Kruse Cholinergic Agonists and Antagonist Flashcards
Direct acting cholinomimetics?
- Acetyolcholine
- Bethanechol
- Carbachol
- Cevimeline
- Methacholine
- Pilocarpine
- Varenicline
Cholinesterase Inhibitors?
- Ambenonium
- Donepezil
- Echothiophate
- Edrophonium
- Galantamine
- Neostigmine
- Physostigmine
- Pyriedostigmine
- Rivastigmine
- Tacrine
Antimuscarinic drugs for motion sickness and GI disorders?
- Scopolamine-motion sickness
- GI disorders
- Atropine
- Dicyclomine
- Glycopyrrolate
- Hyoscyamine
Antimuscarinic drugs used for respiratory disorders?
- Ipratropium
- Tiotropium
Antimuscarinic drugs used for urinary disorders?
- Darifenacin
- Fesoterodine
- Oxybutynin
- Solifenacin
- Tolterodine
- Trospium
Antimuscarinic Drugs used for cholinergic poisoning?
Atropine
Antimuscarinic Drugs used for movement disorders?
- Benztropine
- Biperiden
- Orphenadrine
- Procyclidine
- Trihexyphenidyl
In general, what are acetylcholine mimetics?
(Agonist)
drugs that mimic actions of ACh on nicotinic and muscarinic ACh receptors
Where are M1 receptors found, what G protein, and what mechanism is used?
- Nerves
- Gq
- IP3 DAG cascade
Where are M2 receptors found, what G protein, and what mechanism is used?
- Heart nerves smooth muscle
- Gi
- Inhibit cAMP production
- Activation of K channels
Where are M3 receptors found, what G protein, and what mechanism is used?
- Glands smooth muscle and endothelium
- Gq
- IP3 DAG cascade
- Memory trick: QIQI-Q mart store (M1 Q M2 i M3 Q M4i M5Q)
Where are M4 receptors found, what G protein, and what mechanism is used?
- CNS
- Gi
- Inhibit cAMP
Where are M5 receptors found, what G protein, and what mechanism is used?
- CNS
- Gq
- IP3 DAG cascade
Direct action of cholinergic agonist effects on the eye?
- contraction of iris sphincter and ciliary muscle resulting increase of aqueous humor outflow into canal of schlemm
Direct action of cholinergic agonist effects on the cardiovascular system?
- ALL cardiac actions are mediated by M2 mAChR resulting in decrase in periphreal vascular resistance
- Reduction in BP due to EDFR (NO) release causing vasodilation
Direct action of cholinergic agonist effects in the GIGU system?
- Causes an increase in glandular secretions
- M3 is needed for direct activation of sm mm contraction
- M2 reduces cAMP formation and causes contraction
- sphincter relaxation M3 via NO
What are the clinical uses of direct acting cholinergic agonists for glaucoma?
- Muscarinic stimulants cause contraction of ciliary body that stimulates aqueous humor and reduces intraocular pressure
- however they were replaced by topical Beta blockers and prostaglandin derivatives
How do we treat accommodative esotropia?
Cholinomimetic agonists
____ is the most widely used choline ester for GIGU disorders including post op ileus, megacolon, urinary retention, and esophageal reflux.
What category of drug does this fall under?
Bethanechol is the most widely used choline ester for GIGU disorders including post op ileus, megacolon, urinary retention, and esophageal reflux.
Direct acting cholinergic agonist
Before treating a patient with a GIGU disorder with Bethanechol, what must be done?
Make sure there are no obstructions as the drug may exacerbate the problem or case perforation
What two drugs are used to increase salivary secretion to treat Sjogren’s syndrome?
- Pilocarpine
- Cevimeline
- Both are a direct acting cholinergic agonist
What are major contraindications to the uses of MAChR agonists?
- Asthma
- hyperthyroidism
- coronary insufficiency
- acid peptic disease
Overdoses of Pilocarpine and choline esters has what symptoms? How do you treat the OD?
*bonus what is pilocarpine used to treat?
- cause N/V, diarrheae, urinary urgency, salivation, sweating, cutaneous vasodilation, bronchial constriction
- Blocked by antimuscarinic compounds such as Atropine
- Sjogren’s syndrome
What are the acute toxicities of nicotinic stimulants? How do you treat this?
- CNS stimulation such as convulsions progressing to coma/resp. arrest
- Muscle and respiratory paralysis
- Htn
- Cardiac arrhythmias
- Treat with atropine and diazepam for CNS stimulation
- *Neuromuscular blockade is NOT responsive to pharmacologic treatment
What does Acetylcholine do to the eye?
- Causes Mioisis (reduces pupil size)
What is Bethanechol used for? What type of drug is it? What AE can it cause?
- treat patients with urinary retention and heartburn
- mAChR agonsit
- Produce UTI if sphincter fails to relax
What is Carbachol used for?
- Nonspecific cholinergic agonist used for tx of glaucooma or produce miosis during surgery or ophthalmology exam
What is Cevimeline used for? What pathway is it metabolized?
- Oral tablet to treat xerostomia in Sjogren’s syndrome
- Metabolized via P450
What is Pilocarpine used for?
- Xerostomia in patients with Sjogren’s syndrome
- Head/neck cancer related to xerostomia
- Topical agent to cause Miosis during opthalmic procedures
- Topical for glaucoma
Varenicline use?
- FDA approved for smoking cessation (chantix)
- Partial agonist that binds with high affinity and selectivity to alpha 4 beta2 nicotinic AChR
Varenicline AE and warnings?
- Nausea, Neuropsychiatric sx
- If depression, suicidal ideation, agitation, or behavior changes occur stop taking
What are the three groups of cholinesterase inhibitors? How do they bind and is it reversible or irreversible?
- Alcohols: positive or neutral charge non covalent binding and reversible
- Carbamic acid esters: positive or neutral charge non covalent binding and reversible
- Organophosphates: neutral charge, lipid soluble, covalent and irreversible
What is the net cardiovascular effect of AChE inhibitors?
Bradycardia and an increase in BP
What are the therapeutic uses of AChE inhibitors?
- Glaucoma, accommodative esotropia
- Post op atony, neurogenic bladder
- Myasthenia gravis, curare induced neuromuscular paralysis
- Alzheimer disease
What does intoxication due to anticholinergic agents look like? How do you reverse it?
- Cutaneous vasodilation
- Anhidrosis
- Anhydrotic hyperthermia
- non-reactive mydriasis
- Delirium
- Hallucinations
- reduction or elimination of urination
Use physostigmine to reverse (crosses BBB)
What drugs do AChE inhibitors interact with?
- Nondepolarizing neuromuscular blocking agents
- Succinyolcholine
- Cholinergic agonists (direct acting)
- Beta blockers
- Systemic corticosteroids
How do you diagnose AChE poisoning? How do you reverse it?
- AChE activity in erythrocytes and plasma
- Atropine an mAChR antagonist
- to regenerate AChE at NMJ cholinesterase regenerator can be given
Organophosphate overexposure antidote?
- parenteral atropine, pralidoxime, and benzodiazepine
What receptors do Atropine target? (mAChR antagonist)
What tissues are most sensitive to least?
- antagonizes all 5 mAChR’s and doesnt differentiate
- salivary, bronchial, sweat glands, acid secretion gastric parietal cells
mAChR antagonist effects on respiratory system?
- bronchodilation & reduced secretion
mAChR antagonist effects on GI system?
- Decrease salivary secretion
- Gastric secretion is decreased slightly
- Pancreatic and intestinal secretions largely unaffected as under hormonal control not vagal
- Gastric emptying is prolonged
Why are mAChR antagonists good for urinary incontinence?
- relax smooth muscle of the ureters and bladder wall and slow voiding
What is atropine fever?
- occurs in kids with normal doses of antimuscarinic agents
- Atropine suppresses thermoregulatory sweating y inhibiting sympathetic cholinergic nerve fibers of sweat glands
What three CNS disorders can antimuscarinic agents be used in?
- Parkinsons
- Motion sickness
- Anesthesia
What antimuscarinic agent is used to treat COPD?
- Ipratropium, used an an inhalational agent (first line therapy)
- Newly approved, Tiotropium is used once daily for COPD
How are antimuscarinics used in GI disorders?
- Can be used in treatment of traveler’s diarrhea and other mild conditions of hypermotility
- Usually combined with an opioid antidiarrheal drug to prevent over use
What muscarinic receptor is targeted for reduction of urinary frequency?
- M3
- Darifenacin, Solifenacin, Tolterodine select for M3 & have a long half life and lower incidence of xerostomia and constipation
Contraindications of mAChR antagonists?
- glaucoma
- caution in elderly men with prostatic hyperplasia
- atropine should be avoided with acid peptic disease
MOA for ganglion blocking drugs?
- competitvely block ACh and similar agonists at the nAChR of parasymp and symp autonomic ganglia
How do ganglion blockers impact cardiovascular, GI, GU and eye?
- decrease contractility and moderate tachycardia of heart bc SA node is dominated by PSNS
- reduce secretion and inhibit motility of GI
- Urination hesitancy and retention, possible prevention of ejaculation and erection
- dilation of pupil bc PSNS usually dominates
What ganglion blocker is approved for treatment of HTN?
Mecamylamine
