Nervous System 2

Parasympathetic Nervous System (PNS  Drugs can mimic the parasympathetic nervous system by either: • Directly binding (direct-acting) to acetylcholine receptors • Inhibiting acetylcholine esterase (AchE) – the enzyme that breaks acetylcholine (Ach) down

 Clinical Effects of Muscarinic Receptor Stimulation↓ Heart rate • ↑ Gastric motility • ↑ Urination • ↑ Sweating • ↑ Salivation • ↑ Nasal secretions • ↑ Bronchial secretions • ↑ Bronchoconstriction • Miosis • Direct-acting cholinergics (parasympathomimetics) bind to cholinergic receptors and produce a “rest and digest” response • Select examples of direct-acting muscarinic agonists: • Pilocarpine (Isopto Carpine) – glaucoma treatment • Bethanechol (Urecholine) – urinary retention treatment

Indirect-acting parasympathomimetics inhibit the action of AchE • “Cholinesterase inhibitors”
Select Examples Primary Use Donepezil (Aricept) Alzheimer’s disease Galantamine (Razadyne) Alzheimer’s disease Physostigmine (Antilirium) Reverses effects of anticholinergics* Edrophonium (Tensilon) Dx. of myasthenia gravis Pyridostigmine (Mestinon) Myasthenia gravis

Cholinergic Blockers (Anticholinergics/Muscarinic Antagonists) • ↑ Heart rate • ↓ Gastric motility (irritable bowel syndrome) • ↓ Gastric acid secretion (peptic ulcer disease) • ↓ Urination (incontinence) • ↓ Sweating • ↓ Salivation (anesthesia) • ↓ Nasal secretions • ↓ Bronchial secretions (anesthesia) • ↓ Bronchoconstriction [ipratropium bromide (Atrovent) dilates the bronchi] • Mydriasis • Anticholinergic patient symptoms: “Blind as a bat, dry as a bone, red as a beet, mad as a hatter, and hot as a hare

e Cholinergic Blockers (Anticholinergics/Muscarinic Antagonists Select Examples Primary Uses Ipratropium bromide (Atrovent) COPD Atropine Bradycardia, ↓ secretions for anesthesia, diarrhea, urinary incontinence, others Dicyclomine (Bentyl) Irritable bowel syndrome (IBS) Propantheline (Pro-Banthine) IBS, urinary incontinence, neurogenic bladder Scopolamine (Transderm-Scop) Motion sickness Benztropine (Cogentin) Parkinson’s disease Trihexyphenidyl (Artane) Parkinson’s disease

Treating Parkinson’s Disease Pathophysiology Review: • Caused by decreased dopamine (DA) transmission • Cholinergic transmission begins to dominate in the brain as DA transmission is decreased • Classic triad of findings: 1. Tremor 2. Rigidity 3. Bradykinesias • Treated by either: • Increasing dopamine transmission OR • Blocking cholinergic neurotransmission

Dopaminergic Agents Agents: Carbidopa/levodopa (Sinemet), Levodopa (Dopar) MOA: Metabolized to dopamine in the CNS; stimulates dopamine receptors Adverse Effects: GI upset, arrhythmias, dyskinesias, on-off and wearing-off phenomena, confusion, dizziness, headache, hallucinations Comments: Use with carbidopa greatly diminishes required dosage Use with COMT/MAO-B inhibitors prolongs duration of effect Sinemet is available as immediate release and sustained release

Dopamine Agonists
Agents: Bromocriptine (Parlodel), pramipexole (Mirapex), ropinirole
(Requip)
MOA: Stimulates dopamine receptor
Adverse
Effects:
Nausea, vomiting, postural hypotension, dyskinesias,
confusion, impulse control disorders, sleepiness
Comments: Can be used as monotherapy (mild disease) or in
combination with Sinemet
Pramipexole: adjust dose for renal dysfunction
Ropinirole: many drug-drug interactions
Contraindicated in patients with a history of psychotic illness
or recent MI or active peptic ulceration

Monoamine Oxidase Inhibitors Agents: Rasagiline (Azilect), selegiline (Eldepryl) MOA: Inhibits MOA, slows/prevents the breakdown of dopamine Adverse Effects: Orthostatic hypotension, rash, weight loss, GI upset, arthralgia, ataxia, dyskinesia, headache Comments: Adjunct therapy only Rasagiline is more potent than selegiline May cause serotonin syndrome Many drug interactions: avoid meperidine, tramadol, methadone, propoxyphene, cyclobenzaprine, OTC’s Serotonin syndrome: avoid TCA’s, SSRI’s