Pilocarpine is a muscarinic acetylcholine agonist that is effective in the treatment and management of acute angle-closure glaucoma and radiation-induced xerostomia. Although not a first-line treatment for glaucoma, it is useful as an adjunct medication in the form of ophthalmic drops. Pilocarpine is approved for use as an agent to decrease IOP in cases of glaucoma, as well as in the management of xerostomia resulting from radiation exposure and Sjogren disease.[1] Currently, there is little evidence that supports the use of any other medication in treating specifically radiation-induced xerostomia.[2]

Pilocarpine is an alkaloid pharmacologic used in the treatment of xerostomia resulting from radiation exposure and Sjogren disease as well as glaucoma.[3] Its mechanism of action includes both full and partial agonism of the muscarinic M3 receptor, which is an acetylcholine receptor. There are five subtypes of the muscarinic acetylcholine receptor, the detail of which is beyond the scope of this paper. However, it is important to note that pilocarpine may have effects on the M1-M3 receptor subtypes, which causes parasympathetic side effects later discussed in this paper. The M3 receptor is an excitatory receptor expressed in gastric glands, salivary glands, and smooth muscle cells, such as those present in the pupillary sphincter and ciliary bodies. By stimulating the Gq receptor, the M3 receptor can activate phospholipase C. This leads to the creation of the second messenger’s inositol triphosphate and diacylglycerol, as well as calcium and protein kinase.[3] M3 cholinergic agonists, therefore, result in the upregulation of calcium, and ultimately smooth muscle contraction such as in the pupillary sphincter muscle.  It also is capable of stimulating salivary gland function.[4]

When used as a miotic agent, pilocarpine is available in the form of ophthalmologic eye drops. This dose form will result in ciliary contraction (a contraction of the iris), which will increase aqueous humor outflow, miosis, and accommodation. The ciliary body connects to the zonular fibers that control the accommodation of the lens. Contraction of the ciliary body will relax the zonular fibers, which results in a more spherical shape of the lens and therefore allowing aqueous outflow to occur. This conformational change is helpful to decrease intraocular pressure in glaucoma. Pilocarpine will also cause constriction of the pupillary sphincter muscle, resulting in miosis. The allowable daily dose is 30 mg.[5] With excessive dosing, it can propagate a cholinergic crisis.[6] In the treatment of xerostomia, pilocarpine is available in the form of oral tablets. The typical daily dosing is 5 mg three times per day initially and can be titrated depending on patient response. In Sjogren syndrome, dosing is commonly four times per day. The maximum dosing for oral administration is 10 mg per dose, with a max dosage of 30 mg per day. 

As it acts as a cholinergic agonist, pilocarpine may propagate muscarinic side effects, particularly when used in the oral form. The muscarinic receptors are present in nearly all major organ systems, and muscarinic medications can mediate autonomic function wherever the receptors are present. Due to the receptor's role in mediating the response of the parasympathetic nervous system, stimulation of the receptors will cause "rest and digest" functions throughout the distribution of M1-M5 receptor locations: the neuronal, cardiac, musculoskeletal, pulmonary, digestive, and urinary systems.[3] Due to the location of the M3 receptors in blood vessels, vasodilation will occur, which will result in decreased blood pressure as well as flushing. When postganglionic muscarinic receptors are activated, sweating and diaphoresis can occur. Other symptoms of toxicity may include miosis or excess lacrimation (especially when using the ocular form), hypersalivation, vomiting, bradycardia, bronchospasm, urination, and diarrhea.[2] Sweating is the most common side effect in those on the oral preparation, and even more common in those on higher doses of daily oral pilocarpine. 

Contraindications to any class of cholinergic medication, including pilocarpine, involves disease in the systems affected by the presence of the muscarinic receptors. These include COPD, peptic ulcer disease, arrhythmias, coronary vascular disease, angle-closure glaucoma (ocular prep), hyperthyroidism, intestinal resection or anastomosis, hyperthyroidism, urinary obstruction, orthostatic hypotension, and severe cases of miosis (ocular prep).[6] This drug is also contraindicated in any patient with drug-induced xerostomia, including those taking medications for hyperthyroidism, asthma, or hypertension. Additionally, those with a history of myocardial infarction should avoid the use of pilocarpine due to its affinity not only for the M3 receptor but also for M1 and M2, which are present in the heart.[5]