Cholinergic drugs Flashcards
Acetylcholine (Miochol)
Direct-Acting cholinergic agonist
Bethanechol (Urecholine)
Direct-Acting muscarinic agonist
Pilocarpine (Isopto Crpine; Pilocar)
Direct-Acting muscarinic agonist
Cevimeline (Evoxac)
Direct-Acting muscarinic agonist
Nicotine
Direct-Acting nicotinic agonist
Varenicline (Chantrix)
Direct-Acting nicotinic agonist
Neostigmine (Prostigmin)
Cholinesterase Inhibitor. Carbamate. Quaternary amine. Not absorbed well orally and can’t cross the BBB.
Edrophonium (Tensilon)
Cholinesterase Inhibitor. Must be injected. No CNS penetration. Binds reversibly with a short duration of action (5-10 mins).
Physostigmine (Eserine)
Cholinesterase Inhibitor. Carbamate. Tertiary amine. Can cross the BBB.
Echothiophate
Cholinesterase Inhibitor. Organophosphate.
Donepezil (Aricept)
Cholinesterase Inhibitor
Organophosphate Pesticides
Cholinesterase Inhibitor. Lipid soluble. Phosphorylate AchE with a long lasting bond that ages and increases in strength (can be fatal).
Pralidoxime (2-PAM)
Cholinesterase Inhibitor.
Atropine (generic)
Cholinergic Antagonist
Scopolamine (TransDerm Scop)
Cholinergic Antagonist
Glycopyrrolate (Robunil)
Cholinergic Antagonist
Dicyclomine (Bentyl)
Cholinergic Antagonist
Tolterodine (Detrol)
Cholinergic Antagonist
Fesoterodine (Toviaz)
Cholinergic Antagonist
Darifenacin (Enablex)
Cholinergic Antagonist
Solifenacin (Vesicare)
Cholinergic Antagonist
Oxybutynin (Ditropan)
Cholinergic Antagonist
Ipratropium (Atrovent)
Cholinergic Antagonist
Diphenoxylate-atropine (Lomotil)
Cholinergic Antagonist
Tropicamide (Mydriacyl)
Cholinergic Antagonist
Homatropine (Isoptohomatropine )
Cholinergic Antagonist
d-Tubocurarine
Non-Depolarizing Neuromuscular Blockers
Vecuronium (Norcuron)
Non-Depolarizing Neuromuscular Blockers
Cisatracurium (Nimbex)
Non-Depolarizing Neuromuscular Blockers
Succinylcholine (Anectine)
Depolarizing Neuromuscular Blockers
Mecamylamine (Inversine)
Ganglion blocker
Hexamethonium
Ganglion blocker
Cholinergic stimulants
cholinergic agonists and cholinesterase inhibitors
Acetylcholine MOA
Stimulates both nicotinic and muscarinic receptors. Causes PNS stimulation. Metabolized rapidly. No clinical use.
Bethanechol (Urecholine) MOA
Stimulates muscarinic receptors especially in the urinary and GI tract. No CNS penetration.
Pilocarpine (Pilocar) MOA
Stimulates muscarinic receptors. Sweat and salivary glands are extremely sensitive.
Cevimeline MOA
Stimulates M3 receptors. Less side effects than Pilocarpine (Pilocar).
Nicotine MOA
Stimulates nicotinic receptors.
Varenicline MOA
Stimulates nicotinic receptors.
Varenicline Uses
Smoking cessation. Partial agonist for the nicotinic receptors in the brain to reduce cravings. Side effects include: nausea, vomiting, constipation, sleep distrubance, anxiety.
Muscarinic Agonists MOA
either interact with Gq or Gi
Muscarinic Agonists effect on the eye
Miosis. Contraction of the ciliary muscle for near vision. Decreases intraocular pressure.
Muscarinic Agonists effect on the heart
Decreases AV conduction. Inhibits NE release. Increases NO causing vasodilation. But overall very few cardiovascular effects.
Muscarinic Agonists effect on Respiratory system
Bronchoconstriction especially in asthmatics
Methacholine uses
Diagnosis of asthma
Muscarinic Agonists effect on GI system
Increased secretions and peristalsis. Sphincters are relaxed.
Muscarinic Agonists effect on Glands
Increases salivation, lacrimation and nasopharyngeal glands.
Muscarinic Agonists effect on GU
Stimulate detrusor muscle and relaxes the sphincter. Increases urge to void.
Muscarinic Agonists effect on Brain
M1 muscarinic receptors in the brain are involved in memory.
Use for pilocarpine
Glaucoma DOC. Dry mouth but can cause profound sweating.
Uses for Bethanechol
Stimulates peristalsis and treats urinary retention
Uses for cevimeline
Dry mouth. Selective for M3 receptors (doesn’t cause sweating).
Muscarinic Agonist Side effects
Nausea, vomiting, diarrhea, abdominal cramps, belching, salivation, sweating, cutaneous vasodilation, bronchoconstriction, bladder tightness, blurred vision.
Muscarinic Agonist contraindications
Peptic ulcers, coronary insufficiency, asthma.
Nicotinic Agonsits MOA
Increases permeability to calcium and sodium. Located in the autonomic ganglia, brain and skeletal muscle. Immediate action followed by rapid desensitization. .
Nicotinic Agonists Central effects
Increases alertness and attention. At higher doses and cause tremors, vomiting and increased respiration.
Nicotinic Agonists effect on the heart
Mostly sympathetic. Increased BP (reflex bradycardia), increased HR.
Nicotinic Agonists effect on GI
PNS. Vomiting, diarrhea and urination.
Nicotinic Agonists effect on the neuromuscular junction
Initially cause contraction then desensitize the NMJ leaded to weakness and flaccid paralysis.
Nicotinic Agonists Side Effects
Vomiting, convulsions, coma, respiratory arrest, paralysis, hypertension and cardiac arrhythmias.
Nicotine poisoning treatment
Atropine, anticonvulsants and mechanical respiration
Cholinesterase inhibitors MOA
Inhibit the breakdown of Ach in the synaptic cleft. Useful when cholinergic inputs have been decreased or there is a decreased responsiveness. Effect muscarinic and nicotinic receptors.
Cholinesterase inhibitors carbamates
Neostigmine and physostigmine. Covalently bind and last 30 mins- 6 hours.
2-PAM uses
Treats exposure to organophosphate pesticides to inhibit the “aging” process. Contraindicated for carbamate pesticides but still used in emergency protocol.
Cholinesterase inhibitors effect on the brain
Improves memory by stimulating M1 and Nn receptors. High doses can lead to desensitization (convulsions and respiratory arrest).
Cholinesterase inhibitors effect on the eye
PNS. Miosis. Ciliary muscle contraction for near vision. Decreased intraocular pressure.
Cholinesterase inhibitors effect on the respiratory system
PNS. Bronchoconstriction and increased mucus secretion.
Cholinesterase inhibitors effect on the GI tract
PNS. Increased perastilis and relaxation of the sphincters.
Cholinesterase inhibitors effect on the heart
PNS. Bradycardia, decreased contractility. Desensitization of ganglionic nicotinic receptors will decrease sympathetic stimulation.
Cholinesterase inhibitors effect on the NMJ
Low concentrations will increase the force of contraction at higher concentrations a neuromuscular blockade may occur due to desensitization.
Neostigmine uses
Myasthenia gravis because it may have a direct stimulatory effect on the NMJ. Also used to reverse NMJ blockade after surgery.
Physostigmine uses
Applied directly to the eye to treat glaucoma. Not used orally except to t treat muscarinic antagonist overdose.
Donepezil uses
Alzheimer’s disease. Absorbed into the CNS.
Edrophonium uses
diagnosis of myasthenia gravis (due to it’s short acting effects) and to determine the correct dosing of neostigmine. Can also reverse the NMJ blockade after surgery.
Echothiophate uses
Emergency treatment of closed angle glaucoma. Used along with pilocarpine.
Irreversible cholinesterase inhibitor toxicity symptoms
SLUDGE (salivation, lacrimation, urination, defecation, gastric distress, emesis). Miosis, sweating, bronchoconstriction, bradycardia, hypotension. Paralysis eventually occurs due to desensitization.
Irreversible cholinesterase inhibitor toxicity treatment
Atropine (until pupils dilate), 2-PAM (prevents enzyme aging), mechanical respiration.
Muscarinic antagonists MOA
Bind muscarinic receptors to block the effect of Ach. Antagonize the effects of the PNS.
Atropine on the CNS
Little effect but can cause confusion and coma at toxic levels.
Scopolamine on the CNS
Crosses the BBB at low doses. Causes drowsiness and amnesia. At toxic levels will cause agitation, hallucinations and coma.
Scopolamine uses
Prevents motion sickness. Administered as a patch.
Benztropine uses
Can restore the balance between Ach and DA which can occur due to antipsychotics and parkinson’s drugs.
Muscarinic antagonists effects on the eye
Mydriasis. Cycloplegia (loss of accomodation for near vision). Increased intraocular pressure.
Muscarinic antagonists contraindications
Narrow angle glaucoma, benign prostatic hyperplasia (urinary retention).
Tropicamide uses
Mydriasis and cycloplegia for eye examinations
Homatropine uses
Mydriasis and cycloplegia for eye examinations
Muscarinic antagonists side effects
Dry eyes, dry mouth, decreased bronchial secretions, tachycardia, mydriasis, cycloplegia, decreased GI motility, urinary retention, hot/dry skin.
Muscarinic antagonists effect on the heart
Blocks M2 receptors and cause tachycardia (especially in those with high vagal tone). Used to reverse the effect of reflex vagal discharge.
Glycopyrrolate uses
In surgery to prevent vagal responses due to visceral organs being handled. Also is a second line drug to decrease muscarinic side effects.
Atropine uses
Reverses bradycardia and increased BP produced by muscarinis agonists or cholinesterase inhibitors (organophosphate pesticides). Used in MI to decrease bradycardia and/or AV block.
Muscarinic antagonists Effect on respiratory system
Bronchodilation, inhibit secretions and decrease laryngospasm.
Ipratropium uses
Bronchodilation in COPD
Muscarinic antagonists effect on the GI tract
Inhibits motility and GI secretions
Dicyclomine uses
Antispasmodic for GI tract
Diphenoxylate-atropine (Lomotil) uses
antispasmodic to decrease diarrhea with a decrease opioid abuse potential.
Muscarinic antagonists effect on the GU system
relaxes bladder wall to reduce urge to void.
Tolterodine uses
M3 receptor antagonist that decreases overactive bladder and has little CNS side effects
Oxybutynin uses
Prevents bladder spasm during prostate surgery.
Muscarinic antagonists effect on glands
Decreases sweating (can lead to overheating) and decreases salivary secretion.
Atropine poisoning symptoms
“dry as a bone, blind as a bat, mad as a hatter, red as a beet” Dry mouth, mydriasis, tachycardia, hot/flushed skin, agitation and delirium. Atropine is in TCAs, antihistamines, phenothiazine antipsychotics, mushrooms and jimson weed. Also seen with scopolamine poisoning.
Atropine poisoning treatment
Cholinesterase inhibitor, diazepam (seizures), ice bags, ethanol.
Non-depolarizing NMJ blockers MOA
Highly ionized, so much be injected, have no CNS effects. Competitive antagonists. Also block pre junctional sodium channels which interferes with sodium mobilization of Ach. Adding more Ach will overcome the block. Can be reversed using cholinesterase inhibitors.
Non-depolarizing NMJ blockers order of paralysis
small muscle (eye) followed by limbs and larger muscles. The diaphragm and intercostal muscles are the last to be paralyzed. Recovery occurs in the opposite order.
Depolarizing NMJ blockers MOA
Succinylcholine. Results in initial stimulation and contraction followed by desensitization and blockade. Onset and recovery occur quickly. Hydrolyzed by plasma pseudocholinesterase (genetic differences) addition of cholinesterase inhibitor will delay recovery.
Succinylcholine side effects
Cardiac arrest: as sodium influx increases, potassium efflux increases and can cause arrest. Malignant hyperthermia: due to uncontrolled release of calcium from the SR causing muscle rigidity and high temperatures.
Succinylcholine contraindications
extensive soft tissue damage, rhabdomyolysis, SCI, muscular distrophy. Children younger than 8.
Succinylcholine uses
Quick procedures such as tracheotomy or intubation.
NMJ blockers uses
surgery, ventilation, orthopedics (bone setting), intubation, convulsions (ECT).
Ganglion blockers MOA
Non depolarizing competitive antagonist. Very rarely used because they block all ANS ganglion so inhibit PNS and SNS the effect depends on the predominant tone to that organ.
Ganglion blockers effect on the eye
Cycloplegia with Mydriasis
Ganglion blockers effect on vasculature
SNS tone. Vasodilation. Orthostatic hypotension.
Ganglion blockers effect on heart
Tachycardia and reduced contractility due to reduces vagal tone.
Ganglion blockers effect on GU
Urinary retention is common.
Ganglion blockers effect on sweating
reduced but temperature is maintained by vasodilation.
