Chapter 6: Drug Interactions Flashcards
Drug Interactions- when do they occur?
A drug interaction occurs when another substance alters a drug’s efficacy, effects, or safety.
Drug-Drug interactions
Drug-drug interactions can occur whenever a patient takes two or more drugs.
Consequences of Drug-Drug Interactions: When two drugs interact, there are three possible outcomes:
- One drug may intensify the effects of the other,
- One drug may reduce the effects of the other, or
- The combination may produce a new response not seen with either drug alone.
Drugs can interact through four basic mechanisms:
- direct chemical or physical interaction,
- pharmacokinetic interaction
- pharmacodynamic interaction
- combined toxicity
When do direct interactions occur with drugs?
Direct interactions occur most commonly when drugs are combined in IV solutions.
How do two drugs taken together alter pharmacokinetic interactions?
When two drugs are taken together, one may alter the absorption, distribution, metabolism, or excretion of the other
How does drug interactions affect absorption?
Drug absorption may be enhanced or reduced by drug interactions.
There are two principal mechanisms by which one drug can alter the distribution of another:
- competition for protein binding
- alteration of extracellular pH.
Altered metabolism
Some drugs increase the metabolism of other drugs, and some drugs decrease the metabolism of other drugs.
Drugs that increase the metabolism of other drugs do so by
Drugs that increase the metabolism of other drugs do so by inducing synthesis of hepatic drug-metabolizing enzymes.
Drugs that decrease the metabolism of other drugs do so by
Drugs that decrease the metabolism of other drugs do so by inhibiting those enzymes.
The majority of drug metabolism is catalyzed by
cytochrome (CY) P450 enzymes, which are composed of isoenzyme families
Inducing agents
Drugs that stimulate the synthesis of CYP isoenzymes are referred to as inducing agents.
What do inducing agents do?
Inducing agents can increase the rate of drug metabolism by as much as twofold to threefold.
Drugs can alter all three phases of renal excretion:
- filtration,
- reabsorption, and
- active secretion.
Pharmacodynamic interactions are of two basic types:
- Interactions in which the interacting drugs act at the same site and
- Interactions in which the interacting drugs act at separate sites.
Drug Interactions at the Same Receptor:
Interactions that occur at the same receptor are almost always inhibitory.
Drug Interactions Resulting From Actions at Separate Sites:
Interactions resulting from effects produced at different sites may be potentiative or inhibitory
Combined Toxicity when drugs interact
If drug A and drug B are both toxic to the same organ, then taking them together will cause more injury than if they were not combined.
As a rule, drugs with overlapping toxicity are not used together.
Drug-Food Interactions:
Coadministration with food can significantly alter the efficacy and safety of
some drugs.
The primary mechanisms are by decreased or increased absorption and altered metabolism.
Coadministration with food can significantly alter the efficacy and safety of
some drugs. How?
The primary mechanisms are by decreased or increased absorption and altered metabolism.
Effect of Food on Drug Absorption:
Decreased absorption:
Food frequently decreases the rate of drug absorption and occasionally decreases the extent of absorption.
What does reducing the rate of absorption mean?
Reducing the rate of absorption merely delays the onset of effects; peak effects are not lowered.
What does reducing the extent of absorption mean?
In contrast, reducing the extent of absorption reduces the intensity of peak responses.
Example of food reducing the extent of absorption
The interaction between calcium-containing foods and tetracycline antibiotics is a classic example of food reducing drug absorption.
Hence, if tetracyclines are administered with milk products or calcium supplements, absorption is reduced and antibacterial effects may be lost.
What happens when food increases the extent of absorption of drugs?
When this occurs, peak effects are heightened.
Example of when when food increases the extent of absorption of drugs
a high-calorie meal more than doubles the absorption of saquinavir [Invirase], a drug for HIV infection.
Impact of Grapefruit on Drug Metabolism
Grapefruit juice can inhibit the metabolism of certain drugs, thereby raising their blood levels.
Why should certain drugs be administered on an empty stomach?
the absorption of some drugs can be significantly decreased by food, and hence these drugs should be administered on an empty stomach.
Why should some drugs be administered with meals
the absorption of other drugs can be increased by food, and hence these drugs should be administered with meals.
To administer a drug with food means
To administer a drug with food means to administer it with or shortly after a meal.
To administer a drug on an empty stomach means
To administer a drug on an empty stomach means to administer it at least 1 hour before a meal or 2 hours after.
