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62 Cards in this Set
- Front
- Back
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What do we call substances that "mimic" the effects of parasympathetic nerve discharge? |
cholinomimetics |
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What does the name cholinergic agonist mean? |
have an ability to activate cholinergic receptors |
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What are the two categories of cholinergic agonists? |
1. direct acting
2. indirect acting |
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What is the action of direct acting cholinergic agonists? |
bind to and directly activate muscarinic or nicotinic receptors
(acts/looks like endogenous Ach) |
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How do indirect acting cholinergic agonists produce their primary effects? |
by inhibiting acetylcholinesterase thus increasing synaptic levels of ACh |
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What are the 8 direct acting cholinergic agonists to know? |
1. Acetylcholine 2. Bethanechol 3. Methacholine 4. Carbachol
5. Pilocarpine 6. Muscarine 7. Nicotine 8. Cevimeline |
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What are the two chemical structure groups of direct acting cholinergic agonists? |
esters & alkaloids |
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What are the direct acting cholinergic agonist esters? |
1. acetycholine 2. methacholine 3. carbachol 4. bethanechol |
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How would you further describe the structure of the esters, and what is the implication of that structure? |
-all are permanently charged quaternary amines
-relatively insoluble in lipids |
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What are the direct acting cholinergic agonist alkaloids? |
1. muscarine 2. pilocarpine 3. nicotine |
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How would you further describe the structure of the alkaloids? |
tertiary amines except muscarine, which is a quaternary amine |
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What is important about the fact that esters are relatively insoluble in lipids? |
poorly absorbed and poorly distributed into CNS due to hydrophilicity (charged) |
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What happens to esters following oral administration? |
all are hydrolyzed in GI tract, but do not cross membranes well - diminished effectiveness |
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How is it best to use esters? |
SC |
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What is the susceptibility of esters to hydrolysis by cholinesterase in the body? |
varies - bethanechol and carbachol are least sensitive |
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What is the affinity of esters for muscarinic vs. nicotinic receptors? |
varies |
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Which two esters have virtually no activity at the nicotinic receptor? |
methacholine and bethanechol |
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How well are alkaloids absorbed? |
-well absorbed from most sites of administration
-EXCEPT muscarine, which has limited GI absorption (a quaternary amine) |
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How are alkaloids excreted? |
chiefly by the kidneys |
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Which alkaloid is a particular concern and why? |
nicotine for nicotine poisoning
(lethal at 40 mg - calls to poison centers increased 3x to 15x in 2013) |
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What is Acetylcholine? |
*endogenous NT with no therapeutic values*
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selectivity of Bethanecol |
relatively selective for muscarinic receptors involved in GI tract and bladder control
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specificity of ACh |
not specific (activates both nicotinic and muscarinic receptors equally) |
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hydrolysis of ACh |
readily hydrolyzed by AchE (~5-20 s effect after large IV bolus) |
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sympathetic/parasympathetic activation of ACh |
activates both systems non-discriminately |
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specificity of Bethanecol |
specific (parasympathomimetic) for muscarinic receptors, with less activity at nicotine receptor |
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hydrolysis of Bethanecol |
not readily hydrolyzed by AChE compared to ACh |
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usage of Bethanecol |
promotes bladder/GI motility in:
1. atony 2. neurogenic bladder 3. paralytic ileus 4. gastroesophageal reflux disease |
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movement of Bethanecol in CNS |
does NOT cross BBB |
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side effects of Bethanecol |
1. sweating 2. urinary urgency 3. diarrhea 4. decreased BP and HR 5. nausea 6. abdominal pain 7. bronchoconstriction and spasms (must be careful with asthma patients) 8. increased salivation (sialogogue) 9. increased lacrimation |
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specificity of Methacholine |
more specific for muscarinic receptors |
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hydrolysis of Methacholine |
less hydrolyzed by AChE compared to ACh |
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usage of Methacholine |
methacholine challenge test (MCT)
-bronchoprovocation test for asthma in patients with normal spirometric readings but complain of chest tightness and difficulty breathing |
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selectivity of Carbachol |
relatively selective for nicotinic receptors,
but still has significant activity at muscarinic receptors |
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hydrolysis of Carbachol |
not hydrolyzed by AChE |
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usage of Carbachol |
1. promotes miosis of iris (constrict sphincter); prior to ocular surgery
2. topical application (glaucoma - open angle) |
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What are the first lines of defense we use against glaucoma and why? |
1. alpha-2 agonists (aproclonidine)
2. beta-adrenergic antagonists (timolol)
-they reduce aqueous humor production |
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usage of Pilocarpine |
1. glaucoma (closed angle - emergency)
2. xerostomia |
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specificity of Pilocarpine |
specific muscarinic receptor agonist
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hydrolysis of Pilocarpine |
NOT hydrolyzed by AChE |
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physiological action of Pilocarpine |
causes miosis of iris (constricts sphincter),
decreases intra-ocular pressure,
causes blurred vision (constrict ciliary muscle "forcing" near vision) |
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movement of Pilocarpine in the CNS |
crosses BBB |
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usage of Cevimeline |
treatment of xerostomia as in the case of Sjogren's disease,
patients undergoing antineoplastic treatment or neck radiation,
or aging |
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specificity of Cevimeline |
specific muscarinic receptor agonist at M1 and M3 |
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What is the benefit of Cevimeline and over what drug? |
cheaper than Pilocarpine |
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What is Sjogren's disease? |
autoimmune disease where lacrimation and salivation is destroyed |
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Xerostomia symptoms |
-DRY almost everything (eyes, tongue, throat, mouth, nose) -gritty/sandpaper feelings -difficulty speaking without water -difficulty chewing and swallowing food -mucus in and around eyes |
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How does Cevimeline help with the "dryness" problem? |
if it is an agonist for M1 and M3 receptors, leads to contraction of smooth muscles around glands (like salivary and lacrimal) to increase secretions |
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What are the general cholinergic effects on the eye? |
1. sphincter muscle of iris = contraction (miosis)
2. ciliary muscle = contraction for near vision |
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What are the general cholinergic (side) effects on the heart? |
SA node = decrease in rate (negative chronotropy)
-atria = decrease in contractile strength (negative ionotropy)
-AV node = decrease in conduction velocity (negative dromotropy) increase in refractory period |
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What are the general cholinergic effects on blood vessels? |
1. arteries = dilation (via NO production)
2. veins = dilation (via NO production) |
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What are the general cholinergic effects on lung? |
1. bronchial smooth muscle = contraction (bronchoconstriction)
2. bronchial glands = stimulation (mucous) |
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What are the general cholinergic effects on GI tract? |
1. motility = increased
2. sphincters = relaxation
3. secretion = stimulation |
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What are the general cholinergic effects on urinary bladder? |
1. detrusor muscle = contraction
2. trigone and sphincter = relaxation |
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What are the general cholinergic effects on glands? |
sweat, salivary, lacrimal, nasopharyngeal = secretion |
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What are the five most clinically used direct acting cholinergic agonists? |
1. Bethanechol 2. Carbachol 3. Cevimeline 4. Methacholine 5. Pilocarpine |
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What would you use to treat glaucoma? |
Carbachol - open angle
Pilocarpine - closed angle |
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What would you use to treat postoperative GI atony? |
Bethanechol |
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What would you use to treat neurogenic bladder? |
Bethanechol |
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What would you use to treat dry mouth? |
Cevimeline |
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What would you use for a bronchoprovocation challenge? |
Methacholine |
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How are direct acting cholinergic agonists generally administered? |
topically in the eye or given orally |
