Pharmacology - Drugs Affecting the Parasympathetic Nervous System

Cholinergic Nerve Activity

  • Cholinergic: Nerves and receptors of the parasympathetic nervous system.
  • Acetylcholine (ACH) is synthesized within the cholinergic nerve ending.
    • Stimulation of the nerve releases ACH, which binds to cholinergic receptors.
    • Results in parasympathetic stimulation.
  • Acetylcholinesterase:
    • Enzyme that inactivates ACH outside a nerve ending.
    • Inactivation occurs quickly; effects of ACH last for only a few seconds.
    • Pseudocholinesterase.
    • Acetylcholinesterase enzyme.
    • Hydrolyzes ACH and related drugs.

Cholinergic Receptors

  • Muscarinic.
  • Nicotinic-neural (Nn).
  • Nicotinic-muscle (Nm).

Cholinergic Drugs

  • Mimic the actions of ACH.
    • Known as parasympathomimetics.
  • Direct-acting cholinergic drugs:
    • Bind to the cholinergic receptor and produce:
      • Increased GI secretions and motility.
      • Increased urinary tract function.
      • Pupillary constriction.
  • Indirect-acting cholinergic drugs:
    • Known as anticholinesterases.
    • Allow the accumulation of ACH at all cholinergic receptor sites.
    • Types:
      • Reversible inhibitors.
      • Irreversible inhibitors.
  • Adverse effects:
    • Nausea, vomiting, blurred vision, excessive sweating, muscular tremors, bronchoconstriction, bradycardia, and hypotension.
    • Toxic overdose can lead to muscular paralysis and respiratory depression.
    • Cholinergic crisis - Excessive drug dosage in patients with myasthenia gravis.

Cholinergic Drugs - Clinical Indications

  • Direct-Acting Drugs
    • Acetylcholine (Miochol-E): Miotic in ophthalmology
    • Bethanechol (Urecholine): Urinary retention, postoperative ileus
    • Carbachol (Isopto carbachol): Treatment of glaucoma
    • Pilocarpine (Isopto carpine): Treatment of glaucoma
  • Indirect-Acting Drugs (Anticholinesterases)
    • Echothiophate (Phospholine): Treatment of glaucoma
    • Edrophonium (Tensilon): Diagnosis of myasthenia gravis
    • Neostigmine (Prostigmin): Treatment of myasthenia gravis, postoperative ileus, and urinary retention; antidote to excessive cholinergic blockade with anticholinergic and skeletal muscle blockers
    • Physostigmine (generic): Treatment of glaucoma, antidote to excessive cholinergic blockade with anticholinergics and skeletal muscle blockers
    • Pyridostigmine (Mestinon): Treatment of myasthenia gravis
    • Donepezil (Aricept): Treatment of Alzheimer’s disease
    • Galantamine (Razadyne): Treatment of Alzheimer’s disease
    • Rivastigmine (Exelon): Treatment of Alzheimer’s disease

Clinical Indications for Anticholinesterase Drugs

  • Glaucoma.
  • Myasthenia gravis.
  • Urinary retention.
  • Intestinal stasis.
  • Alzheimer’s disease.
  • Antidotes to skeletal muscle blockers.
  • Anticholinergic drug poisoning.
  • Clinical use of Botulinum toxin.

Anticholinergic Drugs

  • Cholinergic blocking drugs that bind to the muscarinic receptors.
    • Known as parasympatholytic drugs.
  • Competitive antagonism of ACH.
    • ACH is unable to bind to the cholinergic receptors to produce an effect.
  • Produce pharmacological actions on the:
    • Cardiovascular system.
    • Respiratory system.
    • GI system.
    • Genitourinary system.
    • Central nervous system.
    • Eye.
  • Adverse effects
    • Dry mouth.
    • Visual disturbances.
    • Constipation and urinary retention.
    • Flushing and dryness of the skin.
    • Fever and tachycardia.
    • Symptoms of CNS stimulation and depression.

Anticholinergic Drugs - Clinical Uses

  • Atropine (generic)
    • Preparations: Tablets, parenteral injection
    • Main clinical uses: Antidote for cholinesterase inhibitor poisoning, anticholinergic effects
  • Atropine (Isopto atropine)
    • Preparations: Ophthalmic drops, ointment
    • Main clinical uses: Ophthalmic examinations
  • Darifenacin (Enablex)
    • Preparations: Tablets
    • Main clinical uses: Relief of urinary spasms, urgency, incontinence
  • Dicyclomine (Bentyl)
    • Preparations: Tablets, syrup, parenteral injection
    • Main clinical uses: Intestinal disorders, diarrhea, irritable bowel syndrome
  • Flavoxate (Urispas)
    • Preparations: Tablets
    • Main clinical uses: Relief of urinary spasms, urgency, incontinence
  • Glycopyrrolate (Robinul)
    • Preparations: Tablets, parenteral injection
    • Main clinical uses: Intestinal disorders, diarrhea
  • Hyoscyamine (Anaspaz, Levbid, Levsin)
    • Preparations: Oral tablets, capsules, parenteral injection
    • Main clinical uses: Intestinal disorders, diarrhea, irritable bowel syndrome
  • Ipratropium (Atrovent)
    • Preparations: Aerosol, metered-dose inhaler
    • Main clinical uses: Bronchodilation, asthma, COPD
  • Methscopolamine (Pamine)
    • Preparations: Tablets
    • Main clinical uses: Intestinal disorders, spasms
  • Oxybutynin (Ditropan, Ditropan XL, oxybutynin topical) (Oxytrol, OTC)
    • Preparations: Tablets, syrup, transdermal patch, parenteral injection
    • Main clinical uses: Relief of urinary spasms, urgency, incontinence
  • Propantheline (Pro-Banthine)
    • Preparations: Tablets
    • Main clinical uses: Intestinal disorders, diarrhea, irritable bowel syndrome
  • Scopolamine (generic) (Transderm scop)
    • Preparations: Tablets, parenteral injection, Skin patch
    • Main clinical uses: Intestinal disorders, Motion sickness
  • Solifenacin (Vesicare)
    • Preparations: Tablets
    • Main clinical uses: Relief of urinary spasms, urgency, incontinence
  • Tiotropium (Spiriva)
    • Preparations: Aerosol, metered-dose inhaler
    • Main clinical uses: Bronchodilation, asthma, COPD
  • Tolterodine (Detrol, Detrol LA)
    • Preparations: Tablets, capsules
    • Main clinical uses: Relief of urinary spasms, urgency, incontinence
  • Trospium (Sanctura)
    • Preparations: Tablets, capsules
    • Main clinical uses: Relief of urinary spasms, urgency, incontinence

Preferred Treatment

  • Urinary retention:
    • Cholinergic drugs or cholinesterase inhibitors.
    • Males with benign prostatic hyperplasia:
      • Alpha-blockers.
    • Overactive bladder or urge incontinence:
      • Anticholinergic drugs.
  • Intestinal stasis or postoperative ileus:
    • Cholinergic drugs or anticholinesterases.
  • Irritable bowel syndrome:
    • Anticholinergic drugs.
  • Myasthenia gravis:
    • Anticholinesterases.
  • Alzheimer’s disease:
    • Cholinesterase inhibitors.