Understanding Drug-drug Interactions

A drug-drug interaction involves one drug affecting the activity of another usually when both are concurrently administered. Such interactions can result in the reduced or enhanced activity of one or both drugs. While many forms of drug-drug interactions exist, most can be broadly classified into interactions that involve the travel of the drug once administered (pharmacokinetic) or the action of the drug on the body (pharmacodynamic).

Drug-drug interactions that affect the travel of drugs in the body can be further understood as those that affect absorption into the bloodstream, distribution within the body, breakdown into different products or removal from the body.

Absorption interactions can occur when one drug’s particles have a large enough surface area to cause another drug’s particles to stick to them, both drugs may also bind to each other, or one drug alters the acidity of the stomach contents or the rate at which the stomach moves it’s contents. These interactions can alter the ability of one or both drugs to get into the bloodstream. When a drug only reduces the rate of absorption of another, a patient on regular use of both drugs is usually unaffected. However, if one drug reduces the extent of absorption of the other, the patient can be exposed to lower levels of the second drug than required and the second drug may hence be ineffective in treatment.

Distribution interactions may occur when drugs reach the bloodstream and the tissues. Competition between two drugs can arise for binding to the same proteins in the blood or one drug may dislodge another from it’s connection with tissues. It is more common in the second instance when one drug displaces another from the tissues, to find that the displaced drug accumulates in the blood leading to a greater risk of an affected patient experiencing toxicity. An example is when the heart medications quinidine and Lanoxin® (digoxin) are taken concurrently, digoxin blood levels can rise and adversely affect the patient if not monitored appropriately.

While drugs can be broken down at many different sites in the body, the most common site is the liver. Here, a system of enzymes can be up-regulated or down-regulated by one drug to result in the quicker or slower breakdown of the other respectively. Examples of drugs that up-regulate specific enzymes in the liver, include the anti-epileptics Dilantin® (phenytoin) and Tegretol® (carbamazepine). The enzyme up-regulation effect usually takes place gradually with maximal effects observed in 7 to 10 days of starting the drug. It may also take an equal or longer time before normalcy is regained upon discontinuing the drug. Examples of drugs that down-regulate specific enzymes in the liver, include the antibiotics erythromycin and ciprofloxacin. The onset of enzyme down-regulation is usually faster than up-regulation.

The majority of broken down drug products as well as whole drugs are removed from the body through the passing of urine. When one drug affects the pH of the urine, this can affect another drug’s ability to get into the urine depending on how it’s form changes during the filtering process in the kidneys. Transporter molecules in the kidney that facilitate drug removal may also become more or less available to one drug as a result of the presence of another.

Drugs can also interact and exert a net effect by their direct actions on the body. Two drugs with similar effects when administered together can display synergism in action although acting at different sites or receptors in the body. An example is the drowsiness that can be experienced when a sedative like Valium® (diazepam) is taken concurrently with an antihistamine like Polaramine® (dexchlorpheniramine). Conversely when two drugs that have opposing effects are taken concurrently, the response to either or both can be reduced. An example is the opposing wakefulness and drowsiness that can result from consuming a caffeine-based anti-migraine preparation and a sedative.

Another set of action-related drug-drug interactions occurs when two drugs exert toxicity towards the same organ or tissue in the body. Concurrent administration of the two drugs can result in damage to the corresponding organ or tissue despite the individual dose of each drug alone not being enough to result in toxicity under normal circumstances. The common organs that are most often affected by such drug-drug toxicity interactions are the kidneys and the liver. Of note is also that one drug can increase the organ-toxic effect of another even though it does not exert any direct toxicity towards that organ by itself.

Because of the numerous drugs available and the many more that are constantly arriving, drug-drug interactions can be quite common. However, the adverse effects can be minimized through consultation with an experienced medication expert. When such interactions are anticipated early, the most appropriate countermeasures can be readied to maintain well being.