Pharmacodynamics- therapeutic

Question 1

What is efficacy?

Answer 1

Describes the extent to which a drug can produce a biological response when all available receptors or binding sites are occupied- corresponds to Emax on the log dose-response curve

Question 2

What’s the difference between full and partial agonist?

Answer 2

Full- greatest efficacy, max response

Partial- lower efficacy, sub-optimal response, flatter curve

Question 3

What is therapeutic efficacy?

Answer 3

Describe the comparison of drugs that produce the same therapeutic effects on the biological system but do so via different pharmacological mechanisms

Question 4

Describe examples of different therapeutic efficacy

Answer 4

• Diuretics= loop have greater natriuretic efficacy than thiazide (effects at different sites of the renal tube)
• Acid suppressing drugs= proton pump inhibitors more efficacious at inhibiting gastric acid secretions than H2 antagonists

Question 5

What is potency?

Answer 5

Describes amount of a drug required for a given response- more potent= biological response at lower doses…lower ED50
Reflected in recommended dose ranges

Question 6

What is affinity for receptor?

Answer 6

How readily the drug-receptor complex is formed

Question 7

What is the difference between potency and efficacy?

Answer 7

Less potent drugs can have an efficacy similar to one of high potency- differences in potency can readily be overcome by higher doses, efficacy cannot

Question 8

How is the most suitable drug chosen?

Answer 8

Seems logical to choose greatest therapeutic efficacy but same mechanism of action can be responsible for dose-limiting adverse effects
Beta-1 adrenoreceptor blocking drugs

Question 9

How can adverse effects be limited?

Answer 9

Increasing/ titrating the dose- difficult when steeper dose-response curve

Question 10

How is potency involved in choosing the most suitable drug?

Answer 10

Any difference in potency can be overcome my giving higher doses but adverse effects are drug-dose related
Relevant if these occur by a mechanism other than the receptor-ligand interaction that mediates beneficial effect

Question 11

Factors affecting relative merits of drugs

Answer 11

Overall adverse effect profile
Therapeutic index
Ease of administration for the patient
Duration of effect (number of daily doses)
Cost

Question 12

How are receptors named?

Answer 12

Major endogenous agonist (adrenergic, opioid)

Subtyped on basis of selectivity for agonist and antagonists

Question 13

What is agonist selectivity?

Answer 13

Determined by ratio of EC50 of the dose-response curve at the two different receptor subtypes

Question 14

What is antagonist selectivity?

Answer 14

Measured as the relative shift of the agonist dose-response curves achieved by a single dose of antagonist affecting responses mediated by two receptors

Question 15

Why is selectivity different specificity?

Answer 15

Although considered selective for one subtype, can produce significant effects at other subtypes if enough is given
Lower selectivity= difficult to predict drug doses (lowest effective dose)

Question 16

What is the recommended dose range?

Answer 16

Dose range that is expected to be close to the top of the dose-response curve for most patients
Significant dose-related adverse effects- achieve desired therapeutic response at lower end or recommended

Question 17

What is the therapeutic index?

Answer 17

Measure of the ratio between the doses that cause the adverse effects and desired therapeutic effect- expression of how much room for error for choosing dose

Question 18

How are recommended dose ranges constructed?

Answer 18

Average data derived from observations in many individuals= inter-individual variation

Question 19

What causes pharmacodynamic variation?

Answer 19

Differences in receptor number and structure
Receptor-coupling mechanisms
Physiological changes resulting from age, genetics, health
Not same drug tissue concentration- same dose can lead to different drug exposure (pharmokinetic)

Question 20

What is desensitisation?

Answer 20

biological response to a drug diminishes when it is given continuously/ repeatedly
Can be restored by increasing dose but tissues can become completely refractory to this effect

Question 21

What is tachyphylaxis?

Answer 21

Desensitisation that occurs very rapidly, sometimes with initial dose

Question 22

What is tolerance?

Answer 22

More gradual loss of response to a drug that occurs over a few days/ weeks

Question 23

How might tachyphylaxis occur?

Answer 23

Depletion of chemical mediators

Question 24

How might tolerance occur?

Answer 24

Changes in receptor numbers

Development of counter-regulatory reflexes

Question 25

What are the causes of desensitisation?

Answer 25

- Reduction in pharmacodynamic effectiveness= receptor-mediated and non-receptor mediated - Pharmacokinetics= reduction in plasma and tissue drug concentrations due to alterations in the way the drug is handled

Question 26

Mechanisms that include altered pharmacodynamics

Answer 26

- Reduction in receptor number= downregulation - Changes in receptor structure or function= chemical modification (phosphorylation/ specific amino acids in G protein coupled receptors) - Exhaustion of mediators= depletion of signalling molecules (secondary messengers) or stored chemicals (neurotransmitters) - Physiological adaption= repeated exposure to drug diminishes clinical effects (lowered bp vasoconstrictors)

Question 27

Mechanisms that include altered pharmacokinetics

Answer 27

- Increased drug metabolism= repeated exposure increases the capacity of the liver to metabolise drugs Active extrusion of drug from cells

Question 28

What is drug withdrawal?

Answer 28

Chemical, biologic and physiological changes by which body restores equilibrium and offsets action of drug

Question 29

Common drugs that lead to desensitisation

Answer 29

Organic nitrates, opioid analgesics, benzodiazepines, ethanol and nicotine