2. NERVOUS SYSTEM
• IT CONTROLS AND CO-ORDINATE THE HUMAN BODY AND GIVES QUICK RESPONSE TO THE
BODY.
• CLASSIFICATION OF NERVOUS SYSTEM
1.CENTRAL NERVOUS SYSTEM (CNS)
a) BRAIN
b) SPINAL CORD
2. PERIPHERAL NERVOUS SYSTEM (PNS)
a) SOMATIC NERVOUS SYSTEM
b) AUTONOMIC NERVOUS SYSTEM
I) SYMPATHETIC NERVOUS SYSTEM
II) PARASYMPATHETIC NERVOUS SYSTEM
3. NERVOUS SYSTEM
• CNS: IT IS A MAIN SYSTEM OF OUR BODY WHICH CONSIST OF BRAIN AND SPINAL
CORD WHICH COORDINATE WITH THE BODY.
• PNS: IT CONSIST OF ALL NERVES OF OUR BODY WHICH TRANSMIT INFORMATION
FROM BODY TO BRAIN AND BRAIN TO BODY.
• SOMATIC N.S: IN THIS VOLUNTARY MOVEMENT HAPPENED( WHICH WE CAN
CONTROL).E.G : HAND MOVEMENT, WALKING.
• AUTONOMIC N.S: IN THIS,INVOLUNTARY MOVEMENT HAPPENED( WHICH ARE NOT IN
CONTROL).E.G: BREATHING, HEART RATE.
4. ORGANISATION AND FUNCTION OF ANS
• ANS INVOLVES INVOLUNTARY RESPONSES OF THE BODY
• IT IS DIVIDED INTO 2 PARTS:
• 1.SYMPATHETIC N.S
• 2. PARA SYMPATHETIC N.S
5. DIFFERENCE BETWEEN SYMPATHETIC AND PARA
SYMPATHETIC N.S
Sympathetic n.s Para sympathetic n.s
It involved in fight and flight response. Involves in maintaining homeostasis and also
permits the rest and digest response
Active during stressful conditions, preparing the
body to face them.
Active during relaxing times, restoring normal.
It has shorter neuron pathways, hence faster
response time
Has longer neuron pathways hence slower
response time
Increases heart beat, muscles tense up Reduces heart beat, muscles relaxes
Pupil dilates to let in more light Pupil contracts
Saliva secretion is inhibited Saliva secretion increases, digestion increases
On fight or flight situation, adrenaline is
released from adrenal glands, more glycogen is
converted to glucose
No such functions exist in fight or flight
situation.
Its ganglia are linked up to form a chain Its ganglia remain isolated
6. DIFFERENCE BETWEEN SYMPATHETIC AND PARA
SYMPATHETIC N.S
Sympathetic N.S
It works through neurotransmitter ,
adrenaline
It works through release of acetylcholine.
It enhances all the involuntary functions It retards all the involuntary functions
Contracts urinary bladder muscles Relaxes urinary bladder
Inhibits secretion of pancreatic juice Promotes secretion of pancreatic juice
It is formed by 22 pairs of sympathetic
ganglia and 2 sympathetic cords which run
parallel to vertebral column
It has nerve fibre which run along with
cranial and spinal nerves
7. CO TRANSMITTER
• CO TRANSMISSION IS THE RELEASE OF SEVERAL TYPES OF NEUROTRANSMITTER FROM A
SINGLE NERVE TERMINAL.
• CO TRANSMITTER : IT IS A CHEMICAL SUBSTANCE THAT IS RELEASED ALONG WITH
PRIMARY NEUROTRANSMITTER.
• IN ANS. PRIMARY NEUROTRANSMITTER -- ACH
• CO TRANSMITTER : PURINES: ATP
• PEPTIDES : VASO INTESTINAL PEPTIDE
• NITRIC OXIDE
• PROSTAGLANDIN
• E.G: ON RELEASE OF ACH, VIP ALSO GETS RELEASE.
• DIAGRAM( FROM K.D TRIPATHY PG NO: 97)
8. NEUROHUMORAL TRANSMISSION
• IT IS THE PROCESS OF TRANSFER OF ANY MESSAGE OR SIGNAL FROM ONE NEURON
TO ANOTHER NEURON WITH THE HELP OF ANY CHEMICAL MESSENGER (
NEUROTRANSMITTER , HORMONES)
• NEURO + HUMORAL = NERVE OR NEURON + CHEMICAL MESSENGER
• FOR THIS PURPOSE, INITIALLY NEUROTRANSMITTER IS SYNTHESIZED AND STORED IN
VESICLE IN NERVE TERMINALS
• DIAGRAM
• NEUROHUMORAL TRANSMISSION INVOLVES FOLLOWING STEPS:
1. IMPULSE CONDUCTANCE
2. TRANSMITTER RELEASE
3. TRANSMITTER ACTION ON POST JUNCTIONAL MEMBRANE
4.POST JUNCTIONAL ACTIVITY
5. TERMINATION OF TRANSMITTER ACTION
9. NEUROHUMORAL TRANSMISSION INVOLVES
FOLLOWING STEPS:
• 1. IMPULSE CONDUCTANCE :
• AT RESTING STATE(WHEN NERVE IMPULSE IS NOT TRANSMITTED FROM NEURON),
RESTING TRANSMEMBRANE POTENTIAL IS -70MV.
• NA+ ION HAVE HIGH CONC. AT OUT SIDE THE CELL AND MORE +VE CHARGE AT OUT
SIDE THE PLASMA MEMBRANE
• K+ ION HAVE HIGH CONC.AT INSIDE THE CELL AND MORE –VE CHARGE AT INSIDE THE
PLASMA MEMBRANE
• DEPOLARISATION : WHEN ANY KIND OF STIMULUS DETECTED THEN IT CHANGES THE
RESTING MEMBRANE POTENTIAL LESS POTENTIAL ( INCREASE)
• IF STIMULUS CHANGE RESTING POTENTIAL (-70 MV) TO (-55MV) THEN IT IS CALLED
THRESHOLD POTENTIAL..
•
10. NEUROHUMORAL TRANSMISSION INVOLVES
FOLLOWING STEPS:
• THRESHOLD POTENTIAL OPEN NA+ ION CHANNEL. SO NA+ ION ENTERS INSIDE THE CELL
AND +VE CHARGE PRODUCE INSIDE THE CELL AND –VE AT OUTSIDE THE CELL IT IS
CALLED DEPOLARISATION.
• STIMULUS CONTINUES INCREASE THE POTENTIAL, NOW WHEN POTENTIAL REACH AT (+20
MV TO +30 MV) IT OPEN K+ ION CHANNEL AND K+ ION MOVE OUTSIDE THE CELLS.
• THE IONIC DISTRIBUTION IS NORMALISED DURING THE REFRACTORY PERIOD BY THE
ACTIVATION OF NA+ K+ PUMP.
• THE CYCLE OF DEPOLARISATION AND REPOLARISATION IS CALLED ACTION POTENTIAL.
• 2) TRANSMITTER RELEASE : NERVE IMPULSE PROMOTES FUSION OF VASCULAR MEMBRANE
THROUGH CA++ ENTRY WHICH FLUIDIZED MEMBRANE
• THIS PROMOTES TRANSMITTER TO GET RELEASE FROM VESICLE IN SYNAPTIC CLEFT.
11. NEUROHUMORAL TRANSMISSION INVOLVES
FOLLOWING STEPS:
• 3) TRANSMITTER ACTION ON POST JUNCTION MEMBRANE :
• THE TRANSMITTER RELEASE AND ATTACHED WITH SPECIFIC RECEPTOR ON POST
JUNCTIONAL MEMBRANE AND DEPENDING ON NATURE IT INDUCE 2 TYPES OF ACTION
• 1) EPSP : EXCITATORY POST SYNAPTIC POTENTIAL
• 2) IPSP : INHIBITORY POST SYNAPTIC POTENTIAL
• 4) POST JUNCTIONAL ACTIVITY
• EPSP: INC. IN PERMEABILITY TO ALL CATION = NA+, CA++ INFLUX CAUSE
DEPOLARISATION, AND EFFLUX OF K+ WHICH LEADS TO NERVE IMPULSE, CONTRACTION IN
MUSCLES, SECRETION IN GLANDS.
• IPSP : INC. PERMEABILITY TO SMALLER ION OR ANIONS K+ MOVES OUT AND CL- MOVES IN
RESULTING HYPERPOLRISATION
12. NEUROHUMORAL TRANSMISSION INVOLVES
FOLLOWING STEPS:
• 5) TERMINATION OF TRANSMITTER ACTION :
• NEUROTRANSMITTER IS DEGRADED LOCALLY OR ANY OTHER MECHANISM
• IT CAN ALSO BE DEGRADED BY ENZYMATIC ACTION.
13. CLASSIFICATION OF NEUROTRANSMITTER
• THESE ARE THE CHEMICAL MESSENGER WHICH TRANSMIT SIGNAL FROM ONE NEURON
TO TARGET CELLS.
• THEY CAN BE CLASSIFIED IN TWO TYPES :
• 1) STRUCTURAL
• 2) FUNCTIONAL
1) STRUCTURAL CLASSIFICATION
a. AMINES :
EPINEPHRINE , NOREPINEPHRINE , DOPAMINE , SEROTONIN , HISTAMINE
B AMINO ACID AND AMINO ACID DERIVATIVES :
GLUTAMATE , ASPARTATE , GLYCINE, GABA
C. PURINES :
ADENOSINE , ATP ( ADENOSINE TRIPHOSPHATE)
14. CLASSIFICATION OF NEUROTRANSMITTER
D. GAS : NITRIC OXIDE
E. MISCELLANEOUS : ACETYLCHOLINE
2) FUNCTIONAL CLASSIFICATION:
a) EXCITATORY NEUROTRANSMITTER
EG: GLUTAMATE , ASPARTATE, ADRENALINE AND NORADRENALINE, HISTAMINE ,
NITRIC OXIDE AND ACETYLCHOLINE
B) INHIBITORY NEUROTRANSMITTER:
EG : GABA, GLYCINE, ADRENALINE AND NORADRENALINE , DOPAMINE AND
SEROTONIN
15. NEUROTRANSMITTERS
1) ACETYLCHOLINE: (LEARNING) INVOLVED IN THOUGHT, LEARNING AND MEMORY. IT
ACTIVATES MUSCLE CONTRACTION IN THE BODY AND IS ALSO ASSOCIATED WITH
ATTENTION AND AWAKENING
2) ADRENALINE ( FIGHT OR FLIGHT) IT IS PRIMARILY RELEASED BY THE ADRENAL GLAND
BUT SOME NEURONS MAY SECRETE IT AS A NEUROTRANSMITTER. IT S PRODUCED IN
STRESSFUL SITUATION , INCREASE HEART RATE AND BLOOD FLOW. LEADING TO
PHYSICAL BOOST AND HEIGHTENED AWARENESS.
3) NOR ADRENALINE ( CONCENTRATION ) IT IMPROVE ATTENTION AND RESPONDING
ACTIONS IN THE BRAIN. CONTRACTS BLOOD VESSELS
4) DOPAMINE : (PLEASURE) FEELING OF PLEASURE, ALSO ADDICTION , MOVEMENT AND
MOTIVATIONAL
5) SEROTONIN : ( MOOD) CONTRIBUTES TO WELL BEINGS AND HAPPINESS. HELPS SLEEP
CYCLE AND DIGESTIVE SYSTEM REGULATION.
16. NEUROTRANSMITTERS
6) GABA : (CALMING) CALM FIRING NERVES IN THE CNS. HIGH LEVEL WILL IMPROVE FOCUS
AND LOW LEVEL WILL CAUSE ANXIETY. ALSO CONTRIBUTES TO MOTOR CONTROL AND
VISION.
7) HISTAMINE : RELEASED BY MAST CELLS, INVOLVED IN LOCAL IMMUNE RESPONSES.
CONTRACTION OF SMOOTH MUSCLE TISSUE OF THE LUNGS, UTERUS AND STOMACH
8) GLUTAMATE (MEMORY) INVOLVED IN LEARNING AND MEMORY. IT REGULATES
DEVELOPMENT AND CREATION OF NERVE CONTACTS.
17. PARASYMPATHOMIMETICS
• SYNONYM: CHOLINOMIMETIC, CHOLINERGIC AGONIST, CHOLINERGIC DRUGS, CHOLINERGIC
SYSTEM
• DEFINITION :THESE ARE THE CHEMICAL AGENTS OR DRUGS WHICH COPY THE ACTION OF
ACH IN PARASYMPATHETIC NERVOUS SYSTEM.
• PARASYMPATHOMIMETIC = PARASYMPATHO (PARASYMPATHETIC N.S) + MIMETIC (MIMIC,
COPY THE ACTION)
• THESE DRUGS BIND WITH CHOLINERGIC RECEPTORS AND GIVE THEIR ACTION.
• WHEN THE NEUROTRANSMITTER OF PARASYMPATHETIC NERVOUS SYSTEM (ACH) IN BODY IS
LESS AS PER DEMAND THEN WE USE DRUGS EXTERNALLY WHICH ACT AS A CHOLINERGIC
NEUROTRANSMITTER/PARASYMPATHOMIMETICS EG : ACETYLCHOLINE , CARBACHOL,
PHYSOSTIGMINE, NEOSTIGMINE.
18. CLASSIFICATION OF PARASYMPATHOMIMETICS
A) DIRECTLY ACTING CHOLINERGICS
1. CHOLINE ESTERS : ACETYLCHOLINE , METHACHOLINE, CARBACHOL, BETHANECHOL
2. ALKALOIDS : MUSCARINE, ARECOLINE, PILOCARPINE
B) INDIRECTLY ACTING CHOLINERGICS
1. REVERSIBLE ANTICHOINESTERASES : PHYSOSTIGMINE, NEOSTIGMINE, PYRIDOSTIGMINE,
RIVASTIGMINE, DISTIGMINE
2. IRREVERSIBLEE ANTICHOLINESTERASES :
EX : DI - ISO FLUROPHOSPHONATE (DFP), TETRAETHYL PYROPHOSPHATE (TEPP), MALATHION,
PARATHION, ECOTHIOPATE.
19. CHOLINERGIC RECEPTOR
• THERE ARE TWO CLASSES OF CHOLINERGIC RECEPTORS
1. MUSCARINIC RECEPTORS
2. NICOTINIC RECEPTOR
MUSCARINIC RECEPTOR ARE PRESENT IN HEART, SMOOTH MUSCLES ,SECRETORY GLANS,
EYES AND CNS
THREE SUBTYPES OF MUSCARINIC RECEPTOS : M1, M2, M3
NICOTINIC RECEPTORS ARE PRESENT IN THE NEUROMUSCULAR JUNCTION, AUTONOMIC
GANGLIA AND ADRENAL MEDULLA
TWO SUBTYPES OF NICOTINIC RECEPTORS ARE NM AND NN.
NM RECEPTORS ARE PRESENT AT SKELETAL MUSCLE MUSCLE END PLATE AND NN RECEPTORS
AT AUTONOMIC GANGLIA AND ADRENAL MEDULLA
20. BIOSYNTHESIS OF ACH
• DIAGRAM
• ON ARRIVAL OF ACTION POTENTIAL AT THE NERVE ENDINGS, IN PRESENCE OF CALCIUM,
FREE ACH ARE RELEASED IN TO SYNAPTIC CLEFT BY THE PROCESS OF EXOXYTOSIS.
• THE ACTIVE ACH COMBINES WITH THE CHOLINERGIC RECEPTORS ( MUSCARINIC AND
NICOTINIC) ON POSTSYNAPTIC MEMBRANE OF TARGET ORGAN.
• THIS ACH ACTIVATES THE CHOLINERGIC RECEPTOR ON THE POSTSYNAPTIC MEMBRANE
LEADING TO THE DEPOLARIZATION OF THIS MEMBRANE. THUS THE IMPULSE IS
TRANSMITTED ACROSS THE SYNAPSE.
• THE ACH RELEASE IN SYNAPTIC CLEFT IS RAPIDLY HYDROLYSED BY THE ENZYME
ACETYLCHOLINESTERASE (ACHE) WITHIN FEW MILLISECONDS.
• A PART OF CHOLINE IS REABSORBED BY NERVE ENDINGS AND LATER REUSED IN ACH
SYSTHESIS
• A PSEUDOCHOLINESTERASE ENZYME OCCURS IN THE PLASMA AND LIVER , SERVES TO
21. ACETYLACHOLINE
• ACH IS ACETIC ACID ESTER OF CHOLINE AND IS NEUROTRANSMITTER ACTS ON BOTH
MUSCARINIC AND NICOTINIC RECEPTORS.
• MECHANISM OF ACTION OF ACH
THE INTERACTION OF ACH WITH CHOLINERGIC RECEPTOR MAY PRODUCE “ INCREASED
PERMEABILITY OF ALL IONS (NA+, CA++) WHICH RESULT TO DEPOLARIZATION OF POST
SYNAPTIC MEMBRANE.
SELECTIVE PERMEABILITY CHANGE TO CERTAIN IONS ( K AND CL) WHICH PRODUCE
STABILIZATION OR HYPERPOLARIZATION OF POST SYNAPTIC MEMBRANE.
(DEPOLARIZATION INCREASES CELLULAR ACTIVITY AND HYPERPOLARIZATION DECREASES
CELLULAR ACTIVITY)
22. PHARMACOLOGICAL ACTIONS OF ACH
RECEPTORS LOCATION PHARMACOLOGICAL ACTION
Muscarinic M1 Autonomic ganglia CNS Excitation, memory
Muscarinic M2 SA Node
AV Node
Atrium
Ventricle
CARDIAC DEPRESSANT ACTION
Dec. heart rate
Dec. force of contraction
Dec. excitability of heart
Dec. automaticity of heart
Dec. blood pressure
Muscarinic M3 Smooth muscle of GIT, respiratory
tract, urinary tract, eye pupil
Secretary glands of salivary sweat
lacrimal gland pancrease gastric
nasopharyngyl gland
Inc. GIT motility, bronchial
constriction, bladder and ureter
constriction,pupil constriction,
Inc. salivation, inc. sweating, inc. tears,
inc. insulin secretion, inc. gastric acid
secretion, inc. mucus secretion
23. PHARMACOLOGICAL ACTIONS OF ACH
Receptor location Pharmacological
action
Nicotinic NM Neuromuscular junction in skeletal
muscle
Skeletal muscle stimulation
Nicotinic NN Autonomic ganglia adrenal medulla Excitation release of
adrenaline
24. THERAPEUTIC USES OF ACH
• ACH IS NOT USED CLINICALLY BECAUSE
• IT ACTS ON ALL MUSCARINIC AND NICOTINIC RECEPTORS THROUGHOUT THE BODY
.THUS, OVERALL EFFECT IS IRRATIONAL.
• ON ORAL ADMINISTRATION IT IS HYDROLYSED BY GASTROINTESTINAL ENZYMES
• ON INTRAVENOUS ADMINISTRATION, IT IS METABOLIZED IN BLOOD ITSELF BY
PSEUDOCHOLINE ESTERASE ENZYME BEFORE REACHING SITE OF ACTION.
• ACH DOES NOT CROSS BBB HENCE INEFFECTIVE FOR CNS ACTION
• ONLY LITTLE FRACTION OF ACH MOLECULES MAY ENTER IN CNS WHICH GET
METABOLIZED BY ACETYLCHOLINESTERASE ENZYME.
25. DIRECTLY ACTING CHOLINERGICS
1. CHOLINE ESTERS :
EG : ACETYLCHOLINE , METHACHOLINE, CARBACHOL, BETHANECHOL
2. ALKALOIDS :
EG : MUSCARINE, ARECOLINE, PILOCARPINE
MECHANISM OF ACTION:
THESE DRUGS STIMULATE CHOLINERGIC RECEPTORS AND PREGANGLIONIC AND POST
GANGLIONIC NERVE FIBERS.
26. THERAPEUTIC USES
Drug Dose with route Therapeutic uses
1) Methacholine 1 – 4 mg route subcutaneous
and 3% eye drop
In glaucoma and atrial
tachycardia
2) betanecol Dose 205 – 30mg route
subcutaneous
Urinary retention
3) pilocarpine Dose – 4% eye drop Chronic glaucoma, antidote
in belladonna poisoning
27. INDIRECTLY ACTING CHOLINERGICS
REVERSIBLE ANTICHOLINERTERASES
EG : PHYSOTIGMINE , NEOSTIGMINE, PYRIDOSTIGMINE, RIVASTIGMINE, DISTIGMINE
MECHANISM OF ACTION
REVERSIBLE ANTICHOLINESTERASES ARE THE DRUGS THAT COMPETITIVELY
ANTAGONISES THE ACETYLCHOLINESTERASE (ACHE) ENZYME AND PREVENT THE
HYDROLYSIS OF ACETYLCHOLINE
ACHE CAUSES METABOLISM OF ACH . INHIBITION OF ACHE ENZYME INCREASES
BOTH AVAILABILITY AND DURATION OF ACTION OF ACETYLCHOLINE.
28. THERAPEUTIC USES
Drug Therapeutic uses
physostigmine Glucoma
In belladonna poisoning
Alzeimers disease
Mysthenia gravis
Neostigmine Mysthenia gravis
Urinary retention
Expulsion of urinary calculi (stone)
Gall bladder calculi
Snake venom
pyridostigmine Myasthenia gravis
edrophonium Myasthenia gravis
29. IRREVERSIBLE ANTICOLINESTERASES /
ORGANOPHOSPHORUS COMPOUNDS
• DI - ISO FLUROPHOSPHONATE (DFP),
• TETRAETHYL PYROPHOSPHATE (TEPP),
• MALATHION,
• PARATHION,
• ECOTHIOPATE.
• THERAPEUTIC USES
• THEY NEVER USED CLINICALLY . THEY MAY BE USED FOR OPHTHALMIC
DISORDERS IN MINUTE CONCENTRATIONS
30. ANTICHOLINESTERASE
(ORGANOPHOSPHORUS) POISONING
• ANTICHOLINESTERASES ARE EASILY AVAILABLE AND EXTENSIVELY USED AS
AGRICULTURAL AND HOUSEHOLD INSECTICIDES, ACCIDENTAL AS WELL AS SUICIDAL
POISONING IS COMMON.
• SYMPTOMS
• M1 RECEPTORS : IRRITABILITY, DISORIENTATION, UNSTEADINESS, TRENOR,
CONVULSIONS, COMA AND DEATH
• M2 RECEPTORS : HYPOTENTION, BRADYCARDIA, CIRCULATORY COLLAPSE, CARDIAC
ARRHYTHMIAS
• M3 : IRRITATION OF EYE, LACRIMATION, SALIVATION, SWEATING, DEHYDRATION,
TRACHEA BRONCHIAL SECRETIONS, BRONCHOSPASM, BREATHLESSNESS, TIGHTNESS OF
CHEST
• NM RECEPTORS : MUSCULAR FASCICULATION, WEAKNESS AND RESPIRATORY PARALYSIS,
31. MANAGEMENT
1) DECONTAMINATION MEASURES
• THE POISON IS REMOVED FROM THE SITE OF EXPOSURE FROM PATIENT AND PLACED IN
FRESH AIR. THE SKIN , EYES AND MOUTH WASHED WITH SOAP AND WATER
• GASTRIC LAVAGE TO REMOVE THE POISON FROM THE STOMACH INDUCES BY WARM
SALINE SOLUTION AND ACTIVATED CHARCOAL
2) SUPPORTIVE THERAPIES
• THE ARTIFICIAL RESPIRATION IS GIVEN BY VENTILATOR TO RECOVER FROM
BREATHLESSNESS
• THE NORMAL SALINE SOLUTION AND VASOCONSTRICTORS LIKE NORADRENALINE OR
DOPAMINE ARE ADMINISTERED BY IV INFUSION TO MAINTAIN BP AND TO PREVENT
CIRCULATORY COLLAPSE (SHOCK)
• ANTIBIOTICS LIKE AMPICILLINE ARE GIVEN TO PREVENT INFECTION.
32. MANAGEMENT
3) SPECIFIC MEASURES:
• TO REVERSE THE SIDE EFFECTS, ANTIDOTES ARE ADMINISTERED LIKE ATROPINE SULPHATE
(2MG IV OR IM) TO BE BLOCK MUSCARINIC RECEPTORS IN ORDER TO COUNTERACT CNS
EFFECTS AND OTHER COMPLICATIONS
• ACHE REACTIVATORS LIKE PRALIDOXIME, OBLIDOXIME AND PYRUVALIDOXIME. THEY
REACTIVATE THE ACHE ENZYME AT NICOTINIC RECEPTORS SITES ON SKELETAL MUSCLES
