Drug interactions

Question 1

define pharmacokinetics

Answer 1

how the body handles drugs

Question 2

define pharmacodynamics

Answer 2

what the drug, at known concentrations, does to the body

Question 3

what are pharmacokinetic interactions

Answer 3

Pharmacokinetic interactions arise when the presence of one drug alters the concentration of another drug that reaches its target site

Question 4

what can cause pharmacokinetic interactions and give an example of each

Answer 4

• Absorption from the site of administration
• Distribution between tissues and body compartments- digoxin binds to albumin, when bound it is unable to access target site so can’t exert a clinical effect. When given with verampil, verampil competes for albumin biding sites and so more digoxin is available for clinical effect.
• Metabolism to active or inactive products e.g. warfarin and rifampicin (abx which affects cytochrome p450 enzymes which contribute to metabolism of drugs- induces activity of these enzymes), decreased warfarin effect. Warfarin and tamoxifen- potent cytochrome p450 inhibitor= concentration active warfarin increases and so does clinical effect.
• Excretion from the body e.g. digoxin and clarithromycin- inhibits p glycoprotein which reduces digoxin excretion, can manifest as digoxin toxicity.

Question 5

5 examples of cytochrome p450 inducers

Answer 5

rifampicin
carbamazepine
phenytoin
ethanol in chronic use
St John's wort

Question 6

5 examples of cytochrome p450 inhibitors

Answer 6

ritonavir
clarithromycin
fluconazole
tamoxifen
grapefruit juice

Question 7

drugs with a narrow therapeutic index

Answer 7

Morphine (opioids)
Immunosuppressants
Neoplasia drugs, specifically cytotoxic ones
Digoxin

Theophylline and aminothylline
Hypoglycaemic drugs esp insulin
Epilepsy drugs

Gentamicin
Anticoagulants
Psychiatric drugs esp lithium

Question 8

what are pharmacodynamic interactions

Answer 8

when the presence of one drug alters the ‘sensitivity’ of the body to its effects.

Question 9

give 2 examples of pharmacodynamic interactions

Answer 9

morphine and naloxone (opioid receptor antagonist)- naloxone makes the body less sensitive to the effects of morphine

Aspirin and clopidogrel- clopidogrel enhances the effects of aspirin, block two pathways in the same process. Can also combine with lmwh- achieve greater effect than individually.

Question 10

give 5 examples of drugs with shared pharmacodynamic effects and the risk of their interaction

Answer 10

NSAIDs, ACEi, diuretics–> nephrotoxicity

beta blockers, CCB, digoxin, amiodarone–> heart block

warfarin, heparin, aspirin, clopidogrel—> bleeding

macrolides, quinolones, amiodarone, sotalol, methadone–> QT prolongation

opioids, benzos, barbiturates, sedatives–> loss of protective airway reflexes

Question 11

factors involved in risk stratification

Answer 11

• Medicine factors: narrow therapeutic index, enzyme inducers/inhibitors, converging effects on physiological processes
• Patient factors: multiple drugs/ polypharmacy, co-morbidity, organ dysfunction/ poor physiological reserves
• Therapeutic area factors: antithrombotic treatment, antiseizure treatment, anti-infective treatment (TB, HIV)