Lecture

• Acetyl CoA + Choline=ACH
• Outside the nerve ending, ACH gets inactivated by ACHE(acetylcholinesterase)
• Muscarinic receptors are in the PSNS and target smooth and cardiac muscles
• Nn receptors are in the PSNS and the SNS ganglions and they target smooth and cardiac muscles
• Nm receptors are at the NMJ(neuromuscular junction) and they target skeletal muscles; additionally the somatic nervous system its part of, doesn't have any ganglions
• There are 2 types of parasympathomimetics: direct and indirect
• ACH is not useful as a drug because it has a very short duration of action. ACHE metabolizes it very quickly
• Direct acting cholinergic drugs are rarely used because of their short DOA. They're also mostly used locally and have negligible impact on the heart and respiratory smooth muscles
• Direct acting cholinergic drugs increase GI motility and secretions, increase urinary tract function and cause miosis. They're primarily used for glaucoma.
• Acetylcholine (Miochol-E) is used for miosis in ophthalmology
• Direct acting cholinergic drugs are: acetylcholine(Miochol-E), bethanechol(Urecholine), carbachol(Isopto carbachol) and pilocarpine(Isopto carpine)
• bethanechol(Urecholine) is used for urinary retention
• carbachol(Isopto carbachol) and pilocarpine(Isopto carpine) are used for glaucoma
• Indirect acting cholinergic drugs bind to ACHE and split off into: reversible and irreversible
• Reversible ACHE inhibitors have a short duration and are primarily used for Myasthenia gravis and Alzheimer's
• Irreversible ACHE inhibitors have a long duration and are used from chemical warfare and glaucoma at low doses
• Irreversible ACHE inhibitors are derived from organophosphates
• Myasthenia gravis occurs when an autoimmune rxn attacks Nm receptors at the NMJ. Starts off as mild as eyelid droop to difficulty breathing.
• An irreversible ACHE inhibitor is echothiopohate(phospholine)
• echothiophate(phospholine) is an irreversible ACHE inhibitor is used at low doses to treat glaucoma
• Reversible ACHE inhibitors are: Ambenonium (Mytelase), pyridostigimine(Mestinon), galantamine(Reminyl),donepezil(Aricept), rivastigmine(Exelon) and physostigmine
• Ambenonium(mytelase) and the pyridostigmine(mestinon) are used for Myasthenia gravis.
• Galantamine(reminyl), donepezil(Aricept) and rivastigmine(Exelon) are used to treat alzheimer's
• physostigmine is used to treat glaucoma and its also an antidote to anticholinergic toxicity
• Anticholinergic drugs bind to muscarinic receptors and block ACH. They decrease activity in the vagus nerve in the heart.
• Anticholinergic drugs inhibit secretions and bronchoconstriction while decreasing motility of the GI tract
• Anticholinergic drugs are used for bradycardia, asthma, COPD, IBS and perioperative treatment to inhibit secretion
• Anticholinergic drugs are: atropine, ipratropium(atrovent) and tiotropium(Spiriva)
• Atropine is used for bradycardia and to treat cholinergic toxicity
• Ipratropium(Atrovent) and tiotropium(Spiriva) are both used for bronchodilation, asthma and COPD
• Glycopyrrolate is the new drug coming to PCPs in palliative care. It acts to reduce secretions and is an anticholinergic drug
• Atropine is derived from the belladonna plant
• Cholinergic toxicity is excessive activation of the PSNS. S/S are diarrhea, diaphoresis, blurred vision, tremors, bradycardia, bronchoconstriction and hypotension.(All wet symptoms)
• In a cholinergic crisis, skeletal muscles are paralyzed
• SLUDGE acronym for s/s of cholinergic crisis: Salivation, Lacrimation, Urination, Diarrhea, GI issues and Emesis
• Treatment of cholinergic toxicity includes Atropine and Pralidoxime(2-PAM).
• Pralidoxime(2-PAM) actually regenerates ACHE and is slower acting. It is used by CBRNE medics
• Atropine should be used together with Pralidoxime(2-PAM)
• Anticholinergic toxicity is excessive blockage of the PSNS. S/S are dry mouth, urinary retention, visual disturbances, constipation, flushing and lack of sweat
• The treatment for anticholinergic toxicity is inducing vomitting, gastric lavage and physostigimine administered via IV