POTENCY, EFFICACY & THE THERAPEUTIC INDEX

Question 1

What’s the difference between pharmacokinetics and pharmacodynamics?

Answer 1

Pharmacokinetics:
- study of drug movement throughout the body

Pharmacodynamics:
- study of how drugs changes the body

Question 2

What is the ED50: median effective dose?

Answer 2

Dose required to produce a specific therapeutic response in 50% of patients
Often referred to as the standard dose

Question 3

What is the therapeutic index?

Answer 3

Ratio of a drugs LD50 (or TD50) to its ED50

• drugs with a narrow therapeutic index are considered high alert medications

Question 4

What is a median lethal dose (LD50)?

Answer 4

Dose of drug that will be lethal (sufficient to death) in 50% test animals

Question 5

What is the median toxic dose (TD50)?

Answer 5

Dose that will produce a given toxicity in 50% of patients

Question 6

What is dose response curve?

Answer 6

• demonstrates the magnitude of biological response to a drug
• different from quantal yes/no response
• done by observing and measuring patient responses at different doses of a drug

Used to determine:
- therapeutic range of a drug
- efficacy of a drug
- potency of a drug

Question 7

What are quantal effects?

Answer 7

Yes/no patient response
EX. “Did the drug reduce systolic blood pressure by 20 mmHg?”

Specific end point of drug action and determining the number of subjects that achieve this endpoint as a function of drug dosage.

Question 8

Phase 1 of graded effects:

Answer 8

Few target cells are affected by the drug at this dose

Question 9

Phase 2 of graded effects:

Answer 9

Linear relationship between amount of drug administered and degree of client response

Question 10

Phase 3 of graded effects:

Answer 10

Plateau is reached: increasing the dose has no therapeutic effect - may produce adverse affects

Question 11

What is potency?

Answer 11

• Compares the doses of 2 or more drugs with respect to how much drug is needed to produce a specific response
• comparison usually based on the median effective dose
• if a drug is highly potent, it will not take much drug to produce a therapeutic response
• potent drugs typically have a high affinity for the receptor binding site

Question 12

What is receptor binding - affinity?

Answer 12

A drugs affinity for a receptor tells us how well the drug binds to the receptor, but does not tell us anything about the action of the drug at the receptor

Question 13

What types of agonists are there?

Answer 13

• full
• partial
• inverse

Question 14

What types of antagonists are there?

Answer 14

• reversible, competitive or non competitive antagonists
• irreversible antagonists

Question 15

What are full agonists?

Answer 15

They bind to the same receptor suite as the endogenous ligand and produce the same effect as the endogenous ligand at the receptor site

• dexamethasone (long acting glucocorticoid drug) produces the same response as cortisol (the endogenous ligand)

** if an agonist produces the full effect of the endogenous ligand, the drug is called “full agonist with high efficacy**

Question 16

What are partial agonists?

Answer 16

If only part of the endogenous effect is elicited, the drug is called a partial agonist
- arpiprazole produces a smaller biological effect at the dopamine receptor compared to dopamine
- efficacy will always be lower than a full agonist

Question 17

What are inverse agonists?

Answer 17

• Bind to the same receptor site as the endogenous ligand, but induce the opposite response
• only occurs when receptors have an intrinsic (basal) level of activity
• considered to have a negative efficacy

Question 18

What is a GABAa receptor?

Answer 18

Agonists (such as benzodiazepines) elicit a sedative effect
Inverse agonists at this receptor have anxiogenic (anxiety including) effects

Question 19

What are antagonists?

Answer 19

Bind to the same receptor site as the endogenous ligand, but DO NOT stimulate the receptor.
Rather, antagonists occupy the receptor preventing the endogenous ligand from binding

Question 20

What are reversible, competitive antagonists?

Answer 20

• Antagonists complete for the same receptor binding site as the endogenous ligand
• when the antagonist is bound the receptor binding site, it blocks the endogenous ligand from binding
• always dissociates from the receptor

Question 21

What is a reversible, non competitive antagonists?

Answer 21

• binds to a site other than the endogenous receptor binding site “allosteric modulation”
• prevents the endogenous ligand from binding at the receptor binding site
• PCP (phenylcyclididine) and ketamine are non competitive antagonists of the NMDA receptor

Question 22

What are irreversible antagonists?

Answer 22

An antagonist that binds to the receptor binding site and does not dissociate from the receptor