Cholinergic and Anticholinergic Drugs
Welcome to this video tutorial on cholinergic and anticholinergic drugs and their effects on the parasympathetic nervous system!
First, we will take a look at the different divisions of the nervous system.
The Nervous System
The nervous system is made up of the central nervous system (the brain and spinal cord) and the peripheral nervous system (neurons outside the brain and spinal cord). The peripheral nervous system is then divided into the autonomic and somatic nervous system.
The autonomic system is further broken down into the sympathetic and parasympathetic nervous system.
The sympathetic (SNS) and parasympathetic (PSNS) are opposing systems.
The PSNS is the “rest and digest” response (AKA – calming or cholinergic)
When the sympathetic system excites an organ, the parasympathetic system inhibits it. When the parasympathetic system excites an organ, the sympathetic system inhibits the action.
Our focus in this lesson is on how cholinergic and anticholinergic agents affect the parasympathetic nervous system.
Cholinergic Agents
Cholinergic drugs are:
- Drugs that stimulate the parasympathetic system
- Also called parasympathomimetics – they mimic the effects of the PSNS neurotransmitter
- Cholinergic agents copy the action of acetylcholine (ACh) – a neurotransmitter released from nerve endings that bind on the receptors of cell membranes of organs, tissues, and glands
There are two types of cholinergic drugs: direct-acting and indirect-acting.
Direct-Acting Cholinergic Drugs
- Bind to cholinergic receptors on specific effector organs, stimulating the organ in a similar way as ACh
- They are synthetic derivatives of choline
- Have widespread systemic effects including cardiac muscle, smooth muscle, exocrine glands, and the eye
Indirect-Acting Cholinergic Drugs
- Inhibit the enzyme ‘acetylcholinesterase,’ resulting in more ACh available at the receptors
- These drugs have the added cholinergic effect of improved skeletal muscle tone and strength
- Indirect-acting cholinergic drugs for Alzheimer’s disease are widely distributed, including to the central nervous system, thus improving cholinergic neurotransmission in the brain
Cholinergic Drug Effects
- CNS – enhanced cognitive functions such as arousal, attention, and memory encoding – treatment for Alzheimer’s disease and dementia
- Eye – pupil constriction – for surgery and treatment of glaucoma
- GI – smooth muscle stimulant – for post-op abdominal distention or paralytic ileus
- GU – urinary bladder stimulant – for post-op or postpartum urinary retention
- Musculoskeletal (indirect acting cholinergic drugs) – improve muscle tone and strength – for myasthenia gravis
Too much cholinergic medication can result in overstimulation of the parasympathetic nervous system, causing unwanted side effects.
The acronym SLUDGE-M will help us remember the adverse effects of cholinergic drugs.
| S | Salivation |
| L | Lacrimation |
| U | Urination |
| D | Defecation |
| G | Gastroenteritis |
| E | Emesis |
| M | Miosis |
Other Adverse Effects of Cholinergic Drugs
- ↓ HR and BP
- Conduction abnormalities – AV block and cardiac arrest
- Headache, dizziness, convulsions
- ↑ bronchial secretions, bronchospasms
*Overdosing can cause life-threatening problems
*Antidote for cholinergics is the anticholinergic drug atropine
Specific Cholinergic Drugs
1. Direct-acting
- Bethanechol (Urecholine) – ↑ the tone and motility of the bladder and GI tract (should cause urination within 60 min in a pt with urinary retention).
- Pilocarpine (Pilocar) – used to constrict pupils, which ↓ intraocular pressure (glaucoma).
2. Indirect-acting
- Neostigmine (Prostigmin) – given for the diagnosis and treatment of myasthenia gravis—it causes skeletal muscle contractions.
- Donepezil (Aricept) – used to treat mild-moderate Alzheimer’s disease—it ↑ ACh in the brain and helps ↑ or maintain memory or learning capabilities (it manages the symptoms, but is not a cure).
Contraindications to using cholinergic drugs
- Asthma
- Hyperthyroidism
- Peptic ulcer
- Coronary artery disease
*Cholinergic drugs can exacerbate these conditions and should be avoided.
Anticholinergic agents
- Drugs that block the action of ACh on the parasympathetic nervous system.
- These cholinergic blocking agents compete with ACh and block it at the receptors in the PSNS, so ACh is unable to bind to the receptor site and cause a cholinergic effect.
- Most anticholinergic drugs interact with muscarinic cholinergic receptors in the brain, secretory glands, heart, smooth muscle, and eye.
Effects of Anticholinergic Drugs
- CNS – ↓ muscle rigidity and muscle tremors (e.g., Parkinson’s disease)
- Eye – pupil dilation – for exams or surgery
- Salivary & lacrimal glands – ↓ secretion
- Heart – ↑ HR
- Respiratory -↓ bronchial secretions, dilate bronchial airways, ↓ airway resistance – COPD, asthma.
- GI – relax smooth muscle tone of GI tract, ↓ intestinal & gastric secretions, ↓ motility & peristalsis – peptic ulcer disease, and irritable bowel.
- GU – antispasmodic effect on smooth muscle – overactive bladder, and incontinence.
Adverse Effects of Anticholinergics
The effect of the drug may be therapeutic, but becomes an adverse reaction if severe or if the drug is given for another purpose or if there is an overdose.
- CNS – excessive stimulation (tremor, restlessness, confusion), followed by excessive CNS depression (respiratory depression, coma)
- Tachycardia
- Constipation (result of decreased GI motility and muscle tone)
- Dry mouth (result of decreased salivation)
- Urinary retention
- Hot, dry skin (due to decreased sweating)
- Blurred vision, dilation of the pupil (pt may need sunglasses)
*The specific antidote for anticholinergic overdose is
Specific Examples of Anticholinergic Drugs
- Belladonna alkaloids and derivatives
- Atropine – a naturally occurring belladonna alkaloid, given for bradyarrhythmias (it produces a stimulant effect), also given as an antidote for cholinergic poisoning.
- Ipratropium (Atrovent) – causes bronchodilation, used in asthma and COPD.
- Scopolamine – given for motion sickness, N/V.
- Centrally acting anticholinergics used in Parkinson’s disease
- Benztropine (Cogentin) – Also used to treat dystonic reactions caused by antipsychotic drugs
- Urinary antispasmodic, given for overactive bladder
- Oxybutynin (Ditropan)
- Solifenacin succinate (VESIcare)
Contraindications to Using Anticholinergic Drugs
Contraindications include any condition characterized by symptoms that would be aggravated by the drugs (myasthenia gravis, glaucoma, MI).
Review
Cholinergic drugs stimulate the parasympathetic nervous system by copying the action of Ach. They are given for Alzheimer’s disease, glaucoma, paralytic ileus, urinary retention, and myasthenia gravis.
Anticholinergic drugs block the action of ACh on the parasympathetic nervous system. They are given for Parkinson’s disease, asthma, COPD, and overactive bladder
Thank you for watching this video tutorial on cholinergic and anticholinergic effects on the parasympathetic nervous system!
Frequently Asked Questions
Q
What is the main neurotransmitter that cholinergic drugs mimic in the body?
A
Cholinergic drugs mimic the function of the neurotransmitter acetylcholine, which is the most critical neurotransmitter of the parasympathetic nervous system. Acetylcholine resides in locations through the body, including synapses of the autonomic nervous system, neuromuscular junctions, various locations in the central nervous system, and various organs. Acetylcholine is involved in the stimulation of the “rest and digest” functions of the parasympathetic nervous system, such as smooth muscle contraction, decreased heart rate, increased secretions, and dilation of blood vessels.
Q
What is the function of cholinergic receptors?
A
Cholinergic receptors are located on the surfaces of specific cells and are activated by the binding of the neurotransmitter, acetylcholine. There are two types of cholinergic receptors: nicotinic and muscarinic. Nicotinic receptors are found in the central, sympathetic, and parasympathetic nervous systems and, when stimulated, trigger the rapid depolarization of cells. Muscarinic receptors are located in the smooth muscles and when stimulated, trigger contraction. The smooth muscles most impacted by muscarinic receptor stimulation are located in the gastrointestinal tract, the bladder, the heart, and the airway.
Q
What are cholinergic drugs?
A
Cholinergic drugs stimulate the parasympathetic nervous system by copying the action of acetylcholine (ACh), a neurotransmitter released from nerve endings that bind on the receptors of cell membranes of organs, tissues, and glands. There are direct-acting cholinergic drugs that bind directly to cholinergic receptors (such as bethanechol and pilocarpine) and indirect-acting cholinergic drugs that inhibit acetylcholinesterase, the enzyme that blocks cholinergic receptors, allowing more ACh to bind. Examples of indirect-acting cholinergic drugs include neostigmine and donepezil.
Q
What are anticholinergic drugs?
A
Anticholinergic drugs inhibit the parasympathetic nervous system by blocking the action of ACh so that it is unable to bind to receptor sites. They interact with muscarinic cholinergic receptors in the brain, secretory glands, heart, smooth muscle, and eyes. Examples include belladonna alkaloids and derivatives (atropine, ipratropium, and scopolamine), centrally-acting anticholinergics for Parkinson’s disease (benztropine), and urinary antispasmodics for overactive bladder (oxybutynin and solifenacin succinate).
Q
What is the difference between cholinergic and anticholinergic drugs?
A
Cholinergic drugs stimulate the activation of the parasympathetic nervous system by activating receptors for acetylcholine. Anticholinergic drugs inhibit the parasympathetic nervous system by blocking the action of acetylcholine so that it cannot bind to receptors that initiate the parasympathetic response.
Q
What are side effects of cholinergic drugs?
A
Side effects of cholinergic drugs include the following: Enhanced cognitive functions such as arousal, attention, and memory encoding; pupil constriction; increased salivary, lacrimal, and bronchial secretions; smooth muscle stimulation; urinary bladder stimulation; improved muscle tone/strength.
Q
What are side effects of anticholinergic drugs?
A
Side effects of anticholinergic drugs include the following: Decreased muscle rigidity and muscle tremors, pupil dilation, decreased secretion from salivary and lacrimal glands, increased heart rate, decreased bronchial secretions, dilated bronchial airways, and decreased airway resistance.
Q
What is a cholinergic crisis?
A
A cholinergic crisis occurs as a result of excessive stimulation of a neuromuscular junction from increased acetylcholine binding secondary to deficient acetylcholinesterase, the enzyme that controls acetylcholine levels by breaking it down. In a cholinergic crisis, both nicotinic and muscarinic receptors are excessively stimulated, resulting in an excessive parasympathetic response (muscle cramping, excessive secretions, weakness/paralysis, increased gastric motility [diarrhea], and bradycardia). Causes include excessive intake of anticholinergic drugs or exposure to certain organophosphates.
