Pharmacology1 PHL 313 Parasympathetic Nervous System

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Pharmacology-1 PHL 313 Parasympathetic Nervous
System
Fourth Lecture ByAbdelkader Ashour, Ph.D.
Phone [phone] Email aeashour_at_ksu.edu.sa
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Muscarinic agonists







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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

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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 10-15 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

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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

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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

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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