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49 Cards in this Set
- Front
- Back
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1. In what three ways can the cholingergic neuron be affected?
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1. Directly stimulate receptors
2. Can inhibit choline esterases so ACh isn't broken down 3. Stimulate release of ACh |
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2. What does the cholinergic neuron release?
How is this NT produced? (two steps) |
Releases acetylcholine that is produced from acetyl-CoA
1. Take choline in from diet and phospholipids 2. AcCoA + choline form ACh using choline acteyl transferase enzyme |
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3. Once ACh is released from the cholinergic neuron what happens?
(two things) What does acetylcholine esterase do? What two places is it found? |
1. Bind to receptors and produces an effect (stimulate)
2. Stimulate pre-synaptic receptors (M2) to inhibit further release of ACh Breaks down ACh In synapses and placenta |
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4. What are the two classifications of cholingergic agonists?
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1. Direct acting (receptor agonists)
-muscarinic receptor agonist -nicotinic receptor agonist 2. Indirect acting -inhibitors of cholinesterases -stimulators of ACh release |
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5. What are three choline esters?
What is their mechanism of action? What is their therapeutic efficacy due to? |
1. Acetylcholine
2. Bethanechol 3. Carbachol Direct activation of cholinergic receptors Muscarinic acitivty |
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6. What does activation of muscarinic receptors by choline esters result in?
Structurally what do all choline esters have in common? What two thing does this structure result in? |
Increases cGMP and ultimately either increases intracellular Ca or inhibits adenylyl cyclase activity
All have positive charged N 1. Not absorbed orally 2. Won't cross membranes well b/c water soluble **don't cross blood-brain barrier |
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7. What are the effects of using acetylcholine on the cardiovascular system?
Three things... |
1. Vasodilation
-indirectly by NO which decreases BP 2. Decrease HR 3. Decrease force of contraction **2 and 3 are direct effects of ACh |
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8. What are the effects of ACh on smooth muscle cells?
Three systems... |
Affects contraction
GI tract - increase in tone & motility Bronchioles - constriction GU system - contraction of ureter and bladder (urinary frequency) **uterine contraction slightly in humans |
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9. What are the effects of ACh on the eye?
Two things... |
1. Miosis
-pupil constriction 2. Accommodation (near vision) -contract ciliary muscle |
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10. What are the effects of ACh on exocrine glands?
What are the effects of ACh at the neuromuscular juntion? What receptors are stimulated by ACh at the neuromuscular junction? |
Increase secretion
-salivation, lacrimation, sweating, GI secretions Stimulation of motor end plate Nicotinic receptor stimulation |
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11. What is acetylcholine used for clinically?
Is it a good drug to give systemically? What is it's susceptibility to choline esterases (ChE)? Is it selective for muscarinic or nicotinic action? |
Miotic (topically for eye surgery)
Not good for systemic use b/c causes too many things Broken down rapidly (short duration) Equal M and N action |
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12. What is Bethanechol used for clinically?
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1. Non-obstructive decreased urine flow (atony of bladder)
-contracts bladder and increase emptying 2. Paralytic ileum -stimulate GI tract if have abdominal distension -increase motility |
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13. How is the duration of both Bethanechol and Carbachol?
What does Bethanechol have selective action for? Does Carbachol have selectivity? |
Longer duration b/c not susceptible to ChEs
Muscarinic selectivity (GI/bladder) About equal for M and N action |
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14. What are the clinical uses of Carbachol?
Two things... What is methacholine used for? |
1. Miotic
-contract ciliary muscle 2. Glaucoma -increases loss of fluid from eye and reduces intra-occulurar eye pressure -increase drainage of aqueous humor Diagnosis of severity of asthma |
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15. What are natural alkaloids?
What is their action? What are two examples of natural alkaloids? |
Naturally containing N compounds
Muscarinic agonists 1. Muscarine 2. Pilocarpine |
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16. What is muscarine?
What does muscarine exclusively stimulate? What are two classic symptoms of accidental intoxication by muscarine consumption? What is treatment for muscarine intoxication? |
Alkaloid present in various species of wild mushrooms
Stimulates muscarinic receptors and mimics some effects of ACh 1. Abdominal cramping and diarrhea 2. Tightness in chest Muscarinic antagonist Atropine is used for intoxication |
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17. What does Pilocarpine stimulate?
What is Pilocarpine used for? |
Stimulate muscarinic receptors
1. Xerostomia -induce salivation 2. Glaucoma -induce outflow of aqueous humour thus reducing intra-ocular pressure |
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18. For glaucoma treatment what is the onset of action and duration for Pilocarpine?
What are the adverse reactions associated with Pilocarpine use? (five things) |
Onset is 15-30 min with 4-8 hr duration
1. Difficulty focusing 2. Nausea/abdominal pain 3. Blurring of vision, misosis 4. Sweating 5. Bradycardia/hypotension *at high doses |
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19. What are the uses of muscarinic agonists?
Six uses... |
1. Eye surgery (ACh)
2. Glaucoma (Carbachol/Pilocarpine) 3. Non-obstructive atony of bladder (Bethanechol) 4. Paralytic ileus (Bethanechol) 5. Xerostomia (Pilocarpine) 6. Diagnosis of bronchial hyper-reactivity (severity of asthma) (Methacholine) |
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20. What are contra-indications for the use of muscarinic agonists?
Four contra-indications... |
1. Peptic ulceration
-b/c increase acid secretion 2. Bronchial asthma -cause acute exacerbation 3. Hyper-thyroidism -increase possibility of tachycardia b/c heart beats rapidly and ACh shortens refractory period of atrial tissue 4. Parkinsonsim |
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21. What four reversible cholinesterase inhibitors?
What is the duration of the reversible cholinesterase inhibitors? How can reversible cholinesterase inhibitors be adminstered? |
1. Edrophonium
2. Physostigmine 3. Pyridostigmine 4. Neostigmine Work rapidly from minutes up to approximately 6 hrs Lipid soluble so available by every route |
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22. How do irreversible cholinesterase inhibitors work?
Generally what are irreversible cholinesterase inhibitors? What are three specific examples? |
Lose phosphate side group once they bind and undergo "aging" where they form a covalent bond to enzme
*once bind, they don't come off rapidly Organophosphates 1. Echotiophate 2. Malathion 3. Sarin |
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23. What is the mechanism of action for cholinesterase inhibitors?
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Bind to active site of cholinesterase thus preventing binding of ACh to the enzyme
Block hydrolysis of ACh **compete with ACh and the result is more ACh to stimulate receptors |
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24. What is the mechanism of action for Edrophonium?
What can Edrophonium stimulate? What is the duration of Edrophonium? Clinically what is it used for? |
Binds reversibly to AChE preventing access by ACh
Stimulate nicotinic receptors Has shortest duration (5-15 min) Used for diagnosis of myasthenia gravis |
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25. What is the mechanism of action for carbamate esters such as physostigmine, pyridostigmine, and neostigmine?
How are carbamylated enzymes? What else can pyridostigmine and neostigmine do? |
Bind to active site of enzyme preventing binding of ACh
More resistant to hydrolysis than acetylated enzyme Weak agonists at cholinergic receptors |
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26. What is the mechanism of action for organophosphates?
What process do phosphorylated enzymes undergo? What is this? How long are organophosphates active for? |
Bind to enzyme yielding phosphorylated ChE which is extremely stable and hydrolyzed at a very slow rate
Aging Breaking of on the oxygen-phosphorus bonds of the inhibitor further strengthening the phosphorylated enzyme Active until new enzymes are synthesized |
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27. What is the only reversible cholinesterase inhibitor that crosses the blood-brain barrier?
What does this property make is useful for the treatment? What does it do? |
Physostigmine
Anti-muscarinic drug intoxication (atropine, tricyclic antidepressants) Can reverse central and peripheral signs **only used in extreme intoxication |
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28. What are the clinical uses of reversible cholinesterase inhibitors?
Seven things... |
1. Paralytic ileus
2. Neurogenic bladder 3. Glaucoma 4. Myasthenia Gravis 5. Anti-muscarinic drug intoxication 6. Alzheimer's disease 7. Reversal of neuromuscular blockade |
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29. What is Neostigmine used specifically for?
Three things |
1. Post-operative paralytic ileus
-increase abdominal motility 2. Neurogenic bladder -increase frequency of urination 3. Myasthenia gravis -chronic therapy |
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30. What is physostigmine used specifically for?
Two things... |
1. Glaucoma
-may be in combo w/ pilocarpine 2. Anti-muscarinc drug intoxication -crosses blood-brain barrier |
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31. How is Edrophonium used to diagnosis myasthenia gravis?
If ChE-inhibitor is in excessive amount when treating MG what affect can Edrophonium have? If the patient improves with Edrophonium when on ChE-inbibitor what may be indicated? |
If patient has disease Edrophonium should provided short-term improvement in muscle strength
May worsen muscle weakness due to nicotinic depolarizing block **cholinergic crisis (overstimulate N receptors, so stops working) Increase in ChE inhibitor dose may be indicated |
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32. How are cholinesterase inhibitors used for reversal of nueromuscular blockade?
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Used by anesthesiologist to terminate action of curare-like drugs
**curare-like drugs are competitive non-depolarizing neuromuscular blockers |
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33. What two non-competitive reversible cholinesterase inhibitors are used for treatment of cognitive deficits associated with Alzheimer's disease?
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1. Donepezil (Aricept)
2. Rivastigmine (Exelon) **more selective for choline esterase in brain |
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34. What is the solubility of most organophosphates?
What are three properties of Echotiophate? What is it used for? |
Most are highly lipid soluble therefore, readily cross the blood brain barrier
1. Stable in aqueous solution 2. Less lipid soluble 3. Less toxic Topically for open-angle glaucoma |
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35. What are Malathion and Parathion used for?
What is concern with these organophosphates due to? |
Pesticides
Accidental intoxication (respiratory depression) *Malathionic is one of the least toxic OPs |
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36. What are the symptoms of accidental intoxication w/ Malathion or Parathion?
Seven... |
DUMBELS
1. Diarrhea 2. Urinary incontinence 3. Miosis 4. Bronchoconstriction 5. CNS Excitation (seizures 6. Lacrimation 7. Salivation/sweating |
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37. What are Soman/Sarin?
Why are they very harmful? |
Toxic chemicals that are nerve agents w/ potential use in chemical warefare
Age to enzyme very rapidly making antidotes ineffective |
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38. What are the antidotes to organophosphates?
Four things... |
1. Pralidoxime
2. Lorazepam -prevent seizures 3. Oxygen 4. Atropine -block muscarinic effects |
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39. What is Pralidoxime?
How does it work? When is it not effective? (two times) |
Cholinesterase reactivator
Has strong affinity for phosphorylated enzyme and phosphorylates the oxime thus regenerating free enzyme 1. Aging has occurred 2. Carbamate-type inhibitors |
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40. What three things do toxicities of cholinesterase inhibitors include?
What two things is death due to? What two things can exposure to organophosphates cause that is unrelated to ChE-inhibitor potency? |
Muscarinic, nicotinic, and CNS effects
1. Respiratory depression 2. Circulatory collapse 1. Delayed neuropathy 2. Allergic reactions |
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41. Where are nicotinic receptors found?
(three places) What is the mechanism of action for nicotine? What can prolonged activation lead to? |
1. Adrenall medulla
2. Neuromuscular junction 3. Brain Binds to alpha subunits of nicotinic receptors yielding an increase in sodium influx **low doses --> stimulate Depolarizing block where can't re-stimulation |
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42. What are the effects of nicotine on the CNS?
Five things... |
1. Increase rate of depth of respiration at small doses
2. Toxic doses lead to stimulation of respiratory center followed by depression 3. Finger tremors at low-moderates doses 4. Convulsions at toxic doses 5. Irritability, nausea/vomitting, anti-diurectic, increase in alertness and memory |
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43. What are the effects of nicotine on the cardiovascular system?
Three things... What can it exacerbate? |
1. Increase HR
2. Increase total peripheral resistance 3. Increase bp **low doses Can exacerbate... -hypertension -heart disease -angina -peripheral vascular disease |
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44. What are the effects of nicotine on the GI tract?
Two things... |
1. Increase in secretions and motility
2. Exacerbate peptic ulceration |
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45. What are the pharmacokinetics of nicotine?
Where is nicotine inactivated? |
Highly lipid soluble therefore well absorbed from all routes of administration
**Inhalation yields brain levels in 8-10 seconds In liver |
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46. What are the symptoms of acute nicotine intoxication?
Five things... |
1. Respiratory failure
2. Cardiovascular collapse 3. Nausea/vomiting 4. Headache/dizziness 5. Palpitations/convulsions |
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47. What is chronic toxicity with nicotine associated with?
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1. Respiratory and cardiovascular disease
2. Cancer **tolerance develops very rapidly and there can be physical dependence |
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48. What two drugs are used for smoking cessation?
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1. Buropion
-anti-depressant and smoking cessation aid 2. Varenicline |
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49. What is Varenicline?
What does it do? What are adverse reactions/side effects of it? (three things) |
Direct acting nicotinic partial agonist
Reduces symptoms of withdrawal 1. Nausea 2. Headache 3. Sleep disturbances (insomnia) |
