Cholinergics Flashcards
Muscarinic Receptors Eye: Heart: Lung: Bladder: GI tract: Sweat Glands: Blood Vessels:
Eye: Contraction of the ciliary muscle focus lens for near vision; Contraction of the iris sphincter muscle
Heart: Decreased rate
Lung: Constriction of bronchi; secretion
Bladder: Voiding
GI tract: Salivation; Increased gastric secretion; increased intestinal motility
Sweat Glands: Generalized sweating
Blood Vessels: Vasodilation
Nicotinic Receptors
Nm:
Nn:
CNS:
Nm: Skeletal muscle - End-plate depolarization
Nn: Autonomic ganglia and Adrenal medulla - depolarization and firing of post-ganglionic neurons; Depolarization and secretion of catecholamines
CNS: Control of neurotransmitter release
Cholinergic Agonists and Antagonists
Muscarinic Receptor Agonists Acetylcholinesterase inhibitors - Reversible inhibitors - Irreversible inhibitors Muscarinic Receptor Antagonists Ganglionic Blocking Agents Neuromuscular Blocking Agents - Competitive blockers - Depolarizing blockers
Muscarinic Agonists
Direct agonists of muscarinic receptors; produce effects similar to activating post-ganglionic parasympathetic nerves (parasympathomimetics)
Choline Esters
Acetyclcholine; Bethanechol
Bethanechol
Primarily Effects:
Therapeutic Uses:
Primarily effects G.I/G.U systems
Therapeutic Uses: Orally or subcutaneous treatment for urinary retention in the absence of obstruction
Alkaloids
Muscarine; Pilocarpine
Pilocarpine - Therapeutic Effects
- Orally for xerostomia
- Miotic agent used opthalmically to treat wide-angle glaucoma as well as emergency treatment for narrow-angle glaucoma
Bethanechol and Pilocarpine: Route of administration
Not IV
Oral (bethanechol, pilocarpine) or Subcutaneous (Bethanechol)
Opthalmic: pilocarpine, acetylcholine
Bethanechol and Pilocarpine: Side Effects
Salivation, Lacrimation, Urination, Defacation, Gastrointestinal upset, Emesis (SLUDGE)
Also… Hypotension, bradycardia and blurred vision
Toxicity: treated with muscarinic receptor antagonist (atropine)
Bethanechol and Pilocarpine: Use with caution in patients with…
Athsma and COPD
Urinary or GI obstruction and peptic ulcer
Cardiovascular diseases involving bradycardia or hypotension
Acetylcholinesterase Inhibitors
Enhance the effects of endogenously released acetycholine by blocking its natural breakdown by acetylcholinesterase
- Effective at any site where acetycholine is the neurotransmitter
- Also termed anticholinesterase agents
Acetylcholinesterase Sites of action
- Post-ganglionic parasympathetic neuroeffector junction
- Ganglia (Sympathetic and Parasympathetic)
- Neuromuscular junction
- CNS (if able to penetrate)
Reversible acetycholinesterase inhibitors
Edrophonium
Physostigmine
Neostigmine
Edrophonium - Therapeutic Use
- Diagnosis of myasthenia gravis
- Distinguish cholinergic from myasthenic crisis
- Reverse paralysis by competitive neuromuscular blocking agents
Administration of Edrophonium
Rapid onset and short duration of action
Does not penetrate into CNS
Not orally active (IV administration)
Physostigmine - Therapeutic Use:
Treatment of chronic wide-angle glaucoma
Toxicity by antimuscarinic drug poisoning
Physostigmine: Structure
Tertiary Amine (lipophilic) - CNS effects
Neostigmine: Structure
Synthetic: Quarternary amine so no CNS penetration
Neostigmine - Therapeutic Use:
Treatment of myasthenia gravis (oral)
Prevention and treatment of post-operative atony of gut and bladder (oral)
Reversal of paralysis by neuromuscular junction blocking agents
Reversible Acetycholinesterase Inhibitors - Side Effects
SLUDGE
Irreversible Acetycholinesterase Inhibitors are all….
Lipophilic and can pass through mucosal membranes and skin
Nerve gas used in attacks in Japan and Syria
Sarin
Malathion
Insecticide - greater safety than Sarin because it is detoxified in higher organisms
Toxicity of Irreversible Acetycholinesterase Inhibitors (Organophosphate)
- SLUDGE
- Hypotension; Bradycardia; Bronchoconstriction; Blurred vision
- Death due to respiratory failure
- Medullary respiratory center depression
- Symptom onset depends on method of exposure
Treatment for Organophosphate
- Remove poisoning
- Maintain open airway; artificial respiration
- Treat convulsions and shock
Antidotes - Atropine
- Pralidoxime
Pralidoxime
Reactivates Acetycholine esterase peripherally
Must treat quickly (2-3 hours)
Muscarinic Receptor Antagonists
Competitively block muscarinic receptors (Parasympatholytics)
Effects of Muscarinic antagonists
- Relax iris sphincter and ciliary muscles
- Relax non-vascular smooth muscle
- Inhibit exocrine gland secretion
- Increase heart rate
- CNS effects (Sedation (low doses); Excitement, delirium, psycohsis (high hoses))
Atropine - Therapeutic Uses
- Bradyarrhythmias
- Opthalmic uses - mydriasis and cycloplegia
- Block vagal reflexes and reduce secretions during anesthesia
- Acetylcholinesterase and muscarinic toxicity
Scopolamine - Therapeutic Use
Motion sickness and vestibular diseases
Muscarinic Receptor Antagonists: Alkaloids
Atropine; Scopolamine
Muscarinic Receptor Antagonists: semi-synthetic derivative
Ipratropium
Ipratropium - Therapeutic Use
COPD
Less effective for athsma
Ipratropium administration and actions
Administered by inhalation
No CNS penetration and poor systemic absorption when inhaled
Reduces bronchial secretions and reduces bronchoconstriction
Muscarinic Receptor Antagonists: Synthetics
Tropicamide
Oxybutynin
Darifenacin
Glycopyrrolate
Tropicamide - Therapeutic Use
Mydriatic and Cycloplegic Fast onset (20-40 min) and short duration of action (4-6 hours)
Oxybutynin
Therapeutic Use:
Side-effects
Therapeutic use: Overactive bladder, incontinence
SE: xerostomia, blurred vision, constipation
Darifenacin (Has some M3 selectivity)
Therapeutic use:
Overactive bladder, incontinence
Less CNS side effects
Glycopyrrolate - Therapeutic Use:
Used to block parasympathomimetic effects when neostigmine is used to reverse+ skeletal muscle paralysis by neuromuscular blocking agents
No CNS penetration
Muscarinic Receptor Antagonists: Side Effects
Hot as a hare (no sweating) Dry as a bone (Dry mouth) Red as a beet (Due to excess heat) Blind as a bat (Mydriasis, cycloplegia) Drowsiness (CNS actions) Mad as Hatter (at high concentrations)
Muscarinic Receptor Antagonists: Use with caution
Glaucoma
Benign Prostatic hyperplasia
Any disease where tachycardia is a problem (angina)
Neuromuscular blocking agents
Block neurotransmission at the neuromuscular junction producing paralysis of skeletal muscle - Used as adjuvant in surgical anesthesia
All competitive neuromuscular blocking agents are…
Quartenary amines, so no CNS effects, not absorbed
Competitive Neuromuscular blocking agents differ in:
Duration of action (Short, medium, long) Side Effects (Cardiovascular, histamine) Elimination route (Metabolism, renal excretion)
Rocuronium Duration of action: Elimination: CV effects: Histamine Release:
Duration of action: Intermediate (30-60 min)
Elimination: Liver metabolism
CV effects: Minimal
Histamine Release: None
Atracurium Duration of action: Elimination: CV effects: Histamine Release:
Duration of action: Intermediate (30-60 minutes)
Elimination: Spontaneously degrades in plasma
CV effects: Minimal
Histamine Release: Slight
Vercuronium Duration of action: Elimination: CV effects: Histamine Release:
Duration of action: Intermediate (60-90 minutes)
Elimination: Liver metabolism
CV effects: Minimal
Histamine Release: None
Pancuronium Duration of action: Elimination: CV effects: Histamine Release:
Duration of action: Long (120-180 min)
Elimination: Renal excretion
CV effects: Slight increase in HR and BP
Histamine Release: Slight
Depolarizing Neuromuscular Blockers
Activate nicotinic receptors at the neuromuscular junction maintaining motor end plate depolarization and thus prevents transmission of another action potential
Succinylcholine (Depolarizing Neurmuscular Blocker)
Duration of Action:
Metabolized by:
Ultra short duration of action (5-8 minutes)
- Rapid onset (1 - 1.5 minutes)
Metabolized by pseudocholinesterase
Competitive Neuromuscular blockers - Adverse Effects and Toxicity
- Prolonged apnea
- Toxicity or overdose with competitive antagonists can be reversed by administering an acetylcholinesterase inhibitor
- If treat with an acetylcholinesterase inhibitor, treat with glycopyrrolate to minimize muscarinic actions
Depolarizing Neuromuscular blockers - Adverse Effects and Toxicity
- Prolonged apnea
- Malignant hyperthermia
- Post operative muscle pain due to muscle fasciculation
- Hyperkalemia
