Term
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Definition
| Agonist at all AChRs (duh.) Limited clinical use: used intraocularly to produce miosis, intracoronary use causes vasodilation, can be used to diagnose vasospastic angina. |
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Term
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Definition
| Can be used to diagnose asthma through a challenge test. Inhalation of this drug causes bronchoconstriction by acting at muscarinics. Must be used very carefully. |
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Term
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Definition
| Treatment for wide-angle glaucome when other cholinomimetics have failed. Causes pupillary contraction and relief and relief of intraocular pressure. |
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Term
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Definition
| Used postoperatively to reduce bladder/bowel distension (BBB). Can be used as an alternative to pilocarpine for treatment of xerostomia. |
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Term
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Definition
| Potent stimulator of sweat, tears and saliva. Used for wide-angle glaucoma and to treat xerostomia. Also used for emergency treatment of narrow-angle glaucoma with an AChE inhibitor (although this condition requires immediate surgical attention). Prolonged use can cause reduced night vision and difficulty in focusing on far objects. |
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Term
| Side effects of choline esters |
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Definition
| All related to activity at muscarinics (and nicotinics in the case of carbachol) - diarrhea, decreased blood pressure, urination, miosis, bronchoconstriction, bradycardia, excitation of skeletal muscle, lacrimation, salivation and sweating (DDUMBBELSS) |
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Term
| Contraindications for choline ester use |
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Definition
| Asthma, COPD, urinary obstruction and peptic ulcers/disease can all be exacerbated with use. |
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Term
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Definition
| Poisoning with this compound from mushrooms develops rapidly (30-60 mins) and can be readily reversed with atropine. Symptoms are salivation and lacrimation, nausea and vomiting, headache and visual disturbances, bronchospasm, bradycardia and hypotension, shock. |
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Term
| Forms of acetyl cholinesterase |
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Definition
Brain: catalytic subunits bound to membrane anchoring protein
Muscle: tetramers of catalytic subunits linked via long, collagen-like tails that are anchored to the basement membrane
Plasma: 'psuedo' cholinesterase which cleave a variety of esters and are active towards butyrylcholine (not used as a drug) (note that RBCs contain 'true' AChE) |
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Term
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Definition
Quaternary amine: Simple competitive inhibitor
Edrophonium
Carbamates: competitive inhibitors that undergo slow hydrolysis
Physostigmine
Neostigmine
Pyridostigmine |
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Term
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Definition
| Quaternary amine with brief duration (1-5 mins). Used to test for myasthenia gravis where IV administration causes a brief improvement of strength. Also used to judge correct dosage: if brief improvement is seen with use that patient may benefit from a higher dose of carbamate. |
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Term
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Definition
| Crosses BBB into CNS, used for treatment of wide-angle glaucoma, often with pilocarpine. Used to treat atropine overdose ('PHYxes' atropine overdose). Can adversely facilitate formation of cataracts. |
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Term
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Definition
| Short lasting (0.5 - 2hr). Used to treat loss of tone in GI tract and bladder (urinary retention) either from disease or from postoperative recovery from anesthesia. Also used for myasthenia gravis. No CNS penetration ('NEO' CNS penetration). |
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Term
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Definition
| Used to treat myasthenia gravis, longer duration (3-6hr) than neostigmine. |
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Term
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Definition
| Similar to pyridostigmine but even longer acting (4-8hr). |
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Term
| Irreversible AChE inhibitors |
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Definition
| Also termed organophosphates, form highly stable (covalent) phospho-intermediates. Take up to hundreds of hours to be cleaved off of enzyme. Before 'aging' is sensitive to nucleophilic attack by an oxime such as pralidoxime. After 'aging' is no longer susceptible. |
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Term
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Definition
| Used to treat glaucoma, only clinically useful organophosphate. |
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Term
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Definition
| Insecticides responsible for many cases of farm poisonings. Converted to malaoxon and paraoxon, respectively, which are more toxic compounds. Detoxified in mammals and birds via plasmaesterases. |
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Term
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Definition
| 'Nerve gases' that are potent inhibitors of AChE, among the most toxic agents known. |
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Term
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Definition
| Used in treatment of Alzheimer's. Long acting (once-a-day dosing), CNS penetrant, good oral absorption. |
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Term
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Definition
| Carbamate similar to physostigmine used to treat Alzheimer's. Requires twice-a-day dosing. |
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Term
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Definition
| Long-acting drug for Alzheimer's. Not only a AChE-I but also a potent allosteric enhancer of CNS nicotinic receptors. |
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Term
| AChE inhibitor toxicity and symptoms |
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Definition
| Mixture of muscarinic, nicotinic and CNS effects. 'SLUDGE-BAM': salivation, lacrimation, urination, defecation, GI upset, emesis, bradycardia, bronchoconstriction, bowel movement, abdominal cramps, anorexia, miosis. (Also DDUMBBELSS) |
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Term
| Organosphophates vs. Carbamates |
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Definition
| Organophosphates are longer-lasting and tend to have nicotinic excess symptoms, whereas carbamates tend to have more muscarinic symptoms. |
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Term
| Mechanism of lethal AChE-I overdose |
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Definition
| Death is usually from respiratory failure due to bronchoconstriction, bronchorrhea (high volumes of sputum production), central respiratory distress, and weakness or paralysis of respiratory muscles. |
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Term
| Treatment of AChE-I poisoning |
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Definition
| Mixture of atropine (muscarinic blocker) and pralidoxime (regenerator of un-'aged' enzyme), with diazepam to prevent convulsions. |
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Term
| Effect of antimuscarinics: Ocular |
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Definition
| Mydriasis, relaxation of ciliary muscle -> flatten lens for far vision, inhibition of lacrimation. |
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Term
| Effect of antimuscarinics: Cardiac |
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Definition
Standard doses increase HR and conduction by blocking vagal stimulation.
Very low doses may initially decrease HR by blocking presynaptic receptors. |
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Term
| Effect of antimuscarinics: Respiratory |
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Definition
| Bronchodilation and inhibition of secretions. |
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Term
| Effect of antimuscarinics: GI/Urinary |
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Definition
| Relax GI tract wall (but not sphincters), inhibit gastric acid secretion, relax detrusor muscle. |
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Term
| Effect of antimuscarinics: CNS |
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Definition
| Tertiary amines (atropine and scopolamine) can penetrate CNS. Scopolamine is generally more sedating than atropine. Atropine first causes stimulation before sedation. High doses can cause confusion/halucinations. |
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Term
| Effect of antimuscarinics: Other |
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Definition
| Inhibition of sweating, may lead to hyperthermia and then cutaneous vasodilation (note: this is a reflex, not a direct action). |
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Term
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Definition
| Anti-muscarinic. Uses: mydriasis for eye exam (outdated); induce cycloplegia (ciliary muscle paralysis) in children for determination of refractive error; sinus bradycardia and AV block; reduction of salivary and resp. secretions and to prevent airway obstruction in patients under anesthesia (outdated); reduce intestinal spasms and pain; reduce gastric acid secretion (outdated); reverse muscarine or AChE-I poisoning; prevent muscarinic side effects in patients receiving neostigmine or AChE-I; as an antidiarrheal |
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Term
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Definition
| Anti-muscarinic. Used for motion sickness, sedative. Applied as a patch. |
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Term
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Definition
| Fast but short-acting mydriatic agent. |
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Term
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Definition
| Fast but short-acting mydriatic agent. |
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Term
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Definition
| Fast but short-acting mydriatic agent. |
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Term
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Definition
| Quaternary amine anti-muscarinic. Taken by inhalation, causes bronchodilation, used in COPD. |
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Term
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Definition
| Quaternary amine anti-muscarinic. Taken by inhalation, causes bronchodilation, used in COPD. Similar to Ipratropium but longer-acting. |
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Term
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Definition
| Anti-muscarinic. Used to manage overactive bladder, relaxes detrusor to allow for more filling. Contraindicated for patients with narrow-angle glaucoma. |
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Term
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Definition
| Anti-muscarinic. Relaxes intestinal smooth muscle. Used for irritable bowel. |
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Term
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Definition
| Anti-muscarinic. Low doses used to inhibit secretions (e.g. to make intubation easier). Used to prevent excessive generalized sweating and to prevent muscarinic side effects in patients receiving neostigmine (used preferentially over atropine for this use). |
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Term
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Definition
| Anti-muscarinic. Used to relieve extrapyramidal symptoms in Parkinson's patients or patients taking antipsychotics. |
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Term
| Antimuscarinic side-effects |
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Definition
| Block "ddumbbelss": xerostomia, mydriasis and cycloplegia, anhidrosis and cutaneous vasodilation, constipation, difficulty urinating, tachycardia, confusion, sedation, delirium. (Hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter) |
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Term
| Other drugs with anti-muscarinic activity |
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Definition
| Antihistamines, tricyclics (which are antidepressants) and phenothiazine antipsychotics. |
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Term
| Depolarizing nicotinic agonists (blockers) |
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Definition
| Act by initially activating nACh receptors but then rendering them inactive from persistent depolarization. |
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Term
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Definition
| Stimulation of autonomic ganglia followed by blockade (does-dependent), stimulation of adrenal medulla (may see effects of increased epi) and stimulation of CNS: alerting response, change in respiration. |
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Term
| Nicotine toxicity symptoms |
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Definition
| Nausea, vomiting, salivation, diarrhea, cardio effects (depends on state of patient before whether patient shows tachy/bradycardia, etc.), lethargy, confusion, seizures, coma, diaphoresis, tremors, fasiculations, weakness, paralysis, increased epi. |
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Term
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Definition
| Non-depolarizing ganglionic blocker. Was used as an anti-hypertensive. |
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Term
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Definition
| Non-depolarizing ganglionic blocker. Was used for aortic dissection as it lowers BP and prevents the sympathetic reflex. |
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Term
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Definition
| Non-depolarizing ganglionic blocker. Was used for hypertension, can be used to improve GI absorption. Recent interest for use in Tourette Syndrome. |
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Term
| Predominant use for neuromuscular blockers |
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Definition
| Paralyze skeletal muscle during surgical and orthopedic procedures |
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Term
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Definition
| Depolarizing competitive AChR agonist. Phase I: fasiculations; Phase II: desensitization. |
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Term
| Succinylcholine adverse reactions |
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Definition
| Side effects include: apnea, risk of hyperkalemia (in burn/trauma pts where receptors are upregulated), malignant hyperthermia is rare, prolonged action in pts with plasmaChE mutations or liver damage (plasmaChE comes from liver). Stimulates cardiac mAChR: bradycardia, slight release of histamine. |
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Term
| Nondepolarizing neuromuscular blockers: general characteristics () |
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Definition
| All delivered IV. Those metabolized by the kidney will have long half-lives while those metabolized by the liver have shorter half-lives; damage to respective organ can prolong action. Those metabolized by plasmaChE have the shortest half-life. |
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Term
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Definition
(5-15 mins with rapid onset):
Succinylcholine
Mivacurium |
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Term
| Intermediate-acting NM blockers |
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Definition
(20-60 mins):
Vecuronium
Atracurium
Cisatracurium
Rocuronium |
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Term
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Definition
(1-2 hours):
Tubocurarine
Metocurine
Pancuronium
Pipecuronium
Doxacurium |
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Term
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Definition
Short-acting, rapid-onset.
Autonomic ganglia: No effect
Histamine release: Low
Cardiac mAChR: None
Metabolism: plasmaChE |
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Term
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Definition
Medium-acting, rapid-onset.
Autonomic ganglia: no effect
Histamine release: none
Cardiac mAChR: slight
Metabolism: Liver |
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Term
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Definition
Medium-acting, slow-onset.
Autonomic ganglia: no effect
Histamine release: none
Cardiac mAChR: none
Metabolism: Liver (and kidney) deacetylation |
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Term
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Definition
Medium-acting, slow-onset.
Autonomic ganglia: no effect
Histamine release: low
Cardiac mAChR: none
Metabolism: spontaneous hydrolysis |
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Term
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Definition
Medium-acting, slow-onset.
Autonomic ganglia: no effect
Histamine release: slight
Cardiac mAChR: none
Metabolism: Spontaneous hydrolysis |
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Term
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Definition
Long-acting, slow-onset.
Autonomic ganglia: blockade
Histamine release: high
Cardiac mAChR: none
Metabolism: Kidney excretion |
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Term
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Definition
Long-acting, slow-onset.
Autonomic ganglia: blockade
Histamine release: moderate
Cardiac mAChR: none
Metabolism: Kidney excretion |
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Term
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Definition
Long-acting, slow-onset.
Autonomic ganglia: no effect
Histamine release: none
Cardiac mAChR: moderate block (also called 'vagolytic effect': tachycardia)
Metabolism: Kidney deacetylation |
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Term
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Definition
Long-acting, slow-onset.
Autonomic ganglia: no effect
Histamine release: none
Cardiac mAChR: none
Metabolism: Kidney deacetylation |
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Term
|
Definition
Long-acting, slow-onset.
Autonomic ganglia: no effect
Histamine release: none
Cardiac mAChR: no effect
Metabolism: Kidney excretion |
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Term
|
Definition
| Peripheral nerve stimulation, either 'train-of-four' or tetany will display "fade" (response gradually decreases). |
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Term
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Definition
| For blockers other than succinylcholine (and mivacurium) reversal can be accelerated by AChE-I such as neostigmine, with atropine or glycopyrrolate to prevent muscarinic effects. |
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Term
| Typical course of NMJ blockers |
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Definition
| Succinylcholine and mivacurium will be given first for rapid-onset of paralysis followed by use of a long-acting blocker to maintain. Thus, succinylcholine is usually eliminated before reversal with neostigmine (as it would interfere otherwise). |
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