Cholinesterase inhibitors edrophonium

The short-acting cholinesterase inhibitor edrophonium was used to treat supraventricular tachyarrhythmias, particularly paroxysmal supraventricular tachycardia. In this application, edrophonium has been replaced by newer drugs (adenosine and the calcium channel blockers verapamil and diltiazem). 

Another case of asystole has been reported with the very short-acting cholinesterase inhibitor edrophonium (3). 

Since short-acting drugs are usually preferable for diagnostic use, we choose the shortest-acting cholinesterase inhibitor, edrophonium. The answer is (C). 

Reversible cholinesterase inhibitors form a transition state complex with the enzyme, just as acetylcholine does. These compounds are in competition with acetylcholine in binding with the active sites of the enzyme. The chemical stracture of classic, reversible inhibitors physostigmine and neostigmine shows their similarity to acetylcholine. Edrophonium is also a reversible inhibitor. These compounds have a high affinity with the enzyme, and their inhibitory action is reversible. These inhibitors differ from acetylcholine in that they are not easily broken down by enzymes. Enzymes are reactivated much slower than it takes for subsequent hydrolysis of acetylcholine to happen. Therefore, the pharmacological effect caused by these compounds is reversible. 

Metabolites of the cholinesterase inhibitors and in some instances significant amounts of the parent compound are eliminated in the urine. Renal excretion is very important in the clearance of agents such as neostigmine, pyridostigmine, and edrophonium. This is demonstrated by a twofold to threefold increase in elimination half-lives for these drugs in anephric patients. Renal elimination is largely the result of glomerular filtration but probably also involves, at least in the case of quaternary amines, secretion via the renal cationic transport system. 

The organophosphate inhibitors are sometimes referred to as "irreversible" cholinesterase inhibitors, and edrophonium and the carbamates are considered "reversible" inhibitors because of the marked differences in duration of action. However, the molecular mechanisms of action of the three groups do not support this simplistic description. 

In the heart, the effects on the parasympathetic limb predominate. Thus, cholinesterase inhibitors such as edrophonium, physostigmine, or neostigmine mimic the effects of vagal nerve activation on the heart. Negative chronotropic, dromotropic, and inotropic effects are produced, and cardiac output falls. The fall in cardiac output is attributable to bradycardia, decreased atrial contractility, and some reduction in ventricular contractility. The latter effect occurs as a result of prejunctional inhibition of norepinephrine release as well as inhibition of postjunctional cellular sympathetic effects. 

Edrophonium is also used to assess the adequacy of treatment with the longer-acting cholinesterase inhibitors in patients with myasthenia gravis. If excessive amounts of cholinesterase inhibitor have been used, patients may become paradoxically weak because of nicotinic depolarizing blockade of the motor end plate. 

These patients may also exhibit symptoms of excessive stimulation of muscarinic receptors (abdominal cramps, diarrhea, increased salivation, excessive bronchial secretions, miosis, bradycardia). Small doses of edrophonium (1-2 mg intravenously) will produce no relief or even worsen weakness if the patient is receiving excessive cholinesterase inhibitor therapy. On the other hand, if the patient improves with edrophonium, an increase in cholinesterase inhibitor dosage may be indicated. Clinical situations in which severe myasthenia (myasthenic crisis) must be distinguished from excessive drug therapy (cholinergic crisis) usually occur in very ill myasthenic patients and must be managed in hospital with adequate emergency support systems (eg, mechanical ventilators) available. 

Thus either intravenous or intramuscular doses of atropine are indicated to antagonize the muscarinic symptoms. Physostigmine and edrophonium are cholinesterase inhibitors and would exacerbate the problem. Norepinephrine would not be effective in combatting the cholinergic stimulation. Trimethaphan being a ganglionic blocker would also worsen the condition. 

The neostigmine test is used more often to help evaluate limb strength in suspected myasthenics. Neostigmine, a reversible cholinesterase inhibitor with a duration of action longer than that of edrophonium, can be administered either intravenously or intramuscularly. The usual adult dose is 1.5 mg intramuscularly in combination with 0.5 mg atropine to prevent cholinergic-induced side effects. 

Edrophonium chloride, a cholinesterase inhibitor (10 mg IV given over 30 to 45 seconds), may be used as a curare antagonist (to reverse neuromuscular blocking action), and for reversal of nondepolarizing muscle relaxants (see also Figures 17 and 79). 

Edrophonium has the same adverse (cholinergic) effects as other cholinesterase inhibitors. However, the short duration of the drug does not allow for manifestation of these effects. Thus, observed adverse effects are negligible. 

The nurse administered edrophonium (Tensilon), a cholinesterase inhibitor, to a client diagnosed with rule-out myasthenia gravis (MG). Which response by the client indicates the client has myasthenia gravis ... 

Cholinesterase Inhibitors (used to eliminate cholinesterase in the histochemical detection of acetylcholinesterase) diisopropylphosphofluoridate, neostigmine, physostigmine, edrophonium. 

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