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Flashcards in Cholinergic agonists and antagonists Deck (31):
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1. What is the difference b/t a direct-acting and indirect-acting cholinergic agonist?

Direct-acting → binds to and activates muscarinic or nicotinic receptors
Indirect-acting → inhibits acetylcholinesterase thereby increasing the concentration of endogenous acetylcholine

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2. What is the direct effects of Ach on the cardiovascular system?

1. Vasodilation (M3)
2. Decreased cardiac rate (M2)
3. Decreased rate of conduction in SA and AV nodes (M2)
4. Decreased force of contraction (M2)
*some direct effects can be obscured by baroreceptor reflexes – ex. small amts of Ach cause fall in blood pressure accompanied by reflex tachycardia, large amts of Ach cause fall in blood pressure (hypotension) and bradycardia (M2 effect)

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3. How does ACh produce nicotinic effects?

If large dose of ACh is injected post atropine dose, ACh produces a nicotinic effects – initial increase in bp due to sympathetic ganglia vasoconstriction and a secondary release of catecholamines from the adrenal medulla.

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4. What are the different direct-acting cholinergic agonist groups based on chemical structures?

1. Choline esters → Acetylcholine, carbachol, bethanechol, methacholine
2. Naturally occurring alkaloids → Arecoline, muscarine, pilocarpine, nicotine, lobeline

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5. What are choline esters?

Choline esters are quarternary ammonium which are permanently charged ions that are poorly distributed into the CNS. This category includes: Acetylcholine, carbachol, bethanechol, methacholine. These differ in their means to hydrolyze cholinesterase.
1. Acetylcholine –very rapidly hydrolyzed
2. Methacholine – more rapidly hydrolyzed
3. Carbachol and Bethanechol – more resistant to hydrolysis by cholinesterase

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6. What is the systemic and local used of acetylcholine?

Systemic → none b/c it is rapidly hydrolyzed by acetylcholinesterase and butyrylcholinesterase
Local → rapid miosis (pin point pupils) after delivery of lens in cataract surgery

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7. What is the use of Bethanechol?

Postop and post-partum urinary retention or neurogenic atony – it reactivates the bladder. Bethanechol is not hydrolyzed by acetylcholinesterase, has no nicotinic activity and strong muscarinic activity.

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8. What are the adverse reactions of bethanechol?

1. sweating
2. salivation
3. flushing
4. low blood pressure
5. nausea
6. abdominal pain
7. diarrhea
8. bronchospasm

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9. What are the uses of carbachol?

Carbachol is used to cause miosis during surgery and reduces intraocular pressure after cataract surgery. It acts as both a muscarinic and nicotinic agonist and is a poor substrate for acetylcholinesterase.

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10. What is the use of Methacholine?

Methacholine is predominantly a muscarinic agonist. It is used to diagnose bronchial airway hyperreactivity in subjects who do not have clinically apparent asthma.

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11. What is the effect of the natural alkaloids?

1. muscarine → muscarinic agonist
2. Arecoline → muscarinic and nicotinic agonist
3. Pilocarpine → mainly muscarinic agonist [this is the only natural alkaloid that is used clinically]

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12. What are the basic characteristics of Pilocarpine?

Pilocarpine is a tertiary amine that is stable to hydrolysis by acetylcholinesterase and acts as a partial muscarinic agonist. It is used to treat open angle glaucoma, manage acute angle-closure glaucoma, tx dry mouth due to radiotherapy of head and neck for cancer treatment and treat dry mouth caused by Sjogren’s syndrome (autoimmune disease causing dry eyes and dry mouth).

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13. What is a ganglion stimulant?

This is a stimulant of the cell body of the postsynaptic neuron. A common ganglion stimulant is nicotine. At slightly higher cncentrations nicotine can also act on the NMJ.

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14. What is the effect of low dose nicotine?

Low dose nicotine causes ganglionic stimulation and depolarization.
1. CV system → sympathomimetic effects increasing HR and BP
2. GI and urinary tract → mainly parasympathomimetic causing nausea, vomiting, diarrhea, and voiding of urine (SLUDGE?)
3. Secretions → stimulates salivary and bronchial secretions (parasympathetic?)

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15. What is the effect of high dose nicotine?

High dose nicotine causes a ganglionic blockade and neuromuscular blockade.

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16. What is acute nicotine poisoning?

This is the consumption of a large dose of nicotine leading to a neuron blockage causing nausea, salivation, abdominal pain, vomiting, diarrhea, cold sweat, mental confusion and weakness. The blood pressure will fall, pulse will become weak and paralysis of respiratory muscles may occur.

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17. What is the use of nicotine?

Smoking cessation therapy

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18. What are the different chemical groups of indirect-acting cholinergic agonists?

1. simple alcohols bearing quarternary ammonium groups → edrophonium
2. carbamates → physostigmine, neostigmine, pyridostigmine
3. organophosphates → echothiophate, parathion, malathion

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19. What is the mechanism of edrophonium? What is it used for?

Edrophonium is a quaternary ammonium that binds reversible to the active site of acetylcholinesterase. The enzyme-inhibitor complex does not have any covalent bonds and is short lived. It is used to diagnose myasthenia gracis by leading to a rapid increase in muscle strength. It can also be used to rever NMJ blocks produced by non-depolarizing muscular blockers.

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20. What is the mechanism of carbamates?

Carbamates form covalent bonds with anticholinesterase inhibiting the enzymes.

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21. What is the mechanism of organophosphates?

Organophosphates are synthetic compounds that are extremely toxic. They phosphorylate cholinesterases creating a stable covalent bone and allows for slow hydrolysis. The phosphorylated enzymes may undergo ageing which actually strengthens the phosphorous-enzyme bond.

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22. What is the general effect of anticholinesterases?

Anticholinesterases amplify the action of endogenous Ach acting similarly to the effects of the direct-acting cholinomimetic agonist.

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23. How do anticholinesterases affect the cardiovascular system?

Cholinesterase inhibitors have less of an effect on blood pressure compared to direct acting muscarinic agonist due to lack of vascular beds that receive cholinergic innervation therefore causing minimal effects.

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24. What is physostigmine?

Physostigmine is a carbamate with a tertiary amine structure. It can enter and stimulate the CNS allowing it to be used as a treatment for anticholinergic drug overdoses.

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25. What is neostigmine?

Neostigmine is a carbamate with a quarternary ammonium structure. Unlike physostigmine, it does not neter the CNS. It is used to prevent and treat post-op distention and urinary retention, reversal of effects of non-depolarizing NMJ blockers post surgery and symptomatic treatment of myasthenia gravis.

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26. What is pyridostigmine?

Pyridostigmine is a carbamate with a quarternary ammonium structure. It does not enter the CNS and is the most common treatment for myasthenia gravis.

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27. What is Echothiophate?

Echothiophate is an organophosphate used to treat glaucoma.

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28. What are thiophosphate insecticides?

Malathion and Parathion are organophosphates that need to be activated in the body by conversion to oxygen analogs.

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29. What are examples of nerve agents?

1. Tabun
2. Sarin
3. Soman
*These are the most potent synthetic toxic agents known

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30. Which AChE inhbitors are used for Alzheimers disease?

Donepezil, rivastigmine, galantamine
These are centrally acting acetylcholinesterase inhibitors.

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31. What is Pralidoxime?

Pralidoxime is a AChE reactivator. If given before ageing from organophosphates, pralidoxime splits the phosphorus-enzyme bond. It can be used as cholinesterase regenerators for organophosphate insecticide poisoning.