ANS Background and Parasympathetic Flashcards
Explain the branches nervous system?
Define ANS?
A branch of the peripheral nervous system innervating smooth muscle tissue, glands, organs whose activity is not under concious control.
Autonomous - independent, not under control of the brain
Parasympathetic and sympathetic neurones are classified based on their ____ and not based on ____?
Parasympathetic and sympathetic neurones are classified based on their origin from the CNS and not based on the transmitter they release.
Where the Parasympathetic Nerves originate from?
Originate from the medulla (cranial origin) and sacral (sacral origin). CRANIOSACRAL OUTFLOW
Where do Sympathetic Nerves originate from?
Originate from the thoracic and lumbar spinal cord - Thoracolubar Outlflow
What is a Ganglion?
A collection of neuronal bodies found in the voluntary and autonomic branches of the peripheral nervous system (PNS)
Explain the different neurotransmitters released by parasympathetic and sympathetic nerves?
Parasympathetic: Preganglionic nerves release Ach on Nicotinic Receptors on Postganglionic nerves which release Ach on muscarinic receptors in tissues.
Sympathetic: Preganglionic nerves release Ach on Nicotinic Receptors on Postganglionic nerves which release norepinephrine on Andregenic receptors.
What are all the sites where Ach is released?
Where are all the sites where NE is released?
Postganglionic Sympathetic Nerves.
Sympathetic fibres innervating sweat glands in the palms (adregenic sweating).
Why dont we use muscarinic and ganglionic blockers?
Both of them are not specific. Ganglionic Blockers will block parasympathetic and sympathetic fibres. Muscarinic Blockers will block all isoforms of the receptors present in many different tissues.
Both of these will have many various side effects because non specific.
What are 3 different type of specific blocker drugs.
a1B - Alpha 1 Blocker - Aplha 1 found in majority blood vessels and responsible for vasoconstriction. **Drug leads to vasodilation. Useful to treat hypertension and lower blood pressure **
B1B - Beta 1 Blocker - Found in Heart - Increases heart rate and contractility. **Drug leads to lower heart rate and blood pressure - prevents strokes. **
B2B - Beta 2 Blocker - Found in Bronchial Smooth Muscle - Beta 2 Agonist leads to Bronchodilation. Drug has opposite effect.
Very Specific Drugs
What does Non Selective - Beta B do and what is the adverse effect?
Most Widely Used Class of Drugs.
Blocks all Beta Receptors.
Non selective beta blockers cause bronchoconstriction as the adverse effect when treating a cardiovasular condition.
The adrenal medulla releases ____(80%) and ____ (20%) into the circulation when stimulated by preganglionic ____.
The adrenal medulla releases epinephrine (80%) and norepinephrine (20%) into the cirulation when stimulated by preganglionic sympathetic nerves.
What is Phaeochromocytoma?
A tumor of the adrenal medulla that releases large amounts of E and NE into the cirulation. Cause increased blood pressure and heart rate. (Tachycardia and very high blood pressure).
What is Ach synthesized from?
Choline and Acetyl coenyme A.
What causes the breaking down of Ach in the synapse and what is the effect of the inhibition of this?
Acetylcholinesterase - Enzyme
Inhibition leads to very high Ach concentration in the synapse - Cholinergic Crisis
What does botulinum toxin do?
Blocks Ach release - Causes skeletal Muscle paralysis
Does not affet the synthesis but rather it affets the release of ACh
What are catecholamines?
Catechol (benzene with two hydroxyl) + Amine Side Chain
What are NE, E, and Dopamine synthesized from?
How is NE removed from the synapse?
Taking back up into the presynaptic nerve terminal to terminate its action though a specific uptake protein (Protein Uptake 1).
What is the clinical significance of NE uptake blockers?
**Increase NE concentration in the synapse.
**
Uptake blockers useful for conditions with deficiency (depression). Can use serotonin, dopamine blockers to increase concentration and treat depression.
What are the different type of cholinergic receptors?
Explain the different subtypes of Nicotinic Receptors.
Nicotinic Receptors are sodium ion channels.
What are the functions of the Parasympathetic Nervous System(Rest and Digest)?
In each organ
Heart: Rate and Contractility Down
Blood Vessels: Relaxed Blood Vessels, Normal Blood Pressure. (Remember Blood vessels have limited have parasympathetic innervation, more lack of sympathetic ativity that causes this; paraympathetic causes vasodilation in GI and erectile tissue.)
Urinary Bladder: Normal Contractions, Contributes to the relaxation of the sphincter.
GIT including mouth: More Secretions (Saliva etc), and activates peristalsis. Excess Parasympathetic Activity leads to diarrhea, etc.
Eyes: Focus on near objects, constriction of the pupils.
What are the functions of the sympathetic nervous system(fight or flight)?
In each organ
Heart: Increased rate and Contractility
Blood Vessels: Vasoconstriction and increased BP. However skeletal, pulmonary, and coronary vessels dilate. (Muscle and lungs need more oxygen and energy.)
Kidneys: Increased Renin Secretion (Helps Vasoconstriction)
Urinary Bladder: Contraction inhibited and constricted sphincter (Urine Retention).
Lungs/Bronchi: Relaxed Bronchial Muscle - More Oxygen
GIT: Reduced GIT secretions and Peristalsis
Liver: Increased glycogenolysis (More Blood Glucose)
Eyes: Dilated Pupils, Focus on distant obect
What is dominant tone?
The dominant tone in an organ means that the branch of ANS innervating that organ is dominant or more active most of the time than the other.
Drugs especially ____ affecting the system which is ____ will have a more ____ in that organ.
Drugs especially antagonists affecting the system which is dominant will have a more noticeable effect in that organ.
What are 2 types of drugs that can mimick parasympathetic effects and what is their mode of action?
- Muscarinic Receptor Agonists (Direct Acting)
- Acetylcholinesterase Inhibitors (Indirect Acting)
What are 2 types of drugs that can block parasympathetic effects?
- Muscarinic Receptor Antagonists
- Skeletal Neuromuscular junction blockers
In most organs - Parasympathetic Block resembles sympathetic stimulation
Why do cholinesterase inhibitors work?
Increase the duration of action of the relased Ach and potentiate responses at muscarinic and skeletal neuromuscular nicotinic receptors.
How long does released Ach act at the synapse for before it is metabolized?
Few Milliseconds
How many molecules of Ach can a single Acetylcholinesterase enzyme hydrolyze per second?
10^4
One of the fastest known enzymatic reactions
What are the two types of cholinesterase enzymes?
Acetylcholinesterase (AchE)
Butyrylcholinesterase (BuChE)
What is the clinical significance of BuChE?
Located at non neuronal sites, mainly in the plasma and liver - metabolizes certain drugs such as local anesthetics and succinylcholine (muscle relaxant).
Also involved in lots of Gene Polymorphisms - Can affect metabolism of anesthetics.
What are the three types of chemical reactions that compounds can have on cholinesterase enzymes?
- Acetylation - Physiological - Caused by Ach - Extremely Rapid Recovery - Reversible
- Carbamylation - Covalent - Theraputic Used Drugs (Neostigmine) - Recovers more slowly (3-4) hours - Reversible.
- Phosphorylation - Toxic Chemicals (Nerve Gases, Insectisides) - Poisons Enzyme - Irreversible - Most Dangerous
How can we combat phosphorylation of cholinesterases?
Phosphorylated Enzyme will lose chemical groups (“age”) and leave the drug-enzyme complex with no activity (irreversible).
Combat by using an oxime such as 2-PAM, if administered before aging occurs, it can bind and release the phosphate and reverse the enzyme inhibition.
What is the dominant tone in the heart?
Parasympathetic system (except in the ventricles)
What is the main effect of cholinergic crisis caused by nerve gases and such in the heart?
Bradycardia
Decreased Heart Rate and Conduction
What are the different parasympathetic effects and what receptor is found in the heart?
Ach works on M2 Muscarinic Receptors.
What are the therapeutic uses of Muscarinic Agonisits and AChE inhibitors on the heart?
These will both decrease heart rate.
Not common Therapeutic Uses
Adverse effect: Brady Cardia and Hypotension.
What are the therapeutic uses of Muscarinic Receptor Antagonists on the heart?
Increase Heart Rate
Used to Treat Bradycardia
Adverse Effect: Tachycardia
What is the dominant tone in blood vessels?
Sympathetic Activity
Very little cholinergic innervation
What parasympathetic receptor is found on blood vessels and what are the different Parasympathetic effects of Agonists and Antagonists on this receptor?
Muscarinic - M3
What is the dominant tone of the Urinary Bladder?
Parasympathetic
Parasympathetic involved in smooth muscle contractions.
Contraction of detrusor muscle in Urinary Bladder
What are the parasympathetic receptors in the urinary bladder and what are the effects of agonists and antagonists on these receptors?
Muscarinic - M2, M3
What are the therapeutic uses of Muscarinic agonists and AChE inhibition in the urinary bladder?
Used to treat urinary retention common after spinal cord injury, post operative, and post partum.
Adverse Effect: If used for other conditions can cause urinary urgency and increase in piss frequency.
Should not use: When has physical obstruction to urine flow (can cause pressure build up and burst)
How do we treat urinary retention caused by benign prostatic hypertrophy?
Enlarged prostate constricts the neck of the bladder
An Alpha 1 blocker is used to relax sphincter and help micturition.
Nothing wrong with detrusor muscle
What is the therapeutic use of Muscarinic blockers on the urinary bladder?
Used to treat urinary incontincence (overactive bladder - involuntary urination) found in children and seniors. Symptoms: Daytime and Nightime urination frequency, urgency and incontinence(involuntary).
Adverse Effects: When used for other conditions can cause urinary retentions.
Should Not use: In patients with urinary retention or prostatic hypertrophy (not a muscarinic problem).
More Selective Drug: Oxybutynin: selects more for bladder - fewer side effects such as dy mouth and blurred vision.
Inhibits Detrusor Muscle Contraction
What is the dominant tone for the GI Tract?
Parasympathetic
What are the parasympathetic receptors in the GI tract and what are the effects of agonists and antagonists acting on them?
Muscarinic - M2, M3
What are the therapeutic uses of Muscarinic agonists and AChE inhibition in the GI tract?
Used to treat postoperative abdominal distension, hypomotility.
Adverse effect: If used for other conditions can cause diarrhea and cramping, vomiting/nasea
Should not use: Not use if physical obstruction of the GI tract, or acid-peptic disease.
What are the therapeutic uses of Muscarinic blockers on the GI Tract?
Used to treat excessive peristalsis of IBS and cramping.
Adverse effect: If used in other organs can cause unwanted constipation and dry mouth.
Should not use: In patients with atony of the bowel (muscles lose their strength and tone; reduced peristalsis).
What is the dominant tone of the Salivary and Parotid Glands?
Parasympathetic
What parasympathetic receptors are found in salivary glands and what is the effects from using agonists and blockers of these receptors?
Muscarinic - M3, M2
What are the therapeutic uses of Muscarinic Agonists on Salivary Glands?
Mostly direct and not through AChE inhibitor(indirect)
Used to treat dry mouth found following radiation therapy of the head and neck and also in Sjogren syndrome (autoimmune disorder that affects moisture producing glands).
Adverse Effects: Increase salivation when AChE inhibitors are used for other conditions.
Only useful in Sjogren syndrome proving there are functional glands left
What are the therapeutic uses of Muscarinic Antagonists on Salivary Glands?
Used to reduce excessive secretions during anaesthesia, intubation, and in cholinergic crisis.
Adverse Effects: When used to treat other conditions can get unwanted dry mouth and inhibition of sweating.
What is the dominant tone of Tracheal and Bronchial Smooth Muscle?
Parasympathetic
What parasympathetic receptors are found in Bronchial and Tracheal Smooth muscle tissue and what is the effects from using agonists and blockers of these receptors?
Muscarinic - M2, M3
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What are the therapeutic uses of Muscarinic Agonists or AchE inhibitors on Bronchial smooth muscle?
Used to determine bronchial sensitivity and diagnosis COPD or asthma. (Methacholine)
Adverse Effect: Bronchospasm, increased bronchial secretions , difficulty breathing. Major symptom in cholinergic crisis.
Should not use: In patients with asthma, chronic obstructive pulmonary disease.
What are the therapeutic uses of muscarinic antagonists on bronchial smooth musle and glands?
Used to treat asthma and COPD. Ipratropium and Tiotropium are highly ionized and not absorbed into systemic circulation causing fewer side effcts.
Also used as a preanesthetic medicaiton to block excessive secretions during surgery.
Adverse Effects: Not significant
What are two sets of muscles that have autonomic innervation in the eye?
- Iris muscles (Circular and Radial) - Control the Pupil Size
- Cilliary Muscles (Circular and Longitudinal fibres) - control aqueous humor production and lens shape (convex or not) and image focus.
What is the dominant tone of the eyes (pupillary and ciliary muscles?
Parasympathetic
What parasympathetic receptors are found in the eye and what is the effects from using agonists and blockers of these receptors?
Muscarinic
What is glaucoma and how can you treat it?
Glaucoma is characterized by in increase in intraocular pressure with increased secretion of aqaeous humor and decreased drainage.
3 Ways to treat
- Sympathetic Drugs - Beta Blocker - Reduce Secretion of AH by reducing blood flow in cilliary body. Secretion directly proportional to blood flow.
- Muscarinic Agonist - Contracts longitudal Cilliary fibers creating wider trabecular meshwork improving drainage
- Muscarinic Agonist -Treats narrow angle glaucoma by stretching iris away from narrow angle.
Explain the different Autonomic effects on lens shape and how that affects visual perception?
What wide or narrow glaucoma more common?
Wide - 85 Percent of Cases
What are the therapeutic uses of Muscarinic Antagonists on the eyes?
Used to dilate pupils, examine the retina, treat inflammatory uveitis.
Adverse Effect: Mydriasis(light sensitivity), blurred vision (cannot focus on close objects)
Should Not Use: In elderly and patients with narrow angle.
What type of parasympathetic receptors are found in the brain?
Muscarinic - M1, M4
What does muscarinic stimulation in the hippocampus play a role in?
Plays a role in memory (main deficiency in Alzheimers)
What does muscarinic stimulation in the Striatum play a role in?
ACh interacts with dopamine to control muscle contraction (unbalanced in Parkinsons)
What are the therapeutic uses of Muscarinic Agonists in the brain?
To treat memory loss in Alzheimers. Also lipid soluble to cross BBB.
Adverse effects: Can worsen the symptoms of Parkinsons (create more unbalance)
What are the therapeutic uses of Muscarinic Blockers?
Used to treat symptoms of Parkinsons disease (Excess unbalanced Ach), and to treat motion sickness(M1).
Adverse Effects: Can worsen the symptoms of Alzheimers Disease.
First Line of Treatment is Aldopa
What is Botulinum toxin and what are some Clinical uses?
Toxin released by Clostridium Botulinum
Blocks Ach release
Used to paralyze skeletal muscle in excessive involuntary muscle contration.
Clincal Uses: BOTOX
- Treats
- Blepharospasm (contracted eyelid)
- Stabismus
- Hemifacial Spasm
- Remove Facial Wrinkles
What is Cholinergic Crisis?
Excess Ach stimulation of muscarinic and nicotinic receptors.
Muscarinic Symptoms: miosis, salivation, lacrimation, sweating, urination, diarrhea, abdominal cramping, vomiting, bradycardia, bronchospasm.
Nicotinic Symptoms: **Skeletal Muscle fasciculation and paralysis, dyspnea leading to breathing difficulty and finally respiratory paralysis. **
Bolded are very serious.
