ANS Pharmacology MLT-OT

MIRPUR UNIVERSITY OF SCIENCE AND TECHNOLOGY (MUST), MIRPUR
PHARMACOLOGY & THERAPEUTICS-1
Lecture: Organization and Division of Autonomic

Nervous System ( ANS )
Sarwat Shaheen
Lecturer
LECTURE CONTENTS
1. Introduction to ANS
2. Division of nervous system
3. Types of neurons
4. Sympathetic and parasympathetic neurons
5. Innervations by ANS
6. Enteric nervous system
Pharmacology & Therapeutics -1A

LEARNING OBJECTIVES
 Introduction to Autonomic nervous system and divisions of nervous system.
 Understanding of different types of neurons and difference between

sympathetic and parasympathetic nervous system.
 Concept of Enteric nervous system
Pharmacology & Therapeutics -1A 4

Autonomic Nervous System
• Regulation and integration of bodily functions.
• Nervous system exerts its influence by rapid transmission of electrical impulses

over nerve fibers that terminate at effector cells which specifically respond to the
release of neuromediator substances.
• Autonomic drugs by mimicking or altering the effects of autonomic nervous

system.
• Act either by stimulating portions of autonomic nervous system or by blocking its
action.

Divisions of Nervous System

Autonomic Nervous System
7
Contn….
• Efferent neurons: carries nerve impulses from the CNS to the

effectors organs by way of two types of efferent neurons .
• The first nerve cell is called a preganglionic neuron (its cell body is
located within the CNS).
• Postganglionic neuron (neuron has a cell body originating in the
ganglion).
8
Contn….
• Afferent neurons: Important in reflex regulation of this system

and signaling the CNS to influence the efferent branch of the system to
response.
Sympathetic neurons: The preganglionic neurons of the sympathetic
system come from thoracic and lumbar regions of the spinal cord.
The preganglionic neurons are short in comparison to the postganglionic
ones.
9
Contn….
Parasympathetic neurons:
The parasympathetic preganglionic fibers arise from the cranium
(from cranial nerves III, VII, IX, and X) and from the sacral region of
the spinal cord and synapse in ganglia near or on the effectors organs.
Enteric neurons:
It is third division of the autonomic nervous system. It is a collection
of nerve fibers that innervate the gastrointestinal tract, pancreas, and
gallbladder, and it constitutes the “brain of the gut.
10
Functions of the sympathetic nervous system
• Effects of stimulation of the sympathetic division:
• Fight or flight response: The changes experienced by the body

during emergencies have been referred to as the “fight or flight”
response .Triggered both by direct sympathetic activation of the
effector organs and by stimulation of the adrenal medulla to release
epinephrine and lesser amounts of norepinephrine.
11
Functions of the parasympathetic nervous system
• Rest and Digest Response:

The parasympathetic division maintains
essential bodily functions, such as digestive
processes and elimination of wastes, and is
required for life
12
Innervations by Autonomic Nervous System
• Dual innervation: vagal parasympathetic innervation slows the heart

rate, and sympathetic innervation increases the heart rate.
Despite this dual innervation, one system usually predominates in
controlling the activity of a given organ.
• Organs receiving only sympathetic innervations: Adrenal medulla,

kidney, pilomotor muscles, and sweat glands, receive innervations
only from the sympathetic system.
The control of blood pressure is also mainly a sympathetic activity,
with essentially no participation by the parasympathetic system.

Somatic Nervous System
• Efferent somatic nervous system differs from the ANS in that a single
myelinated motor neuron originating in the CNS travels directly to
skeletal muscles without mediation of ganglia.
• It is under voluntary control.
• Responses are generally faster than those in the ANS.

Summary of differences between sympathetic and parasympathetic motor
neurons

Types of Neurotransmitters
Over 50 signal molecules in the nervous system have been identified.

Some commonly involved neurotransmitters are;
• Norepinephrine (and the closely related epinephrine)
• Acetylcholine
• Dopamine
• serotonin
• histamine
• glutamate
• γ-aminobutyric acid GABA
Pharmacology & Therapeutics-1A

Pharmacology & Therapeutics-1A 16
Acetylcholine
• If transmission is mediated by acetylcholine, the neuron is termed

cholinergic .
• Transmission from the autonomic postganglionic nerves to the effector

organs in the parasympathetic system, and a few sympathetic system
organs, also involves the release of acetylcholine.
Norepinephrine and epinephrine:
• When norepinephrine and epinephrine are the neurotransmitters, the fiber is

termed adrenergic

Adrenergic agonists
• The adrenergic drugs affect receptors that are stimulated by norepinephrine or

epinephrine.
• Some adrenergic drugs act directly on the adrenergic receptor (adrenoceptor)

by activating it and are said to be sympathomimetic.
• Others will block the action of the neurotransmitters at the receptors

(sympatholytics).

Contn…
• Adrenergic neurons release norepinephrine as the primary neurotransmitter.
•These neurons are found in the central nervous system (CNS) and also in the
sympathetic nervous system, where they serve as links between ganglia and the
effector organs.
4
•The adrenergic neurons and receptors, located either presynaptically on the
neuron or postsynaptically on the effector organ, are the sites of action of the
adrenergic drugs.
Pharmacology & Therapeutics-1A Pharmacology & Therapeutics-1A

Synthesis and Release of Nor epinephrine from
Adrenergic neurons
1. SYNTHESIS OF NOREPINEPHRINE
 Hydroxylation of tyrosine isthe rate-limiting step
2.UPTAKE INTO STORAGE VESICLES

 Dopamine enters vesicle& is converted to norepinephrine
 Norepinephrineisprotectedfrom degradationin vesicle
 Transport into vesicleis inhibited by reserpine
3.RELEASE OF NEUROTRANSMITTER
 Influxof calcium causesfusion of vesicle w/ cell membrane
 Releaseblockedbyguanethidine & bretylium
4. BINDING TORECEPTOR
 Postsynaptic receptor activatedbybinding of
neurotransmitter
5.REMOVALOF NOREPINEPHRINE
 Releasednorepinephrine is rapidlytakeninto neuron
 Uptake is inhibited bycocaine& imipramine
6. METABOLISM
 Norepinephrineismethylated byCOMT& oxidized by
monoamine oxidase
Adrenergic Receptors
. Adrenoceptors
α- rececptors β- receptors
α1 receptors α 2 receptors β1 receptors β2 receptors β3 receptors

Locations Of Adrenergic Receptors

Effects Of Adrenergic Receptor Stimulation

Drug Classification

Direct Acting Adrenergic Agonists
Epinephrine
• Epinephrine is synthesized from tyrosine in the adrenal medulla and
released, along with small quantities of norepinephrine, into the
bloodstream.
• Epinephrine interacts with both α and β receptors.
• At low doses, β effects (vasodilation) on the vascular system predominate,

whereas at high doses, α effects (vasoconstriction) are strongest.

Actions Of Epinephrine
CARDIOVASCULAR RESPIRATORY HYPERGLYCEMIA LIPOLYSIS
Epinephrine Epinephrine causes Epinephrine hasa Epinephrine initiates

strengthens the powerful significant lipolysis throughits
contractility of the bronchodilation by hyperglycemic effect agonist activity on the β
myocardium (positive acting directly on because of increased receptors of adipose
inotropic: β1 action) and bronchial smooth glycogenolysis in the tissue, which upon
increases its rate of muscle (β2 action). liver (β2 effect), increased stimulationactivate
contraction(positive release of adenylyl cyclase to
chronotropic: β1action). glucagon (β2 effect), increase cAMP levels.
and a decreased release
of insulin (α2 effect).

Therapeutic Uses of Epinephrine
BRONCHOSPASM GLAUCOMA ANAPHYLACTI CARDIAC ANESTHETICS
C SHOCK ARREST

Adverse Effects Of Epinephrine

Pharmacology & Therapeutics-IA 29
Norepinephrine
Because norepinephrine is the neuromediator of adrenergic nerves, it should

theoretically stimulate all types of adrenergic receptors. In practice, when the
drug is given in therapeutic doses to humans, the α-adrenergic receptor is most
affected.

Cardiovascular actions of Norepinephrine
31
Others
• Albuterol, pirbuterol, and terbutaline are short- acting β2 agonists used

primarily as bronchodilators and administered by a metered- dose inhaler.
• Salmeterol and formoterol are β2-adrenergic selective, long-acting
bronchodilators.
• Salmeterol and formoterol are the agents of choice for treating nocturnal
asthma in symptomatic patients taking other asthma medications.

A. Amphetamine
• The marked central stimulatory action of amphetamine is often

mistaken by drug abusers as its only action.
• Used for treating hyperactivity in children, narcolepsy, and appetite
control.
• Should be avoided in pregnancy

Tyramine is not a clinically useful drug, but it is important because it is found
in fermented foods, such as ripe cheese and wine.
• It is a normal by-product of tyrosine metabolism.
Cocaine is unique among local anesthetics in having the ability to block the
Na+/K+-activated ATPase (required for cellular uptake of norepinephrine)
on the cell membrane of the adrenergic neuron

Ephedrine and Pseudoephedrine
• Ephedrine, and pseudoephedrine are plant alkaloids, that are now made
synthetically.
• Ephedrine has been used to treat asthma, as a nasal decongestant and to

raise blood pressure.
• Pseudoephedrine is primarily used to treat nasal and sinus congestion or

congestion of the eustachian tubes.

Drug Classification
38
Alpha Blockers
• Prazosin: Well absorbed orally ; bioavailability is 50-70%

• Terazosin: Bioavailability -high (>90%)
• Doxazosin: One of the interesting action of terazosin and Doxazosin for
BPH is induction of apoptosis in prostate.
• Alfuzosin: Similar affinity at all of the α1 receptor subtypes. Bioavailability
is ~64%, t1/2 duration 3-5 hrs.
• Tamsulosin: Selectivity for α1a (and α1d) subtypes. Efficacious in
treatment of BPH & little effect on BP Well absorbed
39
Therapeutic uses
•Hypertension : Prazosin and its congeners -used successfully in the

treatment of essential HTN.
•Congestive heart failure : α receptor antagonists have been used in
the treatment of CHF, as have other vasodilating drugs.
•Benign prostatic hyperplasia : Prazosin ↓ resistance in some

patients with impaired bladder emptying caused by prostatic
obstruction or spinal injury.
40
Beta Blockers
β antagonists canbe distinguished by the following properties:
• Relative affinity for β1 and β2receptors

• Intrinsic sympathomimetic activity
• Differences in lipid solubility
• Capacity to induce vasodilation
• Pharmacokinetic parameters
42
Therapeutic uses
Cardiovascular Diseases
• Hypertension,
• Angina
• Acute Coronary Syndromes & Congestive Heart Failure
43
Contn…
• Useful for open-angle glaucoma e.g.Carteolol, betaxolol, levobunolol,

metipranolol timolol and levo betaxolol.
• Propranolol, timolol, and metoprolol are effective for the prophylaxis of migraine.
•Propranolol- effective in controlling acute panic symptoms in individuals who are

required to perform in public or in other anxiety-provoking situations.

Adverse Effects And Precautions
• On Cardiovascular System
• Pulmonary function
• May cause a life-threatening increase in airway resistance
•CNS : Fatigue, sleep disturbances (including insomnia and
nightmares), & depression
•Metabolism: Should be used with great caution in patients with
diabetes who are prone to hypoglycemic reactions
• Sexual dysfunction Pregnancy

PHARMACOLOGY & THERAPEUTICS-I
Lecture : CholinergicAgonists/ ParasympatheticAgonists
Sarwat Shaheen
Lecturer
Introduction
Drugs affecting the autonomic nervous system (ANS) are divided into
two groups according to the type of neuron involved in their mechanism
of action; adrenergic drugs and cholinergic drugs.

Synthesis, storage and release of acetylcholine

Cholinergic Receptors
•Two families of cholinoceptors, designated muscarinic

and nicotinic receptors, can be distinguished from
each other on the basis of their different affinities
for agents that mimic the action of Ach (cholinomimetic agents).
• Muscarinic receptors
• Nicotinic receptors

Muscranic Receptors
• Muscarinic receptors belong to the class of G protein–coupled

receptors (metabotropic receptors).
• These receptors, in addition to binding ACh, also recognize
muscarine, an alkaloid that is present in certain poisonous mushrooms.
• In contrast, the muscarinic receptors show only a weak affinity for
nicotine
• There are five subclasses of muscarinic receptors. However, only M1,
M2, and M3 receptors have been functionally characterized
Location of muscranic receptors
• These receptors are found on ganglia of the peripheral nervous system and on the
autonomic effector organs, such as the heart, smooth muscle, brain, and exocrine
glands.
• M1 receptors are also found on gastric parietal cells,
• M2 receptors on cardiac cells and smooth muscles
• M3 receptors on the bladder, exocrine glands, and smooth muscle.

Mechanism Of Ach Signal Transduction
• M1 and M3 through Gq
• M2 Through Gi
Cholinergic Agonists
Direct Acting Cholinergic Agonists
Cholinergic agonists mimic the effects of ACh by binding directly to cholinoceptors

(muscarinic or nicotinic). These agents may be broadly classified into two groups:
1)Endogenous choline esters, which include ACh and synthetic esters of choline,
such as carbachol and bethanechol.
2) Naturally occurring alkaloids, such as nicotine and pilocarpine.

Direct Acting Cholinergic
Agonists
ACETYLCHOLINE
Acetylcholine is a quaternary ammonium compound that cannot penetrate

membranes. Although it is the neurotransmitter of parasympathetic and somatic
nerves as well as autonomic ganglia, it lacks therapeutic importance because of its
multiplicity of actions (leading to diffuse effects) and its rapid inactivation by the
cholinesterases.
55
Acetylcholine
Actions :
Decrease heart rate
Decrease blood pressure
Other actions:
• Increases salivary secretion and stimulates intestinal secretions and
motility.
• It also enhances bronchiolar secretions.
• It increases the tone of the detrusor muscle, causing urination.
56
Bethanechol
Therapeutic applications: In urologic treatment, bethanechol is used to

stimulate the atonic bladder, particularly in postpartum or
postoperative, nonobstructive urinary retention. Bethanechol may also
be used to treat neurogenic atony as well as megacolon.
Adverse effects: Bethanechol causes the effects of generalized

cholinergic stimulation .

Pilocarpine
Actions: Applied topically to the eye, pilocarpine produces rapid miosis

and contraction of the ciliary muscles.
Therapeutic use in glaucoma: Pilocarpine is used to treat glaucoma

and is the drug of choice for emergency lowering of intraocular
pressure of both open-angle and angle-closure glaucoma.

Adverse Effects
• Pilocarpine can cause blurred vision, night blindness, and brow

ache.
• Poisoning with this agent is characterized by exaggeration of various

parasympathetic effects, including profuse sweating (diaphoresis)
and salivation..

Cholinergic Antagonists
Drugs that block cholinergic

receptors (M and/or N) actions of sympathetic
stimulation are left unopposed are called
cholinergic antagonists.
Contn….
These are classified to two subclasses:

• Muscarinic (M1-M5) receptor antagonists: the most useful clinically.
• Nicotinic receptor antagonists: further subdivided to:
• NMJ Blocking agents: inhibit the efferent impulses to skeletal muscle via the
(NM) receptor
• Ganglionic Blocking agents: inhibit the nicotinic neuronal receptor (NN) of
both parasympathetic and sympathetic ganglia
61
Muscranic Antagonists
• Muscarinic antagonists: Atropine (prototype): comes from the plant Atropa

belladonna and is known as a belladonna alkaloid. Belladonna in Latin means
pretty lady. Inhibit all M functions.
• Scopolamine (hyoscine): treatment of motion sickness ; natural occurring
alkaloid
• Homatropine:Cyclopentolate, Tropicamide: mydriasis and cycloplegia
• Ipratropium, Tiotropium: Treatmment of Asthma
• Imipramine a TCA with strong antimuscarinic actions, has long been used to
reduce incontinence in elderly

Atropine
Mechanism of action
• It causes reversible, nonselective blockade of muscarinic receptors.
Therefore, High concentration of Ach or an equivalent muscranic
agonists can be used to counteract the effects of atropine

Pharmacologic actions of atropine
• CNS: at toxic doses can cause restlessness, hallucinations and

delusions.
• CVS: At low doses, atropine reduces heart rate through central
stimulation of the vagus nucleus. At high doses, atropine blocks
muscarinic receptors of the heart and thus induces tachycardia
• GIT: reduces salivary gland secretion and GI motility.

Pharmacology & Therapeutics-1 A 560
Contn….
• Pulmonary system: reduces bronchial secretions and stimulates

bronchodilation.
• Urinary system: blocks muscarinic receptors in the bladder wall,
which results in bladder wall relaxation.
• Eye: causes paralysis of the sphincter muscle of the iris and ciliary
muscle of the lens, resulting in mydriasis and cycloplegia
• Sweat glands: Suppresses sweating, especially in children

Therapeutic uses
• Bradycardia
• Mydriasis and cycloplegia.
• Atropine contraindicated in a patients who has narrow-angle.
glaucoma, because this may result in acute crisis due to closure of
the canal of Schlemm.
• GIT and bladder spasms
• organophosphate poisoning
Pharmacokinetics
• Atropine as a tertiary amine, it is well absorbed from the GIT and

conjunctival membrane.
• It is excreted through both hepatic metabolism and renal function.
• Atropine’s duration of action is ~ 4 hrs, except when it is placed in the
eye, where it usually lasts about 14 days.
Adverse Effects
• Dry mouth (dry as bone)

• Inhibition of sweating especially in young children (hot as a hare)
• Tachycardia and cutaneous vasodilatation(red as beet)
• Blurring of vision (blind as a bat)
• Hallucinations and delirium (mad as a hatter)
REFERENCES
• Humphrey P. Rang & Dale’s Pharmacology.6th Ed. Churchill Livingstone; 2007

• Katzung BG,Masters SB, Trevor AJ. Basic & Clinical Pharmacology.11th Ed.
McGraw Hill;2009.
• Brunton L, Lazo J, Parker K. Goodman & Gillman’s Pharmacological basis of
Therapeutics.


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MIRPUR UNIVERSITY OF SCIENCE AND TECHNOLOGY (MUST), MIRPUR

PHARMACOLOGY & THERAPEUTICS-1

Lecture: Organization and Division of Autonomic

2. Division of nervous system

4. Sympathetic and parasympathetic neurons

6. Enteric nervous system

Pharmacology & Therapeutics -1A

 Introduction to Autonomic nervous system and divisions of nervous system.

 Understanding of different types of neurons and difference between

 Concept of Enteric nervous system

Pharmacology & Therapeutics -1A 4

• Regulation and integration of bodily functions.

• Nervous system exerts its influence by rapid transmission of electrical impulses

• Autonomic drugs by mimicking or altering the effects of autonomic nervous

Pharmacology & Therapeutics -1A 5

Pharmacology & Therapeutics -1A 6

• Efferent neurons: carries nerve impulses from the CNS to the

• Afferent neurons: Important in reflex regulation of this system

• Effects of stimulation of the sympathetic division:

• Fight or flight response: The changes experienced by the body

• Rest and Digest Response:

• Dual innervation: vagal parasympathetic innervation slows the heart

• Organs receiving only sympathetic innervations: Adrenal medulla,

Pharmacology & Therapeutics -1A

• It is under voluntary control.

• Responses are generally faster than those in the ANS.

Pharmacology & Therapeutics -1A

Pharmacology & Therapeutics -1A

Over 50 signal molecules in the nervous system have been identified.

Pharmacology & Therapeutics-1A

• If transmission is mediated by acetylcholine, the neuron is termed

• Transmission from the autonomic postganglionic nerves to the effector

• When norepinephrine and epinephrine are the neurotransmitters, the fiber is

Pharmacology & Therapeutics-1A

• The adrenergic drugs affect receptors that are stimulated by norepinephrine or

• Some adrenergic drugs act directly on the adrenergic receptor (adrenoceptor)

• Others will block the action of the neurotransmitters at the receptors

Pharmacology & Therapeutics-1A

• Adrenergic neurons release norepinephrine as the primary neurotransmitter.

Pharmacology & Therapeutics-1A Pharmacology & Therapeutics-1A

2.UPTAKE INTO STORAGE VESICLES

α1 receptors α 2 receptors β1 receptors β2 receptors β3 receptors

Pharmacology & Therapeutics-1A

Pharmacology & Therapeutics-1A

Pharmacology & Therapeutics-1A

Pharmacology & Therapeutics-1A

• Epinephrine interacts with both α and β receptors.

• At low doses, β effects (vasodilation) on the vascular system predominate,

Pharmacology & Therapeutics-1A

Epinephrine Epinephrine causes Epinephrine hasa Epinephrine initiates

Pharmacology & Therapeutics-1A

Pharmacology & Therapeutics-1A

Pharmacology & Therapeutics-1A

Because norepinephrine is the neuromediator of adrenergic nerves, it should

Pharmacology & Therapeutics-1A 30

• Albuterol, pirbuterol, and terbutaline are short- acting β2 agonists used

Pharmacology & Therapeutics-1A 32

• The marked central stimulatory action of amphetamine is often

Pharmacology & Therapeutics-1A

Pharmacology & Therapeutics-1A

• Ephedrine has been used to treat asthma, as a nasal decongestant and to

• Pseudoephedrine is primarily used to treat nasal and sinus congestion or

Pharmacology & Therapeutics-1A

• Prazosin: Well absorbed orally ; bioavailability is 50-70%