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UNIT 5 DRUGS STIMULATING CHOLINERGIC NEUROTRANSMISSION Cholinoceptor agonists. Anticholinesterases

1. TOPICS TO DISCUSS

1. Diagram of efferent innervation. Localizations of M-cholinoceptors and N-cholinoceptors (of ganglionic and muscle types) on the diagram.

2. Classification of drugs stimulating cholinergic neurotransmission.

3. Subtypes of M-cholinoceptors (M1, M2, M3): main localization and effects of stimulation. Transduction pathways in cardiomyocytes and smooth muscle cells.

4. M-cholinomimetics: pharmacological effects, therapeutic uses and adverse effects.

5. N-cholinomimetics: pharmacological effects and therapeutic uses. Agents for smoking cessation.

6. Pharmacological effects of acetylcholine and carbachol. Therapeutic uses.

7. Classification of anticholinesterases. Mechanism of action. Pharmacological effects. Therapeutic uses. Adverse effects.

8. Toxic effects of M-cholinomimetics and anti-cholinesterases. Agents used in the treatment of overdose with reversible and irreversible anti-cholinesterases. Acetylcholinesterase reactiva-tors. Organophosphate poisoning and its treatment.

2. CLASSIFICATION OF DRUGS

STIMULATING CHOLINERGIC NEUROTRANSMISSION

A. Direct-acting cholinergic agonists

M,N-cholinomimetics:

Acetylcholine, Carbachol

M-cholinomimetics:

Pilocarpine, Bethanechol, Cevimeline

N-cholinomimetics:

Nicotine, Lobeline, Varenicline, Cytisine

B. Indirectly acting cholinergic agonists (Anticholinesterases) Reversible anticholinesterases

Quaternary amines:

Neostigmine, Pyridostigmine, Edrophonium Tertiary amines:

Physostigmine, Rivastigmine, Galantamine, Donepezil

Irreversible anticholinesterases

Echothiophate, Isofluorophate

Note:

Direct-acting cholinergic agonists such as M-cholinomimetics produce effects similar to activation of the parasympathetic nervous system.

Anticholinesterases are referred to as indirectly acting cholinergic agonists because they do not interact with cholinoceptors. They inhibit ace-tylcholinesterase and thus increase concentration of acetylcholine in the synaptic cleft. Effects of anticholinesterases resemble the effects of acetylcholine in neuroeffector and neuromus-cular synapses (at M- and Nm-cholinoceptors respectively).

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