3. Pharmacodynamics, Drug Interaction, and Toxicology

Question 1

What are the conventional mechanisms of action of drugs?

Answer 1

Interactions with endogenous proteins - cell surface receptors, nuclear receptors, enzymes, ion channels, transporters, signal transduction proteins etc.

Question 2

What is the unconventional mechanism of action that vinca alkaloids and colchicine utilise?

Answer 2

Disruption of structural proteins

Question 3

What is the unconventional mechanism of action that streptokinase utilises?

Answer 3

Being enzymes

Question 4

What is the unconventional mechanism of action that cyclophosphamide utilises?

Answer 4

Covalently linking to macromolecules

Question 5

What is the unconventional mechanism of action that antacids utilise?

Answer 5

Reacting chemically with small molecules

Question 6

What is the unconventional mechanism of action that infliximab and drugs for heavy metal poisoning utilise?

Answer 6

Binding to free molecules/atoms

Question 7

What is the ideal standard for a drug?

Answer 7

Acts at one site (selective) and performs one certain action (specific). This isn’t realistic, real drugs have side effects.

Question 8

Give an example of drug selectivity

Answer 8

Penicillin targets an enzyme involved in bacterial cell wall synthesis, but not human cell wall synthesis.

Question 9

Give an example of drug specificity

Answer 9

Adrenergic receptors - Beta 1 in heart, Beta 2 in lungs

Question 10

What is affinity?

Answer 10

Drug tendency to bind to specific receptor types

Question 11

What is efficacy?

Answer 11

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

Question 12

What is potency?

Answer 12

Dose required to produce the desired biological response

Question 13

What is the therapeutic index?

Answer 13

The relationship between concentrations of a drug causing overdose and concentrations causing the desired effect.

Question 14

Is a higher or lower therapeutic index better?

Answer 14

Higher as that means there is a larger margin of safety.

Question 15

What is the therapeutic window?

Answer 15

The range of doses that can be used to treat a pt with a specific drug while remaining safe

Question 16

Name some drugs with a narrow therapeutic window.

Answer 16

Warfarin
Digoxin
Aminophylline
Aminoglycoside abx

Question 17

When drugs interact, at what levels can they interact?

Answer 17

Absorption
Distribution/Protein binding
Metabolism

Question 18

What can be altered to affect GI absorption of a drug?

Answer 18

P-glycoprotein activity (active transporter)

Question 19

Which drugs is protein binding interactions most relevant for?

Answer 19

IV drugs
Drugs with a short haf life
Drugs with a narrow therapeutic window

Question 20

What classes of drugs are the usual suspects for drug interactions?

Answer 20

Anticonvulsants
Antibiotics
Anticoagulants
Antidepressants/psychotics
Antiarrhythmics

Question 21

What other “DDI” is important to remember?

Answer 21

Drug Disease interactions

Question 22

What diseases should we look out for when thinking about drug interactions?

Answer 22

Renal, kidney, and liver disease

Question 23

Why is renal disease important in drug metabolism?

Answer 23

If cleared by kidneys or affect functioning of the kidneys (nephrotoxic), renal disease decreases GFR so clearance is decreased, so can predispose to toxicity.

Question 24

What is the classic example of drug interactions in hepatic disease?

Answer 24

Opiates in cirrhosis -> accumulation of small doses -> coma. Reduced clearance so drug half life increases.

Question 25

Why is cardiac disease important wrt drug interactions?

Answer 25

Reduced CO -> reduced organ perfusion, and an increased response to hypotensive aagents

Question 26

What does grapefruit juice interact with, and how?

Answer 26

Inhibits CYP450 isoenzymes affecting simvastatin, amiodarone, and terfenadine among others.

Question 27

What does cranberry juice interact with, and how?

Answer 27

Inhibits CYP2C9 isoform -» warfarin, anticoagulants. High risk of haemorrhage.