Pharmacokinetics and Dynamics

Question 1

What does ADME stand for when thinking about pharmacokinetics

Answer 1

Absorption, Distribution, Metabolism and Excretion

Question 2

What level do you want Cmax (peak level) to be below

Answer 2

Toxicity level

Question 3

What is the therapeutic window of a drug

Answer 3

The area between the minimal effect concentration and toxicity level

Question 4

What is meant by Tmax of a drug

Answer 4

The time taken to reach Cmax/Peak level of plasma concentration of a drug

Question 5

How fast is the absorption rate from an IV bolus

Answer 5

Considered instant

Question 6

What is meant by zero-order elimination kinetics

Answer 6

Reactions where the rate is not affected by the concentration of the drug used.

Question 7

What is meant by first-order elimination kinetics

Answer 7

Depends on the concentration of only one reactant (drug) and a constant fraction of the drug in the body is eliminated per unit of time

Question 8

Define “drug elimination rate”

Answer 8

The amount of parent drug eliminated from the body per unit of time
Defined with respect to the irreversible removal of the parent drug and does not include metabolites

Question 9

What are phase I and phase II when referring to lipid soluble drug metabolism

Answer 9

Phase I = dug made more water-soluble by catabolic reaction (oxidation, reduction, hydrolysis)
Phase II = made even more water-soluble by an anabolic reaction adding on an endogenous water soluble molecule (synthetic conjugation)

Question 10

What does oxidation by CYP450 do to a drug

Answer 10

Inserts oxygen between carbon and hydrogen on the drug
Gives the drug a hydroxy functional group = very water soluble

Question 11

Name the 3 main routes of excretion of a drug

Answer 11

Kidneys
Hepatobiliary system
Lungs

Question 12

Name the 2 secondary routes of excretion of a drug

Answer 12

Milk
Sweat

Question 13

Name the 3 main stages of renal drug excretion

Answer 13

1. Passive filtration at the glomerulus
2. Secretion of the drug into the proximal tubule
3. Reabsorption back into the body - depends on lipophilicity

Question 14

Define drug clearance

Answer 14

The volume of blood/plasma cleared of parent drug per unit of time
- OR
A constant relating the rate of elimination to the blood/plasma concentration

Question 15

How is drug clearance calculated

Answer 15

The area under the blood/plasma curve

Question 16

Define Bioavailability (F)

Answer 16

Measure of extent of absorption from administration site to measurement site

Question 17

What is AUC when talking about drug clearance

Answer 17

The area under the curve
Inversely proportional to clearance of the drug

Question 18

Define the volume of distribution (Vd)

Answer 18

The volume into which a drug appears to be distributed with a concentration equal to that of plasma
- OR
A proportionality constant relating the Blood/plasma concentration to the amount of drug in the body

Question 19

Are volume of distribution and drug clearance reversible or irreversible processes

Answer 19

Volume of distribution = reversible
Drug clearance = irreversible

Question 20

Define the half-life of a drug

Answer 20

The time for the concentration of the drug to halve

Question 21

Define drug-drug interactions

Answer 21

Altered pharmacologic response to one drug caused by the presence of a second drug

Question 22

Name the 3 categories of drug-drug interactions and give a brief description

Answer 22

1. Pharmaceutical - interaction prior to administration
2. Pharmacokinetic - tissue/plasma levels of a drug altered by another
3. Pharmacodynamic - action of a drug is altered by another

Question 23

Name the 4 potential outcomes of drug-drug interactions and describe

Answer 23

1. Summation - (1+1=2) the combined effect of 2 drugs produces a result that equals the sum of the individual effects of each agent
2. Potentiation - (0+1=2) When a drug on its own does not have an effect but may affect/be affected in combination with another drug
3. Synergism - (1+1=3) Drug combinations produce a therapeutic or toxic effect greater than the sum of each drug’s action
4. No effect

Question 24

Name the 2 mechanisms of interactions for pharmaceutical interactions, and describe

Answer 24

1. Physical - Incompatibility/interactions e.g. binding to plastic or insolubility in some solutions
2. Chemical - pH dependant stability, oxidation/reduction reactions, complex reactions, inactivation

Question 25

Name the 4 mechanisms of interactions for pharmacokinetic interactions and describe

Answer 25

1. Absorption - altered gastric emptying, change in gastric pH
2. Distribution - competition plasma protein binding, some drugs reduce blood flow to tissue => reduced absorption from IM or SC administrations, reduced clearance
3. Metabolism - Inhibition/induction of liver enzymes (CYP450)
4. Excretion - urinary pH alters clearance of really excreted drugs

Question 26

Name the 3 mechanisms of interactions for pharmacodynamic interactions and describe

Answer 26

1. Additive - beneficial or detrimental, can enable reduced doses but can lead to increased toxicity
2. Synergistic - Combination leads to a greater than the sum of each drug’s action, producing an enhanced therapeutic effect or increased toxicity
3. Negation - opposing actions lead to a reduced effect - basis of antidote/reversal agents

Question 27

Name 5 types of adverse events

Answer 27

1. lack of efficacy
2. exaggerated normal response
3. hypersensitivity
4. toxic effects
5. idiosyncratic

Question 28

Define an adverse event

Answer 28

Unintended or noxious response to a drug that occurs within a reasonable time frame following administration

Question 29

Name some ‘use patterns’ associated with increased adverse events

Answer 29

Use of human-label drugs
drugs with low therapeutic indices
Inappropriate use
Multiple drugs
Lack of therapeutic goals
Young, old, altered PK (pharmacokinetic parameters)