off-target effects

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Drugs are designed to bind to their intended target, and they’re designed to be highly potent and highly efficacious. Is it possible for a drug or molecule to bind to other targets in the body as well? Absolutely it is, and that’s a problem, because sometimes by binding to another target, the molecule will cause other responses. These other responses from other targets are called off target effects. Now if these effects are undesirable, they are sometimes casually called side effects, but a more proper term for these is to call them adverse drug reactions or ADRs. Now how do we minimize ADRs? Well one method for minimizing ADRs is to make sure we use as low a dose as possible of our drug. So by minimizing the dose, we minimize the chance that our drug is going to go off in the body and bind to other potential target proteins. Just because the dose is minimized does not prevent all adverse drug reactions. Furthermore, not all adverse drug reactions are caused by off-target effects. ADRs can arise from on target interactions as well. For example the histamine H1 receptor antagonists are designed to treat allergy symptoms by acting on receptors in blood vessels. Some of these drugs also cross the blood-brain barrier and interact with histamine H1 receptors found in the brain to cause drowsiness, an undesired effect. Both effects arise through binding on the same target, histamine H1 receptors. Another issue is that a drug may be selective for the intended target, but the target may control multiple responses. An example of this are the opioid pain relievers. Opioids act on opioid receptors, which can help manage pain but also release endorphins. Endorphin release is connected to the addictive nature of opioids. The risk of on-target adverse drug reactions highlights the importance of carefully selecting the best target possible in a pathway when a drug company first embarks on a drug discovery program. Balancing a molecule’s therapeutic benefit against adverse drug reactions addresses the effectiveness of a molecule. The FDA approves safe and effective drugs. An effective drug has therapeutic benefits while being well tolerated by a patient. This is different from the efficacy. Efficacy is about the response caused on a receptor, but effectiveness is whether it works well based on a patient’s standards.