Question

1. Describe the main effects of cholinesterase inhibitors on structures controlled by the autonomic nervous system and on skeletal muscle, and state the general mechanism by which these effects occur.
2. Compare and contrast the effects of the cholinesterase inhibitors with those of bethanechol, which was described as the most representative muscarinic agonist (see Chapter 14).
3. State the main clinical uses of cholinesterase inhibitors and precautions for and contraindications to their use.
4. Recognize the meaning and importance of the term quaternary when applied to the structure of a drug; compare and contrast the actions of neostigmine and physostigmine in the context of whether they are quaternary compounds.
5. Compare and contrast the cholinergic crisis and the myasthenic crisis in a hypothetical patient with myasthenia gravis, describe simple assessments that would help distinguish the two conditions, and state the rationale for using cholinesterase inhibitors to help confirm the diagnosis.
6. Describe the signs and symptoms associated with cholinesterase inhibitor overdose and the general approaches to managing it.
7. State the rationales for administering a cholinesterase inhibitor to a patient who has been intentionally paralyzed (e.g., for surgery) with a neuromuscular blocking drug. State which class of neuromuscular blockers causes effects that can be reversed by the cholinesterase inhibitor. State the other main drug that is given as part of the postoperative reversal procedure and explain when and why it is given.
8. Describe the signs and symptoms associated with “irreversible” cholinesterase inhibitors and the general approaches used to manage poisoning caused by these substances.

Answer 1

1.Cholinesterase inhibitors are responsible for the breakdown of acetylcholine at cholinergic synapses and the termination of cholinergic neurotransmission. Cholinesterase inhibitors lead to increased levels of acetylcholine and prolonged transmission in cholinergic synapses an action which is mainly used in the treatment of disorders of neuromuscular transmission and the antagonism of nondepolarizing neuromuscular blockade. Because the actions of cholinesterase inhibitors also affect ANS synapses, causing strong padasympathomimetic actions, coadministration with parasympatholytics such as atropine is recommended.

2Bethanecol is a direct -acting muscarine agonist. At therapeutic doses, bethanecol acts selectively at muscarine receptors ,having little or no effect on nicotinic receptors either in ganglia or in skeletal muscle. They can produce a broad spectrum of pharmacologic effects, the drug is approved only for urinary retention.

.Cholinesterase inhibitors increase acetylcholine levels by inhibiting cholinesterase. They are clinically used for Alzheimer's disease, reversal of non- depolarizing muscle relaxation, myasthenia Gravis and central anticholinergic syndrome.

3.These drugs can elicit a broad spectrum of responses as the use of these results in transmission at all cholinergic junctions. It can produce skeletal muscle stimulation, ganglionic stimulation activation of peripheral muscarine receptors and activation of cholinergic receptors in the central nervous system. Due to lack of selectivity, cholinesterase inhibitors have limited therapeutic applications.

Contraindicsted in Pregnancy risk category C, obstruction of Gastrointestinal and rensl system, seizure disorders, hyperthyroidism, peptic ulcer disease, asthma, bradycardia and hypotension.

4Quaternery means hard to cross the membrane.