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Complications

Drug interactions

As well as adverse drug reactions and allergic reactions to drugs, consideration should be given to the interactions between drugs.

A drug interaction occurs when the effect of a particular drug is altered when it is taken with another drug, herbal medicine, food or drink (Baxter 2008). These interactions can result in an increased effect, causing toxicity, or a decreased effect, resulting in a decreased efficacy of the drug. Interactions can be unwanted but in some cases they can be desirable, for example vitamin K is used to oppose the effects of warfarin when toxicity has occurred.

Drug interactions can be divided into pharmacokinetic (Table 13.1) and pharmacodynamic interactions (Table 13.2).

Table 13.1 Types of pharmacokinetic interactions

Type of interaction Interaction caused by Example of when to consider in clinical practice

Drug absorption interactions Changes in the GI pH

Adsorption or chelation in the GI tract

Changes in GI motility

Induction or inhibition of transporter proteins or malabsorption

Allopurinol and mercaptopurine – allopurinol inhibits xanthane oxidase, an enzyme which metabolizes mercaptopurine to an inactive metabolite, thereby resulting in increased mercaptopurine toxicity such as bone marrow suppression. If used together, the mercaptopurine dose should be decreased to a third of the original dose (Baxter 2008)

Drug distribution interactions Protein binding or inhibition or induction of drug transporter proteins Therapeutic drug monitoring as drugs that can be displaced in this way can appear subtherapeutic when monitored but doses would not need to be increased (Baxter 2008)

Drug metabolism interactions Changes in first-pass metabolism, enzyme induction, enzyme inhibition and genetic factors

The hepatic cytochrome P450 enzyme system is the major site of drug metabolism and most drug–drug interactions occur at this site

Grapefruit juice can inhibit the cytochrome P450 isoenzyme CYP3A4, thus reducing the metabolism of calcium channel blockers (Baxter 2008)

Drug excretion interactions Changes in urinary pH, active renal tubular excretion, renal blood flow and biliary excretion or the enterohepatic shunt Probenecid and penicillin compete for the same active transport systems in the renal tubules. As a result, probenecid reduces the excretion of penicillin which can lead to penicillin toxicity (Baxter 2008)

Table 13.2 Types of pharmacodynamic interactions

Type of interaction Interaction caused by Example of when to consider in clinical practice

Additive or synergistic interactions Two drugs have the same pharmacological effect and therefore the results can be additive Opioids with benzodiazepines causing increased drowsiness (Baxter 2008)

Antagonistic or opposing interactions Two drugs have opposing activities Vitamin K and warfarin resulting in the effects of the anticoagulant being opposed (Baxter 2008)

Beijnen and Schellens (2004).

Herbal and complementary medicines have been increasingly used in the UK over recent years and as a result there has been an increase in the reporting of interactions between these agents and conventional drugs. Some of the most common herbal interactions are those involving St John’s wort, a popular herbal product used as an antidepressant. Mathijssen et al. (2002) found that St Johns wort (or Hypericum perforatum) interacts with irinotecan. Five patients with various types of cancer were given 350 mg/m2 irinotecan intravenously with or without 900 mg St Johns wort once a day orally for 18 days. The researchers found that in the presence of St Johns wort the plasma concentrations of the active metabolite of irinotecan decreased by 42% and myelosuppression was worse in the absence of St Johns wort.

Interactions can also occur between drugs and food. Food can have an effect on drugs by changing GI motility or by binding to drugs whilst in GI transit. An example of interactions between food and a drug can be seen with procarbazine and tyramine-containing foods. Tyramine is a chemical