4.4.10 Drug-drug interactions

Drug-Drug Interactions

Drug-drug interactions occur when two or more drugs interact with each other, leading to either an increase or decrease in the effectiveness or toxicity of one or more of the drugs involved. This can result in a change in the intended therapeutic effect, the development of adverse events, or a reduction in the overall effectiveness of the medications.

Drug-drug interactions can occur at various stages in the body, including the absorption, distribution, metabolism, and elimination of drugs. Interactions can be classified into different types, such as pharmacokinetic interactions (which affect the absorption, distribution, metabolism, and elimination of drugs) and pharmacodynamic interactions (which affect the biological effect of drugs) (Jackson, 2014).

Examples of common drug-drug interactions include:

• Enzyme inhibition or induction, which can affect the metabolism of drugs
• Competition for protein binding sites leads to changes in the distribution of drugs
• Additive or synergistic effects, which can increase the risk of adverse events or toxicity

Pharmacokinetically mediated:

Pharmacokinetically mediated drug-drug interactions occur when the pharmacokinetics of one drug is affected by another drug. These interactions can alter the absorption, distribution, metabolism, or elimination of one or more drugs involved, leading to changes in the drug concentration and therapeutic effect.

The following are examples of pharmacokinetically mediated drug-drug interactions:

1. Enzyme inhibition: One drug can inhibit the metabolic enzymes responsible for breaking down another drug, leading to an increase in the concentration of the latter drug.
2. Enzyme induction: One drug can induce the metabolic enzymes responsible for breaking down another drug, leading to a decrease in the concentration of the latter drug.
3. Competition for transport proteins: Drugs can compete for the same transport proteins in the body, leading to changes in the absorption and distribution of the drugs involved.
4. Altered drug clearance: Changes in the liver or kidney function can alter the clearance of drugs from the body, leading to changes in drug concentration and therapeutic effect.

Pharmacodynamically mediated:

Pharmacodynamically mediated drug-drug interactions occur when two or more drugs interact at the level of their biological effects, leading to changes in therapeutic efficacy or toxicity.

The following are examples of pharmacodynamically mediated drug-drug interactions:

1. Additive effects: Two drugs with similar mechanisms of action can combine to produce an increased therapeutic effect or increased risk of adverse events.
2. Antagonistic effects: Two drugs with opposing mechanisms of action can reduce the therapeutic effect of each other.
3. Synergistic effects: Two drugs can interact to produce a therapeutic effect that is greater than the sum of their individual effects.
4. Potentiation: One drug can enhance the effects of another drug, leading to an increased risk of toxicity.
5. Toxicity: Two drugs can interact to produce an increased risk of toxicity or adverse events.

It is important to regularly assess and manage pharmacokinetically and pharmacodynamically mediated drug-drug interactions, as they can result in changes in therapeutic effects or adverse events. This can be done by reviewing medication lists and using drug interaction checker tools to identify potential interactions (Brunton, 2018).

References:

(1) Brunton LL, Chabner BA, Knollmann BC. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 13th ed. McGraw-Hill Education; 2018.

(2) Jackson ML, Nelson C, Neuman TR, Fink HA. Adverse drug events in ambulatory care. N Engl J Med. 2014 Jan 2;370(1):47-56.