GANGLION Stimulating & Blocking Drugs

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History of Tobacco: 

History of Tobacco By 17th century In Western Europe, used as treatment for migraines Japan & China stop enforcing prohibition of use Russia opens door to West

Nicotine Forms: 

Nicotine Forms Tobacco Smokeable Cigarette Pipe Cigar Leaf (Chewing) Snuff (powdered) Transdermal Patch

History of Tobacco: 

History of Tobacco 1828 - Nicotine was isolated Cigarettes first appeared in 1850s, but chewing still more popular

Ganglionic stimulating drugs: 

Ganglionic stimulating drugs Nicotine Alkaloid isolated from leaves of tobacco. Volatile liquid Tertiary amine ( lobeline also) Dimethylphenyl-piperazimium (DMPP) Succinylcholine

Nicotine (Ganglion stimulant) : 

Nicotine (Ganglion stimulant) Complex unpredictable Initially stimulates the ganglia & then blocks because of consistent depolarization. CVS ↑ H.R ↑ B.P (Stimulation of sympathetic ganglia & adrenal medulla).

Nicotine Pharmacology: 

Nicotine Pharmacology Biphasic action- nicotinic acetylcholine receptors Agonist – low doses Antagonist – high doses Works in CNS and PNS One of the most toxic dependence-producing psychoactive compounds overall Nicotine acts to stimulate dopamine release in mesolimbic dopamine pathway (reward center).

Effect of nicotine on GIT: 

Effect of nicotine on GIT ↑ tone & ↑ motor activity of bowel. Nausea Vomiting Diarrhea (occasionally)

Effect of nicotine on exocrine glands: 

Effect of nicotine on exocrine glands Initially stimulation of salivary secretion followed by inhibition.

Effect of nicotine on CNS: 

Effect of nicotine on CNS Markedly stimulates CNS Moderate doses → tremors Convulsion (in large doses) Stimulation of CNS followed by depression Death from respiratory failure

Effect of nicotine on PNS: 

Effect of nicotine on PNS Small doses stimulate the ganglion cells & facilitate transmission of impulses. Large doses initial stimulation followed very quickly by blockade of transmission.


Biotransformation/Excretion Broken down by lung and liver >90% in liver Excreted through kidneys (urine) Lungs do some excretion

Pharmacokinetics : 

Pharmacokinetics Rapidly absorbed from respiratory tract, buccal mucosa & skin. Metabolized mainly in liver but also in kidney & lungs.


Dependence One of the most dependence-producing drugs Pharmacology – Stimulates reward center influences ANS Function – Weight control, coping with negative affect/stress, cognitive enhancement Social Factors – Friends, habit, context

Withdrawal Symptoms of Nicotine: 

Withdrawal Symptoms of Nicotine Lethargy, decreased arousal Constipation Headaches Disrupted sleep cycles Irritability/anxiety Excessive hunger (blood sugar drop)

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Pharmacology of the Ganglion-Blocking Drugs

Ganglion-Blocking Drugs: 

Ganglion-Blocking Drugs Hexamethonium Trimetaphan Tubocurarine Pancuronium Atracurium Vecuronium

Ganglion-Blocking Drugs: 

Ganglion-Blocking Drugs Hexamethonium Mecamylamine Prevents reflex changes in H.R Most are no longer available clinically because of toxicities.

Ganglion-Blocking Drugs: 

Ganglion-Blocking Drugs Prevent reflex changes in H.R elicited by vasoconstriction ( α 1) & vasodilation ( β 2). Do not prevent changes in H.R elicited directly by the drug ( β 1 & M2).


Introduction Block the action of ACh and similar agonists at nicotinic receptors of both parasympathetic and sympathetic autonomic ganglia. Ganglion-blocking drugs are important and used in pharmacologic and physiologic research because they can block all autonomic outflow. Lack of selectivity confers such a broad range of undesirable effects that they have limited clinical use.

Chemistry & Pharmacokinetics: 

Chemistry & Pharmacokinetics All ganglion-blocking drugs of interest are synthetic amines. Tetraethylammonium (TEA) : The first to be recognized as having this action, Has a very short duration of action. Hexamethonium ("C6") was developed and was introduced clinically as the first drug effective for management of hypertension. Decamethonium , the "C10" analog of hexamethonium, is a depolarizing neuromuscular blocking agent.

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There is an obvious relationship between the structures of the agonist acetylcholine and the nicotinic antagonists tetraethylammonium and hexamethonium.

Chemistry & Pharmacokinetics: 

Chemistry & Pharmacokinetics The quaternary amine ganglion-blocking compounds were poorly and erratically absorbed after oral administration . Mecamylamine, a secondary amine, was developed to improve the degree and extent of absorption from the GIT. Trimethaphan, a short-acting ganglion blocker, is inactive orally and is given by intravenous infusion.


Pharmacodynamics Mechanism of Action Ganglionic nicotinic receptors are subject to both depolarizing and nondepolarizing blockade Nicotine and even acetylcholine (if amplified with a ch E inhibitor) can produce depolarizing ganglion block. Drugs now used as ganglion blockers are classified as nondepolarizing competitive antagonists. Hexamethonium actually produces most of its blockade by occupying sites in or on the nicotinic ion channel, not by occupying the cholinoceptor itself. Trimethaphan appears to block the nicotinic receptor, not the channel.

Organ System Effects: 

Organ System Effects Central Nervous System Mecamylamine, unlike the quaternary amine agents and trimethaphan, crosses the BBB and readily enters the CNS . Sedation, tremor, choreiform movements, and mental aberrations

Organ System Effects: 

Organ System Effects Eye Cycloplegia with loss of accommodation because the ciliary muscle receives innervation primarily from the parasympathetic nervous system. The effect on the pupil is not so easily predicted, Moderate dilation of the pupil because parasympathetic tone usually dominates this tissue.

Organ System Effects: 

Organ System Effects Cardiovascular System Blood vessels receive chiefly vasoconstrictor fibers from the sympathetic nervous system; therefore, ganglionic blockade causes a marked decrease in arteriolar and venomotor tone. Hypotension is marked in the upright position Cardiac effects include diminished contractility and, Sinoatrial node is usually dominated by the parasympathetic nervous system, a moderate tachycardia.

Organ System Effects: 

Organ System Effects Gastrointestinal Tract Secretion is reduced, although not enough to effectively treat peptic disease. Motility is profoundly inhibited, and constipation can be marked. Genitourinary Hesitancy in urination Erection and ejaculation may be prevented by moderate doses

Clinical Applications & Toxicity: 

Clinical Applications & Toxicity Use of the ganglion blockers is infrequent Mecamylamine is being studied for possible use in reducing nicotine craving in patients Trimethaphan is occasionally used : treatment of hypertensive emergencies and dissecting aortic aneurysm; to produce controlled hypotension, which can be of value in neurosurgery to reduce bleeding in the operative field; and in patients undergoing electroconvulsive therapy. Toxicity - limited to the autonomic effects already described. For most patients, these effects are intolerable except for acute use.

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