2 Cholingergic Agents Flashcards
Transport of newly synthesized ACh into synaptic vesicles is blocked by a compound called…
Vesamicol
Get it, VES-amicol…
Release of ACh from the presynaptic terminal into the synaptic cleft is blocked by …
Botulinum toxin (onabotulinumtoxinA, or Botox)
AChE inhibitors are used clinically to …
Prolong the action of released ACh
Effects of muscarinic receptor agonists are most pronounced in..
The eye, GI tract, bladder, and salivary/sweat glands
Cholinergic agonists and inhibitors of ACh breakdown (cholinesterase inhibitors) are considered together to be …
Cholinergic stimulants
Non-selective cholinergic agonists, as well as cholinesterase inhibitors, will have very diverse actions due to…
Stimulation of BOTH muscarinic and nicotinic receptors
Drugs that are selective for either muscarinic or nicotinic receptors will have more discrete effects
Drugs that bind to and activate the receptor are _______ and most will ___________ between muscarinic and nicotinic receptors
Direct-acting, will discriminate
Cholinesterase inhibitors are considered _____________.
Indirect acting - they amplify the effects of ACh, and increase its effectiveness at BOTH nicotinic and muscarinic receptors
Effects of muscarinic stimulation on the eye
Constricts circular muscle of the iris sphincter, causing MIOSIS
Constracts the ciliary muscle, causing ACCOMMODATION for near vision
Constriction of the pupil opens the angle between the iris and the lens, increasing access to the trabecular meshwork, promoting drainage of aqueous humor and DECREASING intraocular pressure
Also causes the lens to become rounder, facilitating near vision but causing BLURRED VISION
Effects of muscarinic stimulation on the cardiovascular system
Vagal inputs releasing ACh normally SLOW the HR (M2 receptors decrease cAMP and open K+ channels, slowing SA node).
Conduction is also decreased through the AV node
Presynaptic M2 receptors inhibit NE release —> enhances reduction in HR by removing some NE stimulation
The effect of cholinergic stimulation in the heart is primarily on the
Atrium
Vagal inputs affect the SA node
Even though blood vessels are not innervated by parasympathetic neurons, stimulation of M3 receptors can cause coronary vasodilation. How does that shit work?
Stimulation of M2 cholinergic receptors on ENDOTHELIAL cells in the blood vessels release nitric oxide —> vasodilation.
This is most commonly seen when ACh is injected IV, but is rare at therapeutic doses of other cholinergic agonists
Although vagal stimulation can have profound effects on the heart, at therapeutic levels, muscarinic agonists ….
Have very few cardiovascular effects
Respiratory effect of muscarinic agonists
Bronchoconstriction
Can be quite striking in asthmatics exposed to cholinergic agonists
GI effect of muscarinic agonists
Secretory activity and peristalsis is INCREASED in the GI tract, and sphincters are relaxed
Muscarinic agonist with the most pronounced GI, bladder, and GU effects
Bethanechol
GU effect of muscarinic agonists
Muscarinic receptors stimulate the bladder destructor muscle and relax the trigone and sphincter muscles. This increases void pressure and decreases bladder capacity.
Salivary and gastric effect of muscarinic agonists
Gland secretion is increased greatly by muscarinic stimulation.
Muscarinic agonsists with particularly significant effects on salivary glands
Pilocarpine and cevimeline
Glandular effect of muscarinic agonists
Secretion of sweat, lacrimal, and nasopharyngeal glands is increased by cholinergic agonists, especially pilocarpine
Brain effect of muscarinic agonists
M1 muscarinic receptors in the brain are involved in MEMORY, but no selective drugs are available yet. Maybe one day.
ACh will cause effects similar to those of parasympathetic stimulation, with the exception that…
ACh will cause vasodilation due to direct stimulation of muscarinic receptors on blood vessels, and sweating, while parasympathetic stimulation will not cause either of these effect
Does ACh cross the BBB?
Nope
It’s an ester with a quaternary amine, so will not cross.
It’s also not absorbed orally
Why doesn’t ACh have any clinical use?
It’s too rapidly metabolized (5-20 sec)
A quaternary ester similar to ACh but not rapidly hydrolyzed and selective for muscarinic receptors.
Bethanechol (Urecholine)
It does NOT cross the BBB
Effects are primarily in the Urinary and GI tracts
Relatively specific drug for muscarinic receptors that is an alkaloid, and therefore well absorbed orally and easy to get into the brain.
Pilocarpine (Pilocarpine)
Sweat and salivary glands are very sensitive to pilocarpine
________ also stimulates M1/M3 receptors, but causes less sweating than pilocarpine
Cevimeline
_________ is selective for nicotinic receptors
Nicotine
Duh.
Nicotine patches and VARENICLINE are used clinically to help people quit smoking.
______________ rapidly decrease intraocular pressure and are used in narrow-angle glaucoma
Muscarinic agonists (generally pilocarpine)
Muscarinic agonists are rarely used for open-angle glaucoma. Why?
Due to side effects, in particular BLURRED VISION
Conditions that involve decreased GI activity without obstruction (ie post-op lieu’s and congenital megacolon) may be treated with ….
Muscarinic agonists
Bethanechol most common to stimulate peristalsis and increase voiding in patients with urinary retention
DOC for dry mouth
Cevimeline
Somewhat more selective for M1 receptors and does not cause as much sweating as pilocarpine.
Drugs used to increase salivation in treatment of Sjogren’s syndrome or dry mouth following radiation
Pilocarpine or cevimeline
Pilocarpine causes PROFOUND SWEATING but cevimeline less so (more selective for M1 over M3)
Side effects and toxicity of muscarinic agonists
Nausea, vomiting, diarrhea Abdominal cramps, belching Salivation and sweating Cutaneous vasodilation Bronchoconstriction Bladder tightness Blurred vision
Contraindications for use of a muscarinic agonist
Peptic ulcer
Coronary insufficiency
Asthma
Bowel obstruction
Nicotinic receptors are located in…
The autonomic ganglia, the brain, and on skeletal muscle
Nicotinic receptors are _______ channels
Ligand-gated ion channels
Nicotinic agonists cause an immediate activation, followed by a rapid desensitization if the receptors continue to be stimulated. Receptor activation opens the channel and increases permeability to Na+ and Ca2+ ions
Central effects of nicotinic agonists
Low doses of nicotine can increase alertness and attention.
Higher doses cause tremor, vomiting, and increased respiration
Peripheral effects of nicotine
Similar to discharge of both parasympathetic and sympathetic neurons, due to stimulation of autonomic ganglia
CV effects mostly sympathetic - HTN and inc HR, which may alternate with vagal bradycardia
GI/GU - mostly parasympathetic - vomiting, diarrhea, and urination
NMJ - initially cause stimulation of the muscle depending on the size of the stimulus, depending on size of the stimulus; long lasting stimulation —> desensitization —> flaccid paralysis
Nicotine poisoning can occur in children who eat tobacco products (just two cigarettes can be fatal if eaten). What are the predicted side effects?
Vomiting, generally fairly rapidly
CNS stimulation may cause convulsions, coma, resp arrest
NMJ stimulation may cause muscle contractions, then desensitization —> paralysis
HTN and cardiac arrhythmias
Treatment for nicotine poisoning
Atropine to block muscarinic receptors
Anticonvulsants to decrease seizures
Mechanical respiration
How does varenicline (Chantix) work to stop someone from smoking?
Partial agonist on a nicotinic receptor in the brain.
In smokers, nicotine increases dopamine release —> pleasure. A craving developers when levels of dopamine become low during nicotine abstinence
VARENICLINE substitutes for nicotine to cause just enough dopamine release to relieve the craving
But because it’s a partial agonist, it blocks the full effects of nicotine if a person smokes so smoking becomes less pleasurable
Common side effects of varenicline (Chantix)
Nausea, vomiting, fatigue, headache, constipation, and flatulence
Some serious CNS side effects: sleep disturbance, vivid nightmares, psychosis and mania, anxiety, and possible suicide
How do cholinesterase inhibitors work?
Inhibit the breakdown of ACh following its release into the synaptic cleft —> increased duration of action of ACh on receptors
Especially useful in diseases in which cholinergic inputs have been decreased, or where the responsiveness of receptors to ACh is reduced
Also used to reverse teh effects of neuromuscular blocking agents in surgery
The effects of each group of cholinesterase inhibitors difference based on…
their chemical structures
As a cholinesterase inhibitor group, ____________ form a covalent bond with an effect lasting 30 min to 6 hours
Carbamates
Ex:
Neostigmine and pyridostigmine - both quaternary amines (not well absorbed orally and DO NOT cross the BBB)
Physostigmine - tertiary amine so it IS absorbed orally and will get in to the brain
__________ must be injected, but will bind reversible to AChE with a very short duration of action (5-10 min)
Edrophonium
______ forms an irreversible bond with AChE. It is occasionally used in the eye to treat narrow angle glaucoma because it provides a long-lasting effect
Echothiophate
__________ are cholinesterase inhibitors used as pesticides and as nerve gases
Organophosphates
Note: they are highly lipid soluble, and phosphorylation the AChE to form a very long-lasting bond. This bond then undergoes “aging” - breaking one of the phosphorus-oxygen bonds increasing the strength of the bond until it’s irreversible.
So yeah. Bad.
__________ is a strong nucleophile which attracts the organophosphates and irreversibly binds to them. If added before aging occurs, it binds to the organophosphate and prevents attachment to AChE
Pralidoxime (2-PAM)
If not used to treat organophosphate exposure before aging, the poisoning may be fatal
Use with caution - can also produce HTN
Do we use 2-PAM for carbamate poisoning too?
It’s controversial.
Since the carbamates don’t undergo aging, 2-PAM itself binds to and inhibits AChE if it isn’t binding to organophosphate, so it could make things worse
But some EM protocols say use it anyway, esp if you don’t know what the pesticide was.
Why are the effects of cholinesterase inhibitors similar to stimulation of both muscarinic and nicotinic receptors?
Because the effect of ACh is enhanced at the tissues. The effect in a particular tissue will reflect the predominant tone in that tissue.
Effects of AChE inhibitors on the brain:
Increase alertness and improve memory via stimulation of M1 and Nn receptors in low doses
High concentrations act similarly to nicotine and may desensitize nicotinic receptors, cause convulsions, and produce respiratory arrest
Effects of AChE inhibitors on the eyes, respiratory tract, GI/GU tract:
Parasympathetic tone is dominant in these tissues, so the effect is similar to that of muscarinic agonists
Effects of AChE inhibitors on the CV system:
In the heart, responses are mostly parasympathetic, including bradycardia, decreased force of atrial contraction and decreased CO
There is little effect on the vasculature since there is no direct cholinergic innervation.
Desensitization of ganglionic nicotinic receptors decreases sympathetic stimulation tho.
Effects of AChE inhibitors on the NMJ
Low concentrations INCREASE the strength of contraction of skeletal muscle (useful in diseases such as myasthenia gravis or reversal of neuromuscular blockade following surgery)
Toxic concentrations —> initial contraction followed by neuromuscular blockade resulting from desensitization of nicotinic receptors
An autoimmune disease in which antibodies to nicotinic receptors on the neuromuscular endplates develops.
Myasthenia Gravis
The patient develops weakness and fatigue of muscles.
Cholinesterase inhibitors are used in MG to prolong the action of ACh in the synaptic cleft
DOC for myasthenia gravis
Neostigmine (and pyridostigmine) for chronic therapy
Do not cross the BBB and though absorption is poor are given orally to increase the duration in MG patient
In addition to the inhibition of AChE in MG patients, neostigmine may also have some direct stimulators effect on the NMJ that has beneficial effect
How is neostigmine/pyridostigmine administered for myasthenia gravis patients?
Orally, more than once a day b/c they are fairly short acting
Because the actions of ACh are everywhere, there are often muscarinic side effects (usually able to be tolerated. If not give a muscarinic agonist)
How is edrophonium used for myasthenia gravis patients?
As a diagnostic, due to its short action
If the patient has MG, the edrophonium will cause an improvement in muscle strength that lasts about 5 min then fade
Can also be used to adjust the dosage of their chronic (long acting) meds.
The effects of non-depolarizing neuromuscular blocking agents can be reversed by administration of …
Cholinesterase inhibitors such as NEOSTIGMINE OR EDROPHONIUM
Acute close-angle glaucoma is treated with a combo of…
Pilocarpine and a cholinesterase inhibitor until the pressure is controlled and surgery can correct the problem.
Muscarinic agonists are generally NOT used for open angle-glaucoma because…
Side effects (blurred vision and brow ache)
An long action organophosphate AChE inhibitor applied in the eye when long-term control of intraocular pressure is required (ie - in narrow angle glaucoma emergencies).
Echothiophate
It is not lipid soluble so does not get absorbed systemically
An overdose of muscarinic antagonists can produce…
CNS toxicity
Since there are no good agonists that penetrate the CNS to reverse this, physostigmine is used.
The only systemic use for physostigmine
Treatment of muscarinic antagonist poisoning, because it can increase ACh to overcome the CNS effects of the antagonist.
It’s also applied directly in the eye to treat narrow angle glaucoma (rarely)
Prototype for the organophosphate class
Diisopropyl fluorophosphate (DFP) Was developed as a pesticide
Malathion and dichlorvos are other commonly used pesticides
Woman and sarin are similar but are used as nerve agents with rapid action
AChE inhibitors similar to physostigmine that are used to treat Alzheimer’s disease
Donepezil, rivastigmine, and galantamine. All well absorbed orally and get into the brain.
How to remember the symptoms of toxicity to irreversible cholinesterase inhibitors
SLUDGE Salivation Lacrimation Urination Defecation Gastric distress Emesis
Other possible Sx: miosis, sweating, bronchoconstriction, nausea, vomiting, diarrhea, bradycardia, hypotension
The usual cause of death in AChE inhibitor poisoning?
Paralysis of respiratory muscles due to neuromuscular blockade
Think people choking on sarin gas. Not pretty.
Usually within 5 min to 24 hours, depending on amount and the specific agent.
CNS effects of AChE inhibitor toxicity
Confusion, ataxia, slurred speech, convulsions and coma
All similar to nicotine overdose
If exposure to an irreversible AChE inhibitor is by inhalation, what effects will be observed first?
Those on respiration and the eye (miosis, ocular pain, vision impairment)
Oral administration of a toxic dose of AChE inhibitors is more likely to cause…
GI symptoms and decreased BP
Treatment for toxic AChE exposure
Administer atropine until pupil become dilated to show you’ve successfully blocked the muscarinic receptors
Inject pralidoxime (PAM) to prevent enzyme aging (must be done RAPIDLY)
2-PAM is NOT used if you know the poisoning is from a carbamate, but should SHOULD be used if you have any suspicion of organophosphate exposure
Maintenance of respiration
Cholinergic antagonists are subdivided into __________ blocking drugs and _________ antagonists
Muscarinic receptor blocking drugs and Nicotinic antagonists (used primarily as neuromuscular blocking agents in surgery)
Muscarinic antagonists bind to muscarinic receptors and block the effects of _________.
Acetylcholine
Their effect will be to antagonize the actions of the parasympathetic stimulation
The prototype drug for muscarinic antagonists?
Atropine
Atropine and scopolamine are naturally occurring alkaloids of the belladonna plant. Atropine also found in Jimson weed
_________ does not penetrate the CNS well until high doses are reached so the majority of its actions in non-toxic doses are peripheral
Atropine
________ enters the CNS very easily and causes sedation and amnesia, even euphoria if abused. It is well absorbed by the skin though and is applied in a patch form for prevention of motion sickness
Scopolamine
The effect of blocking muscarinic receptors will depend to a great deal on …
The amount of prevailing parasympathetic tone in different tissues
Because of this, there is a dose-related sequence of effects of cholinergic blockage, demonstrated by increasing doses of atropine
_________, ________, and _______ are affected at low doses of atropine.
Salivary glands, sweat glands, and bronchial tissues.
The initial side effects are dry mouth and decreased sweating
Order of side effects noted as dose of atropine increases
0.5 mg - dry mouth and decreased sweating
1 mg - increased HR, very dry mouth and thirst
2 mg - blurred vision, tachycardia, and palpitations
5 mg - urinary retention, hot and dry skin, restlessness, and fatigue
10 mg - rapid and weak pulse, ataxia, hallucinations, delirium, and coma
_______ has little effect on the CNS at normal doses but will cause hallucinations, delirium, and coma at toxic doses
Atropine
__________, which crosses the BBB more readily, causes drowsiness and amnesia at low doses. At toxic doses, it may cause excitement, agitation, hallucinations, and coma
Scopolamine
__________ is often used as a part of a pre-anesthetic regimen, both to cause sedation and amnesia, and to dry secretions
Scopolamine
______________ is very effective at preventing motion sickness when administered as a transdermal patch
Scopolamine
The patch decreases side effects by the way. How cool.
Anti muscarinic drugs are used to restore the balance between ____________ and __________ in the corpus striatum in conditions where dopamine receptors are blocked or dopamine is reduced
Acetylcholine and Dopamine
Examples:
Use of some antipsychotic drugs
Parkinson’s disease
Benztropine, trihexyphenidyl and diphenhydramine (Benadryl) are commonly used for this purpose
Atropine and other cholinergic antagonists block activation of the ____________ by parasympathetic stimulation, causes eyes to dilate
Circular muscle, or iris sphincter
Term for this is mydriasis
Useful for dilated eye exams
Muscarinic agonists also decrease cholinergic stimulation of the ciliary muscle, causing…
Cycloplegia (loss of accommodation for near vision)
The reflex to light is also blocked, producing photophobia
Short-acting drugs administered directly into the eye for producing short-acting mydriasis
Tropicamide and homatropine
Because anticholingeric drugs inhibit the ciliary muscle and close the trabecular system, they may
increase intraocular pressure, especially in narrow angle (closed) glaucoma
_______________ is a contraindication to the use of anticholinergics
Narrow angle glaucoma
But can be used in patients with OPEN angle glaucoma that is being successfully treated
Due to blockade of parasympathetic inputs that increase secretions, anticholinergic drugs cause…
Dry eyes
With muscarinic antagonists, the blockade of postsynaptic M2 receptors in the SA node removes vagal effects, resulting in ….
Tachycardia
Most noticeable in a healthy young adult with high vagal tone (increase of 25-35 bpm).
Babies and elderly people have little vagal tone, so cardiac effects of muscarinic blockage are smaller
Atropine is sometimes used to reverse the effects of reflex vagal discharge (e.g. due to pain, stimulation of the carotid sinus, pressure on the eyes, irritation of the larynx following intubation), which may cause …
Enough depression of the SA and AV node to cause significant bradycardia and decrease CO
___________ is used in surgery to prevent vagal bradycardia when visceral organs are to be handled
Glycopyrrolate
_______ reverses bradycardia produced by muscarinic agonists or cholinesterase inhibitors
Atropine
Atropine is used in myocardial infarction s to …
Decrease bradycardia or AV block by blocking vagal inputs to the heart —> facilitation of AV conduction
Muscarinic antagonists have little effect on peripheral resistance or BP because…
Blood vessels do not receive parasympathetic inputs
BUT, vasodilation may result from release of NO from endothelial cells in response
Atropine in toxic doses may cause vasodilation in the …
Face
It’s a reflex action to get rid of excess heat
Why don’t we give muscarinic agonists to asthmatics?
Because they cause bronchoconstriction
Blockade of muscarinic receptors can reverse bronchoconstrictions, so its helpful in patients with …
COPD or acute asthma
Muscarinic blockade may also decrease responsiveness to inflammatory meds in the lungs
Jimsom weed and belladonna cigarettes, which contain atropine, have been used for asthma treatment for centuries
Two of the many muscarinic antagonists used for bronchodilation?
Ipratropium (Atrovent) and tiotropium (Spiriva)
All of the compounds used in the lung are quaternary ammonium compounds, which are inhaled and not well absorbed systemically, so really just effects the lungs
How do muscarinic antagonists generally effect the GI and GU tract?
Inhibit motility and secretions
Have been used as antispasmodics ie Dicyclomine(Bentyl)
Atropine combined with an opioid (diphenoxylate or Lomotil) is used to treat…
Diarrhea
The powerful effect of the opioid to decrease GI motility is potentiated by addition of atropine
The unpleasant effect of atropine at high doses lowers the abuse potential of the opioid
Smooth muscle of the ureters and bladder wall are relaxed by __________ and voiding is reduced
Anticholinergics
A number of drugs have been recently approved for treatment of overactive bladder and urinary frequency
___________ is a selective M3 receptor antagonist being marketed to decrease bladder overactivity
Tolterodine (Detrol)
It has few CNS side effects and is the preferred treatment in the elderly, in whom CNS muscarinic blockade can lead to delirium
__________ is often used to prevent bladder spasm after prostate surgery
Oxybutynin (Ditropan)
Why does body temp rise in atropine poisoning?
Because sweating is blocked
Especially common in children
________ is a common side effect of even low doses of anti muscarinic drugs
Dry mouth
Because salivation is very sensitive to atropine
Summary of the main side effects of anticholinergic drugs
Dry mouth Decreased bronchial secretions Tachycardia Mydriasis and cycloplegia —> blurred vision Decreased GI motility and constipation Urinary retention Hot, dry skin Decreased sweating
All predictable if you think of the mechanism and dose
The two main contraindications for use of anti muscarinic agents
Narrow angle glaucoma
Benign prostatic hyperplasia (BPH)
Funny little line to describe atropine poisoning
Dry as a bone, blind as a bat, mad as a hatter, red as a beet
Dry mouth and mucous membranes Mydriasis Tachycardia Decreased bowel sounds Hot flushed skin Agitation and delirium
Scopolamine main cause toxic psychosis too
Other drugs that have anticholinergic effects and may have toxic effects similar to atropine…
Tricyclic antidepressents, antihistamines, and phenothiazine antipsychotics
Treatment for atropine poisoning?
Supportive and symptomatic (e.g. physostigmine, diazepam (Valium) to prevent seizures, ice bags and ethanol to reduce body temp, assist respiration)
Physostigmine is used because it gets into the brain, whereas the other therapeutic AChE inhibitors do not
When using atropine to treat organophosphate poisoning, you inject large doses until…
Dry mouth and mydriasis appear, indicating that muscarinic receptors are being effectively blocked.
Continue administration unti the effects of the AChE inhibitor wears off.
What are the two types of NMJ blocking agents?
1) Non-depolarizing competitive antagonists - bind to the receptor and cause blockade, holding channel closed. B/c they are competitive, their effect can be overcome by increasing ACh
2) Succinylcholine is the only depolarizing blocker - it initially depolarizes the NMJ but the action is prolonged and the receptors desensitize, so that the subsequent release of ACh does not have any effect and the muscle is paralyzed
The prototype non-depolarizing competitive NMJ antagonist
D-Tubocurarine
NMJ blocking agents are especially useful in surgery because…
They provide paralysis of skeletal muscle
But they DON’T produce unconsciousness or anesthesia because they don’t enter brain
So the patient will be paralyzed but awake 😲
NMJ blockers must be injected because…
They will not be absorbed orally due to their high degree of ionization
Because no depolarizing NMJ blockers are competitive antagonists, their action can be reversed by…
Increasing the amount of ACh in the synaptic cleft with cholinesterase inhibitors such as neostigmine
Order of effect with the use of NMJ blockers
Small muscles (eye, jaw, larynx) generally affected first, followed by larger muscles (limbs, trunk). Intercostal muscles and diaphragm last and the first to recover
Recovery occurs in the reverse order of paralysis
____________ is the only depolarizing NMJ blocker in use
Succinylcholine
Results in the initial stimulation and contraction of the muscle. The action of succinylcholine lasts longer than that of ACh, so receptor desensitization and blockage occur.
Both onset of action and recovery are very rapid
How is succinylcholine deactivated?
Hydrolyzed by plasma pseudocholinesterase
There are genetic differences in ability to metabolize succinylcholine, expressed in terms of dibucaine number. Dibucaine is a local anesthetic that causes inhibition of cholinesterase. When might you test with dibucaine?
If a family member has had problems with succinylcholine (ie taken hours to get over its effects instead of minutes)
Because succinylcholine is hydrolyzed by cholinesterase, addition of a ____________ will delay recovery
cholinesterase inhibitor
__________ may occur with repeated doses of succinylcholine and inhaled anesthetic, esp halothane, resulting from an uncontrolled release of Ca2+ from the SR —> muscle rigidity and high temp.
Malignant hyperthermia
Treated with dantrolene
Patients who should not receive succinylcholine
Patients with extensive soft tissue damage or burns
Patients with non traumatic Rhabdomyolysis
Spinal cord injuries with paraplegia or quadriplegia
Muscular dystrophy
Children under 8
Why can patients with burns or nerve degeneration, head traumas, etc receive succinylcholine?
May cause a pronounced release of potassium into the blood —> cardia arrest (life threatening, especially in patients with CHF)
Uses of NMJ blockers
Surgery: to relax muscles for surgery Ventilation: to paralyze diaphragm Ortho: to allow manipulation of bones Intubation, bronchoscopy etc Convulsions: used in ECT to decrease muscle spasms
Ganglion blockers are considered a subset of …
No depolarizing competitive antagonists
Hexamethonium and mecamylamine are not used clinically
Because they block all autonomic ganglia, effects of ganglion blockers are similar to …
Inhibition of sympathetic and parasympathetic inputs - effects depend on the predominant tone of an organ
Primary effects of ganglion blockers based on predominant ANS tone…
Eye: ciliary muscle primary affected —> cycloplegia; also, mydriasis
Blood vessels: primarily sympathetic —> orthostatic hypotension
Heart: contractility of heart reduced —> tachycardia due to decreased vagal tone
GU: urinary retention
Skin: sweating blocked but temp maintained due to vasodilation
