Myasthenia gravis neostigmine

The relative inaccessibility of physostigmine led to molecular dissection studies to define the parts of the molecule necessary for activity. A surprisingly simple derivative of m-hydroxy-aniline, neostigmine (40), proved to have the same activity as the complex heterocyclic molecule. In addition, this drug has found use as a cholinsterase inhibitor in pathologic conditions such as myasthenia gravis, marked by insufficient muscle tone. Reaction of m-dimethylaminophenol (37) witn pnosgene affords tne... 

D.F.P. was administered intramuscularly in small doses to ten patients for periods varying from 2 weeks to 2 years. It was concluded that D.F.P. was not a very suitable drug for the routine treatment of myasthenia gravis, since it did not relieve signs and symptoms as effectively and consistently as neostigmine. 

A young patient is being treated for myasthenia gravis, which requires frequent adjustment of the optimal dose of neostigmine. The patient is challenged with edrophonium to evaluate the effectiveness of the cholinesterase inhibition. Optimal dosing will be indicated by... 

Contraindications Bladder neck obstruction due to prostatic hypertrophy, cardiospasm, intestinal atony, myasthenia gravis in those not treated with neostigmine, narrow-angle glaucoma, obstructive disease of the GI tract, paralytic ileus, severe ulcerative colitis, tachycardia secondary to cardiac insufficiency or thyrotoxicosis, toxic megacolon, unstable cardiovascular status in acute hemorrhage... 

Neostigmine is a drug of choice in the treatment of myasthenia gravis, a chronic disease characterized by muscular weakness and rapid fatiguability of the skeletal muscles due to impaired neuromuscular transmission. The defect may be presynaptic or postsynaptic. 

Apart from neostigmine, pyridostigmine and ambenonium are the other standard drugs used in the treatment of myasthenia gravis. 

It structurally and pharmacologically resembles neostigmine but has longer duration of action and less potent than neostigmine and better tolerated by myasthenia gravis patients. 

Neostigmine Forms covalent bond with AChE, but hydrolyzed and released Like edrophonium, but longer-acting Myasthenia gravis t postoperative and neurogenic ileus and urinary retention Oral and parenteral quaternary amine, does not enter CNS. Duration 2-4 h Toxicity and Interactions Like edrophonium... 

Uses treatment of myasthenia gravis (has fewer side effects -salivation, Gl disturbances, bradycardia- than neostigmine) antidote to nondepolarizing blockade caused by muscle relaxants during surgery. 

Neostigmine Prostigmin Postoperative gastrointestinal and urinary atony, myasthenia gravis, reversal of neuromuscular blocking drugs... 

The therapeutic uses of neostigmine include the treatment of atony of the urinary bladder and postoperative abdominal distention. In addition, it antagonizes the action of rf-tubocurarine and curariform drugs. Edrophonium, neostigmine, or pyridostigmine may be used to diagnose myasthenia gravis. Because edrophonium has the shortest duration of action, it is most often used for this purpose. 

As mentioned in Part 2, there are drugs that can interfere with the inactivation of neurotransmitters. In that particular case the reversible cholinesterase inhibitor neostigmine was discussed within the context of treating myasthenia gravis. Excessive blockade of acetylcholinesterase at both muscarinic and nicotinic synapses results in a sustained excess of acetylcholine, which persistently activates the effector they innervate. Muscarinic stimulation results in excessive salivation, lacrimation, bronchiolar secretions, and bronchoconstriction. Nicotinic stimulation produces effects such as those described earlier for nicotine. 

Pyridostigmine [peer id doe STIG meen] is another cholinesterase inhibitor that is used in the chronic management of myasthenia gravis. Its duration of action (3-6 hours) is longer than that of neostigmine (2-4 hours). 

The actions of edrophonium [ed roe FOE nee um] are similar to those of neostigmine, except that it is more rapidly absorbed and has a short duration of action (10-20 minutes). Edrophonium is a quarternary amine and is used in the diagnosis of myasthenia gravis. Intravenous injection of edrophonium leads to a rapid increase in muscle strength. Care must be taken since excess drug may provoke a cholinergic crisis. Atropine is the antidote. 

Neuromuscular paralysis This side effect most often results after direct intraperitoneal or intrapleural application of large doses of aminoglycosides. The mechanism responsible is a decrease in both the release of acetylcholine from prejunctional nerve endings and the sensitivity of the postsynaptic site. Patients with myasthenia gravis are particularly at risk. Prompt administration of calcium gluconate or neostigmine can reverse the block. 

PROPAFENONE PARASYMPATHOMIMETICS 1 efficacy of neostigmine and pyridostigmine Uncertain propafenone has a degree of antinicotinic action that may oppose the action of parasympathomimetic therapy for myasthenia gravis Watch for poor response to these parasympathomimetics and t dose accordingly... 

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