Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Anticholinesterases Dr. S. Parthasarathy MD., DA., DNB, MD (Acu), Dip. Diab. DCA, Dip. Software statisticsPhD ( physiology), IDRA What are these ? • These agents are used in clinical practice to inhibit the action of acetylcholinesterase at the neuromuscular junction, thus prolonging the half-life of acetylcholine • So it antagonizes • neuromuscular blockade Cholinesterase means acetyl cholinesterase – true E d r o p h o ni Neo A c e t yl a t P h o s Opc • • • • • Pouring acetyl choline in junctions Antagonizes neuro muscular blockers Initiate depolarization Start contraction Also presynaptic action • If we don’t have blockers at the site , it may cause persistent depolarization to cause weakness Its pouring acetyl choline !! • The anticholinesterases produce effects equivalent to excessive stimulation of the cholinergic system, • i.e. stimulation of muscarinic receptor responses at the autonomic effector organs, • and stimulation of cholinergic receptors in the CNS. Drugs – structure Neostigmine Edrophonium Pyridostigmine No NH4+ Crosses membranes Physostigmine Organophosphorous compounds – lipid soluble – cross BBB Systems CVS • Vagal influence of conducting tissue • Bradycardia • Decreased BP and output Respiratory system • cause bronchial smooth muscle contraction leading to bronchospasm and hypoxia, • aggravated by an increase in secretions GIT • Oesophageal motility, gastric motility and production of gastric secretions are enhanced • Rarely vomiting Local application on eye • Miosis • Loss of accommodation • Tacrine is a short-acting anticholinesterase that can cross the blood–brain barrier producing central effects. • used in the past to extend the duration of action of succinylcholine. • Currently, it is used in the management of Alzheimer’s disease. Edrophonium • Dose 0.5 to 1 mg / kg • • • • Onset 1 minute Duration 10 minutes Need spontaneous recovery Atropine Neostigmine • • • • • 50 – 60 mic/ kg 1 minute 20 – 30 minute Glyco 15 mg neostigmine bromide PO is equivalent to 0.5 mg neostigmine methylsulfate parenteral • Nausea • Intestinal obstruction • Phase 2 block ?? Pyridostigmine • Derivative of neostigmine • Onset - 16 minutes • duration - 6 hours • Not for reversal • Myaesthenia Physostigmine • Physostigmine (also known as eserine from éséré, the West African name for the Calabar bean) is a parasympathomimetic alkaloid, • Physostigmine is metabolized by plasma esterases; • elimination does not depend on renal excretion, but others depend Uses of physo • Physostigmine is used to treat glaucoma, Alzheimer's disease, and delayed gastric emptying. It has been shown to improve long term memory. • Recently, it has begun to be used in the treatment of orthostatic hypotension. Physostigmine • Because it is a tertiary amine, it can cross the blood–brain barrier, and physostigmine salicylate is used to treat the central nervous system effects of atropine, scopolamine, and other anticholinergic drug overdoses. • Physostigmine is the antidote of choice for Datura stramonium poisoning. It is also an antidote for Atropa belladonna poisoning, the same as for atropine Pharmacokinetics- neostigmine • Metabolism • Liver microsomal enzymes and hydrolysis by cholinesterase enzymes • Elimination • Half-Life: 47-60 min (IV); 51-90 min (IM); 4260 min (PO) • Excretion: 50% urine Tensilon test • Discontinue all anticholinesterase agents for >8 hr • Give atropine 0.011 mg/kg IV (if IM give 30 minutes before) with neostigmine 0.022 mg/kg IM • If cholinergic response, stop test and give 0.4-0.6 mg atropine IV • If inconclusive, retest another day with neostigmine 0.031 mg/kg IM preceded by 0.016 mg/kg atropine • Edrophonium is used mainly to diagnose myasthenia gravis. • A test dose of 2 mg followed 30 s later by 8 mg i.v. causes transient improvement in muscle power. • Myesthenic crisis or cholinergic crisis Myasthenia gravis • Acute: 0.5-2.5 mg IV/IM/SC q Day • Maintenance: 15-375 mg/day PO divided q68hr • Use injectable with 0.6-1.2 mg atropine IV to counteract muscarinic effects Nondepolarizing Neuromuscular Blockade, Reversal • 30 – 70 mic./kg • Dose varies with type of drug, • time duration after NMBs • Administer an IV anticholinergic (eg, atropine, glycopyrrolate) prior to, or concomitantly with neostigmine for NMB reversal; if bradycardia present, give anticholinergic before neostigmine Alzheimer’s disease • A deficiency of structurally intact cholinergic neurones leads to progressive dementia in patients with Alzheimer’s disease • Donezipil • Rivastigmine Post op urinary retention • Prevention: Neo -- 0.25mg IM after surgery. Repeat q4-6hr for 2-3 days • Treatment: 0.5-1 mg IM and up to q3hr PRN (for 5 doses for retention) • Colonic Pseudo-obstruction Central anticholinergic syndrome • . It can be reversed by intravenous physostigmine 2 mg followed by additional doses as required. • Chemical warfare • Oximes and atropine Side effects • • • • Allergic: Allergic reactions and anaphylaxis Neurologic: Dizziness, convulsions, loss of consciousness, drowsiness, headache, dysarthria, miosis and visual changes • Cardiovascular: • Cardiac arrhythmias (including bradycardia, A-V block and nodal rhythm) and nonspecific EKG changes have been reported, Side effects • Respiratory: • Increased oral, pharyngeal and bronchial secretions, and dyspnea; • respiratory depression, respiratory arrest and bronchospasm have been reported following the use of the injectable form Frequency of side effects not studied • Dermatologic: Rash and urticaria • Gastrointestinal: Nausea, emesis, flatulence, and increased peristalsis and salivation • Genitourinary: Urinary frequency • Musculoskeletal: Muscle cramps and spasms, arthralgia • Miscellaneous: Diaphoresis, flushing and weakness • Possible intraarticular neostigmine – used for analgesia Summary • Ach – cholinesterase – anticholinesterase – pour Ach every where • • • • Types Anionic – esteritic sites – Uses Side effects