CPT S2 Pharmacokinetics II

Question 1

Give examples of where drugs can act

Answer 1

Cell surface receptors
Nuclear receptors
Enzyme inhibitors
Ion channel blockers
Transport inhibitors
Signal transduction protein inhibitors

Question 2

Why is digoxin poisoning so common?

Answer 2

Predominantly excreted by the kidneys
Long half life
Old people have reduced/declining renal function
Old people take digoxin

Question 3

Why would you give a loading dose?

Answer 3

If you want a drug to reach a steady state quickly

If that drug has a long half life

Question 4

What occurs in a paracetamol overdose?

Answer 4

Paracetamol is no longer metabolised primarily by glucuronide or sulphate as the pathways are saturated. They undergo p450 oxidation to NAPQI, a hepatotoxin. This would be conjugated with glutathione to be eliminated, but this becomes depleted.

Question 5

How is paracetamol overdose treated?

Answer 5

Give N-acetylcysteine to replace glutathione and assist conjugation of NAPQI.

Question 6

Give some examples of mechanisms of action

Answer 6

Interaction with endogenous proteins (agonists, antagonists)
Disruption of structural proteins
Being enzymes (eg streptokinase)
Covalent lay linking macromolecules
Reacting with small molecules (antacids)
Binding free molecules or atoms (heavy metal poisoning drugs)

Question 7

Define potency

Answer 7

The dose required to produce a specific response

Question 8

Define efficacy

Answer 8

The level of response that occurs as a result of the drug binding to the target receptor.

Question 9

Explain drug selectivity

Answer 9

The more selective a drug is for its target, the less chance it will interact with different receptors, so is likely to have fewer undesirable side effects

Question 10

Give the equation for the therapeutic index

Answer 10

TI= toxic dose (TD50)/effective dose (ED50)

Question 11

Give some CYP450 inducers

Answer 11

Phenytoin
Carbamazepine 
Barbituates
Rifampicin
Alcohol
Suphonylureas&St John's Wort

Question 12

Give some CYP450 inhibitors

Answer 12

Omeprazole
Disulfiram
Erythromycin
Valproate
Isoniazid
Cimetidine and ciprofloxacin
Ethanol
Sulphonamides

Question 13

Give some common drug/food interactions

Answer 13

Grapefruit juice - inhibits several CYPs, decreasing clearance of many drugs including simvastatin and amiodarone.
Cranberry juice - inhibits a CYP, decreasing warfarin clearance and increasing risk of bleed.

Question 14

What chronic conditions can cause changes in drug clearance?

Answer 14

Renal disease
Hepatic disease
Cardiac disease

Question 15

How can renal disease affect clearance?

Answer 15

Falling GFR
Reduced clearance of renally excreted drugs
Disturbances in electrolytes may predispose to toxicity
Drug buildup may cause further kidney damage

Question 16

How can hepatic disease affect clearance?

Answer 16

Reduced clearance of hepatic metabolised drugs
Reduced CYP activity
Longer half lives
Toxicity

Question 17

How can cardiac disease cause reduced clearance?

Answer 17

Falling cardiac output
Excessive response to hypotensives
Reduced organ perfusion
Therefore reduced hepatic metabolism
And reduced renal elimination