Cholinergic agonists and antagonists Flashcards
- 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
- What is the direct effects of Ach on the cardiovascular system?
- Vasodilation (M3)
- Decreased cardiac rate (M2)
- Decreased rate of conduction in SA and AV nodes (M2)
- 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)
- 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.
- What are the different direct-acting cholinergic agonist groups based on chemical structures?
- Choline esters → Acetylcholine, carbachol, bethanechol, methacholine
- Naturally occurring alkaloids → Arecoline, muscarine, pilocarpine, nicotine, lobeline
- 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.
- Acetylcholine –very rapidly hydrolyzed
- Methacholine – more rapidly hydrolyzed
- Carbachol and Bethanechol – more resistant to hydrolysis by cholinesterase
- 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
- 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.
- What are the adverse reactions of bethanechol?
- sweating
- salivation
- flushing
- low blood pressure
- nausea
- abdominal pain
- diarrhea
- bronchospasm
- 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.
- 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.
- What is the effect of the natural alkaloids?
- muscarine → muscarinic agonist
- Arecoline → muscarinic and nicotinic agonist
- Pilocarpine → mainly muscarinic agonist [this is the only natural alkaloid that is used clinically]
- 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).
- 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.
- What is the effect of low dose nicotine?
Low dose nicotine causes ganglionic stimulation and depolarization.
- CV system → sympathomimetic effects increasing HR and BP
- GI and urinary tract → mainly parasympathomimetic causing nausea, vomiting, diarrhea, and voiding of urine (SLUDGE?)
- Secretions → stimulates salivary and bronchial secretions (parasympathetic?)
- What is the effect of high dose nicotine?
High dose nicotine causes a ganglionic blockade and neuromuscular blockade.