Cholinergics & Anticholinergics Flashcards
True/False. Acetylcholine is ALWAYS released by pre-ganglionic neurons.
True
What receptors are located at the neuromuscular junction?
Nicotinic
What type of receptors are located on sweat glands?
Muscarinic receptors stimulated by Ach released by the SANS
True/False. All cholinergic receptors are ligand-gated ion channels.
False. Nicotinic receptors are ligand-gated, with a fast excitatory response. Muscarinic receptors are G-protein receptors with a slower response and may be excitatory or inhibitory
What muscarinic receptor is always inhibitory? Where is it located?
M2 receptor on the heart
What muscarinic receptor is always excitatory?
M1 & M3
Where are M1 receptors found?
CNS, gastric glands
Where are M3 receptors found?
Bronchi, bladder, eye, GI tract, periphery
What is the MOA of botulinum toxin?
Prevents release of Acetylcholine into the synaptic cleft
What are the effects of PANS stimulation on the eye?
Accommodation of the lens for near vision, miosis (pupil constriction), decreased intraocular pressure due to outflow of aqueous humor
What effects are associated with PANS stimulation?
Increased peristalsis & secretion in the GI tract, decreased HR, bronchoconstriction, urination
Blood pressure decreases in response to a direct cholinergic agonist, but not an indirect agonist. Why is this?
Blood vessels are not innervated by the PANS, however, PANS stimulation of M3 receptors on endothelial cells leads to release of NO. This in turn causes vasodilation. Indirect agonists require AchE for effect, but none is present as the PANS does not innervate blood vessels.
Both muscarinic antagonists and alpha-1 agonists cause mydriasis (pupil dilation). How can you differentiate between the two?
Muscarinic antagonists will cause cycloplegia (paralysis of accommodation) since they bind and block M3 receptors
What is the difference between direct and indirect cholinergic agonists?
Direct agonists bind and act directly on cholinergic receptors. Indirect agonists inhibit the action of AchE, thus increasing availability of Ach
What are common clinical uses of direct cholinergic agonists?
Urinary retention, dry mouth, acute glaucoma
What direct muscarinic agonist is used to treat acute glaucoma?
Pilocarpine
These muscarinic agonists may be used to treat Sjogren’s Syndrome and dry mouth.
Pilocarpine & Cevimeline
What is the site of action for Bethanechol?
Direct muscarinic agonist that acts on the GI tract & bladder
What is the clinical use for Methacholine?
Diagnosis of bronchial airway hyperactivity
Indirect cholinergic agonists are especially effective in treating what types of disorders?
Myasthenia gravis, muscle paralysis, Alzheimer’s disease
Therapeutic doses of indirect cholinergic agonists can promote strength of muscle movements and cognition. What ADRs are associated with high does?
Muscle paralysis, disorientation, convulsions
What indirect cholinergic agonists crosses the BBB and can treat atropine overdose?
Physostigmine
What indirect cholinergic agonists are used for treatment of myasthenia gravis?
Neostigmine, Pyridostigmine
What is the clinical use of Rivastigmine?
Indirect cholinergic agonist - treatment of Alzheimer’s disease
What ADRs are associated with indirect cholinergic agonists?
Salivation, miosis (pupil constriction), bradycardia, diarrhea, muscle twitches, paralysis, convulsions
What indirect cholinergic agonist may be used for clinical diagnosis of myasthenia gravis?
Edrophonium
True/False. Organophosphates are irreversible AchE inhibitors
True - causes cholinergic crisis
What drug can be administered as an antidote for cholinergic agonist overdoeses?
Atropine
What drug, when administered soon after exposure to organophosphates, can regenerate AchE?
Pralidoxime
What drug is used in smoking cessation and acts as a partial agonist to mediate the reward effect of nicotine on the brain?
Varenicline
True/False. Anti-muscarinic drugs are administered locally to prevent unwanted side effects.
True - Anti-muscarinic drugs are non-selective for muscarinic receptors so they are administered locally to gain a level of selectivity
What drug can be administered via transdermal patch to treat motion sickness?
Scopolamine
What anti-muscarinic drugs are used in ophthalmic settings to induce mydriasis?
Cyclopentolate, tropicamide
What is the clinical use for ipratropium?
Muscarinic antagonist - treat asthma & COPD
What is the clinical use for Benztropine?
Treat tremors due to Parkinson’s disease
What muscarinic antagonists can be used to treat irritable bowel syndrome?
Dicyclomine, hyoscyamine
What is the clinical use for Oxybutynin?
Overactive bladder, urinary incontinence
What ADRs are assoicated with muscarinic antagonists?
Hyperthermia, flushing, dry mucosa, blurred vision, constipation, urinary retention, tachycardia, disorientation
What is the MOA of succinylcholine?
A neuromuscular blocker - continuous stimulation of the Nm receptor leads to paralysis to act as a muscle relaxant
What is a major ADRs associated with depolarizing neuromuscular blockers?
Respiratory paralysis & death in patients with low or absent plasma AchE
What are the non-depolarizing neuromuscular blockers?
Rocuronium, pancuronium, vecuronium
