It seems like the more potent a drug/medication is, the more risks are involved with it, where as drugs with very little risk don’t help nearly as much.
In: Biology
The human anatomy is very complex, and for a lot of conditions to be successfully treated without side effects, a degree of selectivity for specific cells and/or receptors in specific parts of the body would be required, and this is often very difficult to achieve in medicine. For example, opioids are very powerful and effective pain relievers that can be life savers for sufferers of chronic and severe acute pain, but they can come with a variety of very serious consequences associated with the fact that opioid receptors are present all over the place in the nervous system and body and opioids will hit all of them fairly indiscriminately. For example, when an opioid receptor agonist (eg morphine, hydrocodone, oxycodone, heroin, fentanyl…) binds to opioid receptors in the brain stem, gut motility gets reduced and cardiorespiratory depression occurs which can lead to side effects like constipation, nausea, hypotension, and in cases of overdose hypoxia due to blood pressure decreasing to a dangerous extent and breathing and heart rate slowing down. In high enough doses and/or when mixed with other sedative compound, they can kill you by stopping your breathing and your heart. Along with this, you have opioid receptors that disinhibit and increase the release of dopamine in the reward centers of the brain and reduce the release of norepinephrine from a certain part of the brain resulting in anxiety relief, sedation, and a powerful reward response and consequently addiction/abuse potential. Then there’s also a fairly rapid tolerance development and a dependence, which will mean that you’ll need to take more and more opioids with time to get the desired effects and after taking opioids for a certain period of time, you’ll experience withdrawals when stopping and between doses which can become fairly severe and extremely unpleasant (can be downright hellish) at higher doses.
Now we have found some ways to circumvent some of these issues with opioids that have unique structures and interact with opioid receptors in unique fashions. Various biased agonists like tramadol’s active metabolite, O-desmethyltramadol, and the alkaloids of a plant called kratom (namely 7-hydroxymitragynine and mitragynine pseudoindoxyl) have a limited ability to recruit beta arrestin 1 resulting in less prominent cardiorespiratory depression and constipation, although tolerance, addiction potential, and dependence (along with some other side effects, some related to non-opioid activity in the case of tramadol) still very much remain issues with said compounds. To find an opioid compound that only causes the desired pain relief without much of the other risks while still remaining effective would at the very least be extremely difficult for medical scientists. We got pretty close with a compound whose name is abbreviated to IBNtxA that seemed to cause pain relief with very limited side effects and addiction potential on rats and humans, although the compound for some reason or another failed clinical trials unfortunately.
Most medications out there come with this risk for side effects from a lack of selectivity, although there are a few medications out there that do come with enough selectivity for the drug to very rarely produce side effects, like for example, the treatment for type two diabetes, Tradjenta, with the most common side effects happening in only 2 percent of patients. That’s downright miraculous, especially considering that it still very much maintains it’s efficacy. Even then however, considering everyone’s biology fundamentally differs in subtle ways, the drug despite not causing side effects or problems in most patients will still cause issues in a few for various reasons. As a result, it’s probably impossible to create a drug that doesn’t cause side effects in anyone. I hope that this helps clarify somewhat.
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