"On-target" Mechanisms of ADRs
Drugs are intended to interact with specific receptors (intended receptors) in specific tissues (intended tissues). An “on-target” ADR occurs when a drug interacts with its intended receptor in the intended tissue.6 With the exception of overdose, therapeutic doses of drugs may result in suboptimal or exaggerated responses because of drug-drug, drug-food, drug-herbal, and drug-disease interaction-related induction or inhibition of pharmacokinetic or pharmacodynamic processes.
Many drug targets are expressed in more than one cell type. An “on-target” ADR may also occur when a drug interacts with its intended receptor, but in an unintended tissue.6 For example, intended targets for H1-histamine receptor antagonists are found in peripheral tissues, i.e., vascular smooth muscle, vascular endothelial cells, lungs, and nerve fibers. However, H1-histamine receptor antagonists with high lipid solubility can cross the blood brain-barrier, interact with H1-receptors in the brain, and cause drowsiness.
A relevant example for oral healthcare providers relates to the use of local anesthetic agents (LAs) intended to block sodium channels in neuronal tissues at or near the site of administration. However, an overdose; or rapid absorption, unintentional intravascular injection, low plasma protein binding, and slow metabolism or clearance of LAs can lead to high plasma levels. This can cause sodium channel blockade in the heart and cardiac depression-induced ventricular arrhythmia, atrioventricular block, and cardiac arrest.6