Acetylcholine Receptor Antagonists Flashcards
Muscarinic receptor antagonists - MoA
Compete with Ach for its receptors at parasympathetic neuroeffector junctions and thereby inhibits the effects of parasympathetic nerve stimulation
Muscarinic receptor antagonists - Effects
Ocular: Mydriasis (relaxing of iris sphincter muscle). Flattenes the lens (relaxing ciliary muscle–> focus distal objects), Dry eyes (inh lacrimal gland secretion)
Cardiac: Increased HR and AV conduction velocity (block the effect of vagal nerve of SA and AV node)
Respiratory: Bronchial smooth muscle relaxation and bronchodilation, reduced secretion in upper and lower resp tract
GI and UT: Gastroesophageal reflux (reduced lower esophageal muscle tone), increased gastric emptying time (relaxes GI muscle tone), reduces intestinal motility, inh gastric acid secretion. Relaxes urinary bladder (relaxing detrusor muscle)
CNS: produce sedation and excitement
Other: hyperthermia (inh sweating)
Muscarinic receptor antagonists - Indications
Ocular: Produce mydriasis (ophthalmoscopic exam of peripheral retina), produce cycloplegia, iritis and cyclitis
Respiratory: Reduce salivary and resp secretions –> prevent airway obstruction in pt who are receiving general anesthetics
GI and UT: intestinal spasms and pain, urinary bladder spams in pt w overactive bladder
CNS: Parkinson, motion sickness
Muscarinic receptor antagonists - Adverse effects
Cycloplegia Dry eyes and mouth, decreased sweating Constipation Urinary retention Delirium and Hallucinations Hyperthermia (Hot, dry, flushed skin) Increased HR, tachycardia, palpitations Blurred vision Thirst Decreased clearance of mucus from lungs (because of impaired ciliary activity) --> accumulation of viscid material in airways
Muscarinic receptor antagonists - Groups
Belladonna alkaloids
Synthetic
Belladonna alkaloids
Atropine
Scopolamine
Hyoscyamine
Atropine - Indication
Sinus bradycardia
Symptomatic AV block (Increase AV conduction velocity)
Prevent muscarinic side effects when cholinesterase inh are given to pt with myasthenia gravis
Atropine - Adverse effects
Atropine toxicity: Antisecretory, paralysis of accommodation, vasodilation
Ventricular fibrillaton
Supraventricular or ventricular tachycardia
Scopolamine - MoA
Blocks Ach neurotransmission from vestibular apparatus to the vomiting center in the brain stem
Scopolamine - Indication
Motion sickness
Hyoscyamine - Indication
Intestinal spasms + other GI symptoms
Synthetic muscarinic receptor antagonists
Glycopyrrolate Ipratropium Tiotropium Dicyclomine Oxybutynin Solifenacin Tolterodine Fesoterodine Darifenacin Trospium Tropicamide Cyclopentolate Pirenzepine
Glycopyrrolate - MoA
Blocks muscarinic receptors throughout the body
Glycopyrrolate - Indication
Increases AV conduction velocity
Reduces salivary and resp secretions –> prevent airway obstruction in anesthesia
Anesthesia: inh secretory and vagal effects on cholinesterase inh used to reverse nondepolarizing neuromuscular blockade induced by curari form drugs
Prevents muscarinic side effects when cholinesterase inh are used in myasthenia gravis
Which synthetic muscarinic receptor antagonists are used for obstructive lung diseases?
Ipratropium and Tiotropium
Dicyclomine - MoA and Indication
Relaxes intestinal smooth muscle
Irritable bowel symptoms - intestinal cramping
Oxybutynin, Solifenacin, Tolterodine, Fesoterodine, Darifenacin and Trospium - Indication
Overactive bladder: reduces daytime urinary frequency, nocturia, urgency and incontinence
Oxybutynin, Solifenacin, Tolterodine, Fesoterodine, Darifenacin and Trospium - Adverse effects
Dry mouth and blurred vision
Tropicamide and Cyclopentolate - Indication
Short-term mydriasis
Pupillary dilator before ophthalmoscopy for exam of peripheral retina
Pirenzepine - MoA
Blocks M1 receptors on paracrine cells and inh release of histamine. Reduces gastric acid secretion
Pirenzepine - Indication
Peptic ulcer
Nicotinic receptor antagonists - Groups
Ganglionic and Neuromuscular blocking agents (nondepolarizing blockers and depolarizing blockers)
Ganglionic blocking agent
Mecamylamine
Ganglionic blocking agents - MoA
Block autonomic ganglia to reduce excessive activity of the sympathetic and parasympathetic nervous system by inh transmission between preganglionic and postganglionic neurons. No selectivity for sympathetic or parasympathetic ganglia.
Ganglionic blocking agents - Indication
Used for severe essential hypertension and malignant hypertension before, but not used today due to no selectivity and adverse effect
Neuromuscular blocking agents - MoA
Binds to the muscle type of nicotinic ACh receptor and inh neurotransmission at skeletal neuromuscular junctions, causing muscle weakness and paralysis
Neuromuscular blocking agents - Special consideration/ Adverse effect
Complete respiratory failure in a pt lacking external ventilatory support
Anesthesia awareness
Nondepolarizing neuromuscular blocking agents / Curariform drugs
Atracurium Cisatracurium Pancuronium Rocuronium Tubocurarine Vecuronium Doxacurium
Nondepolarizing neuromuscular blocking agents - MoA
Competitive antagonists of ACh at nicotinic receptos in skeletal muscle at the neuromuscular junction. Stimulate release of histamine and block autonomic ganglia and muscarinic receptors.
Nondepolarizing neuromuscular blocking agents - Effects
First: paralyzes the small and rapid moving muscle of the eyes and face
Then: paralyzes larger muscles of the limbs and the trunk
Last: paralyzed intercostal muscles and diaphragm –> respiration cease
Nondepolarizing neuromuscular blocking agents - Indication
Induce muscle relaxation (surgery) Electroconvulsive therapy (prevent injuries due to muscle contraction) Intubation of resp tract (endoscopic procedure)
In what kind of patients are the paralytic agents more pronounced? And how are they potentiated?
Patients with neuromuscular disorders such as myasthenia gravis.
Potentiated by inhalation anesthetic agents, aminoglycosides, tetracyclines and calcium channel blockers
How can muscle relaxing effect of nondepolarizing neuromuscular blocking agents be reversed?
Adm a cholinesterase inhibitor
Nondepolarizing neuromuscular blocking agents - Adverse effects
Bronchospasm
Hypotension
Tachycardia
Caused by histamine release
Pancuronium - Indication
Lethal injection protocols
Sugammadex - MoA
Forms a tight inactive complex with rocuranium and vecuronium and removes the drugs from the neuromuscular junction.
Sugammadex - Indication and Effect
Complete paralysis
Reverses neuromuscular blocking agents
Which nondepolarizing neuromuscular blocking agents have long duration of action
Pancuronium and Doxacurium. Rest have intermediate
Depolarizing neuromuscular blocking agent
Succinylcholine
Succinylcholine - MoA
Binds to nicotinic receptors in skeletal muscle and causes persistent depolarization of the motor end plate.
Phase 1: depolarization –> muscle fasciculations
Phase 2: desensitization caused by overstimulation and leads to resistance
Succinylcholine - Indication
Produce muscle relaxation (surgery, intubation)
Preferred for adults with emergency airway situations
Succinylcholine - Special considerations and Contraindication
Short duration of action (5-10 min)
Effects not reversed by cholinesterase inh
Monitor serum potassium
Contraindication: Atypical cholinesterase (no metabolization –> prolonged neuromuscular paralysis and apnea), Patients with unhealed skeletal muscle injury, spinal cord injury, Children
Succinylcholine - Adverse effects
Hyperkalemia –> Cardiac arrest in pt with unhealed skeletal muscle injury or conditions involving muscle weakness, Children
Postop myalgia (muscles of neck, back, abdomen)
Malignant hyperthermia (inhalation anesthetics)
Muscarinic receptor antagonists - Contraindications
Narrow-angle glaucoma
Coronary artery disease
BPH
Antimuscarinic drugs for Parkinsons disease
Benzatropine
Trihexyphenidyl
