stay in the blood stream if it is particularly acidic or alkaline?

Answer 24

Attach to proteins as proteins are large molecules so find it hard to pass out of the bloodstream

Question 25

What determines the extent and ease of a drug's distribution?

Answer 25

The drugs physicochemical properties

Question 26

What plasma proteins do acidic drugs tend to bind to?

Answer 26

Albumin

Question 27

What plasma proteins do basic drugs tend to bind to?

Answer 27

a1-acid glycoprotein

Question 28

What 3 factors can affect plasma binding proteins?

Answer 28

1. Age 2. Inflammatory conditions 3. Pathologic stress

Question 29

What is a free drug?

Answer 29

An active version of a drug, not bound to a plasma protein, which is able to distribute to tissues and exert pharmacological action

Question 30

What equation allows the calculation of the volume of distribution of a drug?

Answer 30

Amount in Body = Vd x [Plasma] | Vd = Amount in Body / [Plasma]

Question 31

What is the first step to make a lipid-soluble molecule water-soluble?

Answer 31

Phase I reactions uncover or add chemical reactive group by oxidation, reduction or hydrolysis

Question 32

What is the second step to make a lipid-soluble molecule water-soluble?

Answer 32

Phase II reactions involve attachment of an additional chemical group (conjugation) by glucuronidation, acetylation or sulphation

Question 33

What enzymes carry out Phase I Metabolism reactions?

Answer 33

Superfamily of enzymes Cytochrome P450 (CYP)

Question 34

What is the general equation for Phase I Metabolism reactions?

Answer 34

Drug-H + 0₂ (in presence of CYP) = Drug-OH

Question 35

What happens when pro-drugs are metabolised?

Answer 35

Metabolised to more active metabolites

Question 36

Give an example of the metabolism of a pro-drug?

Answer 36

Enalapril is metabolised to enalaprilat

Question 37

Where do Phase II Metabolism reactions mainly occur?

Answer 37

Liver

Question 38

How would Drug-glucuronide be excreted and why?

Answer 38

Bile or urine as it is inactive and polar

Question 39

What 5 things can cause interindividual differences in drug metabolism?

Answer 39

1. Age 2. Disease conditions 3. Genetic variation 4. Enzyme induction 5. Enzyme inhibition

Question 40

What is the most common cause of drug interaction?

Answer 40

One drug can increase or decrease the metabolism of another drug

Question 41

What is enterohepatic recycling of a drug?

Answer 41

Drug conjugates excreted in bile are hydrolysed in lower intestine, releasing original drug for reabsorption into the bloodstream, so prolonging action

Question 42

What is the apparent volume of distribution?

Answer 42

The volume of plasma into which the drug appears to be dissolved

Question 43

What is the elimination half life?

Answer 43

Time taken for the amount of drug in the plasma to decrease by half

Question 44

What is clearance?

Answer 44

The volume of plasma cleared of drug per unit time e.g. litres/hour

Question 45

What is MTC?

Answer 45

Minimum toxic concentration

Question 46

What is MEC?

Answer 46

Minimum effective concentration

Question 47

What is the window between the MEC and MTC called?

Answer 47

Therapeutic window