Pharmacodynamics

Question 1

Define agonist

Answer 1

Activate endogenous proteins

Full = 100% efficacy

Partial = <100%

Question 2

Define antagonist

Answer 2

Antagonise, block or inhibit endogenous proteins

Competitive = blocks site

Non-competitive = works at site distant to receptor

Question 3

Where do drugs typically work?

Answer 3

Cell surface receptors

Nuclear receptors

Enzyme inhibitors

Ion channel blockers

Transport inhibitors

Inhibitor of signal transduction proteins

Question 4

Define drug selectivity

Answer 4

The more the selective a drug is for its target, the less chance that it will interact with diff targets and have less undesirable side effects

Question 5

Define drug specificity

Answer 5

Targeting drugs against specific receptor subtypes often allows drugs to be targeted against specific organ

Question 6

Define Affinity

Answer 6

The tendency of a drug to bind to a specific receptor type

Question 7

Define Efficacy

Answer 7

Ability of a drug to produce a response as a result of the receptor or receptors being occupied

Describes the max effect of a drug

Question 8

Define Potency

Answer 8

Dose required to produce the desired biologic response

Question 9

Define the Therapeutic Window

Answer 9

Range of [plasma] that the drug has a desired effect

= EC50 (adverse effect) / EC50 (desired effect)

Like to devel drugs that have a large therapeutic index

Question 10

Describe with examples pharmacokinetic and pharmacodynamic drug interactions

Answer 10

Alcohol + food = lowers [alcohol]

Tetracycline + Fe = bind forming chelate = lowers [plasma tetracycline]

Cimetidine + warfarin = raises [plasma warfarin] = increased prothrombin time

Question 11

Describe the induction and inhibition of the Cytochrome P450 system

Answer 11

Induction = increases amount of enzyme, takes time

Inhibition = block enzyme, half-life increased, plasma conc higher for a longer period of time

Question 12

What drugs induce CYP450s?

Answer 12

P CBRAS

P – phenytoin

C – carbamazepine

B – barbituates

R – rifampicin

A – alcohol

S – sulphonylureas

Question 13

What drugs inhibit CYP450s?

Answer 13

O DECICES

O – omperazole

D – disulfiram

E – erythromycin

V – valproate

I – isoniazid

C – cimetidine

E – ethanol

S – sulphonamides

Question 14

Outline how hepatic disease affects drugs

Answer 14

Reduced clearance of hepatic metabolised drugs

Reduced CYP 450

Longer half-lives

Toxicity

Opiates in cirrhosis = small doses accumulating leading to coma

Question 15

Discuss how renal disease effects drugs

Answer 15

Reduced clearance

Disturbances of electrolytes may predispose to toxicity

Question 16

Outline how cardiac disease affects drugs

Answer 16

Reduced organ perfusion = reduced hepatic blood flow and clearance, reduced renal blood flow and clearance

Question 17

Give an example in a drug interaction has altered a normal ECG

Answer 17

Erythromycin + fluconzole = prolonged QT = torsade de pointes

Question 18

Discuss some drug-food interactions

Answer 18

Grape fruit juice = inhibits CYP450 isoenzymes

Cranberry juice = inhibits bacterial adherence to urothelium, inhibits CYP2C9 which decreases clearance of warfarin

Question 19

Recognise the main ADR types and give examples of these

Answer 19

A – augmented pharmacologic effects = hypoglycaemia due to insulin

B – bizarre effects = anaphylaxis due to penicillin

C – chronic effects = colonic dysfunction due to laxatives

D – delayed effects = 2nd cancers in those treated with alkylating agents for hodgkins disease

E – end of treatment effects = withdrawal seizures when anticonvulsants are stopped

Question 20

Recognise circumstances in which drug interactions are most likely to occur

Answer 20

Polypharmacy

Extremes of age

Multiple medical problems

Use of drugs with narrow therapeutic indexes

Drugs are being used near their minimum effective conc