Drug Interactions

Question 1

Explain the potential for interacting drugs to cause beneficial and harmful effects.

Answer 1

Graph on the bottom of page 118.

Question 2

What are pharmacokinetic interactions?

Give an example.

Answer 2

They alter CONCENTRATION.
By absorption, metabolism, and elimination.

Warfarin - which is an anticoagulant works by inhibiting Vitamin K synthesis of clotting factors. Thus causing blood thinning. Pharmacokinetic drug interactions reduce the amount of warfarin by interacting with it and causing its metabolism and exertion, thus altering its concentration.

Question 3

What are pharmacodynamic interactions?

Answer 3

The interacting drug alters the effect.

Can be receptor mediated - acting on the same receptor system.
Non-receptor mediated - acting on the same organ system but different receptor systems.

Question 4

What are the sources of information for drug interactions?

Answer 4

Medsafe

NZ Formulary

Question 5

What’s an example of a drug interaction that affects absorption?

Answer 5

• can change GI pH, drug binding in tract, gut motility, absorption
• eg. calcium binds thyroxine and reduces absorption (recommended to be taken at least 4 hours
apart)

Question 6

What are the interactions of drugs with hepatic function?

Answer 6

• enzyme inhibitors cause rapid increases in serum [substrate], time to maximal interaction determined by:
• half-life and time to steady state of inhibitor
• time to new steady state of substrate
• enzyme inducers cause slow change (requires enzyme synthesis)

Question 7

What are the subtrates, inducers and inhibitors of CYP3A4 enzyme?

Answer 7

Substrates - calcium channel blockers and erythromycin.

St John’s Wort can cause organ rejection when taken with cyclosporin (inducing CYP3A4)

Viagra can cause big decrease in bp if taken with a CYP3A4 inhibitor.

Question 8

What are the subtrates, inducers and inhibitors of CYP2C9 enzyme

Answer 8

• substrate = warfarin
• inhibitors = amiodarone
• inducer = St John’s Wort

Question 9

What are the interactions of drugs involving CYP2C19 enzyme?

Answer 9

Proton pump inhibitors inhibit activation of clopidogrel

Question 10

What are the interactions of drugs involving CYP2D6 enzyme?

Answer 10

SSRI prevent formation of morphine from codeine (lack of pain relief)

Question 11

Interactions with renal elimination

Answer 11

can change renal blood flow, urine pH, competition for secretion or reabsorption
P-glycoprotein

Question 12

What is P-glycoprotein? what are its substrates, inducers and inhibitors?

Answer 12

important efflux transporter (transports drugs out of cells into intestine, urine or bile)

St John’s Wort increases the efflux, reducing the levels of digoxin available for transport to the rest of the body.

substrates = digoxin, erythromycin, calcium channel blockers
• inhibitors = amiodarone, grapefruit juice