Kaplan Section 2 Chapter 2 Cholinergic Pharmacology
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| How does choline enter the presynaptic nerve ending? | active transport linked to Na+ pump
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| Hemicholinium | drug that inhibits choline uptake into the presynaptic nerve ending at the Na+ pump
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| What is ChAT (choline acetyl transferase)? | choline + acetyl CoA ---(ChAT)---> Acetylcholine
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| What does the influx of Ca2+ into the presynaptic nerve ending do? | causes fusion of the synaptic vesicle containing Ach with the presynaptic membrane --> exocytosis of Ach
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| What is synaptobrevin? | membrane protein on the presynaptic nerve ending that interacts with botulinum toxin to inhibit the release of Ach
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| Botulinum toxin | interacts with synaptobrevin on the presynaptic nerve ending to prevent Ach release
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| Acetylcholine esterase (AchE) | Breaks down Ach in the nerve junction (Ach ---(AchE)---> acetate + choline)
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| Name the nicotinic cholinomimetics. | Drug that mimics Ach at the nicotinic receptor: nicotine.
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| Name the muscarinic cholinomimetics. (also called muscarinic agonists or parasympathomimetics) | BETH MET a CARB-eating muscle man named PILO. Bethanechol, Methacholine, Carbachol, Pilocarpine.
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| As a group, what do the muscarinic cholinomimetics do? | Decrease CV function (rest), increase secretions and smooth muscle contraction (poop). All M receptor activators are non-specific for M1 M2 M3.
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| Name the Nm and Nn nicotinic cholinoceptor blockers | NaM SPAT on NaN's HEXAgon in MECCA. Nm: Mivacurium, Succinyl choline (depolarizing), Pancuronium, Atracurium, Turbocurarine. Nn: Hexamethonium, Mecamylamine.
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| Name the muscarinic cholinoceptor blockers | THIMBAGS: Tropicamide, Homatropine, Ipratropium, Methscopolamine, Benztropine, Atropine, Glycopyrrolate, Scopolamine.
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| Name the irreversible inhibitors of AchE | I can't reverse what I do if I drink PEMS on the Thames. Parathion, Echothiophate, Malathion, Sarin (nerve gas).
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| Name the reversible inhibitors of AchE | I'd like to reverse the PPENDing charges against AchEw. Pyridostigmine, Physostigmine, Edrophonium, Neostigmine, Donepezil, Tacrine.
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| What happens when you stimulate Nn or Nm receptors? | opening of Na/K channels
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| Bethanechol | Muscarinic agonist, AchE resistant. Prescribed to patients with ileus or urinary retention to stimulate bowel movements.
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| Methacholine | Muscarinic agonist, susceptible to hydrolysis by AchE. Dx bronchial hyperreactivity, which occurs in asthma. Methacholine challenge test: pt breathes in nebulized methacholine --> bronchoconstriction --> pts with asthma react to lower levels of drug
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| Carbachol | Muscarinic agonist, AchE resistant. Prescribed to patients with glaucoma --> miosis and increased aqueous humor outflow --> relieve pressure in the eye.
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| Pilocarpine | M agonist, AchE resistant. 1. Rx for pts with glaucoma --> miosis & increased aqueous humor outflow --> relieve pressure in the eye. 2. Rx for pts with xerostomia (dry mouth) --> secretion of saliva and sweat. 3. stimulate sweat glands in CF sweat test
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| Physostigmine | Reversible AchE inhibitor (indirect cholinomimetic). INTERmediate acting, crosses BBB. Treatment for glaucoma; antidote in atropine OD. Big physical man with girl OD'ed on atropine on one shoulder and a big eye on the other. Of intermed intelligence.
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| Pyridostigmine | Reversible AchE inhibitor. INTERmediate acting, does NOT cross BBB. Treatment for ileus/urinary retention (like bethanechol); treatment for MG (combats Ach receptor block that leads to muscle weakness), reversal of non-depolarizing neuromuscular block
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| Edrophonium | Reversible AchE inhibitor. Short acting. Used to diagnose myasthenia gravis (MG) and distinguish between MG (not enough Ach stimulation) and cholinergic crisis (too much Ach). Edrophonium makes MG pts better, while making pts wi CholCrisis worse.
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| Neostigmine | Reversible AchE inhibitor. INTERmediate acting, does NOT cross BBB. Treatment for ileus/urinary retention (like bethanechol); treatment for MG(combats Ach receptor block that leads to muscle weakness), reversal of non-depolarizing neuromuscular blockers
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| Donepezil | Reversible AchE inhibitor (indirect cholinomimetic). Lipid soluble, crosses BBB. Treatment for Alzheimer dz. Like Tacrine.
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| Tacrine | Reversible AchE inhibitor (indirect cholinomimetic). Lipid soluble, crosses BBB. Treatment for Alzheimer dz. Like Donepezil.
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| What is myasthenia gravis? | autoimmune disorder --> abs block Ach receptors at neuromuscular junction --> block effects of Ach --> serious muscle weakness
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| What happens if you get AchE inhibitor poisoning? | DUMBBELSS: Diarrhea (NVD), Urination, Miosis, Bradycardia, Bronchoconstriction, Excitation (muscle and CNS), Lacrimation, Salivation, Sweating.
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| How do you treat AchE inhibitor poisoning? | Atropine (M antagonist) plus Pralidoxime (unphosphorylates the AchE--phosphorylated by the organophosphate)
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| Does atropine enter CNS? | Yes
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| What is the mechanism of atropine? | Muscarinic antagonist
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| What are the effects of atropine? | Dry as a bone (decreased secretions), red as a beet (urinary retention and constipation, tachycardia, vasodilation), hot as a pistol(hyperthermia), blind as a bat (mydriasis and cycloplegia), mad as a hatter (behavioral excitation and hallucinations)
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| What is cycloplegia? | paralysis of the iris of the eye -- ciliary muscle, resulting in a loss of accommodation (loss of near vision)
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| What is atropine used for? | 1. Treat OD of AchE inhibitors (treat DUMBBELSS) 2. antidiarrheal (causes constipation) 3. antisecretory (makes pt dry as a bone) 4. antispasmodic (causes sedation) 5. paralyzes iris muscle and causes cycloplegia and mydriasis
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| Tropicamide | Muscarinic antagonist. Causes mydriasis and cycloplegia. Used to prepare eye for ophthalmic procedures. Pour Tropicana OJ on your eye.
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| Ipratropium | I pray for those with asthma and COPD. Inhaled in asthma and COPD. Blocks M receptors in the lung --> block bronchoconstriction and mucous secretion. Doesn't cross BBB, doesn't diffuse into the blood, no change in mucous viscosity.
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| Scopolamine | Muscarinic antagonist. Anti-motion sickness; causes sedation and short-term memory block. If you're motion sick, you want to sleep and not remember the nauseating experience.
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| Homatropine | Muscarinic antagonist. Causes mydriasis (dilate the pupil) and cycloplegia (paralyze accommodation). One-eyed gay guy.
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| Methscopolamine | Muscarinic antagonist. 1. Treat motion sickness. 2. Like glycopyrrolate: reduce stomach acid secretion --> treat ulcers; reduce GI/GU spasms; reduce salivation. He's taking meth (addicted=salivating for it) and worried about getting caught (ulcers/spams)
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| Benztropine | Muscarinic antagonist. Lipid soluble --> enters CNS. Treatment for Parkinson's (reduces tremors) and dystonia (abnl muscle contraction). Guy riding in BENZ with Parkinson's and dystonia.
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| Glycopyrrolate | Muscarinic antagonist. Like methscopolamine. Eat lots of sugar so salivate for it and secrete gastric acids. Reduce salivary and gastric secretions -- used as a pre-op drug or anti-ulcer drug. No CNS entry.
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| For organs that have both SANS and PANS receptors, where is SANS dominant and where PANS dominant? | PANS: SA and AV nodes, pupil, GI/GU muscles & sphincters. SANS: vascular tone and thermoregulatory sweat glands.
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| What happens to SANS innervation when Nn blocker is used? | (blocking SANS in vessels and sweat glands) Vasodilation, hypotension, decreased venous return, decreased cardiac output, anhydrosis
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| What happens to PANS innervation when Nn blocker is used? | (blocking PANS in heart, eyes, and GI/GU) Tachycardia, mydriasis and cycloplegia, constipation and urinary retention, xerostomia (dry mouth)
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| Hexamethonium | Nn antagonist. Block reflex vagal responses.
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| Mecamylamine | Nn antagonist. Block vagal responses. Used in severe HTN, Tourette's, and smoking cessation.
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| What types of drugs are these: tubocurarine, atracurium, pancuronium | Nm blockers, nondepolarizing muscle relaxants
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| What type of drug is succinylcholine? | Nm block, depolarizing, muscle relaxant
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| Open angle glaucoma | Chronic; increased intraocular pressure because of decreased reabsorption of aqueous humor --> painless visual loss. Balance between fluid formation and fluid drainage from the eye.
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| Angle closure glaucoma | Acute (painful) or chronic (genetic); increased intraocular pressure because of blockage of the canal of Schlemm.
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