Download autonomic nervous system

AUTONOMIC NERVOUS SYSTEM:
The nervous system is concerned with the initiation, control and coordination of various
body functions
The nervous system is divided into 2systems:
1. Central nervous system
2. Peripheral nervous system
Peripheral nervous system is divided into:
 somatic nervous system
 autonomic nervous system
Autonomic nervous system is again subdivided into
 sympathetic nervous system
 para -sympathetic nervous system
The autonomic nervous system (ANS or visceral nervous system) is the part of the
peripheral nervous system that acts as a control system functioning largely below the
level of consciousness, and controls visceral functions.[1] The ANS affects heart rate,
digestion, respiration rate, salivation, perspiration, diameter of the pupils, micturition
(urination), and sexual arousal. Whereas most of its actions are involuntary, some,
such as breathing, work in tandem with the conscious mind.
It is classically divided into two subsystems: the parasympathetic nervous system and
sympathetic nervous system. With regard to function, the ANS is usually divided into
sensory (afferent) and motor (efferent) subsystems. The enteric nervous system is
sometimes considered part of the autonomic nervous system, and sometimes
considered an independent system.
The sympathetic nervous system has ganglia away from organs where as in para
sympathetic system the ganglia is nearer to the organs and away from CNS.
The different actions shown by both the systems are given below:
SYMPATHETIC NERVOUS SYSTEM:
They originate from thoraco-lumbar region also known as adrenergic neuron.
It is always active at a basal level (called sympathetic tone) and becomes more active
during times of stress. Its actions during the stress response comprise the fight-or-flight
response. At synapses within the sympathetic ganglia, preganglionic sympathetic neurons
release acetylcholine, a chemical messenger that binds and activates nicotinic
acetylcholine receptors on postganglionic neurons. In response to this stimulus,
postganglionic neurons principally release noradrenaline (norepinephrine). Prolonged
activation can elicit the release of adrenaline from the adrenal medulla.
Once released, norepinephrine and epinephrine bind adrenergic receptors on peripheral
tissues. Binding to adrenergic receptors causes the effects seen during the fight-or-flight
response. These include pupil dilation, increased heart rate, occasional vomiting, and
increased blood pressure. Increased sweating is also seen due to binding of cholinergic
receptors of the sweat glands.
Dopamine is the predominant neurotransmitter in the brain.
Adrenaline, noradrenaline and dopamine are Catecholamines.
BIOSYNTHESIS OF NEURO-TRANSMITTER:
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tyrosine ,the precursor is an esse4ntial aminoacid present in food,blood fluids and
synthesized in the body from related aminoacid phenylalanine
tyrosine is takrn up from the circulation by the adrenergic neuron and in the
presence of tyrosine hydroxylase which catalyses conversion of tyrosine to
dihydroxy phenyl alanine(DOPA)
DOPA in the presence of decarboxylase is converted into dopamine
Dopamine is now actively taken up by synaptic vescicle &in the presence of
dopamine b-hydroxylase is converted to Nor-adrenaline
Adrenal medulla contains an enzyme N-methyl transferase which converts
Noradrenaline to adrenaline
TERMINATION OF CATECHOLAMINES:
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Nor-adrenaline and adrenaline serves the function of neurotransmitter as well as
they are hormones in the body
After they are releaed from synaptic cleft .they have the following fate:
1. uptake of nor-adrenaline:
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75-90% released neurotransmitter is taken up by adrenergic neuron or
extraneuronal site uptake
2. metabolic degradation of catecholamines:
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these catecholamines are metabolized by 2 enzymes:
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endogenously by MONOAMINO OXIDASE(MAO)
exogenously by CATECHOL-O-METHYL TRANSFERASE(COMT)
a) MONOAMINO OXIDASE:
 This enzyme is abundantly present in almost all of the outer membrane of
mitochondria
 It is present in the adrenergic nerve terminal ,CN,platelets,liver,kidney
&intestine.
 They belong to protein family of flavin-containing amine oxidoreductases.
In humans there are two types of MAO: MAO-A and MAO-B.
b) Both are found in neurons and astroglia.
c) Outside the central nervous system:
 MAO-A is also found in the liver, gastrointestinal tract, and placenta.
 MAO-B is mostly found in blood platelets.
  Serotonin, norepinephrine (noradrenaline), and epinephrine (adrenaline)
are mainly broken down by MAO-A.
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Both forms break down dopamine equally.
Specific reactions catalyzed by MAO include:
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epinephrine or norepinephrine to 3,4-Dihydroxymandelic acid
metanephrine or normetanephrine to vanillylmandelic acid
dopamine to dihydroxyphenylacetic acid
b)CATECHOL-O-METHYL TRANSFERASE:
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It is widely distributed in the body both at Neuronal &Non-Neuronal tissues.
Catechol-O-methyl transferase is involved in the inactivation of the
catecholamine neurotransmitters (dopamine, epinephrine, and norepinephrine).
The enzyme introduces a methyl group to the catecholamine, which is donated by
S-adenosyl methionine (SAM).
Specific reactions catalyzed by COMT include:
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Norepinephrine -> Normetanephrine
Epinephrine -> Metanephrine
Dihydroxyphenylethylene glycol (DOPEG) -> Methoxyhydroxyphenylglycol
(MOPEG)
3,4-Dihydroxymandelic acid (DOMA) -> Vanillylmandelic acid (VMA)
ADRENOCEPTOR:
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The adrenergic receptors (or adrenoceptors) are a class of G proteincoupled receptors that are targets of the catecholamines, especially
noradrenaline (norepinephrine) and adrenaline (epinephrine).
Although dopamine is a catecholamine, its receptors are in a different
category.
Dopamine has been used as a neurotransmitter since the beginning of nerve
system evolution.
There are two main groups of adrenergic receptors, α and β, with several
subtypes.
α receptors have the subtypes α1 (a Gq coupled receptor) and α2 (a Gi coupled
receptor). Phenylephrine is a selective agonist of the α receptor.
β receptors have the subtypes β1, β2 and β3.
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All three are linked to Gs proteins, which in turn are linked to adenylate
cyclase.
Agonist binding thus causes a rise in the intracellular concentration of the
second messenger cAMP (cyclic adenosine monophosphate).
Downstream effectors of cAMP include cAMP-dependent protein kinase
(PKA), which mediates some of the intracellular events following hormone
binding.
Isoprenaline is a selective agonist.
Receptor Agonist
α1:
 Noradrenaline
 Phenylephrine
 Methoxamine
 Cirazoline
 Xylometazoline
α2:
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Dexmedetomidine
Medetomidine
Romifidine
Clonidine
Detomidine
Lofexidine
Xylazine
Tizanidine
Guanfacine
Amitraz
β1
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Noradrenaline
Isoprenaline
Dobutamine
Antagonist
 Alfuzosin
 Doxazosin
 Phenoxybenzamine
 Phentolamine
 Prazosin
 Tamsulosin
 Terazos
 Yohimbine
 Idazoxan
 Atipamezole
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Metoprolol
Atenolol
β2
 Salbutamol (Albuterol in
USA)
 Bitolterol mesylate
 Formoterol
 Isoprenaline
 Levalbuterol
 Metaproterenol
 Salmeterol
 Terbutaline
Ritodrine
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Butoxamine
Propranolol
β3
 Amibegron
 Solabegron
Dopamine
L-DOPA
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SR 59230A
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Chlorpromazine
Trichlorperazine
Dopamine
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Haloperidol
Risperidone
Domperidone
D1
D2
PARA-SYMPATHETIC NERVOUS SYSTEM:
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They origate from craniosacral outflow also known as Cholinergic Neuron
The preganglionic fibre is long &the post ganglionic fibre is shorter
The neurotransmitter at the effector end organ is acetyl choline(Ach)
Ach is an ester of choliune &acetic acid
BIOSYNTHESIS OF ACETYL CHOLINE:
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Choline is a member of Vit B complex & essential nconstituent of the food is
taken up by active transport from the circulation by cholinergic neurons
Acetyl coenzyme-A derived from pyruvate donates acetyl group to choline to
form acetyl choline with the help of the enzyme choline acetyl transferase
Acetyl choline is stored in synaptic vesicle
TERMINATION OF CTION OF ACH::
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After it’s release from synaptic vesicle , acetyl choline combines with
receptors remain bound for less than millisecond & is quickl;y hydrolysed by
an enzyme called Acetyl cholinesterase
It is terminated by hydrolysis of ester linkage of the molecule
There are 2 types of choline esterase enzyme
acetylcholinesterases (AChEs)(True ache)
the butyryl or pseudocholinesterases (BuChE) (pseudo cholinesterase)
True cholinesterase is present in cholinergic neuron,synapse &neuro muscular
junction
Pseudo cholinesterase `is present in blood ,liver, intestine &other organs
CHOLINERGIC RECEPTORS:
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They are classified into
MUSCARINIC RECEPTORS
NICOTINIC RECEPTORS
MUSCARINIC RECEPTORS AGONISTS:Acetyl choline ,pilocarpine , muscarinie
MUSCARINIC RECEPTOR ANTAGONIST:atropine ,pirenzepine
LOCATION:
M1=ganglia &stomach
M2=heart
M3=smooth muscles , secretary glands
CLASSIFICATION:
1)ETERS OF CHOLINE:acetyl choline, methacholine, carbachol, bethachol
2)CHOLINOMIMETIC ALKALOIDS: pilocarpine , muscarine, arecholine
3)CHOLINESTERASE INHIBITORS:
These are also known as anti-cholinesterases
Physostigmine, neostigmine,pyridostigmine, edrophonium, ambenonium,
demecarium
4)IRREVERSIBLE ANTICHOLINESTERASE:
These are also known as organo phosphorous compounds
Malthion, parathion, DDT, diisopropyl fluro phosphate(DFP), octa methyl pyro
phosphate tetramide(DMPA)
ACETYLCHOLINE:
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ACH is an ester of choline with acetic acid
Chemically acetylcholine is quarternary amino compound &acetyl choline is
extremely hygroscopic
Given orally itb is rapidly destroyedc in the GIT
When given by IV route it fails to produce its actions even at large doses
This is becoz ach is destroyed in the plasma by the enzyme
pseudocholinesterase
The only important action after IV administration of Ach is transient fall in
B.P
PHARMACOLOGY OF METHACHOLINE:
Source: synthetic
Category: cholinergic agonist
Class:esters of choline
Mechanism of action: it occupies muscarinic receptors & stimulate it
Route of administration is by oral route
PHARMACOKINETICS: well absorbed orally
Totally resistant to pseudocholinesterae& has longer derivation of action
It is metabolized in liver, &excreted through urine
ADVERSE EFFECTS:nausea, vomiting, diarrhea
CONTRAINDICATIONS:it is contraindicated in hyperthyroidism, bronchial
asthama, peptic ulcers
CARBACHOL:both true & pseudocholinesterase
It is better absorbed from GIT than the cholinesterase
ROA: oral, topical & parenteral
Paralytic ileus & retention of urine
More potent than methacholine &bethacholine
PILOCARPINE:
Source: : Pilocarpine, alkaloid of vegetable origin, with primarily muscarinic
properties from the leaves of pilocarpus microphyllus & other species pilocarpus
jaborandi
elicits sweat and salivary hypersecretion.
pilocarpine is especially used in the form of ophthalmic solutions for treatment of
glaucoma where, by reducing iris diameter, it facilitates the flow of aqueous humor
by trabeculum and canal of Schlemm .
It is also used by general route in the treatment of hyposialy. It is present in several
proprietary formulations.
ADVERSE EFFECTS:nausea, vomiting &pulmonary edema
MUSCARINE:
It is an alkaloid obtained from poisonous mushroom Amantia muscarina
It has only muscarinic action
It is not uised therapeutically
ARECHOLINE:
It is found in betel nut Areca catechu
It has muscarinic as well as nicotinic actions
Use in vomiting practice
Doesn’t have therapeutic applications in humans
B.NICOTINIC
Autonomic ganglia:
Both sympathetic & para sympathetic ganglia are stimulated
Thios effect is manifested at higher doses
High dose of Ach after atropine causes tachycardia &raise in B.P due to timulation of
sympathetic ganglia and releae of catecholamines
SKELETAL MUSCLES:
It induce the contraction of skeletal muscles
Intraarterial high dose cause twitching &fasciculation
CNS:
Ach injected IV , doen’t penetrate BBB & no central effects are seen
Cholinesterase are rarely usede.