Acetylcholinesterase (Ache) Inhibitors

Ans. is `a’ i.e., It is a quartarnary amounium compound

Tertiary amine Vs quartenary ammonium compound

o Neostigmine is a quartenary ammonium compound.

o Quartenary ammonium compounds are lipid insoluble and diffuse poorly across the membrane : – Li Oral absorption —> Poor

         CNS penetration –> poor No CNS action

         Applied to eye         No penetration of cornea.

         More marked effect on skeletal muscles, ganglia, but muscarinic effects are less prominant.

o In contrast, physostigmine is a tertiary amine derivated.

o Tertiary amine compounds are lipid soluble and diffuse easily across the membrane :-

 Oral absorption       Good

         CNS penetration —> Good      Produce CNS actions.

         Applied to eye –> Penetrate cornea.

         More marked muscarinic and CNS effect.

Ans. is ‘c’ i.e., Increasing the release of Acetylcholine at the motor end palate

o Anticholinestrases act by inhibiting the action of acetylcholinesterase (an enzyme that degrades acetylcholine by causing its hydrolysis).

o Anticholinesterases thus increase the level of acetylcholine at the neuromuscular junction.

o Neostigmine also has some additional direct action on cholinergic receptors i.e., it depolarizes motor end plate.

o It does not increase the release of ACH. Accumulated ACH acts on prejunctional muscarinic autoreceptors and inhibits the release of ACH.

Ans. is ‘a’ i.e., Tertiary ammonium compound

o Neostigmine is a synthetic compound (a carbamic acid ester) and is a quarternary ammonium compound.

o It causes reversal of the paralysis of competitive neuromuscular blocking drugs.

o Neostigmine enhances gastric contractions and increases the secretion of gastric acid so it is used in the treatment of paralytic ileus.

o Neostigmine is used for the treatment of atony of the detrusor muscle of the urinary bladder, thus postoperative dysuria is relieved, and the time interval between operation and spontaneous urination is shortened.

Ans. is ‘a’ i.e., Edrophonium

• Edrophonium (anticholinesterase) injected slowly i.v improves muscle strength only in myaesthenia gravis and not in other muscular dystrophies.

Ans. is ‘d’ i.e., Myasthenic ptosis

Ans. is ‘d’ i.e., Alzheimer disease

o Donepezil is a cerebroactive drug. It is used in Alzheimer’s disease (AD).

Ans. is ‘a’ i.e., TCAs

o Cholinergic transmission is diminished in Alzheimer’s disease.

o All agents that benefit the conduction act to enhance acetyhcholine activity by inhibition of the acetylcholinesterase which metabolises and inactivates acetylcholine.

o Consequently acetylcholine remains usable for longer.

o Rivastigmine acts in similar way.

o Tricyclic antidepressants (TCAs) have anticholinergic property, therefore they counteract that cholinergic effect of rivastigmine.

Ans. is ‘b’ i.e., Tricyclic antidepressant

Rivastigmine (cholinesterase inhibitor) should not be used with drugs that have cholinergic antagonistic activity like tricyclic antidepressants (TCA) as the combination is counter productive.

A i.e. dTC + Pancuronium

As d-TC & Panduronium, both are non-depolarizing muscle relaxant, so neostigmine is used to reverse the drugs.

Answer is C (Edrophonium test):

Edrophonium test is the most sensitive test to suggest the diagnosis of myasthenia gravis amongst the options provided.

Proximal weakness of muscles, ptosis and easy fatigability suggests a diagnosis of Myasthenia Gravis.

Edrophonium (Tensilon) test is a highly sensitive test with 85% sensitivity in ocular and 95% sensitivity in systemic myasthenia.

The diagnosis of MG is highly probable if Edrophonium test is unequivocally positive.

Note

Conventional (EMG) is not a sensitive diagnostic test for MG.

The conventional needle EMG is usually normal in patients with MG although certain findings may indicate probability of MG.

Conventional EMG evaluation in MG serves mostly in excluding other causes of weakness like motor neuron disease, neuropathy or myopathy

Ans. B i.e. Edrophonium test

Myasthenia gravis

Decreased myoneural junction transmission

Features:

Dysarthria,

Dysphagia,

Proximal muscle weakness,

Sensory modalities and deep tendon reflexes are NORMAL

• MC used cholinergic drugs: Pyridostigmine/neostigmine
• Surgical procedure (should be done in all cases): Thymectomy

Ans. D: Edrophonium test

Myasthenia gravis/ MG:

• A disease characterized by episodic muscle weakness, chiefly in muscle innervated by cranial nerves and characteristically improved by anti-cholinesterase inhibiting drug

There is decreased myoneural junction transmission due to auto-immune attack on the acetylcholine receptor of the post-synaptic neuromuscular junction, which results in loss of dysfunction of Ach receptors and jeopardizing normal neuromuscular transmission

• Dysarthria, dysphagia and proximal limb weakness is common
• Sensory modalities and deep tendon reflexes are normal
• Pyridostigmine/ Neostigmine are the MC used cholinergic drugs
• Thymectomy is indicated in all patients with generalized MG
• Plasmapheresis may be useful for preparing refractory cases fro thymectomy and during respiratory crisis

Ans. is ‘d’ i.e., Glaucoma

Ans. is ‘a’ i.e., Edrophonium

Edrophonium is the shortest acting anti-ChE.

Why is it so, lets see :

When carbamates (other than edrophonium) and organophophates react with cholinesterase, they form covalent bond at esteratic site, which is considerably resistant to hydrolysis.

In contrast, edrophonium binds electrostatically and by hydrogen bonds at anionic site (not at esteratic site) of cholinesterase. The enzyme inhibitor complex does not involve a covalent bond and is correspondingly short lived (2-10 minutes).

So edrophonium is also called as noncovalent inhibitor.

The patient represented in the picture above is most probably suffering from myasthenia gravis as drooping eyelid is the most frequently early sign in these cases.

The diagnostic sensitivity of three laboratory tests [serum antiacetylcholine receptor antibody (AChR-ab) assay, the repetitive nerve stimulation (RNS) test, and, the single fiber EMG (SFEMG)] for myasthenia gravis (MG) was compared in 120 patients. In all cases, at least one of the tests was abnormal. SFEMG was the most sensitive test, being abnormal in 92% of cases, followed by the RNS test (77%) and the AChR-ab assay (73%). SFEMG was abnormal in all cases with negative AChR-ab and RNS tests, in 97% of cases with negative AChR-ab assay, in 89% of cases with negative RNS test, and in 89% of cases with mild MG. We conclude that one of these three tests is abnormal in all cases of MG, and that the SFEMG is most sensitive in the diagnosis of MG.

Ans. is ‘d’ i.e., Dementia

• Rivastigmine, Donepezil, Galantamine and tacrine all are central cholinesterase inhibitors and are used in senile dementia of Alzheimer’s desease.