Pharmacology Lecture 3

Question 1

Define drug-drug interaction

Answer 1

When two or more drugs interact in such a way that the effectiveness or toxicity of one or more of the drugs is altered.

Includes drug-food, drug-alcohol, drug-tobacco

Question 2

Are all drug interactions harmful?

Answer 2

No.
Some examples of beneficial drug interactions include increasing blood levels and additive therapeutics/treatment of disease.

Question 3

Which patients are most likely to be affected by drug-drug interactions?

Answer 3

Those

• taking multiple drugs
• with impaired renal or hepatic function
• with concomitant/other disease(s)
• with certain genetic characteristics (may metabolise drugs more quickly/slowly, therefore more likely to have a drug-drug interaction)

NB that elderly patients are generally more susceptible because the first 3 points apply to them.

Question 4

When are drug-drug interactions most likely to occur?

Answer 4

When a drug is being started or stopped.

Question 5

What is the difference between pharmacodynamic and pharmacokinetic drug interactions?

Answer 5

Pharmacodynamic interaction is where the effects of one drug are changed by the presence of another drug at its SITE OF ACTION.

Pharmacokinetic interaction is where one drug is changed by the presence of another drug in the body. The way the drug is handled (ADME), not the way the drug is acting.

Question 6

List the 3 main categories of pharmacodynamic interactions of drugs

Answer 6

1. Additive interactions (same pharmacological effect/same toxicity)
2. Antagonistic (opposite reactions, cancel each other out)
3. Disturbances in electrolyte balance (Na+, K+ levels in plasma), which can increase sensitivity to the toxic effects of another drug

Question 7

Explain the difference between enzyme inhibition and induction.

Answer 7

Enzyme inhibition is where enzymes are inhibited by other drugs (one drug will get preferentially metabolised, and block the enzyme metabolism for another drug, and so will see an increased effect) whereas enzyme induction involves an increase in endoplasmic reticulum and cytochrome P450 (which may in turn metabolise other drugs more quickly and show a reduced effect of that other drug).

Enzyme inhibition results in an increase effect of a drug.
Enzyme induction results in a reduced effect of a drug.

Effects of enzyme inhibition take 2-3 days whereas effects of induction can take 2-3 weeks.

Question 8

Name the pharmacokinetic drug interactions associated with absorption

Answer 8

• Rate is affected by the time to reach site of absorption: Not clinically important
• Extent of absorption: Formation of (insoluble) complexes, Changes in pH of stomach (effect ionisation of drug, if ionised, more difficult to pass through lipid membrane and less absorbed)

Question 9

In the blood, some drugs are bound to plasma proteins. Is it the free component or the bound component which is pharmacologically active/metabolised/excreted?

Answer 9

Free component is pharmacologically active and metabolised/excreted?

Question 10

Why are pharmacokinetic drug interactions associated with displacement only transient?

Answer 10

One drug can displace another on the plasma proteins. This can effect the active levels of a drug.
However, the balance of active drug is quickly restored by metabolism/excretion.

Question 11

Pharacokinetic drug interactions

Answer 11

Absorption
Displacement
Metabolism (most common interaction. Involves enzyme inhibition and induction)
Excretion

Question 12

Which phase of metabolism is associated with more drug interactions and why?

Answer 12

Phase 1

Phase 1 oxidation involves cytochrome P450 enzymes which are very sensitive to induction and inhibition

Question 13

Describe/explain the pharmacokinetic drug interactions associated with Glomerular filtration (GFR) in excretion.

Answer 13

Glomerular filtration is partially controlled by prostaglandins.
If a drug affects prostaglandin synthesis, it will effect the GFR.

Question 14

Describe/explain the pharmacokinetic drug interactions associated with Tubular reabsorption in excretion.

Answer 14

Only non-ionised form of drug can diffuse back into the blood.
Depends upon drug PH (pKa. Whether the drug is acidic/basic) and urinary pH.

Question 15

Describe/explain the pharmacokinetic drug interactions associated with Tubular secretion in excretion.

Answer 15

Some drugs compete for the active excretory mechanism, the ‘loser’ is retained and so will build up in the bloodstream.

Question 16

What the categories of drug interactions assigned by the BNF?

Answer 16

Unknown, mild, moderate and severe.

Question 17

Which resources provides more detailed information on drug interactions: BNF or Stockley?

Answer 17

Stockley

Question 18

How does ionisation affect tubular reabsorption?

Answer 18

Only non-ionised form of drug can diffuse back into the blood.
So reduced reabsorption into plasma.