Term
| What does Hemicholinium do? |
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Definition
| Blocks Ach synthesis by blocking Choline reuptake |
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Term
| What does botulinum toxin do? |
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Definition
| Blocks Ach Release. Leads to flaccid paralysis |
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Term
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Definition
| Physostigmine is a tertiary compound that inhibits acetylcholinesterase, thereby preventing Ach metabolism and prolonging its effect. As a tertiary compound, it is capable of crossing the BBB and exherting its effect on the CNS. |
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Term
What is atropine
what are its uses and contraindications? |
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Definition
atropine is a muscarinic receptor antagonist. It will therefore result in increased firing at the SA and AV node of the heart by reducing the parasympathetic (vagal) tone imparted by the M2 receptors.
Atropine is often used in the treatment of AV nodal block. It is also used in cardiac failure if epinephrine does not adequately stimulate cardiac function.
In patients with BPH, dangerous because relaxation of the detrusor muscle (M3) increases their difficulty in urinating |
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Term
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Definition
| Nicotine is a nicotinic receptor agonist (Nn and Nm) |
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Term
| Where does tubocurarine act? |
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Definition
| Tubocurarine is a non-depolarizing nicotinic receptor antagonist at the neuromuscular junctions (Nm) |
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Term
| What is the second messenger system for M3 receptors? |
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Definition
Gq to IP3/DAG
M receptors are "quick" (QIQ) because mice are quick... (mouse = mus musculis = muscarinic)
M1=Gq
M2=Gi
M3=Gq |
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Term
| What is the second messenger system for M2 receptors? |
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Definition
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Term
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Definition
Carbachol is a quaternary choline ester. It is therefore a muscarinic agonist that also stimulates nicotinic receptors. Because it is a charged quaternary compound, it does not cross the blood brain barrier.
Carbachol also has a low sensitivity to AchE and therefore benefits from a longer duration of action.
action mainly on M1, M3 receptors
used to lower intraocular pressure after cataract extraction. This occurs because M3 stimulation of the ciliary muscle opens up the trabecular meshwork and increases outflow through the canal of schlemm |
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Term
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Definition
A muscarinic agonist that does NOT stimulate nicotinic receptors
Like carbachol, bethanechol has a low sensitivity to AchE and therefore a long duration of action.
action mainly on M1, M3 receptors
Like most agonists of the parasympathetic system, bethanechol is contraindicated in patients with asthma (bronchoconstriction) and peptic ulcers. |
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Term
| How are M3 receptors related to vasculature? |
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Definition
| M3 receptors are found on vascular endothelial cells. They activate the DAG/IP3 system that stimulates endothelial nitric oxide synthase (ENOS). This results in the formation of NO, which diffuses to the vascular smooth muscle to cause relaxation in a paracrine fashion. This occurs through NO mediated activation of cytoplasmic guanylate cyclase. The resulting increase in cGMP inactivates MLCK via phosphorylation. |
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Term
| Choline ester drugs that are not degraded by AchE to a large extent |
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Definition
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Term
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Definition
Pilocarpine is a tertiary amine that activates muscarinic receptors M1, M2, M3
It is used locally for open angle glaucoma and sometimes for xerostomia(dry mouth)
M3 receptors of ciliary muscle will increase lens curvature and make far-vision difficult, a common side effect. This also opens up the trabecular meshwork and allows for greater aqueous humor outflow.
M3 receptor of the sphincter muscle of the eye will cause miosis and therefore make vision in low light more difficult. |
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Term
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Definition
a quaternary ammonium compound from mushrooms.
M1, M2, M3 agonist |
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Term
| list two important Carbamate AchE inhibitors |
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Definition
Physostigmine (enters CNS)
Neostigmine (does not enter CNS)
carbamate AchE inhibitors have a longer half life because they undergo a 2-step degredation process |
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Term
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Definition
Edrophonium is a reversible AchE inhibitor with a short half life. Because of its short half life, it is used in the diagnosis of myasthenia gravis.
Edrophonium can also be used to differentiate between cholinergic crisis and myasthenic crisis as follows:
-In a cholinergic crisis, where there is an excess of Ach in the synapses, it will decrease muscle strength (via depolarization blockade) and cause fasciculations
-In a myasthenic crisis, in which there is a decrease of Ach stimulation of receptors, it will increase muscle strength |
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Term
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Definition
Physostigmine is a tertiary amine AchE inhibitor. Because it is a tertiary amine, it can cross into the CNS. This drug also has a good bioavailability.
because it enters CNS, moderate doses of physostigmine may increase alertness, high doses may cause confusion/ataxia/coma |
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Term
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Definition
Neostigmine is an AchE inhibitor. it is a charged, quaternary compound and therefore does NOT enter the CNS (unlike physostigmine). Also unlike physostigmine, neostigmine has poor oral bioavailability.
Neostigmine is the Drug of choice for the treatment of Myasthenia Gravis because it has no associated CNS effects. Often, atropine is co-administered to block the muscarinic action of neostigmine and minimize GI effects. Recall, myasthenia gravis affects only the nicotinic receptors, so there is no need to target the muscarinic receptors with neostigmine in this treatment.
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Term
| AchE Inhibitor toxicity can be treated with what drug(s)? |
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Definition
Atropine, or other muscarinic antagonists. These will pharmacologically counteract the excess acetylcholine created by cholinesterase inhibitors.
Additionally, if the cholinesterase inhibitor was an organophosphate (parathion), cholinesterase reactivators such as Pralidoxime are efficient as long as the cholinesterase hasn't undergone aging |
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Term
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Definition
| These are AchE reactivators. They are effective only for organophosphate poisoning and only if the cholinesterase enzyme has not undergone aging. They are unable to reverse AchE blocked by carbamates(neostigmine, physostigmine) |
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Term
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Definition
| Donepezil is an AchE inhibitor in the CNS. It has little effect on peripheral AchE and has been shown to be moderately useful in slowing degeneration due to Alzheimer's. Recall that acetylcholine is the the neurotransmitter most heavily implicated in Alzheimer's Disease. |
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Term
| How do Carbachol, Pilocarpine, Physostigmine aid in open angle glaucoma treatment? |
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Definition
| These drugs all increase M3 activation of the ciliary muscle, resulting in contraction. This opens the trabecular meshwork and increases aqueous humor outflow through the canal of schlemm. Any cholinomimmetic or muscarinic agonist would produce this effect on the ciliary muscle. |
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Term
| What are some effects and uses of Atropine? |
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Definition
Atropine is a non-selective muscarinic antagonist. As a tertiary amine, atropine is capable of entering the CNS.
effects: Atropine results in tachycardia (decreased vagal tone on heart M2 receptors), decreased peristalsis, relaxation of detrusor muscle, mydriasis, cycloplegia(M3 receptors block relaxes peristalsis, detrusor muscle, and ciliary muscle), decreased sweating (M3) leads to increased body temperature = "atropine fever" and vasodilation of cutaneous vessels to release the built up heat = "atropine flush"
Uses: cardiovascular disorders, excessive salivation (M3 receptors in exocrine glands), visceral hypermotility and spasms, AchE inhibitor overdose, Ophthalmology
Nodal block in the heart |
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Term
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Definition
Scopolamine is a non-selective, muscarinic antagonist. Similar to atropine, it is a tertiary amine, meaning it has effects on the CNS.
In total, its effects are the same as atropine, but it also depresses vestibular function and is therefore useful in treating motion sickness. Like atropine, it can be used in opthalmology.
Again, like atropine, overdose may result in delerium, hyperthermia, and death. |
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Term
| Why would you use Darifenacin? |
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Definition
Darifenacin is a selective M3 antagonist. It would be used in URINARY/URGE INCONTINENCE because of its relaxing effect on the detrusor muscle.
Not surprisingly, this means it is contraindicated in patients with difficulty urinating (ex: BPH). |
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Term
Glycopyrrolate
Ipratropium
What is an indication for ipratropium? |
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Definition
Glycopyrrolate and ipratropium are non-selective muscarinic antagonists. They are both quaternary compounds, in this case meaning that they also exhibit antagonist activity at nicotinic receptors, including ganglionic (Nn).
They both relax hyperactive smooth muscle of gut and are therefore used in treatment of irritable bowel syndrome
Ipratronium is special because it is chosen when a patient requires a muscarinic antagonist but has asthma. Other antimuscarinic drugs decrease bronchial secretions and mucociliary clearance, whereas for unknown reasons, ipratropium does not affect these processes. |
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Term
| What is the difference between administration of high and low doses of nicotine? |
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Definition
nicotine is a stimulating drug at nicotinic receptors (Nn and Nm), including autonomic ganglia (both sympathetic and parasympathetic)
when given at low doses it is activating. Giving it at high doses, however, results in a depolarizatin blockade (prolonged depolarization inhibits the neurons from repolarizing, and therefore prevents further neurotransmitter release... this hinders neuronal transmission)
As far as toxicity is concerned, moderate doses yield effects similar to Epinephrine whereas toxic doses can lead to cardiovascular collapse |
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Term
| What are signs of nicotine poisoning? |
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Definition
Nicotine stimulates the Nicotinic neuronal and muscular receptors. Excessive stimulation of these receptors leads to salivation, nausea/vomiting, cold sweat, tachypnea, tachycardia, headache/dizziness, and muscle weakness (depolarization blockade)
(mixed sympathetic and parasympathetic effects)
respiratory failure is one of the largest dangers, and may occur in minutes |
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