1. Name some drugs that activate muscarinic cholinoceptors. What are these compounds used for?

These may be of two broad types based on the mechanism of muscarinic activation:

• Through direct stimulation: examples include carbachol, bethanechol and pilocarpine. Bethanechol has been used for the management of postoperative paralytic ileus and urinary retention. Pilocarpine is used for the management of closed angle glaucoma

• Through indirect stimulation: anticholiesterases promote increased cholinergic stimulation by preventing the hydrolysis of ACh at the synapse. Examples include neostigmine and edrophonium (both quaternary ammonium compounds). Note that these agents are used therapeutically for the reversal of neuromuscular (nicotinic cholinoceptors) blockade. However, as a side effect of preventing ACh hydrolysis, they may also increase the activity of muscarinic cholinoceptors, e.g. at autonomic ganglia

2. What physiologic effects does stimulation of muscarinic receptors lead to?

Essentially, there is increased activation of the PNS:

• Cardiac: with negative inotropic and chronotropic effects, with a reduction in the arterial pressure. This latter effect is exacerbated through peripheral vasodilatation

• Increased glandular secretion: such as increased bronchial, salivary and mucosal secretion. Also increased lacrimation

• Increased smooth muscle contraction: such as in the gut and bronchi. Increased bronchial secretions exacerbate the pathologic effects of bronchoconstriction

• Eye changes: see below

3. Outline the effects of muscarinic stimulation in the eye.

Stimulation leads two main parasympathetic effects:

• Contraction of the constrictor pupillae muscle, reducing the size of the pupil. This also has the effect of improving the drainage of the aqueous humour in those with raised intraocular pressure. In this respect, pilocarpine, a muscarinic agonist, has been used for closed angle glaucoma

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