Overview of parasympathetic nervous system structure, receptors, and neurotransmitters.
Brief discussion of Alzheimer's disease and myasthenia gravis, referencing prior pathophysiology knowledge.
Emphasis on understanding the neurotransmitter's role in the nervous system.
Cholinergic nerves produce acetyltransferase, which, with choline from the diet, creates acetylcholine (ACh).
ACh$$ACh$$ is the primary neurotransmitter in the parasympathetic nervous system.
Some cholinergic receptors exist in the sympathetic nervous system, but ACh$$ACh$$ primarily acts in the parasympathetic system.
The parasympathetic nervous system promotes "rest and digest" or conservation of energy, opposite to the sympathetic nervous system's "fight or flight."
Increased GI motility and secretion leading to rapid and frequent bowel movements.
Increased urination due to increased urine production and urgency.
Decreased heart rate caused by blood vessel dilation and reduced cardiac contractility.
Bronchoconstriction and increased pulmonary secretions, leading to reduced air movement and thicker lung secretions.
Pupil constriction.
Brief review of action potential, synapse, and synaptic cleft, emphasizing understanding from previous discussions.
Parasympathetic impulses originate from cranial and sacral points in the central nervous system.
Acetylcholine communicates between nerves and muscles, facilitating skeletal muscle contraction.
It's involved in thought processes like memory and learning, linking it to Alzheimer's disease.
Altering acetylcholine levels can impact thought, learning, memory, and awakening processes.
After message transmission, acetylcholine is broken down by acetylcholinesterase, an enzyme in the synapse.
Acetylcholinesterase deactivates acetylcholine, preventing overstimulation of cholinergic receptor sites.
The enzyme acts within approximately 80 seconds to deactivate acetylcholine.
Without acetylcholinesterase, muscles can convulse due to continuous stimulation.
Two main subtypes: nicotinic and muscarinic, both inactivated by cholinesterase (think "erase").
Activated by muscarine, found in visceral effector organs (GI tract, bladder, heart, sweat glands, vascular smooth muscle).
Stimulation leads to pupil constriction, increased GI motility and secretion, salivation, bladder contraction, and reduced heart rate.
Located in the central nervous system, adrenal medulla, autonomic ganglia, and neuromuscular junction.
Stimulation causes skeletal muscle contraction, autonomic responses (secondary stress reaction), and release of norepinephrine and epinephrine from the adrenal medulla.
Low dose triggers muscarinic receptors: bradycardia, bronchoconstriction, increased GI motility, bladder constriction, decreased blood pressure, salivation, and lacrimation.
High dose triggers nicotinic receptors: sympathetic nervous system stimulation, ganglionic stimulation, adrenaline release, and increased blood pressure.
Atropine blocks muscarinic receptors; it's clinically significant with wide applications.
Atropine does not affect nicotinic receptors.
M1, M2, M3 receptor types and their locations (sympathetic nervous system, salivary glands, parietal cells, heart, smooth muscle, exocrine glands) and specific effects (CNS excitation, gastric acid secretion, decreased heart rate/force/AV conduction, smooth muscle contraction, vasodilation, glandular secretion).
NN, NG, NM receptor types and their locations (CNS/adrenal medulla, autonomic ganglia, skeletal muscle) and specific effects (CNS excitation, adrenaline release, ganglionic transmission, muscle contraction).
Cholinergic agonists cause action by mimicking acetylcholine, increasing activity of acetylcholine receptors throughout the body.
Effects are widespread and can lead to undesirable systemic effects.
Cholinergics increase secretions (sweat, saliva, bowel secretions).
Categorized into direct-acting (muscarinic or nicotinic) and indirect-acting agonists, and Alzheimer's-specific agents.
Cholinergic agonists are parasympathomimetic, causing a parasympathetic response via direct or indirect action.
They are not specific, which can lead to widespread and undesirable effects.
Direct-acting agonists mimic acetylcholine and parasympathetic stimulation and occupy receptor sites on effector cells of postganglionic cholinergic nerves.
These drugs are now infrequently used because of toxic effects.
Indirect-acting agonists increase acetylcholine receptor site stimulation by reacting with acetylcholinesterase.
This prevents the breakdown of acetylcholine, leading to an accumulation and prolonged action.
Slowed heart rate, decreased cardiac contraction, dilated blood vessels, constricted lungs, increased mucus, increased GI movement/secretions, increased bladder tone, relaxed GI/bladder sphincters, and pupil constriction.
Well-absorbed orally, with a short half-life (1-6 hours).
Metabolism and excretion are not well-understood.
Topical use usually does not lead to systemic effects.
Bethanechol (Duvoid): For non-obstructive post-op or postpartum urinary retention and neurogenic bladder; administered orally or subcutaneously.
Acetylcholine chloride (Miochol-E): Ophthalmic agent for rapid meiosis during eye procedures and glaucoma (reduces intraocular pressure).
Cevimeline and Pilocarpine: For Sjogren's syndrome (autoimmune disorder causing dry secretions); systemic, increasing mouth and eye secretions.
Bradycardia, low blood pressure, asthma/COPD, intestinal blockage, epilepsy, Parkinson's, pregnancy, and lactation.
Bradycardia, arrhythmias, heart block, hypotension, cardiac suppression, nausea, vomiting, diarrhea, increased salivary secretions, involuntary defecation, dehydration, flushing, and sweating.
Nicotine binds to nicotinic cholinergic receptors in the peripheral and central nervous systems.
It increases neuronal activity in the prefrontal cortex, thalamus, and visual system.
Releases dopamine, creating a reward feeling that leads to dependence.
Also releases norepinephrine, acetylcholine, serotonin, GABA, glutamate, and endorphins.
Absorption rates and half-life vary by delivery (inhaled, patch, gum, pill).
Used for smoking cessation (e.g., Nicorette gum, patches).
Bupropion (BUP) and Varenicline (Chantix) are also used but are discussed more in-depth in psychiatric contexts.
Allergy.
Bupropion is contraindicated for patients with seizure disorders.
Caution with pregnancy and lactation due to the effects of smoking tobacco versus nicotine replacement.
Tachycardia, hypertension, airway irritation (for inhaled versions).
Bupropion and Chantix increase the risk of seizures and neuropsychiatric events (depression, mania, agitation, anxiety, paranoia).
Other effects include nausea, dry mouth, dizziness, skin rash, strange dreams, and hypertension.
Significant drug-drug interactions with Bupropion and Chantix require careful monitoring.
Stopping smoking (with or without nicotine replacement) requires medication adjustments (e.g., insulin, propranolol, Tylenol, caffeine).
Doses need to be reduced as nicotine's amplifying effect is removed.
Also known as indirect-acting parasympathomimetics and acetylcholinesterase inhibitors.
They prevent the breakdown of acetylcholinesterase, resulting in acetylcholine accumulation or inhibited metabolism.
Act at all acetylcholine receptors (parasympathetic, CNS, neuromuscular junction).
Can be reversible (therapeutic) or irreversible (not therapeutic).
Effects pass with time as acetylcholinesterase is released to break down acetylcholine.
Examples: Pyridostigmine (Mestinon), Neostigmine (Bloxiverse), Donepezil (Aricept), Galantamine (Razadyne), Rivastigmine (Exelon).
Bind to acetylcholinesterase for much longer; breakdown may not occur without intervention.
Examples: Nerve gas, mustard gas, organophosphates, and specific eye drops (not discussed in detail).
Autoimmune destruction of nicotinic acetylcholine receptors, leading to decreased muscle activity (including diaphragm).
Neostigmine improves muscle strength by preventing acetylcholine breakdown.
Also used for reversal of non-depolarizing neuromuscular blocking agents (paralytics).
(Mestinon): Same mechanism of action and use as Neostigmine for myasthenia gravis.
Also used as an antidote for neuromuscular junction blockers/nerve gas exposure (military use).
Progressive loss of acetylcholine-producing neurons in the brain cortex.
Characterized by confusion, memory loss, difficulty with familiar tasks, poor judgment, emotional changes, and social withdrawal.
Reversible indirect-acting cholinergic agonists can help manage Alzheimer's symptoms (confusion, memory loss) by allowing acetylcholine buildup.
Does not reverse the disease or produce more neurons.
Metabolized in the liver and excreted in urine.
Take pills daily.
Adverse effects are bradycardia, hypotension, blurred vision, chest pain, confusion, dyspnea, palpitations, sweating, fasciculations, and fatigue.
Aricept is recommended to be taken at night.
Increased risk of GI bleeding with NSAIDs.
Overdose can cause a cholinergic crisis, requiring withdrawal of cholinergic drugs and administration of atropine.
A state of cholinergic toxicity that causes sludge (Salivation, Lacrimation, Urinary incontinence, Diarrhea, GI cramps, Emesis). As well as shortness of breath, hypotension, cardiac arrest, and bradycardia.
Weaponized nerve gas and pesticides (organophosphates) are dangerous.
They do not allow for acetylcholine breakdown, causing toxicity and crisis.
Systemic effects: slowed heart rate, constricted pupils and lungs, continuous muscle contraction, respiratory arrest, leading to death.
Atropine (temporarily blocks cholinergic activity).
Pralidoxime (Protopam chloride) helps to free up acetylcholinesterase.
Salivation, Lacrimation, Urinary incontinence, Diarrhea, GI cramps, Emesis.
Shortness of breath, hypotension, cardiac arrest, and bradycardia.
Example: Pesticide exposure. Symptoms: excessive secretions.
Anticholinergic drugs decrease responses.
Additive effect with adrenergic antihistamines.
Decreased responsiveness with sympathomimetics.
Increased response with other cholinergic drugs.
Children: More susceptible to GI upset, diarrhea, and choking.
Adults: Nasal motor issues, flushing, sweating, salivation, GI upset, urinary urgency, dizziness, drowsiness, blurred vision; caution with driving.
Elderly: More CNS, cardiovascular, GI, respiratory, and urinary effects; higher risk of toxicity.
Assess medication history, allergies, GI/GU issues, recent surgery, hypotension, peptic ulcer disease, and coronary artery disease.
Perform baseline vital signs and labs.
Administer doses evenly apart at the same time daily.
Have atropine available.
Overdosing is life-threatening.
Report weakness, abdominal cramps or diarrhea, or dyspnea.
Take Aricept at the evening.
Myasthenia gravis patients should take medications 30 minutes before eating to improve chewing and swallowing.
Cholinergic agonists are also known as parasympatholytics and cholinergic antagonists.
Examples for the medications are atropine, Detrol, Ditropan XL, scopolamine, benztropine, ipratropium, and dicyclomine.
It prevents that binding.
When parasympathetic system is blocked, that means the effects of the sympathetic system are more prominent, and then the parasympathetic system becomes less known.
Cardiovascular sense, I expect to have increased heart rate and contract and conduction.
Respiratory capacity, I expect to have decreased bronchial secretions and also open bronchial airways.
Central nervous system, it causes a bit of drowsiness and disorientation and hallucinations.
Eye, it dilates pupils and it causes, or allows for a decreased accommodation caused by paralysis of ciliary muscles.
The GI tract, it decreases intestinal and gastric secretions, and then it relaxes the smooth muscle tone of the GI tract, and it decreases motility and peristalsis.
Genitourinary, it's gonna relax that detrusor muscle and increase constriction of the internal sphincter.
Glandular effects where it's gonna decrease the bronchial secretion, salivation, and sweating.
Cardiovascular sense, tachycardia and dysrhythmias.
Central nervous system, it can actually cause much tooth excitation causing disorientation, hallucinizations, and even worse than it would be delirium.
Eye, dilated pupils, decreased visual accommodation, and then it can actually increase intraocular pressure.
Respiratory sense, you're gonna have thickening and drying of respiratory secretions that can actually cause a mucus plug, and patient can, again, choke on the respirations for a dis I'm sorry, their secretions for a different way.
GI, they will have decreased salivation and dry mouth and constipation because we've slowed it all down and dried it up.
Bladder, they will retain urine. Sometimes that's desirable. Right?
Decreased sweating.
Only blocks the muscarinic effectors, in the parasympathetic nervous system and those in the in the sympathetic nervous system.
Does not block nicotinic receptors.
Therapeutic is it can be used for advanced life support and treatment of bradycardia. I can also use it if I want to stop somebody from having a vagal response.
It blocks the parasympathetic cholinergic effectors on pacemakers of the SA and AV nodes in the heart. And if it does that, you can imagine that it's going to increase the heart rate.
Only blocks muscarinic vectors in the parasympathetic nervous system and those in the SNS, same as atropine. Same as atropine. K? These two are the same.
Can be used to decrease nausea, vomiting, motion sickness as I said, but also it can be really helpful when we have patients who are on a, who have a trach, who are on a ventilator, or who have profuse secretions such as somebody like a child who has a chronic, illness that produces a lot of secretions.
Can also relieve urinary problems, and it can dilate the pupils as you can kind of see.
Medication that can be used as treatment for over active bladder because, remember, it allows for bladder retention or urinary retention.
Also, it's gonna relax the the detrusor muscle of the bladder, which is gonna increase constriction of the internal sphincter.
You need to perform a baseline assessment of vital signs and physical exam, of course, just like the other one, assess for allergies, but you also need to assess for presence of possible contraindications like benign prostate hyperplasia. Right? That should make sense.
For the ones complaining of urinary, incontinence. If I wanna give them that control over their bladder again and I'm gonna give them Ditropan.
Studying group leaders and older cohorts, they had this information. I've left it in here, but I need to make a disclaimer. If a patient has an overdose on atropine, your book still mentions physostamine. This is not the same one that I had in in your other part of lecture with cholinergic agonists. Phisostamine is a cholinesterase inhibitor, but it's been discontinued in The United States.
When atropine is given in a life saving event for bradycardia, we give a dose of one milligram, but we maximize it at three milligrams total. That means that we can only give one milligram three total times.
Giving atropine for somebody who is needing it for bradycardia.
Parasympathetic Nervous System, Cholinergic Agonists, and Anticholinergic Agents