Drug-Drug interactions Flashcards Preview

Toxicology and Pharmacology > Drug-Drug interactions > Flashcards

Flashcards in Drug-Drug interactions Deck (27):

What is drug-drug interaction?

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


How can interactions occur?



What sort of pharmacodynamics results in drug drug interaction?

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


Whats example one of beneficial drug drug interaction?

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

Different targets may produce a synergistic effect.


Whats example two of beneficial drug drug interaction?

Anti-malaria therapy is often used in combination:
- Synergistic action, kills parasites faster.
- Reduces the potential for the development of parasitic drug resistance


Whats the third example of beneficial drug drug interactions?

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

No pharmacokinetic interaction


How can interactions occur?

Pharmacokinetics: Drugs compete within the ADME model


What aspect of Absorption do drugs compete?

Compete for uptake i.e same transporter


What aspect of metabolism does drugs interaction occur?

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


What aspect of distribution does drug drug interaction occur?

- Compete for transporters
- Compete for binding proteins


What aspect of excretion does drug drug interaction influence?

- Compete for efflux transporter.. prolonged plasma concentration


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

- 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


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

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.


Whats example two of drug drug interactions for metabolism?

- 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.


How may drug drug interaction vary with dose?

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


How are inhibitors graded with drug drug interaction?

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


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

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


How can food interact with drugs?

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


How does alcohol affect absorption?

Alcohol can affect the absorption of drugs
- Can alter the rate of gastric emptying


How does alcohol affect metabolism?

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

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


How can alcohol alter the threshold of drug toxicity?

Alcohol can reduce the threshold of drug toxicity
- Through depletion of chemical protection
i.e Glutathione depletion


How can alcohol alter renal excretion?

It can enhance renal elimination
- It is a diuretic


How does alcohol have pharmacodynamic interaction?

Alcohol has pharmacodynamic interaction particularly through GABA receptors (benzodiazapines)


Describe a drug that interacts with smoking

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.


What is polypharmacy?

The administration of 4-5+ medications per a day

Associated with increased risk of adverse drug reactions


What is hyperpolypharmacy?

Taking 10+ medications per a day

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


Whats the take home message of this lecture?

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