**2.1 Mechanisms of action**

The cholinergic receptors are divided into muscarinic receptors or nicotinic receptors. There are five subtypes of muscarinic receptors, M1-M5 and two types of nicotinic receptors, NM (skeletal muscle) and NN (neuronal). M1 are found in the CNS (i.e., the cerebral cortex, hippocampus, striatum and thalamus), autonomic ganglia, gastric and salivary glands and the enteric nerves of the GI tract. M2 are located in the CNS (i.e., the hindbrain, thalamus, cerebral cortex, hippocampus, striatum, heart, smooth muscle, and autonomic nerve terminals). M3 receptors have less of a presence in the CNS although they are found in the cerebral cortex and hippocampus. They are abundant in smooth muscle and glands and the heart. M4 is preferentially expressed in the CNS (i.e., forebrain, striatum, cerebral cortex and hippocampus) while M5 are only expressed in low levels in the CNS and periphery and are found primarily in the substantia nigra and ventral tegmentum area. NM are located at the neuromuscular junction and are involved in muscle contraction. Nn are found in the autonomic ganglia and adrenal medulla [3].

At the cellular level, anticholinergic agents act by opposing the effects of acetylcholine either at the muscarinic or nicotinic receptors. In the geriatric population, most anticholinergic drugs affect the muscarinic receptors. On the organ system level, these compounds have varying effects. Although some effects are therapeutic, it's their toxic effects that are most worrisome, especially in geriatric patients.

While M1-M5 receptors are found in the brain, most of the deleterious effects on the CNS come from antagonizing M1 receptors. This can lead to delirium, cognitive impairment, dizziness, sedation and confusion. The predominant form of muscarinic receptors in the eyes are M3 although M1-M5 receptors are also present. Blocking these receptors leads to mydriasis and blurred vision. It is for this reason that ophthalmic atropine, a potent anticholinergic agent, is used to produce pupillary dilation and/or cycloplegia. Blocking of M1 and M3 receptors in salivary glands leads to dry mouth and difficulty swallowing whereas opposing the effects of M3 receptors in sweat glands leads to the inability to dissipate heat and can result in overheating, especially during the warmer months. The heart is primarily composed of M2 receptors and antagonizing these receptors leads to sinus tachycardia and increased contractility. Systemic atropine is used in the management of symptomatic sinus bradycardia and atrioventricular nodal block. The lungs primarily contain M1-M4 receptors and blocking these receptors results in bronchodilation. The use of long- and short-acting inhalation antimuscarinic agents in chronic obstructive pulmonary disease (COPD) takes advantage of this beneficial effect. Opposing M2 and M3 receptors in the GI tract can lead to gastric stasis and constipation. On the other hand, dicyclomine is an anticholinergic drug that is used for abdominal pain associated with irritable bowel syndrome. Antagonism of M3 receptors in the bladder inhibits detrusor and bladder contractions and is used therapeutically for urinary incontinence. This blockade can also lead to urinary retention. The role of cholinergic agents in the skin, which contains primarily M3 receptors, is complex resulting in increased nitric oxide production and vasodilation and it also involves interplay with nicotinic receptors [4].

Nicotinic agents act either as neuromuscular blockers (i.e., atracurium, vecuronium, tubocurarine, pancuronium) or ganglionic blockers (i.e., mecamylamine). Succinylcholine is a NM receptor agonist [4].
