E1- Cholinergic Agents Flashcards
What are the effects of muscarinic agonist/cholinomimetics?
Bradycardia A lot of secretions Near vision accommodation Defecation Decreased intraocular pressure Urination Miosis Bronchoconstriction Vasodilation "BAND DUMB V"
What are the effects of muscarinic antagonist/cholinergic blockers?
Far vision accommodation/cycloplegia Increased intraocular pressure Tachycardia Mydriasis Bronchodilation Absent secretions "FIT MBA"
What is the main effect of neuromuscular blocking agents?
Paralysis of skeletal muscle
DO NOT produce unconsciousness or anesthesia because they do not enter the brain
How do depolarizing neuromuscular blocking agents work?
Initially depolarize the NMJ
If the depolarizing action is prolonged, the receptors desensitize, so that subsequent release of ACh does not have any effect and the muscle is paralyzed
What are the direct acting muscarinic agonist? (3)
Acetylcholine
Bethanechol (Urecholine)
Pilocarpine (IsoptoCarpine)
Why does ACh have no clinical use?
Very short half-life, rapidly hydrolyzed by AChE
The IV infusion of acetylcholine is similar to parasympathetic stimulation except the decreased BP is caused by what?
Production of NO and cGMP by endothelial cells in the blood vessels
What is the MOA of Bethanechol (Urecholine)?
Non-specific muscarinic agonist with highest effects in urinary bladder and GI tract
Resistant to AChE
What is DOC for increasing GI motility and tx of urinary retention?
Bethanechol (Urecholine)
Does Bethanechol (Urecholine) cross the BBB?
No, charged ammonia ion prevents it from crossing BBB
What is the MOA of Pilocarpine (IsoptoCarpine)?
Non-specific muscarinic agonist
What can Pilocarpine (IsoptoCarpine) be used for?
Topical: closed angle glaucoma (not a DOC)
Oral: xerostomia
Why is Pilocarpine (IsoptoCarpine) not a DOC for tx of glaucoma?
Side effects (blurred vision)
What are side effects of Pilocarpine (IsoptoCarpine)?
Topical: blurred vision
Oral: sweating
Both: HA
What are contraindications of the direct acting muscarinic agonist? (Acetylcholine, Bethanechol, Pilocarpine)
Asthma/COPD
Peptic ulcer
Bowel obstruction
What are side effects of the direct acting muscarinic agonist? (Acetylcholine, Bethanechol, Pilocarpine)
Diarrhea Abdominal cramps Salvation Sweating Bronchoconstriction Blurred vision Miosis
Besides overdose, what else can cause muscarinic toxicity?
Mushroom poisoning
How does muscarinic toxicity present?
“SLUDGE”
- Salvation
- Lacrimation
- Urination
- Defecation
- Gastric distress
- Emesis
How is muscarinic toxicity treated?
Atropine (antagonist) and albuterol (beta agonist)
What are the direct acting nicotinic agonist? (2)
Nicotine
Varenicline
Does nicotine activate sympathetic or parasympathetic neurons?
Both
What is the effect of nicotinic on sympathetic neurons?
HTN, tachycardia alternating with vagal bradycardia
What is the effect of nicotinic on parasympathetic neurons?
N/V, diarrhea, urination
What are the effects of nicotine at low doses?
Increases alertness and attention
What are the effects of nicotine at high doses?
Tremor, N/V, increased respiration
What are the effects of nicotine at toxic doses?
Convulsions, seizures
How does nicotine toxicity present?
- Vomiting
- CNS stimulation (seizures, coma, respiratory arrest)
- Skeletal muscle depolarization (initial muscle twitch followed by depolarizing blockade and paralysis)
- HTN
- Arrhythmia
What is the MOA of Varenicline (Chantix)?
Partial agonist on the nicotinic receptor subtype that stimulates reward system in the brain by releasing DA
What is Varenicline (Chantix) used for?
Smoking cessation
- Provides some nicotinic stimulation to decrease cravings as it releases a small amount of DA
- Also blocks effect of nicotine if they do smoke
What are some adverse effects of Varenicline (Chantix)?
N/V Constipation, flatulence Nightmares Mania, psychosis Anxiety, suicidal ideation
What are the indirect acting/cholinesterase inhibitors? (6)
Neostigmine Pyridostigmine Physostigmine Edrophonium Donepezil Organophosphates
What is the MOA of Neostigmine and Pyridostigmine?
Form covalent bond with AChE
Effects last 30min-6hours
What are Neostigmine and Pyridostigmine used for?
- Myasthenia gravis
- Reverse neuromuscular blockade following surgery
- Postop/neurogenic ileus or atony of urinary bladder
Can Neostigmine or Pyridostigmine cross the BBB?
No, quaternary ammonia ions
What can be used to tx muscarinic antagonist (atropine) poisoning?
Physostigmine
Can Physostigmine cross the BBB?
Yes, tertiary ammonia ion
What is the MOA of Edrophonium?
An alcohol that binds briefly to AChE
Reversible, very short acting (5-10min)
Injection only
What is Edrophonium used for?
- Dx and determine treatment dose for myasthenia gravis
- Reverse neuromuscular blockade in surgery
Can Edrophonium cross the BBB?
No, quaternary ammonia ion
What is the MOA of Donepezil?
Binds with AChE
Well absorbed orally
What is Donepezil used for?
Alzheimer’s disease
What is the MOA of organophosphates (Di-isopropyl flurophosphate)?
Phosphorylate and form covalent bond with AChE, producing long lasting and irreversible effect
“Aging”
What is aging?
When one of the phosphorus-oxygen bonds on the drug breaks, making the bond to AChE irreversible
How does cholinesterase inhibitor toxicity present?
“SLUDGE”
- Salvation
- Lacrimation
- Urination
- Defecation
- Gastric distress
- Emesis
Miosis, sweating, bronchoconstriction, N/V, diarrhea
Bradycardia and hypotension
CNS effects
Neuromuscular stimulation followed by blockade –> respiratory paralysis –> death
How do you tx cholinesterase inhibitor toxicity?
- Atropine until pupils dilate
- Administer 2-PAM (Pralidoxime) if less than 3-4 hours since exposure
- Maintain respiration
- Diazepam (Valium) for convulsions
What precautions should you take when precribing 2-PAM (Pralidoxime) for tx of cholinesterase inhibitor toxicity?
Only prescribe if less than 3-4 hrs since exposure as only works before “aging occurs”
DO NOT use if unsure if the poisoning is from an organophosphate
What is atropine used for?
- Decrease bradycardia due to excessive vagal stimulation
- Reverse heart block
- Block muscarinic effects of organophosphate or mushroom poisoning
- Diarrhea when combined with an opioid
What are contraindications of atropine?
Closed-angle glaucoma
Benign prostate hyperplasia
How is scopolamine administered?
Transdermal patch
What is scopolamine used for?
Motion sickness
What are some adverse effects of scopolamine?
Crosses BBB and can cause:
- Drowsiness, short-term memory loss
- Toxicity: hallucinations, agitation, coma
What is Tropicamide (Mydriacil) used for?
Used to dilate pupils for eye exam (topical)
What is Ipratropium (Atrovent) used for?
- COPD to reverse bronchoconstriction
- Occasionally used in acute asthma attacks
Does Ipratropium cross the BBB?
No, quaternary ammonia ion
What are Tolterodnine, Fesoterodine, Darifenacin, and Solifenacin used for?
Overactive bladder (greater M3 selectivity)
What drugs have greater M3 selectivity? (4)
Tolerodnine, Fesoterodine, Darifenacin, and Solifenacin
What is Oxybutynin used for?
To decrease bladder spasms
What is Dicyclomine (Bentyl) used for?
GI antispasmodic agent to decrease abdominal cramping and tx diarrhea-predominant IBS
What is the MOA of OnabotuliniumtoxinA (Botox)?
Blocks release of ACh
Injection only
What is OnabotuliniumtoxinA (Botox) used for?
- Urinary incontinence in pts who are refractory to antimuscarinic drugs
- Chronic migraine prophylaxis
- Wrinkles
What is an adverse effect of OnabotuliniumtoxinA (Botox)?
Asthenia (difficulties with speech, swallowing, numbness, ptosis)
What is an example of a depolarizing neuromuscular blocker?
Succinylcholine
What is the MOA of Succinylcholine?
Initial stimulation and contraction
Longer lasting than ACh –> receptor desensitization and blockade –> muscle paralysis
How is succinylcholine administered?
IV only
Rapid onset: <90 sec
Rapid recovery: 5-10min
What is succinylcholine used for?
Used to paralyze muscles for procedures where a rapid and short-acting effect is needed
- Tracheotomy
- Intubation
What are contraindications of succinylcholine?
Hx of malignant hyperthermia
Extensive soft tissue damage/burns
What are adverse effects of succinylcholine?
Hyperkalemia
Malignant hyperthermia
How is malignant hyperthermia treated?
Dantrolene
What are adverse effects of the muscarinic antagonists? (Atropine, Scopolamine, Tropicamide, Ipratropium, Tolterodine, Fesoterodine, Darifenacin, Solifenacin, Oxybutynin, Dicyclomine, OnabotuliniumtoxinA)
Mydriasis Cycloplegia Photophobia Tachycardia Dry mouth Dry eyes Decreased GI motility Urinary retention Little effect on CNS at low doses, but can cause hallucinations, delirium, and coma at toxic/high doses
What are the muscarinic antagonists? (11)
"F SODAS DITTO" Fesoterodine Scopolamine Oxybutynin Darifenacin Atropine Solifenacin Dicyclomine Ipratropium Tropicamide Tolterodine OnabotuliniumtoxinA
How does muscarinic antagonists overdose present?
- Hot, dry
- Constipated, urinary retention
- Dilated pupils, poor vision
- Tachycardia
- Agitation, delirium, dementia
- Cardiovascular and respiratory collapse
“Hot as a hare, dry as a bone, blind as a bat, red as a beet, mad as a hatter”
How is muscarinic antagonists overdose treated?
Supportive
Physostigmine to increase ACh levels in the brain
Does Succinylcholine cross the BBB?
Does not cross BBB
Do NOT produce unconsciousness
Because Succinylcholine is hydrolyzed by plasma pseudocholinesterase, the addition of a ____ will delay recovery.
Cholinesterase inhibitor
____ in pseudocholinesterase activity can prolong effects (last for hrs instead of min.)
Genetic variations
How is Nicotine toxicity treated?
Anticonvulsants and assisted respiration (there is no antidote and have to just stabilize until nicotine wears away)
What are the cardiovascular effects of AChE inhibitors?
While both sympathetic and parasympathetic nerves will be stimulated, parasympathetic dominates on the heart and will cause bradycardia and decreased cardiac output
How can a non-depolarizing blockade be reversed?
By the addition of AChE to increased ACh
