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PHARMACOLOGY OF THE AUTONOMIC NERVOUS SYSTEM

(Lecture Synopsis)

Two major division:

Sympathetic nervous system
Parasympathetic nervous system

Neurotransmission:
Adrenergic neurotransmission - sympathetic system, noradrenaline (NA) as
neurotransmitter.
Cholinergic neurotransmission - parasympathetic system, acetylcholine (Ach)
neurotransmitter.

RECEPTOR TYPES IN THE SYMPATHETIC SYSTEM

Two major types of adrenergic receptors:

receptors responsible for most excitatory effects. Eg., vasoconstriction,
contraction of the uterus and spleen.
receptors responsible for inhibitory effects. Eg., vasodilation and
relaxation of respiratory smooth muscle.

receptors:

1 receptors mediate constriction or contraction of smooth muscle in:

Arterioles in skin, mucosa, viscera & kidney.
Veins throughout the body.
Uterus, spleen, male sex organs & radial muscle of the iris in the
eyes.

2 receptors - regulate NA release. Activation causes further inhibition of NA

release. Responsible for relaxation of GI smooth muscle.

-receptors:

1 receptor - important exception of receptors. Activation of an increase in

heart rate and force of contraction which are excitatory effects.

2 receptors - mediate relaxation of smooth muscle in:

Arterioles in skeletal muscle and liver.
Many veins throughout the body.
Bronchial and uterine smooth muscle.

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receptors also involve in several metabolic function by increasing cellular

cAMP levels.
2 receptor activation by adrenaline - results in glycogenolysis.
Adrenaline also activates 1 receptors in adipose tissue -
stimulate lipolysis.

SYMPATHOMIMETIC AGENTS

Agonist drug acting at the sympathetic nervous system - also called sympathetic drugs or
adrenergic drugs.

Clinical application of sympathomimetic drugs

agonists
1 agents vasoconstriction:
Control hemorrhage:
o Adrenaline can constrict blood vessels in the area of superficial
surgery.
o Help control capillary bleeding - useful especially in tooth
extraction.

Adjunct to local anaesthetic:

o Injected along with local anaesthetics to cause localized
vasoconstriction.
o Reduce blood flow and slow down the absorption of the
anaesthetics and localized its effect.
o Produce more effective anaesthesia in the area of surgery.
o Minimize the systemic toxicity from the anaesthetic.

Nasal decongestant:
o Applied locally or taken orally to constrict swollen vessel in
edematous tissue.
o Relieve the symptom of nasal congestion during common cold,
hay fever etc.
o Phenylpropanolamine and phenylephrine are used in many
over-the-counter (OTC) nasal decongestant product.

Allergic shock (anaphylaxis):

o Treat allergic shock.
o Relieve the swelling of edematous mucosa, glottis and facial
tissue.
o Reverse the life-threatening respiratory crisis in allergic shock.

Hypotension:

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o Hypotensive situation for eg. during spinal anaesthesia or in

certain cases of shock.
o Used for their pressor action.
o Administered IV to raise blood pressure.
Ergot alkaloids
o Naturally occuring or semisynthetic derivatives of lysergic acid found in
ergot fungus.
o Classified as agonist - most of its clinically important actions can be
blocked by antagonist phentolamine.
o Causes a very strong contraction of the smooth muscle, including vascular
smooth muscle through receptor activation resulting in dramatic
vasoconstriction.
o The poisoning of ergot alkaloids is called ergotism .
profound vasoconstriction resulting in necrosis.
significant CNS effect - confusion, depression, delirium and
hallucination.
o Primarily used for their ability to cause contraction of vascular and uterine
smooth muscle.
o Bromocriptine is used in treating hyperprolactinemia, inhibits the release of
prolactin from the pituitary.
o Methysergide - used in the prophylaxis of migraine.

2 agents central control of blood pressure:

o Mechanism involve 2 adrenergic receptor subtypes.
o Cause a reduction in sympathetic outflow from the CNS and a lowering in
blood pressure.
o Clonidine and -methyldopa widely used in hypertension.

agonists

1 agents used in cardiac stimulation

o Increases both heart rate and force of contraction of the heart.
o Isoprenaline or dobutamine (1 selective agent) - used as cardiac stimulant
in cases of bradycardia, heart block, congestive heart failure or cardiac
arrest.

2 agents used for bronchial relaxation:

o Causes relaxation of bronchial smooth muscl, decreasing airway resistance.
o Beneficial in asthma.
o AD and isoprenaline - used in metered-dose inhalers to relieve asthmatic
attack.
o Subcutaneous injection - used in treating severe asthmatic attack (status
asthmaticus).

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o Significant side effect - cardiac stimulation due to non-selective action on both

receptors.
o 2 selective agents for eg. terbutaline and salbutamol are widely used in
asthma treatment.

OTHER THERAPEUTIC USES OF SYMPATHOMIMETIC AGENTS

Narcolepsy dextroamphetamine and other stimulants are used to prevent daytime

sleepiness in patients with narcolepsy.
Weight loss adrenergic agonist has anorexic central action and drugs such as
phenteramine and fenfluramine can be used as an adjuncts to weight loss program.

ADVERSE EFFECTS OF SYMPATHOMIMETIC AGENTS

Tachyarrythmias, palpitation and ventricular fibrillation.

Hypertension side effect of 1 activity.
Localized ischemia occur with 1 agonist. Vasoconstriction reduce/block the
blood flow causing ischaemia in local tissue.
Hypotension on withdrawal occur from infusion of 1 agonist.
CNS stimulation nervousness, anxiety, insomnia and drug dependence

SYMPATHOLYTIC AGENTS

Antagonist at sympathetic nervous system - also called adrenergic antagonist.

Major application - to lower blood pressure in hypertensive patients by decreasing sympathetic

influence on the vasculature.

Mechanisms:
By blocking 1-adrenergic receptors that mediate vasoconstriction.
By blocking 1 adrenergic receptors that mediate renin release.
By blocking peripheral sympathetic neuron activity.
By altering CNS mechanism and decreasing centrally mediated sympathetic outflow.

Other important application - decreasing sympathetic stimulation of the heart in patients with
certain cardiac disease.

Clinical application of blockers:

Hypertension (main application):
The suggested mechanisms of antihypertension:

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- Decreased cardiac output negative chronotropic effect and negative

ionotropic effect. Decrease 15% of cardiac output.
- Decreased central sympathetic output.
- Inhibition of presynaptic receptor decrease NA release.
- Inhibition of renin release.
Cardiac arrythmias & angina pectoris:
Decreases heart rate and contractility, cardiac output and myocardial oxygen
demand - valuable in treating angina pectoris and supraventricular and
ventricular tachyarrythmias.

Glaucoma:
Timolol decreases the production of aqueous humor by the ciliary body in the
eyes.

Migraine headache:
Propranolol used chronically can produced marked decrease in the number of
attacks of migraine.
Block dilation of extracranial arteries - prevent the pain associated with the
expansion of these vessels.

Stage fright:
Relieve the anxiety of performing artists and public speakers - preventing
palpitation associated with stage fright.

Clinical application of blockers:

Hypertension:
Non-selective blockers can cause profound orthostatic hypotension and
reflex tachycardia except for Prazosin which is selective towards 1
receptors. It produces less tachycardia than the non-selective agents.
Prazosin block 1 adrenoseptor inhibition of Ach release and therefore will
increase Ach release. This combination of increase Ach and decrease NA
release will explain the low incidence of tachycardia with prazosin therapy.

Pheochromocytoma:
A pheochromocytoma cause the release of large amounts of NA and AD into
the bloodstream.
A combination of and blockers treatment during surgical removal of the
tumour can protect the patients from the cardiovascular effects of the two
catecholamines.

Shock:
Shock can cause the release of large quantities of adrenaline into the
bloodstream and produce profound vasoconstriction.

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Constriction can concentrate blood which exacerbate the inadequate perfusion

that occur during shock.
blockers and other vasodilators can be used to reverse this vasoconstriction.

Agents with both and blocking actions

Labetalol - has both (1 selective) and (non-selective 1 and 2) blocking
activity.
It lowers total peripheral resistance without producing tachycardia - useful in
treating hypertension.
Oral preparation - treat essential hypertension.
IV administration - for treating hypertensive emergencies.
Adrenergic neuron blocking agents
Drugs or agents that can decrease the effects of sympathetic activity by several other
mechanisms:
Depression of NA output from peripheral sympathetic neurons - neuron-blocking
drugs.
The primary clinical interest - essential hypertension.
Interfere with:
Synthesis of NA - -methyl tyrosine
Packaging of NA reserpine
Release of NA bretylium and guanethidine

Synthesis of NA:
Inhibitors of tyrosine hydroxylase - decrease the synthesis of
neuronal NA and lower the adrenergic activity.
-methyl tyrosine can effectively inhibit this enzyme -
produce severe side effects which include sedation, diarrhea,
anxiety and tremors.
Not really useful in the management of essential hypertension.
Occasionally used in pheochromocytoma.

Packaging of NA:
Reserpine can cause a long-lasting depletion of NA in the
peripheral sympathetic systems and CNS. So reserpine
treatment will ensure the lowering of blood pressure.
Also causes orthostatic (postural hypotension) as a side
effects.
Other side effect - GI discomfort (diarrhea and abdominal
cramps) - due to the parasympathetic tone is unopposed by
sympathetic activity following the chemical sympathectomy
produced by reserpine.
severe depression.

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Release of NA:
Bretylium and guanethidine - block neuronal NA release.
Produced orthostatic hypotension and supersensitivity to
sympathomimetic drugs.
Guanethidine reserved for severe hypertension.
Bretylium is used as antiarrythmic agents in emergency
situation. It increases cardiac action potential duration and
effective refractory period.

Adverse effects of sympatholytic agents

Hypotension orthostatic hypotension, mainly with antagonist and neuron

blocking agent.
Nasal congestion occur with antagonist.
Bradycardia occur with blocking agents, contraindicated in patients with
bradycardia, heart failure and arrythmias.
Bronchoconstriction occur with blockers (especially 2 selective agent).
Contraindicated in asthma and chronic bronchitis.
Sedation
Severe CNS depression associated with reserpine, causes depletion of NA in CNS.
Diarrhea due to blockade of receptors in the guts, increases the gut motility.
Inhibition of glycogenolysis causes hypoglycaemia in patients treated with insulin
and oral antidiabetic.

PHARMACOLOGY OF THE PARASYMPATHETIC SYSTEM

PHARMACOLOGY OF ACETYLCHOLINE (ACH)

The pharmacological activity of Ach is divided into two types:
Muscarinic activity
Nicotinic activity

Muscarinic action:
Mediated through muscarinic receptor.
Corresponds to parasympathetic stimulation.
Similar to Ach effects at postganglionic parasympathetic nerve endings.

Nicotinic action:
Produced through nicotinic receptor.

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Actions include stimulation of all autonomic ganglia and voluntary muscle

and secretion of adrenaline from the adrenal medulla.
Similar to those of Ach acting on autonomic ganglia of the sympathetic and
parasympathetic systems, the motor endplate of voluntary muscle and the
secretory cells of the adrenal medulla.

Ach receptors

Two major classes:

Nicotinic
Muscarinic

Nicotinic receptors
Two types:
Muscle
Neuronal
Muscle receptors - skeletal neuromuscular junction.
Neuronal receptors - autonomic ganglia and brain.
Ligand-gated ion channels with similar molecular structures but differ in their
pharmacological action.
Differentiated from one another by the action of different agonist and
antagonist at the receptors.
Agonists at nicotinic receptors:
Decamethonium potent depolarizing agent at neuromuscular
junction. It blocks the ganglion.
Epibatidine extremely potent and selective agonist at neuronal
nicotinic receptor..
Antagonists:
-bungarotoxin block muscle receptor at very low
concentration (very potent).

Mecamylamine blocks neuronal receptor.

Muscarinic receptors
Five types - M1, M2, M3, M4 & M5, only four have been distinguished
functionally and pharmacologically.
Three have been well characterised M1, M2 & M3.
G-protein-coupled receptors.
M1, M3 & M5 - act through the inositol phosphate pathway
M2 & M4 - act by inhibiting adenylate cyclase and therefore reducing
intracellular cAMP.
M1-receptors:
Neural receptors.
Found mainly in the CNS, peripheral neurons and gastric
parietal cells.

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Mediates excitatory effects by decreasing K+ conductance that

causes membrane depolarisation.
Also involved in increasing gastric acid secretion following
vagal stimulation.
M2-receptors:
Cardiac receptors.
Found in the heart and presynaptic terminals of the peripheral
and central neurons.
Mediate inhibitory effects by increasing K+ conductance and
inhibiting Ca2+ channel.
Responsible for the vagal inhibition of the heart and
presynaptic inhibition in the CNS and the periphery.
M3-receptors:
Glandular/smooth muscle receptors.
Mediate excitatory effect - stimulation of glandular secretion
(salivary, bronchial, sweat, etc.) and contraction of visceral
smooth muscle.
Also mediates relaxation of vascular smooth muscles.
M4-receptors:
Largely found in CNS.
Functional and pharmacological role not well understood.
Agonists & antagonists:
Most agonists at muscarinic receptors are non-selective. Eg.,
methacholine.
Oxotremorine the only selective agonist for M1 receptor.
The antagonists show more selectivity.
Pirenzipine is a selective antagonist at M1 .
Gallamine is selective towards M2.
Darifenacin is a selective antagonist at M3 receptor.

PARASYMPATHOMIMETIC AGENTS

Drugs that mimic the action of Ach at muscarinic receptors.

Occur at the postganglionic neuroeffector junctions of the parasympathetic system.
Effects nearly the same as the physiological responses of stimulating parasympathetic
system.

Classification of parasympathomimetic drugs

Classified into three different groups:

Choline esters
Cholinergic alkaloids
Cholinesterase inhibitors

Stimulate muscarinic receptors by mimicking the action of Ach.

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Muscarinics, cholinergics, cholinomimetics or parasympathomimetics.

The esters and alkaloids - used therapeutically and they possess agonists activity at
muscarinic receptors.
The cholinesterase inhibitors - work by blocking the enzyme acetylcholinesterase and this
allow the concentration of Ach to build up or to increase in synapse and therefore increases
its activity.
Cholinesterase inhibitors are not selective for muscarinic sites because they also have
significant effect at some nicotinic sites.

Choline esters
Therapeutic uses of choline esters:
Used therapeutically in situation whereby stimulation of the smooth muscle is
required.
Atonic intestine Bethanechol used to assist bladder emptying or to
stimulate the GI motility in this situation.
Urinary retention which normally occur after operation and labour
(postpartum).
Reflux esophagitis Choline esters can be used to reverse this
situation.
Cholinergic alkaloids

Pilocarpine - major clinical application is in the treatment of open angle glaucoma,

used as an eye drop.

Pilocarpine will contracts the ciliary muscle and the iris sphincter. This will relieve
the constriction in the region of the canal of schlemm and allows for better outflow of
the aqueous humor from the chamber.

Cholinesterase inhibitors
Stimulate the muscarinic sites indirectly by blocking the terminating step in Ach
transmission.
Not specific for muscarinic sites because they also have significant effect at some
nicotinic receptors.
There are two major classes:
The reversible drugs used therapeutically and most are carbamates.
The irreversible drugs primarily used as insecticides and chemical
warfare agents, most are organophosphates.

The model drug for the reversible group is the quarternary carbamates neostigmine.
Two other reversible drugs are physostigmine and edrophonium.

Physostigmine - not a quarternary compound and can gain access to the CNS and
produce unwanted side effects. Useful in reversing the central effect of antimuscarinic
drugs (eg. atropine).

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Edrophonium does not contain carbamate group, very short acting in low doses.
Useful in diagnosing myasthenia gravis.

The irreversible cholinesterase inhibitors are organophosphate compounds. Useful as

pesticides (eg, palathion, malathion, tetraethylpyrophosphate) and as nerve gases
used in chemical warfare (eg, soman, sarin).

Clinical importance of organophosphate cholinesterase inhibitors:

Clinically very important because of their toxicity. The toxic effects are an
exaggeration of muscarinic symptoms which include:
Tremendous salivation and respiratory secretion.
Tearing, blurring and burning of the eyes.
Profound muscle twitching, fasciculation and cramps.
Peripheral and centrally mediated respiratory paralysis which can
cause death.

Very lipid soluble and readily absorbed through skin and easily enter the CNS.
Organophosphate toxicity can be treated by assisting respiration and by
administering large amounts of atropine (muscarinic antagonist) to reverse the
muscarinic effect.
Atropine will also improve the CNS toxicity because most of the receptors for Ach in
the brain are muscarinic.

Therapeutic uses of cholinesterase inhibitors:

Reversible cholinesterase inhibitors are used to stimulate smooth muscle
activity (at muscarinic sites) and skeletal muscle activity (at nicotinic sites) in
several clinical situations.
Also used to treat glaucoma and to increase intestinal activity.
Neostigmine - used to reverse the peripheral effects of antimuscarinic
agents, for eg, atropine.
The effects of neostigmine and edrophonium on the somatic nicotinic Ach
receptor is used in reversing the action of muscle relaxers (eg, curare) and also
in the treatment of myasthenia gravis.
SIDE EFFECTS OF PARASYMPATHOMIMETIC AGENTS

Miosis
Excessive sweating
Marked salivation
Increased GI motility, diarrhea
Bradycardia
Urinary urgency

CONTRAINDICATIONS FOR PARASYMPATHOMIMETICS

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Bradycardia or hypotension
Asthma
Hyperthyroidism.
Peptic ulcer

PARASYMPATHOLYTIC AGENTS

Classification of antimuscarinic (parasympatholytic) drugs

Naturally occuring antimuscarinic includes:

Atropine
Hyoscine (known as scopolamine in USA)

Synthetic antimuscarinic includes (there are many more):

Cyclopentolate
Tropicamide
Pirenzipine
Ipratropium
Benzhexol

Effects of antimuscarinic drugs

The main effects:
Inhibition of secretion:
Salivary, lacrimal, bronchial and sweat glands are all inhibited by very low
doses of atropine - produce a very uncomfortable dry mouth and dry skin.
Gastric secretion is only slightly reduced.

Effects on heart rate:

Atropine causes tachycardia due to blockade of cardiac muscarinic receptors.

Effects on the eyes:

Atropine causes dilation of the pupil (mydriasis) and the eyes becomes
unresponsive to light. Relaxation of the ciliary muscle will cause paralysis of
accomodation (cycloplegia) and this will impair near vision.
Also cause an increase in the intraocular pressure, can be dangerous in
patients suffering from glaucoma.

Effects on the GI tract:

GI motility is inhibited by atropine.
Normally used in pathological condition whereby there is an increased
gastrointestinal motility.

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Pirenzipine - selective for M1, it can inhibit gastric secretion in doses that do
not affect other systems.

Effects on smooth muscles:

Causes relaxation on the bronchiol, biliary and urinary tract smooth muscle.

Effects on CNS:
Causes mild restlessness at low doses and at high doses it can cause agitation
and disorientation.

ATROPINE POISONING
Characterized by marked excitement and irritability and results in hyperactivity and a
rise in body temperature.
Ability to sweat is also lost and this will aggravate the rise in body temperature.
The central effects are due to the blockade of muscarinic receptors in the brain.
Effective antidote - physostigmine, an anticholinesterase drugs.

Therapeutic uses of antimuscarinic drugs

Reverse bradycardia:
Atropine given IV is used to reverse bradycardia resulting from myocardial
infarction or from excessive vagal tone.

To produce mydriasis and cycloplegia:

Tropicamide in the form of eye drops is used in opthalmology to facilitate
eye examination by causing dilation of the pupil (mydriasis) and paralysis of
accomodation (cycloplegia).
Tropicamide is short acting. - lasts for about 3 to 4 hours.
Cyclopentolate - has effects that last in 24 hours.

Adjunct to anaesthesia:
Used before, during and after surgery.
Inhibit the copious secretion produced by anaesthetics.
Used nowadays to protect against bradycardia during anaesthesia.
Also used to prevent the muscarinic side effects during the reversal
neuromuscular blockade with neostigmine after surgery.

Parkinsons disease:
Trihexyphenidyl - a centrally acting antimuscarinic agents used to treat
parkinson disease, but normally in conjunction with L-DOPA
(antiparkinsonism).
Benzhexol is used to counteract the movement disorder caused by
antipsychotic drugs.

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GI disorder:
Some GI disorders for eg. spastic colon can be treated with antimuscarinic
agents atropine.
Pirenzipine which is a selective M1 receptor antagonist is effective in treating
ulcers and it also produce fewer side effects than atropine.

Chronic obstructive pulmonary disease (COPD):

Ipratropium bromide is the antimuscarinic that is useful in treating some
COPD and asthmatic patients.

Treat anticholinesterase poisoning:

Atropine is an essential antidote in treating poisoning with anticholinesterase
agents.

Motion sickness:
Hyoscine - effective in preventing motion sickness (travel sickness) and given
orally or applied as dermal patches.
Nausea and vomiting in motion sickness is caused by the increase in GI
motility.

Side effects of antimuscarinic drugs

Dry mouth, dilated pupils, tachycardia and decrease gut and bladder activity.
Agents that can cross the BBB can cause CNS effects. High doses of hyoscine and
atropine can cause excitation of CNS, delirium and hallucination.
Coma and death - possible but very rare in adults but a real possibility with children.
Atropine-poisoned children normally experienced dramatic rise in body temperature
and they stop sweating and central temperature regulation is also lost.
Intoxicated children will become red, hot and delirious and may die if immediate
treatment with specific antidote physostigmine is not carried out.

GANGLION BLOCKING AGENTS

Can shut down the entire autonomic nervous system, both sympathetic and parasympathetic
division.

Ganglion can be blocked through 3 different mechanisms:

By interference with Ach release - Botulinum toxin, hemicholinium &
magnesium ion. All three can cause paralysis of the skeletal muscle and at the same
time block the ganglion.
By prolonged depolarisation - nicotine can block ganglia after the initial
stimulation by causing prolonged depolarisation. Inhibition of enzyme
cholinesterase can increase the effect of Ach on postsynaptic membrane and
therefore prolonged the depolarisation.

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By interference with postsynaptic action of Ach - a few important ganglion-

blocking drugs act by blocking nicotinic receptors or the associated ion
channels.

Hexamethonium:
First recognized as an antihypertensive agent, but no longer used clinically.
It is only used as experimental tool.
It blocks Ach from stimulating the ganglion.
Cause inhibition of the gastric, sweat and saliva secretion and can also interfere with
bowel function and gall bladder function. It also causes tolerance, so dose needs to be
increased.
Nicotine:
Nicotine is the classic depolarising ganglionic blocker.
It will first produce stimulation followed by a block at ganglionic nicotinic receptors.
Not used as therapeutic agent but important as an experimental tool.
Its toxicology is clinically important - used in a number of pesticide preparations to
poison insects.
Also used in many tobacco smoke preparation.
Pharmacology is very complex - highly lipid soluble and readily absorbed across all
membrane. Can cause simultaneous stimulation and blocking throughout the body.
In tobacco smoke, nicotine usually produces net stimulation of the CNS and the
cardiovascular systems.

Mecamylamine:
Effect similar to hexamethonium if given IV.
Given orally, the effect is better.
Side effects are the same as hexamethonium.
Also have central effect - depression.

Trimetaphan:
Used clinically.
Very short acting - administered as an IV infusion for certain types of anaesthetic
procedure.
Used to lower blood pressure during hypertensive crisis that occur in anaesthesia.
Also used for certain surgical procedures - orthopedic maneuvers, neurosurgery and
surgery of the blood vessel, minimise bleeding during the procedure.

Effects of ganglion-blocking agents

The most important effects are on the cardiovascular system.
Blocking of sympathetic ganglia can cause arteriolar vasodilatation which
can result in a fall of arterial blood pressure. Most cardiovascular reflexes
are also blocked.

Reduced venoconstriction.

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Venoconstriction occurs when a person stands up and necessary to prevent

the central venous pressure from falling sharply. Ganglionic blockers
reduced this effect.
Venoconstriction controlled by sympathetic activity will balance the
sudden fall in cardiac output and arterial pressure (postural hypotension).
Similarly, during exercise, vasodilatation of the skeletal muscle will occur
which is accompanied by vasoconstriction elsewhere produced by
sympathetic activity. This is to prevent the fall in peripheral resistance and
blood pressure (post-exercise hypotension). If the sympathetic activity is
blocked, then fainting may occur due to the post-exercise hypotension.

Other effects - inhibition in GI tract secretion and motility that can lead to
constipation.
Disturbance of gall bladder function and causes water retention.

Ganglion stimulants
Ganglion stimulants are basically nicotinic receptor agonists.
Affect both ganglionic and motor endplate receptors.
Nicotine, lobeline, carbachol and dimethylpiperazinium (DMPP).
Nicotine and lobeline - tertiary amines.
DMPP is a synthetic drug and selective for ganglionic response, three times more
potent than nicotine.
Carbachol - stimulate the ganglion but only a weak effect.

Effects of ganglion-stimulating agents

No therapeutic value - used mainly as experimental tools.
Cause mixed sympathetic and parasympathetic responses.
Cause an increase in arterial blood pressure due to action on cardiovascular system.
Sympathetic stimulation can also cause vasoconstriction that increases the arterial
blood pressure.
Nicotine action on parasympathetic ganglia can increase the bowel tone and the
gastric motility - lead to nausea, vomitting and diarrhea.
Cause initial stimulation of the saliva and mucus secretions and followed by
inhibition.
Acute nicotine poisoning - symptoms include nausea, vomiting, abdominal pain,
salivation and so on, followed by a fall in blood pressure and difficulty in breathing.
In severe cases, death may occur from respiratory failure.

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