PH3110 - How human biology influences drug handling and action 1

Question 1

What is pharmacokinetics?

Answer 1

The study of what the body does to a drug

Question 2

What is pharmacodynamics?

Answer 2

The study of what the drug does to the body

Question 3

What is the therapeutic window?

Answer 3

Minimum effective dose to minimum toxic dose

Question 4

What effect does pharmacokinetics have on the therapeutic window?

Answer 4

Provides information on the dosage regimen to achieve a given ‘window’ of plasma drug concentration

Question 5

What effect does pharmacodynamics have on the therapeutic window?

Answer 5

Provides information on the effect likely to be achieved with regards to a given ‘window’ of plasma drug concentrations

Question 6

What are the effects of drugs?

Answer 6

Stimulation (e.g. adrenaline)
Depression (e.g. quinidine)
Irritant (e.g. deep heat)
Replacement (e.g. insulin)
Cytotoxicity (e.g. antibiotics, chemotherapy)

Question 7

What are the three classifications of a response to a drug?

Answer 7

Clinical (subjective vs objective)
Surrogate endpoint (e.g. blood pressure - risk factor for CV event)
Biomarker (e.g. PSA in prostate cancer)

Question 8

What is the difference between subjective and objective clinical responses to a drug?

Answer 8

Subjective - e.g. 1 - 10 in pain score
Objective - e.g. measuring a parameter (e.g blood sugar)

Question 9

What type of receptors can be used as drug targets?

Answer 9

Cell surface and intracellular receptors
Enzymes
Structural proteins

Question 10

What is the relationship between Dose and Concentration?

Answer 10

Pharmacokinetics

Relationship changes with time

Question 11

What is the relationship between Concentration and Effect?

Answer 11

Pharmacodynamics

Relationship DOES NOT change with time

Question 12

What is the relationship between concentration and response?

Answer 12

Michaelis Menten curves

Question 13

What is the equation for the Michaelis Menten curve?

Answer 13

E = Emax x C / Ec50 + C

Question 14

What is the EC50 of a drug?

Answer 14

The concentration of drug that gives 50% of the maximum response

Question 15

What is the concentration-effect rule?

Answer 15

Concentration and effect relationship does not change with time

If the concentration is 40, then effect on body is the same whether drug is being absorbed or eliminated. E1=E2

Question 16

What is the difference between efficacy and potency?

Answer 16

Efficacy is the maximum effect of a drug (Emax)

Potency affords comparison between a set of drugs and indicates the doses of drugs required to produce the same effect

Question 17

Why is concentration used, rather than dose?

Answer 17

Concentration (exposure) in body gives rise to effect
Concentration drives effect
Proportionality between dose and concentration

Question 18

What is the problem with using dose in epilepsy medication?

Answer 18

Massive variation in concentration due to pharmacokinetics. Epilepsy is controlled with plasma concentrations between 10-20mg/L

Question 19

Why aren’t plasma concentrations routinely monitored?

Answer 19

Limited pharmacokinetic variability
Wide safety margins (e.g. antibiotics)
Cost
Plasma concentrations correlates poorly with response
- tolerance
- multiple active species
- time delays
Single dose therapy (e.g. salbutamol after an asthma attack)
Duration vs intensity

Question 20

What are multiple active species?

Answer 20

Conversion of parent drugs to active metabolites (e.g. codeine -> morphine)

Alprenolol more active when given orally than IV
- first pass metabolism doesn’t occur so less active formed
- higher concentration in blood but less effect