Lecture 69

Question 1

graded dose-response curve

Answer 1

• plotting the magnitude of response against increasing doses of drug produces a graded dose-response curve
• beyond a certain point, response does not increase any further by increasing drug concentration
• x-axis: drug dose or concentration
• y-axis: usually response (effect) or % of maximal response (% of maximal effect)
• in a graded-dose response curve, response increases with increasing drug concentration until maximal response is achieved
• usually done on a semi-logarithmic curve

pg 1800-1801

Question 2

DRC: full vs partial agonist

Answer 2

partial agonists cannot produce maximal response even at maximal receptor occupancy

pg 1803

Question 3

DRC: full agonist followed by partial agonist

Answer 3

1. the full agonist is occupying all the receptors producing maximal response (when no partial agonist is present)
2. increasing concentrations of the partial agonist starts displacing the full agonist (overall response is decreased)
3. at high concentrations of the partial agonist, all the full agonist is displaced (the response is determined by intrinsic activity of the partial agonist)

pg 1804

Question 4

agonist, antagonist, partial agonist, inverse agonist

Answer 4

• full agonist: 100% response
• partial agonist: less than 100% response
• antagonist: no response, remains at baseline
• inverse agonist: negative response (decrease from baseline)

pg 1805

Question 5

DRC: agonist + antagonist

Answer 5

• a non-competitive antagonist shifts the DRC downwards (adding drug will NOT increase response)
• a competitive antagonist shifts the DRC to the right (need greater concentration of drug to elicit total response)

pg 1806

Question 6

efficacy

Answer 6

• look at y-axis
• the magnitude of a response elicited by a drug when it interacts with a receptor
• measurement: efficacy is measured by E_max
• E_max: maximal effect achieved by a drug when all receptors have been occupied

pg 1814

Question 7

potency

Answer 7

• look at x-axis
• a drug is more potent when it achieves the same magnitude of response with a lower drug concentration
• measurement: potency is measured by EC₅₀
• EC₅₀: drug concentration that achieves 50% of this drug’s maximal achievable effect

pg 1815

Question 8

steep dose response curve

Answer 8

• small change in concentration → large change in response
• safety issue
• on a less steep curve, the same change in response requires a large dose change (safer drug)

pg 1823

Question 9

quantal dose-response curve

Answer 9

• dose vs % showing response
• plotting the relationship between drug dose and proportion of the patient population responding to it produces a quantal dose-response curve
• there is NO graded response; the effect either occurs or doesn’t occur (YES or NO)
• based on population data

pg 1828

Question 10

median effective dose (ED₅₀)

Answer 10

drug dose that causes a therapeutic response in half of the population

pg 1829

Question 11

median toxic dose (TD₅₀)

Answer 11

drug dose that causes a certain toxic effect in half of the population

can be called median lethal dose (LD₅₀) if the toxic effect is death

pg 1829

Question 12

therapeutic index (TI)

Answer 12

• ratio of the TD₅₀ to the ED₅₀
• TI = TD₅₀/ED₅₀
• reflects the selectivity of a drug to elicit a desired vs a toxic response
• want this to be as high as possible for a safe drug

pg 1830

Question 13

therapeutic window (TW)

Answer 13

• range between the minimum toxic dose and the minimum therapeutic dose
• more clinically relevant
• defines the range of doses over which the drug is effective for most of the population (with a minimal/acceptable toxicity)

pg 1830

Question 14

effective curve vs toxic curve

Answer 14

want the toxic curve to be shifted far to the right for the safest drug

Question 15

drugs with lower TI

Answer 15

• warfarin, theophylline, lithium
• often require therapeutic drug monitoring (TDM), especially at inhibition of therapy

pg 1832