Term
| What are the different classes of cholinomimetic/parasympathomimetic drugs? |
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Definition
| Direct acting (cholinergic agonists) and indirect acting (acetylcholinesterase inhibitors) |
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Term
| What are the different classes of cholinergic antagonist/parasympatholytic drugs? |
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Definition
| Muscarinic antagonists and nicotinic antagonists |
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Term
| What choline esters act as cholinergic agonists? |
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Definition
| Acetylcholine, methacholine, carbachol, bethanechol |
|
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Term
| What natural alkaloids at as cholinergic agonists? |
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Definition
| Muscarine and pilocarpine |
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Term
| What neurotransmitters/drugs are hydrolyzed by acetylcholinesterase? |
|
Definition
| Acetylcholine and methacholine |
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Term
| Which cholinergic drugs have receptor specificity for both muscarinic and nicotinic receptors? |
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Definition
| Acetylcholine, methacholine, and carbachol. Others are only specific for muscarinic receptors |
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Term
| What are the clinical uses of Bethanechol (Duvoid)? |
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Definition
| Disorders associated with decreased parasympathetic tone, postoperative or postpartum urinary retention and/or inadequate emptying of bladder, postoperative abdominal distention of GI atony or paresis. Acts at muscarinic receptors to contract detrusor muscle or increase GI motility |
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Term
| What are the clinical uses of pilocarpine (ocusert, pilocar) |
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Definition
| Topical formulations to reduce intraocular pressure in certain glaucomas, treat dry mouth (xerostomia), or to reverse the effects of atropine (used to dilate pupil) |
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Term
| How does pilocarpine reduce intraocular pressure? |
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Definition
| Improves drainage by contracting the sphincter pupillae (M3 receptor) and reducing angle block (however, crossing the conjunctiva may lead to systemic effects) |
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Term
| How does pilocarpine reduce xerostamia (dry mouth)? |
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Definition
| M3 receptors on salivary gland |
|
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Term
| What are the clinical uses of cevimeline (Exovac) |
|
Definition
| Treats xerostamia following head irradiation or xerostamia associated with Sjogren's syndrome |
|
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Term
| What is the mechanism of action of cevimeline? |
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Definition
| Acts as M3 receptor specific agonist, selective for salivary and lacrimal glands, fewer side effects than pilocarpine |
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Term
| What are some side effects of muscarinic agonists? |
|
Definition
| Diarrhea, diaphoresis, miosis, nausea, salivation, urinary urgency, CNS disturbances with drugs that cross the blood brain barrier such as pilocarpine |
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Term
| What are some contraindications for use of muscarinic agonists? |
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Definition
| Patients with asthma due to induced bronchoconstriction and increased mucous secretions, patients with heart disease due to slowed conduction of cardiac APs through the AV node and potential hypotension and reduced coronary blood flow if given intravenously |
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Term
| What is the difference between real and pseudo cholinesterase? |
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Definition
| Acetycholinesterase (real) resides in the synapse and degrades Ach, plasma cholinesterase and butyryl cholinesterase (pseudo) circulate and are non-specific esterases that removes circulating Ach (reason why Ach cannot be used pharmacologically) |
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Term
| What are the potential sites of action for acetylcholinesterase inhibitors? |
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Definition
| All effector organs innervated by parasympathetics such as the eye, GI, urinary bladder, the nueromuscular junction, all autonomic ganglia |
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|
Term
| What are the short lasting (~10 min) reversible AChE inhibitors? |
|
Definition
| Erdophonium (phonies can't make it!) |
|
|
Term
| What are the intermediate lasting reversible AChE inhibitors? |
|
Definition
| PHYSOSTIGMINE, NEOSTIGMINE, PYRIDOSTIGMINE, RIVASTIGMINE, GALANTAMINE, AMBENONIUM, DONEPEZIL, TACRINE |
|
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Term
| What are the irreversible, long lasting AChE inhibitors? |
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Definition
| Synthetic organophosphates - ecothiophate and isofluorophate - and nerve gasses such as sarin and soman |
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Term
| Which AChE inhibitors are used to treat myasthenia gravis? |
|
Definition
| Edrophonium (diagnostic test only), Neostigmine, Pyridostigmine, Ambenonium |
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Term
| Which AChE inhibitor is used to treat hypertonia of the bladder and GI? |
|
Definition
|
|
Term
| Which AChE inhibitors are used to treat glaucoma? |
|
Definition
| Physostigmine and ecothiophate |
|
|
Term
| What AChE inhibitors are used to treat alzheimer's disease? |
|
Definition
| Donepezil, rivastigmine, tacrine, and galantamine |
|
|
Term
| What is the cause for deficient Ach receptors at the neuromuscular junction in cases of myasthenia gravis? |
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Definition
| Auto-immune antibodies mistakenly destroy receptors |
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|
Term
| What are the clinical characteristics of neostigmine? |
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Definition
| Cannot enter the brain, used to treat myasthenia gravis, effect at NMJ is greater than that of physostigmine, can have general cholinergic effects and drop blood pressure, overdose can cause cholinergic crisis and muscle paralysis |
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|
Term
| What are the clinical characteristics of physostigamine? |
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Definition
| Plant alkaloid that can cross the BBB, potentiates Ach effects at muscarinic and nicotinic receptors of the ANS and nicotinic receptors at the NMJ. Used as an antidote for atropine and other anticholinergic drugs, reverses CNS side effects, reduces intraoccular pressure much like pilocarpine |
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|
Term
| What are some adverse effects of physostigamine? |
|
Definition
| Diarrhea, nausea, sweating, miosis, urinary urgency, can cause convulsions, bradycardia, and hypotension at high doses |
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|
Term
| What is organophosphate poisoning? |
|
Definition
| Found in many insecticides and pesticides, exhibits symptoms involving activation of nicotinic and muscarinic receptors due to long acting AChE inhibitors: SLUD = Salivation, Lacrimation, Urination, Defecation |
|
|
Term
| What are organophosphates? |
|
Definition
| Long acting AChE inhibitors, inactivates Ach permanently via an "aging" process |
|
|
Term
| How is organophosphate nerve gas poisoning treated? |
|
Definition
| Pyridostigmine used prophylactively, high doses of muscarinic antagonist atropine or scopolamine followed by an injection of pralidoxime (reactivates Ach but is ineffective once "aging" begins) can also treat poisoning |
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|
Term
| Which belladona alkaloids are muscarinic receptor antagonists? |
|
Definition
|
|
Term
| Which synthetic and semi-synthetic muscarinic receptor antagonists should you know? |
|
Definition
| Ipratropium, triotropium, and tolterodine |
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|
Term
| What are the clinical uses of atropine? |
|
Definition
| Reverses severe bradycardia, produces mydriasis and cycloplegia for eye exams, antispasmodic, represses respiratory secretions prior to surgery, treats organophosphate poisoning and mushroom poisoning |
|
|
Term
| What is the mechanism of action of atropine? |
|
Definition
| Belladonna alkaloid is a tertiary amine that can cross the BBB, is a non-selective muscarinic antagonist, blocks all parasympathetic effects in the eye (causes mydriasis and loss of accommodation), reduces GI motility, and reduces salivary/lacrimal secretions |
|
|
Term
| What are some side effects of atropine? |
|
Definition
| Dry mouth, constipation, dilated pupils (mydriasis), blurred vision, hot/dry flushed skin, tachycardia, fever, CNS disturbances |
|
|
Term
| What are the clinical uses of scopolamine? |
|
Definition
| Prophylactic for motion sickness, adjunct drug in anesthesia to produce sedation and amnesia, has ophthalmic use. Crosses BBB much more than atropine |
|
|
Term
| What are some side effects of scopolamine? |
|
Definition
| Similar to what is seen with atropine except CNS effects are more prominent |
|
|
Term
| What are the clinical uses of ipratrapopium bromide? |
|
Definition
| Used in asthma and chronic obstructive pulmonary disorder (COPD)to cause bronchodilation as an adjunct to albuterol (can also be a substitute for people unable to take adrenergic agonists) |
|
|
Term
| What is the mechanism of action of ipratrapopium? |
|
Definition
| Blocks muscarinic receptors, reduces bronchoconstriction, minor mucocilliary effect and CNS effects |
|
|
Term
| What are the clinical uses of tiotropium bromide (SPIRIVA)? |
|
Definition
| Used to treat COPD and asthma, very selective at the bronchioles and greater affinity for M3 over M2 receptors |
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|
Term
| What are the clinical uses of tolterodine (DETROL)? |
|
Definition
| Treats overactive bladder by blocking M3 receptors on detrusor muscles, reducing parasympathetic mediated contraction. Also blocks parasympathetic tone to the sphincter and prevents leaks |
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|
Term
| What other drugs are M3 antagonists similar to tolterodine? |
|
Definition
| Fesoterodine (Toviaz), Solifenacin (Vesicare), Darifenacin (Enablex), Oxybutynin (Ditropan) |
|
|
Term
| What are some contraindications for using M3 antagonists? |
|
Definition
| Not appropriate for individuals with urinary retention problems |
|
|
Term
| What are some contraindications for using muscarinic antagonists? |
|
Definition
| Glaucoma, benign prostatic hyperplasia or any urinary condition or kidney condition with urinary problems, myasthenia gravis, excessive constipation |
|
|
Term
| What is the function of ganglionic blockers? Examples? |
|
Definition
| Blocks ganglionic Nn receptors, very few are used clinically, ex. Hexamethonium bromide and trimethopham |
|
|
Term
| What is the function of neuromuscular junction blockers? |
|
Definition
| Blocks cholinergic transmission at motor end plate between somatic nerve and nicotinic receptors, used as muscle relaxants |
|
|
Term
| What non-polarizing NMJ blocker should you know? |
|
Definition
| Atracurium (all of them end with "curium") |
|
|
Term
| What NMJ blocker is depolarizing? |
|
Definition
|
|
Term
| What is the function of non-polarizing NMJ blockers? |
|
Definition
| Blocks nicotinic receptors at the NMJ, prevents action of Ach, can be overcome with increasing Ach at the synapse (w/ AChE inhibitor) |
|
|
Term
| What makes up succinyl choline? How is it metabolized? |
|
Definition
| Two Ach molecules linked end to end, metabolized by plasma cholinesterase but not by AChE, has rapid onset and short duration of action |
|
|
Term
| What is the phase 1 in the mechanism of action by depolarizing NMJ blockers (succinyl choline)? |
|
Definition
| Acts as an agonist at nicotinic receptors, initially depolarizes muscle membrane which is then removed, causing muscle paralysis. AChE inhibitors worsen initial phase |
|
|
Term
| What is phase 2 in the mechanism of action by depolarizing NMJ blockers (succinyl choline)? |
|
Definition
| Membrane becomes repolarized but is then resistant to further activation by Ach in the NMJ due to being resistant to hydrolysis by AChE, remains in the junction longer, high doses can cause phase II blockase |
|
|
Term
| What are some side effects of succinyl choline? |
|
Definition
| Muscle pain postoperatively possibly due to fasciculations, hyperkalemia, blockage of ganglionic nicotinic recpeotrs may also decreased heart rate and increased intraocular pressure, may cause malignant hyperthermia (treat with Dantrolene) |
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