BLOG: Why all medicines have side effects?


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Biologist Vieri Failli explains the details. 

Undoubtedly necessary, pharmacological treatments have often undesired secondary effects. That much is true in any field, not only for spinal injuries. Cold remedy makes you sleepy, sinus decongestant makes your heart race and even aspirin can cause serious side effects including bleeding and gastric ulcers. Why are medication having such side effects?

The body is an immensely complex structure built from chemicals that must be regulated in order to function smoothly. Molecules such as hormones usually make these adjustments and if something disturbs them, as for example during a disease, medicines often work by taking the place of one of the body’s regulating chemicals to readjust the balance.

However, it is not so simple
Unfortunately, two things complicate this ideal picture. First, the body often uses the same chemical to regulate more than one process. This means that a medicine might readjust one balance while disturbing others that would normally not need retuning. The drug prednisone for example turns off inflammation, but also raises the blood levels of sugar and causes thinning of bones.
Secondly, medicines are not always as discerning as we would wish. This means that the medicine may alter other unrelated molecules at the same time. For example, the drug amitriptyline is commonly used after spinal cord injury to manage neuropathic pain by acting on serotonin receptors. Amitriptyline however, can also cause blurred vision, dry mouth and constipation by blocking acetylcholine receptors, lower blood pressure by affecting norepinephrine receptors and produce sleepiness and weight gain by binding to histamine receptors.

Spinal cord injuries - is there a concern?
Persons with a spinal cord injury are at risk of developing many secondary complications during their lives. Those include problems with the respiratory, cardiovascular and excretory systems (bladder and bowel) as well as spasticity, osteoporosis, pain and pressure ulcers. The direct result is the use of a “cocktail” of medications that will even change over time. Considering the possibility of drug interactions, people with a spinal cord injury are much more likely to face the issue of side effects.

Alternative and herbal medications
Many patients and even some physicians wrongly assume that herbal medicines are harmless since they do not come with a drug label that contains a long list of potential side effects. In fact, many such products, including aloe vera, ginkgo biloba, ginseng, garlic and green tea, can interact with conventional cardiovascular drugs and lead to serious adverse reactions. Since these remedies are “natural”, their potential dangers are not considered the same way they would be if they were real medications. For many reasons, patients tend not to disclose to their doctors if they are taking herbal remedies, including fear that their doctors will not approve or that they will be told to stop them. This is the reason why it is important to disclose as much information as possible while setting up any medical treatment.

One size does not fit all
An astonishing aspect of medications is that their effects vary greatly from person to person. This is true for the desired effect (for example as painkiller) but mostly for the side effects. One person may have little to no side effects, while another may have severe or troublesome problems that make the medicine intolerable. This surprising effect mostly accounts for the genetic variability of each individual, in which regulated mechanisms can be slightly or dramatically different.
Another aspect comes from the problem of drug interaction. A given medication has the potential to interact with other molecules, which could either be another medication that the patient is currently taking or simply compounds found in the food or beverages. This interaction can boost the positive effect of a medication while in some cases it can potentially increase the undesired side effects. By considering the variability of response and the fact that millions of people are using a medication over several years, the list of observed side effects can become horrendously long.

Precision medicine: Using genomic data for effect prediction.
As mentioned earlier genetic variability accounts for the diverse side effects seen in large groups receiving the exact same medication. Scientists decided to take advantage of this effect and the North American National Institutes of Health (NIH) has set up a large international study that aims at using “Big Data” tools to identify a drug’s potential side effects before they are used on large scale. This innovative approach, which analyzes vast amount of genomic and clinical data collected over many years from more than 50.000 people, should allow for the development of drugs that ought to be better tolerated.

The good in the evil
Although side effects are usually unwanted and harmful, they can sometimes be beneficial and have led to the discovery of new therapeutic indications for drugs. For instance, sildenafil (also known as Viagra) was initially developed to treat angina, a condition where the heart muscle does not get enough blood supply, but the surprising side effect of prolonged penile erections in human volunteers led to a complete change in its therapeutic target. A group of scientists inspired by this story decided to take advantage of the information available through the side effects of known medications. To put it simply, they tried to identify medications that had similar side effects and used it to predict new potential therapeutic uses. In doing so, they uncovered numerous unexpected new targets and although further studies will have to confirm these findings, they pave the way to a new type of drug development strategy.
Another interesting aspect to consider is that sometimes physicians even take advantage of the side effects. One example of this is the use of a specific antidepressant for anorexic patients because one of side effects that they will likely experience will be weight gain.

Spinal cord injury - side effects and drug repurposing
Just as it happened in other conditions, some drugs seem to have the unexpected side effect of promoting recovery after a spinal cord injury. This led to repurposing of several drugs such as riluzole (anti-epileptic), ibuprofen (pain, fever and inflammation), imatinib (cancer) and taxol (cancer) all of which are, or will be tested in clinical trials. A recent study supported by Wings for Life also found that an early administration of Gabapentinoids was able to improve the motor recovery in humans after a spinal cord injury. Interestingly gabapentinoids are a class of anticonvulsants drugs that are known to diminish neuropathic pain and are routinely used in subjects with a spinal cord injury.

Reducing your risk
Side effects can happen when you start taking a drug, change its amount or stop it altogether. Carefully reading the pharmacy label for possible side effects will increase your awareness and help detect any possible reaction. Always keep in mind that these considerations require doctors to assess the risk of side effects versus the expected benefit of any medication, so the first reflex should always be to communicate any discomfort to your treating physician.

Yours Vieri Failli

Vieri Failli is a Biologist and an insider in the field of spinal cord research.
Vieri Failli is a Biologist and an insider in the field of spinal cord research.