Lectures 13 - 14: Cholinergic System 1 and 2 Flashcards
Treatment of anticholinesterase overdoses.
Atropine
Can cause prolonged/excessive skeletal muscle paralysis
Gentamycin (aka aminoglycosides)
Treatment of Parkinson’s disease and tardive dyskinesia.
Benztropine
Block of choline uptake
Hemicholinium
Is also an antiemetic.
Scopolamine (Hyoscine)
Oxime Compounds (cholinesterase re-activators)
Pralidoxime
Antispasmodic: relax GI tract and bladder.
Atropine
Direct acting cholinergic agonists
Pilocarpine
High dose: excitation effect such as restlessness, disorientation and hallucinations.
Atropine
Actions of Muscarinic Antagonists (atropine, Benztropine, Ipratropium, Scopolamine (Hyoscine))
-Peripheral
● Block secretions (saliva, bronchial, GIT, etc.).
● Dilates pupil (mydriasis).
● Mydriasis can precipitate narrow angle glaucoma in the predisposed.
● Relaxes ciliary muscle to cause cycloplegia (lens fixed for far vision).
● Tachycardia (block of vagal influence).
● Blocks GIT motility (constipation).
● Relaxes bronchial smooth muscles.
Choline esters (longer duration than Ach)
Bethanechol
Blocks the rate-limiting step (uptake of choline into the neuron)
Hemicholinium
Muscarinic antagonists (no action on nicotinic receptors)
Atropine
Blocks nicotinic receptors on skeletal muscles
Gentamycin (aka aminoglycosides)
Antisecretory: block secretions in the upper and lower respiratory tracts prior to surgery.
Atropine
Long-acting reversible anticholinesterases
Neostigmine, Physostigmine
Block of Ach storage
Vesamicol
Induce reactivation of enzymes inactivated by phosphorylation.
Pralidoxime
Adverse Effects of Muscarinic Agonists (Acetylcholine, Pilocarpine, Bethanechol)
-Hypotension:
● Due to vasodilation :
Caused by the muscarinic receptor mediated release of NO from endothelium.
● Also due to decreased cardiac output:
due to decreased heart rate and force of contraction.
● Reflex tachycardia often overrides bradycardia.
-Bronchospasm:
● No significance in normal individuals, but may precipitate asthma in asthmatics.
-Others:
● Nausea, vomiting, GIT cramps, and diarrhea.
Actions of Acetylcholine
-Heart: decreases heart rate and cardiac output.
-Blood vessels: vasodilation and decrease in blood
pressure.
-GI tract: increases salivary secretion and stimulates
intestinal secretion and motility.
-Lungs: enhanced bronchiolar secretions and
bronchoconstriction.
-Genitourinary tract: increased tone of the detrusor
urinae muscle causing the expulsion of urine.
-Eye: muscle contraction for near vision and pupil
constriction (miosis).
Irreversible (Long-acting) Anticholinesterases:
Organophosphates
War gases and pesticides.
Ecothiophate
Treatment of paralytic ileus and bladder atony
Neostigmine
Block Ach release
Botulinum toxin
Eye: persistent mydriasis
Atropine
Muscarinic Antagonists
Ipratropium, Scopolamine (Hyoscine)
Increase Ach release
Latrotoxin
Therapeutic uses of Scopolamine (Hyoscine)
- Treatment of motion sickness.
- Blocking short term memory and is used as an adjunct with anesthesia.
Block of post-synaptic Ach receptors
Atropine
Has no CNS effect at low doses.
Atropine
Treatment of Alzheimer’s disease
Physostigmine
Toxicity of Anticholinesterases (common with organophosphates)
(Ecothiophate, Neostigmine, Physostigmine):
-Acute
● Vomiting, colic and diarrhea.
● Constricted pupils that are unresponsive to light.
● Sweating and salivation.
● Bronchoconstriction.
● Bradycardia
● Agitation, confusion and respiratory depression. (Especially, physostigmine and organophosphates)
-Chronic
● Demyelination: sensory loss and respiratory paralysis
Treatment of GIT cramps.
Scopolamine (Hyoscine)
Treatment of Organophosphate Poisoning
Pralidoxime
Anticholinesterases (Indirect-acting cholinergic agonists)
Ecothiophate, Neostigmine, Physostigmine
Naturally occurring alkaloids (longer duration than Ach)
Pilocarpine
Treatment of asthma and chronic bronchitis.
Ipratropium
Greater action on the CNS than atropine and a longer duration of action.
Scopolamine (Hyoscine)
Plant product
Scopolamine (Hyoscine)
Treatment of myasthenia gravis
Neostigmine
Contraindications of Muscarinic Agonists (Acetylcholine, Pilocarpine, Bethanechol)
- Coronary insufficiency (worsened by hypotension).
- Hyperthyroidism (may precipitate atrial arrhythmias).
- Peptic ulcer.
- Asthma.
Used for glaucoma
Pilocarpine
Treatment of atropine poisoning
Physostigmine
Direct acting cholinergic agonists
Bethanechol
Treatment of glaucoma
Ecothiophate, Physostigmine
Selective muscarinic receptors
Pilocarpine, Bethanechol
Adverse Effects of Muscarinic Antagonists (Atropine, Benztropine, Ipratropium, Scopolamine (Hyoscine) )
- Urinary retention.
- Dry mouth.
- Blurred vision.
- Tachycardia.
- Constipation.
- Confusion.
- Myadriasis
- contraindicated in people who are predisposed to glaucoma.
Used for paralytic ileus and urinary retention
Bethanechol
Reversal of competitive neuromuscular block
Neostigmine
Is a depressant at therapeutic dose.
-Sedation, drowsiness, and amnesia.
Scopolamine (Hyoscine)
Effects of Anticholinesterases (Ecothiophate, Neostigmine, Physostigmine)
-Peripheral ● Enhanced neuromuscular transmission. ● Increased GIT motility/bladder contraction. ● Bradycardia. ● Pupil constriction. ● Bronchoconstriction. -Central ● General CNS stimulation (agitation and convulsion) followed by respiratory depression (death).
Useful in Parkinsonism
Benztropine
Can cause prolonged/excessive skeletal muscle paralysis
Gentamycin (aka aminoglycosides)
Found in spider venom
Latrotoxin
Alkaloid found in Atropa belladonna
Atropine
Quaternary nitrogen compound
Ipratropium
Clinical Uses of Muscarinic Antagonists
Atropine, Scopolamine (Hyoscine)
- Surgery: as pre-anesthetic to inhibit salivary and bronchial secretions.
- Antidote: in treatment of anticholinesterase poisoning.
- Treatment of GIT cramps.
- Treatment of Parkinson’s disease and tardive dyskinesia.
- Treatment of sinus bradycardia after MI.
