Interaction mechanisms

Last updated: Thursday, November 23, 2017

Here is a quick refresher on the five most important drug interaction mechanisms:

1. Absorption 

One drug decreases the absorption of a second drug from the gut. For example:
  • Some antacids can decrease the absorption of drugs such as ciprofloxacin and iron by reacting with them chemically. 
Patients that already have poor absorption due to disease may be at enhanced risk (e.g. patients with Crohn's disease, a short bowel, or cystic fibrosis).
Quick ward question 
How do you manage a patient prescribed both an antacid and iron sulphate tablets?    Consider, then click for answer.
Stagger the doses for antacids such as magnesium trisilicate that impair absorption of iron, leaving a couple of hours between iron and antacid doses if you can. Alternatively, choose an antacid that is not known to interact e.g. Gaviscon Advance.

2. Metabolism

One drug increases or decreases the metabolism of a second drug. For example:
  • Rifampicin enhances the metabolism of female sex hormones, making the contraceptive pill unreliable. 
  • Allopurinol inhibits the metabolic destruction of a cytotoxic metabolite of azathioprine, so that it can accumulate to cause toxicity. 
The activity of enzymes that metabolise drugs are subject to genetic control. A poor metaboliser of warfarin for example may require lower doses and be at greater risk of bleeding. So there is also likely to be genetically-related variation between individuals in terms of the severity of some metabolic interactions.

            

Azathioprine and allopurinol  Courtesy of Giorgiogp2, Wikimedia Commons

3. Elimination

One drug increases or decreases the rate at which a second drug is removed from the body by organs such as the kidney or liver. For example:
  • Amiodarone reduces the elimination of digoxin by the kidney. 
  • Cholestyramine enhances the biliary excretion of the active metabolite of leflunomide.
The mechanisms of excreting drugs from the body are affected by age and disease. Elderly patients, for example, often have a reduced renal function so they may be more vulnerable to any interaction that further reduces elimination.

4. Cell transport

One drug affects the movement of another drug across cell membranes. For example:
  • Cicloporin inhibits an organic anion-transporting polypeptide (OATP) and this reduces passage of rosuvastatin into the liver for metabolism. Statin levels rise, which may cause myopathy. 
  • The herb St John’s Wort induces the transport protein p-glycoprotein in the intestine and reduces the absorption of digoxin.
These are relatively newly discovered mechanisms of interaction and we are still learning about them.
Quick ward question
Let's say you have a patient on ciclosporin and rosuvastatin, as above. What are the symptoms of myopathy?    Consider, then click for answer.
Myopathy can present as muscle aches and pains, weakness, tenderness, cramps, fatigue and stiffness. The symptoms may be worse with exercise. Inpatients with any of these symptoms on a statin require urgent review.

5. Pharmacodynamic

Two drugs have additive or opposing pharmacological effects. For example:
  • NSAIDs cause fluid retention, which may counteract the action of diuretics. 
  • Sedative drugs have additive CNS depressant effects with alcohol.
The likelihood of a pharmacodynamic interaction being clinically important is influenced by a patient’s clinical condition. Sedation, for example, may be particularly undesirable in a patient with a head injury or severe liver disease.