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
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