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.

Drugs Acting on Autonomic Ganglia

Effects of Autonomic Ganglionic Blockade

Site Predominant tone Effects of ganglion blockade

   Arterioles      Sympathetic                               Arteriodilation, ↓PR,        hypotension

Veins Sympathetic Venodilation, ↓venous return, ↓cardiac output, hypotension    

         Heart Parasympathetic                   Tachycardia                           

          Iris  Parasympathetic       Mydriasis

CiliaryMuscle Parasympathetic Cycloplegia

GIT Parasympathetic                  ↓Tone and motility, constipation

Bladder Parasympathetic                       Urine retention

Salivary gland Parasympathetic                          Xerostomia(dry mouth)

Sweat gland Sympathetic                                   Anhidrosis(absence of sweating)

Ganglion Blocks (Cont.)

A. Nicotine (high dose)

Nicotine is a poison with many undesirable actions. It is without therapeutic benefit and is deleterious to health. •Depending on the dose, nicotine stimulates (low doses) then inhibits (high doses) autonomic ganglia. •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. •At higher doses: fall in BP, decreased activity of the GI tract and bladder.

B. 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. Competitive Neuromuscular blockers•

The first drug that was found to be capable of blocking the skeletal neuromuscular junction was curare.•Curare was used by native hunters of the Amazon in South America to paralyze animals. •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, it has been largely replaced by other agents. 

Competitive Neuromuscular blockers (Cont.)

•Mechanism of action: They interact with the nicotinic receptors to competitively prevent the binding of acetylcholine. •They are pure antagonists i.e. they produce no initial stimulation.•They are antagonized by neostigmine.•These agents possess two or more quaternaryamines in their bulky ring structure, making them orally ineffective. Therefore, all neuromuscular blocking agents are administered IV.

TubocurarineAtracuriumCisatracuriumDoxacuriumMetocurineMivacuriumPancuroniumRocuroniumVecuronium

Competitive Neuromuscular blockers (Cont.)

Side Effects:•Tubocurarinemay release histamineand lower BP. •Atracuriummay release histamineand may provoke seizures.

Drug interactions:a. Cholinesterase inhibitors: Drugs such as neostigmine, physostigmine, pyridostigmine, and edrophonium: Antagonismb.Halogenatedhydrocarbon anesthetics(e.g. halothane): Potentiationc. Aminoglycoside antibiotics: Synergism(Drugs such as gentamicin or tobramycin inhibit acetylcholine release from cholinergic nerves by competing with calcium ions)d.Calcium-channel blockers:These agents may enhancethe neuromuscular block of tubocurarineand other competitive blockers as well as depolarizing blockers.

B. Depolarizing Neuromuscular Blockers(Succinylcholine, Decamethonium)

Mechanism of action•Succinylcholine(as an example) binds to the nicotinic receptor and acts like AChto depolarize the junction. However, succinylcholinepersists at high concentrations in the synaptic cleft for a relatively longer time and providing a prolonged stimulation. •The drug first causes the opening of the sodium channel associated with the nicotinic receptors, which results in depolarization of the receptor (Phase I). This leads to a transient twitching of the muscle (fasciculations). •With time, continuous depolarization gives way to gradual repolarizationas the sodium channel closes or is blocked. This causes a resistance to depolarization (Phase II) and a flaccid paralysis.

Succinylcholine(Cont.)

•They are potentiated by neostigmine. •Normally, the duration of action of succinylcholineis short, because it is rapidly oken down by plasma cholinesterase (pseudo-cholinennsterase). Genetic variants in which plasma cholinesterase levels are low or absent may suffer prolonged neuromuscular paralysis.•Therapeutic uses:Because of its rapid onset and short duration of action, succinylcholineis useful for endotrachealintubationand during electroconvulsive shocktreatment.

Succinylcholine(Cont.)

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.•Malignant hyperthermia: When halothane is used as an anesthetic, administration of succinylcholinehas occasionally caused malignant hyperthermia (with muscular rigidity and hyperpyrexia) in genetically susceptible people. This is treated by rapidly cooling the patient and by administration of dantrolene, which blocks release of Ca2+from the sarcoplasmicreticulum of muscle cells, thus reducing heat production and relaxing muscle tone.•Hyperkalemia: Succinylcholineincreases potassium release from intracellular stores. This may be particularly dangerous and cause cardiac arrest.