1. Pharmacology-1 PHL 313 Parasympathetic Nervous System
Fourth Lecture By Abdelkader Ashour, Ph.D. Phone:

2. Bladder* and Gl hypotonia
Muscarinic agonists
Drug
Structure
Receptor specificity
Hydrolysis by AChE
Clinical uses
Musc
Nic
Acetylcholine
+++
None
Carbachol ++ -
Methacholine +
Bethanechol
Bladder* and Gl hypotonia
Muscarine
None†
Pilocarpine
Glaucoma
Oxotremorine

3. Muscarinic Effects on the Eye
The parasympathetic (muscarinic) nerves to the eye supply:
the ciliary muscle, which adjusts the curvature of the lens  Contraction of the ciliary muscle pulling the ciliary body forwards and inwards, thus relaxing the tension on the suspensory ligament of the lens, allowing the lens to bulge more, reducing its focal length
This parasympathetic reflex is necessary to accommodate the eye for near vision
the constrictor pupillae muscle, which is important not only for adjusting the pupil in response to changes in light intensity but also in regulating the intraocular pressure
The main use of muscarinic agonists is in treating glaucoma, by local instillation in the form of eye drops. Pilocarpine is the most effective as, being a tertiary amine, it can cross the conjunctival membrane
The anterior chamber of the eye, showing the pathway for secretion and drainage of the aqueous humor

4. Muscarinic Effects on the Eye
Aqueous humour is secreted slowly and continuously by the cells of the epithelium covering the ciliary body, and it drains into the canal of Schlemm
The intraocular pressure is normally mmHg above atmospheric, which keeps the eye slightly distended
Abnormally raised intraocular pressure (associated with glaucoma) damages the eye and is one of the commonest preventable causes of blindness
In acute glaucoma, drainage of aqueous humour becomes impeded when the pupil is dilated because folding of the iris tissue occludes the drainage angle, causing the intraocular pressure to rise. Activation of the constrictor pupillae muscle by muscarinic agonists in these circumstances lowers the intraocular pressure
The anterior chamber of the eye, showing the pathway for secretion and drainage of the aqueous humor

5. Muscarinic Agonists (Cholinomimetics, Parasympathomimetics)
Pilocarpine (Salagen®)
Indications: It is more commonly used than bethanechol to induce salivation, and also for various purposes in ophthalmology
Treatment of primary open-angle glaucoma and also to lower intraocular pressure prior to surgery for acute angle-closure glaucoma
Treatment of symptoms of dry mouth from salivary gland hypofunction caused by radiotherapy for cancer of the head and neck
Adverse Effects: (most of them are related to its non-selective action as a muscarinic receptor agonist)
Excessive sweating
Excessive salivation
Bronchospasm and increased bronchial mucus secretion
Bradycardia, hypotension
Nausea and diarrhea
It may result in miosis when used chronically as an eye drop

6. Muscarinic Antagonists
Nonselective Muscarinic Antagonists
The classical muscarinic antagonists are derived from plants and are nonselective competitive antagonists. Atropa belladonna contains atropine. Hyoscyamus niger contains primarily scopolamine and hyoscine
Clinically, atropine is used for raising heart rate during situations where vagal activity is pronounced (for example, vasovagal syncope). It is also used for dilating the pupils. Its most widespread current use is in pre-anesthetic preparation of patients; in this situation, atropine reduces respiratory tract secretions and thus facilitates intubation
Ipratropium is used by inhalation as a bronchodilator
Cyclopentolate and tropicamide are developed for ophthalmic use and administered as eye drops (for dilating the pupil to aid examination of the eye)
Oxybutinin and tolterodine are new drugs developed for urinary incontinence

7. Muscarinic Antagonists
Side effects of muscarinic antagonists include:
constipation
urinary retention
xerostomia (dry mouth)
hypohidrosis (decreased sweating)
mydriasis (dilated pupils)
precipitation of glaucoma
decreased lacrimation
tachycardia
decreased respiratory secretions
Selective Muscarinic Antagonists
Pirenzepine shows selectivity for the M1 muscarinic receptor
Because of the importance of this receptor in mediating gastric acid release, M1 antagonists such as pirenzepine help patients with ulcer disease or gastric acid hyper-secretion
Pirenzepine reduces gastric acid secretion with fewer adverse effects than atropine and other less selective agents. Pirenzepine passes the BBB, but only to a small extent, therefore it has no central effects