Ask the doctors: Understanding medication side effeects and homeostasis

Dear Doctors: I would like to know why it is that so many medications have side effects. Is it the medications themselves, or is it the additives that are used in making them? Also, why do some people have severe side effects and others don’t have any at all?

Dear Reader: The answer to your question begins with a concept known as homeostasis. As with many medical terms, it has its roots in Greek: The prefix “homeo” means similar, and the suffix “stasis” means stable. The term was coined in 1926 to describe the dynamic feedback loops that allows the many – and often competing – physiological processes that contribute to health to remain in balance. Add in the fact they take place simultaneously, dictated by constant changes inside and outside of the body, and you get a sense of the complexity of it all.

Homeostasis starts at the cellular level. It includes functions such as the maintenance of pH levels and ion concentrations in the fluids inside and surrounding the cells; the manufacture of lipids, hormones and proteins; enzyme balance; the production and distribution of energy; and the safe transport and elimination of waste products. That is a pretty long list, and we’ve only scratched the surface.

If the body detects a potentially harmful imbalance, it sends out instructions with the corrections that are needed. The organs and tissues then respond, with the goal of maintaining homeostasis. These finely calibrated feedback loops oversee functions such as regulation of blood pressure, blood sugar control, oxygen transport, digestion, and nutrient production and absorption. They also are crucial to feelings of hunger and thirst and circadian cycles, and they even play a role in mood and emotion.

A departure from homeostasis can result in discomfort, pain or malfunction. When prolonged, it can lead to disease. But the medications that we take, or the treatments that we undergo, can also have an effect on homeostasis. It is those disruptions that can give rise to side effects. For example, a drug known as hydralazine, which relaxes blood vessels, is effective for the management of hypertension. It is believed to work by affecting calcium ion homeostasis. But the drug can also stimulate the sympathetic nervous system, which can lead to side effects such as dizziness or headache.

Another example is non-steroidal anti-inflammatories, or NSAIDs, which ease pain and inflammation. They work by reducing production of an enzyme the body uses to mount an inflammatory response. But NSAIDs also change the behavior of cells in the stomach that help maintain optimal pH levels, which can lead to tissue damage. This side effect of NSAIDs is caused by an unintended disruption of homeostasis.

How a drug affects someone, including the side effects they may experience, depends on a number of factors. These include the person’s size and weight, age, metabolism, kidney and liver function, activity level, genetic makeup and habits such as smoking or drug use. Genetics plays a role, as well. Bottom line: Our response to medications, and the side effects they may cause, are as varied and individual as people taking them.

Send your questions to askthedoctors@mednet.ucla.edu.