Cholinergic agonists: Uses, common brands, and safety info

Cholinergic agonists have limited but important uses and a lengthy list of potential side effects. Both the good and bad come from the drug class’s utilization of the body’s parasympathetic nervous system. Our parasympathetic system sets the tone for the resting mode of our autonomic nervous system and is complemented by the sympathetic system, which takes over in times of stress. Parasympathetic activity controls bodily functions like salivation, lacrimation (tear formation), defecation, urination, heart rate reduction, and erection formation. These actions are controlled by acetylcholine (ACh), a neurotransmitter that carries signals between neurons (nerve cells). Cholinergic agonists function at the same cellular receptor site as ACh, triggering some of the same physical responses in the body. This article will review the members of the cholinergic agonist class and touch on their mechanism of action, uses, side effects, and costs.

Other cholinergic agonists

• Miostat (carbachol) eye injection

What are cholinergic agonists?

Cholinergic agonists stimulate acetylcholine receptors, producing a parasympathetic-type effect. For example, the goal of some drugs in the class is to produce salivation, while others aim to promote urination. In an ideal world, a cholinergic agonist would only produce its intended effect, but in reality, other parasympathetic effects often occur. For example, while aiming for benefits on bladder emptying, bethanechol use can produce gastrointestinal effects like diarrhea and cramps or pulmonary consequences like bronchial tube spasm.

How do cholinergic agonists work?

Acetylcholine receptors come in two main varieties: muscarinic receptors and nicotinic receptors. These differ in bodily location and function. Different cholinergic agonists activate different types of ACh receptors in order to achieve a particular effect. 

The pharmacology of cholinergic agonists differs from other cholinomimetics (drugs that promote the action of acetylcholine). Cholinergic agonists are direct-acting agents, stimulating the parasympathetic system themselves. In comparison, acetylcholinesterase inhibitors are another type of cholinergic drug class, one that is indirect-acting. Acetylcholinesterase inhibitors block acetylcholinesterases, enzymes that break down ACh. The enzyme blockers result in more of the neurotransmitter acetylcholine being available and consequently more acetylcholine parasympathomimetic (parasympathetic promoting) activity. Aricept (donepezil) is a cholinesterase inhibitor used in the treatment of Alzheimer’s disease, helping to reverse the cholinergic insufficiency inherent to this dementia.

What are cholinergic agonists used for?

• Xerostomia (dry mouth) from head and neck cancer treatment

• Xerostomia from Sjogren’s syndrome

• Urinary retention (inability to empty the bladder)

• Neurogenic bladder (retention related to nerve dysfunction)

• Eye surgery adjunct

• Glaucoma

• Smoking cessation

Types of cholinergic agonists

Muscarinic receptor agonists

Salagen and Evoxac stimulate muscarinic ACh receptors in the salivary glands with the primary goal of increasing saliva secretion. This proves beneficial for those experiencing xerostomia in the setting of Sjogren’s syndrome (an autoimmune condition) or head and neck cancer radiation treatment. While these two drugs act on muscarinic receptors stimulating salivary glands, bethanechol does so at the bladder in order to provide relief for those experiencing urinary retention. 

Miostat is a muscarinic receptor that is injected into the eye, resulting in miosis (pupil dilation) which is helpful during eye surgery. Pilocarpine eye drops have a utility similar to Miostat but also have an indication for glaucoma treatment.

Nicotinic receptor agonists

Nicoderm CQ nicotine patches and Chantix (varenicline) act on nicotinic receptors. Therapeutically, they are used to reduce the craving for nicotine and increase the chance of successful smoking cessation.

Who can take cholinergic agonists?

Can men and women take cholinergic agonists?

Both men and women can take cholinergic agonists.

Can you take cholinergic agonists while pregnant or breastfeeding?

Most cholinergic agonists have not been studied adequately in pregnancy and breastfeeding, so alternatives are typically recommended. However, Nicoderm CQ and related nicotine replacement products have enough benefit in helping to quit smoking in pregnancy and breastfeeding to justify the risk for most women. In addition, pilocarpine eye drops can also be used in these situations, and Miostat can be used during breastfeeding if needed.

Can children take cholinergic agonists?

Children can be prescribed bethanechol and pilocarpine eye drops. Adolescents age 17 and older may be treated with varenicline to help quit smoking. Other cholinergic agonists are not used in children.

Can seniors take cholinergic agonists?

While seniors can take cholinergic, the higher incidence of comorbid conditions such as cardiovascular disease could make adverse effects more intolerable.

Are cholinergic agonists safe?

Black box warnings

The Food and Drug Administration (FDA) does not have black box warnings on this drug class.

Recalls

• Pilocarpine eye drops [March 2019]

• Chantix (brand name varenicline) [September 2021]

RELATED: Pfizer issues voluntary Chantix recall

Restrictions

The prescribing healthcare provider should review the coinciding medical conditions to see if any contraindications to a particular cholinergic agonist exist.

• A history of hypersensitivity allergic reactions to a cholinergic agonist is a contraindication to using this drug class. 

• Other reasons for avoiding members of the class include steering clear of Salagen and Evoxac in the setting of acute asthma, acute glaucoma, and acute iritis or uveitis (inflammatory eye conditions). 

• Nicoderm CQ and other nicotine replacement products should not be used within two weeks of acute myocardial infarction (MI or heart attack) or during worsening angina or serious heart arrhythmias. 

• Bethanechol has a host of contraindications; examples being bladder and intestinal obstructions, coronary artery disease, severe hypotension (low blood pressure), severe bradycardia (slow heart rate), and Parkinson’s disease.

Are cholinergic agonists controlled substances?

Cholinergic agonists are not listed as controlled substances by the Drug Enforcement Agency.

Common cholinergic agonists side effects

The list of this class’s common adverse effects reads very similarly to parasympathetic nervous system actions. 

• Lacrimation (tear formation)

• Salivation

• Heart rate changes

• Blood pressure changes

• Abdominal pain

• Diarrhea

• Nausea

• Urinary urgency

• Sweating

• Light sensitivity

A beneficial parasympathetic effect from a cholinergic agonist in one condition may be considered an adverse effect for another member of the class in a different condition.

How much do cholinergic agonists cost?

The price of a brand-name cholinergic agonist like Evoxac can be $300 for a one-month supply. A generic drug like bethanechol can be about $40 for one month. Whether a brand-name or generic option is recommended by your healthcare professional, a SingleCare discount card can help you save money on cholinergic agonists.