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Drugs active at parasympathetic ganglia are equally effective at sympathetic ganglia, and vice versa. Nicotine stimulates postganglionic neuron receptors in the autonomic ganglia. Hexamethonium and mecamylamine effectively block these "nicotinic" receptorsites.
↓cardiac output. hypotension Tachycardia Mydriasis Cycloplegia GIT Bladder Salivary gland Sweat gland Parasympathetic Parasympathetic Parasympathetic Sympathetic ↓Tone and motility. constipation Urine retention Xerostomia(dry mouth) Anhidrosis(absence of sweating) . hypotension Venodilation. ↓venous return.Effects of Autonomic Ganglionic Site Predominant tone Blockade Effects of ganglion blockade Arterioles Veins Heart Iris CiliaryMuscle Sympathetic Sympathetic Parasympathetic Parasympathetic Parasympathetic Arteriodilation. ↓PR.
Nicotine (high dose) Nicotine is a poison with many undesirable actions.) A. •Depending on the dose. •The stimulatory effects: increased BP and HR (due to release of transmitter from adrenergic terminals and from the adrenal medulla) and increased peristalsis and secretions. . decreased activity of the GI tract and bladder. nicotine stimulates (low doses) then inhibits (high doses) autonomic ganglia.Ganglion Blocks (Cont. •At higher doses: fall in BP. It is without therapeutic benefit and is deleterious to health.
•The drug was ultimately purified and introduced into clinical practice in the early 1940s. •Although tubocurarineis considered to be the prototype agent in this class.B. Competitive Neuromuscular blockers• The first drug that was found to be capable of blocking the skeletal neuromuscular junction was curare. Trimetaphan&Mecamylamine •Trimetaphan: IV only and short acting •Mecamylamine: can be given orally & has a long duration •They are be used in emergency hypertension A.•Curare was used by native hunters of the Amazon in South America to paralyze animals. it has been largely replaced by other agents. .
Competitive Neuromuscular blockers (Cont.e. •These agents possess two or more quaternaryamines in their bulky ring structure. making them orally ineffective. •They are antagonized by neostigmine. Therefore. Tubocurarine Atracurium Cisatracurium Doxacurium Metocurine Mivacurium Pancuronium Rocuronium Vecuronium . they produce no initial stimulation.) •Mechanism of action: They interact with the nicotinic receptors to competitively prevent the binding of acetylcholine. •They are pure antagonists i. all neuromuscular blocking agents are administered IV.
Competitive Neuromuscular blockers (Cont. and edrophonium: Antagonism b.Calcium-channel blockers:These agents may enhancethe neuromuscular block of tubocurarineand other competitive blockers as well as depolarizing blockers.) Side Effects: •Tubocurarinemay release histamineand lower BP. pyridostigmine. physostigmine. Cholinesterase inhibitors: Drugs such as neostigmine.Halogenatedhydrocarbon anesthetics(e. Drug interactions: a. . halothane): Potentiation c.g. •Atracuriummay release histamineand may provoke seizures. Aminoglycoside antibiotics: Synergism(Drugs such as gentamicin or tobramycin inhibit acetylcholine release from cholinergic nerves by competing with calcium ions) d.
This causes a resistance to depolarization (Phase II) and a flaccid paralysis. However. which results in depolarization of the receptor (Phase I). continuous depolarization gives way to gradual repolarizationas the sodium channel closes or is blocked.B. •The drug first causes the opening of the sodium channel associated with the nicotinic receptors. Depolarizing Neuromuscular Blockers (Succinylcholine. •With time. Decamethonium) Mechanism of action •Succinylcholine(as an example) binds to the nicotinic receptor and acts like AChto depolarize the junction. succinylcholinepersists at high concentrations in the synaptic cleft for a relatively longer time and providing a prolonged stimulation. . This leads to a transient twitching of the muscle (fasciculations).
the duration of action of succinylcholineis short. •Normally.Succinylcholine(Cont. . Genetic variants in which plasma cholinesterase levels are low or absent may suffer prolonged neuromuscular paralysis.) •They are potentiated by neostigmine. succinylcholineis useful for endotrachealintubationand during electroconvulsive shocktreatment. •Therapeutic uses:Because of its rapid onset and short duration of action. because it is rapidly oken down by plasma cholinesterase (pseudo-cholinennsterase).
Succinylcholine(Cont. •Hyperkalemia: Succinylcholineincreases potassium release from intracellular stores.) Adverse effects •Apnea: Administration of succinylcholineto a patient who is genetically deficient in plasma cholinesterase or has an atypical form of the enzyme can lead to prolonged apnea due to paralysis of the diaphragm. This may be particularly dangerous and cause cardiac arrest. thus reducing heat production and relaxing muscle tone. This is treated by rapidly cooling the patient and by administration of dantrolene. . administration of succinylcholinehas occasionally caused malignant hyperthermia (with muscular rigidity and hyperpyrexia) in genetically susceptible people. which blocks release of Ca2+from the sarcoplasmicreticulum of muscle cells. •Malignant hyperthermia: When halothane is used as an anesthetic.