3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.3. Pharmacology
                  3.1.3.8. Acetylcholine-related drugs
 3.1.3.8.2. Cholinergic agonists 

Cholinergic agonists

[SH4:p263-264]

  • ACh has no therapeutic application because of its rapid hydrolysis and non-specific site of action
  • Synthetic cholinergic agonist drugs
    * Primarily activate muscarinic receptors which are innervated by postganglionic parasympathetic nerves
    * Also act on autonomic ganglia and on cells with cholinergic (nicotinic) receptors
    * Blocked by atropine

Synethetic cholinergic agonists

Synthetic ACh-derivatives with clinical applications are:

  • Methacholine
  • Carbachol
  • Bethanechol

Side effects

Can exacerbate

  • Asthma (Bronchoconstriction)
  • Coronary artery disease (Vasodilation causing decrease in diastolic BP)
  • Peptic ulcer disease (Increased gastric acid secretion)

Methacholine

  • Slower hydrolysis by AChE
    --> Longer duration of action than ACh
  • Almost totally resistant to plasma cholinesterase
  • Greater receptor selectivity than ACh
    * Predominant muscarinic action
    * Lack of significant nicotinic action
  • Rarely used clinically due to unpredictable muscarinic effect (especially CVS effects)

Carbachol and bethanechol

  • Toally resistant to hydrolysis by AChE or plasma cholinesterase
  • Bethanechol more selective (muscarinic)
  • Carbachol has more significant nicotinic activity
    * Especially on autonomic ganglia

Side effects

  • Both carbachol and bethanechol
    * CVS effects not very prominent
    * More prominent effects on GIT and urinary tract
  • GIT effects include:
    * Increased lower oesophageal sphincter tone
    * Increased peristalsis
    * Enhanced secretion
    * N&V
    * Spontaneous defaecation
  • Urinary effects include:
    * Stimulation of urethral peristalsis
    * Contraction of detrusor muscle
    * Trigone and external sphincter relaxation

Clinical use

  • Bethanechol is used as stimulant of smooth muscles of GIT and urinary bladder (e.g. neurogenic bladder)
  • Carbachol is not used for its action on GIT or urinary bladder
    * Due to relatively greater effects at autonomic ganglia
  • Carbachol is used as a topical drug on eyes
    * Chronic treatment of narrow-angle glaucoma
    * Produce miosis during intraocular surgery

Cholinomimetic alkaloids

Cholinomimetic alkaloids derived from plants include:

  • Pilocarpine
  • Muscarine
  • Arecoline

Pilocarine

  • Dominant muscarinic effects
  • Sweat glands are particularly sensitive to pilocarine
  • Clinically used
    * As a topic agent (on eyes) --> For treatment of glaucoma
    * As oral agent --> Treatment of xerostomia (associated with Sjogren syndrome or radiation therapy)
  • Pilocarine, used as a topical agent on eyes, causes:
    * Miosys (persists for several hours)
    * Paralysis of ciliary muscles, with loss of accommodation (cycloplegia) (usually recovers within 2 hours)
    * Sustained decrease in intraocular pressure

NB:

  • Xerostomia = Dry mouth

Muscarine

  • Almost only act exclusively at muscarinic cholinergic receptors