Drug-Drug interactions

Question 1

What is drug-drug interaction?

Answer 1

The effect of one drug influenced by the co-administration of another drug.

• Also foods and some herbal medicines / other chemicals

May be desirable
- Better treatment outcomes
- Counteract poisoning
May be undesirable 
- Reduced treatment outcome
- toxicity

Question 2

How can interactions occur?

Answer 2

Pharmacodynamics

Question 3

What sort of pharmacodynamics results in drug drug interaction?

Answer 3

Two+ drugs may act at the same pharmacological target
- additive effects
- get antagonistic effects
Compounds work at different targets in the same pathway
- Synergistic effect

Question 4

Whats example one of beneficial drug drug interaction?

Answer 4

Highly Active Antiretroviral Therapy (HAART) for HIV, many drugs act at the same target for additive effects

Different targets may produce a synergistic effect.

Question 5

Whats example two of beneficial drug drug interaction?

Answer 5

Anti-malaria therapy is often used in combination:

• Synergistic action, kills parasites faster.
• Reduces the potential for the development of parasitic drug resistance

Question 6

Whats the third example of beneficial drug drug interactions?

Answer 6

The use of paracetamol and ibuprofen in combination.
Studies indicate that the combination give faster and better pain relief.

No pharmacokinetic interaction

Question 7

How can interactions occur?

Answer 7

Pharmacokinetics: Drugs compete within the ADME model

Question 8

What aspect of Absorption do drugs compete?

Answer 8

Compete for uptake i.e same transporter

Question 9

What aspect of metabolism does drugs interaction occur?

Answer 9

• reduced clearance
• Inhibition of pathways, could lead to toxicity
• Induction of enzymes, increased clearance

Question 10

What aspect of distribution does drug drug interaction occur?

Answer 10

• Compete for transporters

- Compete for binding proteins

Question 11

What aspect of excretion does drug drug interaction influence?

Answer 11

• Compete for efflux transporter.. prolonged plasma concentration

Question 12

Whats the example of drug-drug interaction at the absorption level?

Answer 12

• Some antibiotics form insoluble complexes with metal ions i.e Ca2+ (milk) Al3+ (Antacid) in the intestines

This results in decreased absorption, thus decreased plasma concentration thus decreased effectiveness

Question 13

Whats an example of drug drug interaction at the level of metabolism?

Answer 13

Drug B or Chemical can inhibit the enzyme that metabolizes Drug A.

• Not used as a strategy to increase drug concentrations unless drug A has a very short half life
• May cause elevated plasma concentrations of drug A that increase side effects or adverse drug reactions.

Question 14

Whats example two of drug drug interactions for metabolism?

Answer 14

• Drug B/chemical can induce the enzyme (increase the amount of protein) responsible for the metabolism of drug A
• Plasma concentration of drug A is less than expected therefore less activity and therapeutic failure.

Question 15

How may drug drug interaction vary with dose?

Answer 15

Effects can be mixed, On a single dose there may be inhibition, on chronic therapy there may be induction

Drug A may have on type of interaction with drug B and a different interaction with drug C

Question 16

How are inhibitors graded with drug drug interaction?

Answer 16

Strong = >5 fold increase in drug conc.
Moderate = >2 fold increase in drug con.
Weak = 1.25

Question 17

Whats a real life example of drug drug interaction at the level of metabolism?

Answer 17

St johns wort (used for depression) is a potent inducer of enzymes involved in metabolism >70% of all drugs

Question 18

How can food interact with drugs?

Answer 18

Food may alter absorption

• solids delay gastric emptying
• Ca inhibits antibiotic absorption

Food may alter metabolism

• Caffeine is metabolized by CYP1A2 and inhibits the metabolism of clozapine
• Grapefruit juice has a number of clinically relevant interactions with drugs metabolized by CYP3A4

Question 19

How does alcohol affect absorption?

Answer 19

Alcohol can affect the absorption of drugs

- Can alter the rate of gastric emptying

Question 20

How does alcohol affect metabolism?

Answer 20

Can inhibit drug metabolism (acute high dose)
- Decreased Warfarin and benzodiazapine metabolism

Can induce drug metabolism (chronic use)
- Increase phenytoin + Benzodiazapine metabolism

Question 21

How can alcohol alter the threshold of drug toxicity?

Answer 21

Alcohol can reduce the threshold of drug toxicity

• Through depletion of chemical protection
  i. e Glutathione depletion

Question 22

How can alcohol alter renal excretion?

Answer 22

It can enhance renal elimination

- It is a diuretic

Question 23

How does alcohol have pharmacodynamic interaction?

Answer 23

Alcohol has pharmacodynamic interaction particularly through GABA receptors (benzodiazapines)

Question 24

Describe a drug that interacts with smoking

Answer 24

Clozapine and smoking interaction occurs.

• CYP1A2 metabolizes clozapine (antipsyhcotic)
• Smoking increase CYP1A2 activity (decrease plasma levels)
• However this affect is discontinued if the patient stops smoking therefore this needs to be considered during dosing.

Question 25

What is polypharmacy?

Answer 25

The administration of 4-5+ medications per a day

Associated with increased risk of adverse drug reactions

Question 26

What is hyperpolypharmacy?

Answer 26

Taking 10+ medications per a day

Gives rise to the concept of deprescribing
- to avoid adverse drug reactions

Question 27

Whats the take home message of this lecture?

Answer 27

Drug interactioons with drugs, herbal medicines and foods may occur. Some are predictable while others are not.

Pharmacokinetics and pharmacodynamics can be used to predict these

not all drugs are bad some are good