Autonomic Nervous System - PPT 1
Autonomic Nervous System - PPT 1
Autonomic Nervous System - PPT 1
SYSTEM
BY:
2
Nervous System
Peripheral NS Central NS
Autonomic Somatic
Sympathetic Parasympathetic
Feedback loop of the
autonomic nervous system.
4
Anatomy
5
ANATOMY
1) SYMPATHETIC
(THORACOLUMBAR) DIVISION.
2) PARASYMPATHETIC
(CRANIOSACRAL) DIVISION.
EFFERENT NEURONS
PREGANGLIONIC NEURONS
POSTGANGLIONIC NEURON
7
Brain stem or spinal cord
pregnanglionic neuron
ganglia
postganglionic neuron
effector organ
How neurons regulate other cells.
The basic steps in the process by which neurons elicit
responses from other cells are
9
The basic anatomy of the parasympathetic and sympathetic nervous systems and the
somatic motor system. 10
Transmitters employed at specific junctions of the peripheral nervous system
11
Steps of Synaptic Transmission
13
Steps in synaptic transmission.
Step 1, Synthesis of transmitter (T) from precursor molecules (Q, R, S
Step 2, Storage of transmitter in vesicles.
Step 3, Release of transmitter:
Step 4, Action at receptor:
Step 5, Termination of transmission:
14
AUTONOMIC
NEUROTRANSMITTERS
15
NEUROTRANSMITTERS
Epinephrine
Nor epinephrine
Acetylcholine
Dopamine
16
SITES OF RELEASE OF Ach
&
NOR EPINEPHRINE
17
Sites where Ach is released
18
Sites where Nor epinephrine is
released
19
AUTONOMIC RECEPTORS
20
AUTONOMIC RECEPTORS
CHOLINERGIC RECEPTORS ----- 2 Types
– Muscarinic receptors
– Nicotinic receptors
Alpha -2
Beta -1
(ii) beta adrenoceptor
21
Subtypes of Cholinergic and
Adrenergic Receptors
Cholinergic receptor
– Nicotinic n
– Nicotinic m
– Muscarinic
Adrenergic receptor
– Alpha1 and alpha2
– Beta1 and beta2
– Dopamine
22
23
24
25
26
27
FUNCTIONS OF AUTONOMIC
RECEPTORS
28
Functions of Cholinergic
Receptor Subtypes
Nicotinic n (neuronal)
– Promotes ganglia transmission
– Promotes release of epinephrine
Nicotinic m (muscle)
– Contraction of skeletal muscle
Muscarinic
– Activates parasympathetic nervous system
29
Functions of Adrenergic
Receptor Subtypes
Alpha1
– Vasoconstriction
– Ejaculation
– Contraction of bladder neck and prostate
Alpha2
– Located in presynaptic junction
– Minimal clinical significance
30
36 years old male patient came in medical OPD at tehseel
headquarter hospital renalakhurd, district okara, Punjab,
Pakistan. He told his doctor about his history of having
hypertension, urinary retention. He also told when asked by
doctor that he has problem in sexual intercourse with his
wife. Doctor asked more about his sexual problem. He shied
but replied that he do not ejaculate during intercourse, every
time. Doctor guessed that he has problem of delayed
ejaculation.
Which neurotransmitter may be involved in this clinical
scenario:
(a) Dopamine
(b) Norepinephrine /Epinephrine
(c) Acetylcholine
(d) Nicotine
(e) Histamine 31
Functions of Adrenergic
Receptor Subtypes (cont.)
Beta1
Heart
– Increases
heart rate
force of contraction
velocity of conduction in AV node
Kidney
– Renin release
32
A 25 years old female patient came in cardiac OPD,
complaining chest pain. She was hypertensive. Her
plasma renin level was increased. ECG revealed
increased heart rate, force of cardiac contraction,
and increased velocity of conduction in AV node.
Which receptor type may be involved when
stimulated, in this case.
(a) Muscrinic cholinergic
(b) Nicotinic cholinergic
(c) Beta-1 adrenergic
(d) Beta-2 adrenergic
(e) All of above receptor types
33
Functions of Adrenergic Receptor
Subtypes (cont.)
Beta2
– Bronchial dilation
– Relaxation of uterine muscle
– Vasodilation
– Glycogenolysis
Dopamine
– Dilates renal blood vessels
34
Effect of
Organ Sympathetic Parasympathetic
Action Receptor Action Receptor
Eye
Iris
-------- -------
Radial muscle Contracts α1
-------- ---------
Circular muscle Contracts M3
Ciliary muscle Relaxes β contract M3
Heart
SA node Accelerate β1 Decelerates M2
----------
Ectopic pacemaker Accelerate β1
Contractility Increases β1 Decreases M2 35
Vascular Sympathetic Parasympath
Smooth Muscle etic
Skin, ……
Splanchnic Contract
α -----
vessels
Skeletal Muscle Relaxes β2 --------- --------
vessels
36
Bronchial smooth Relaxes β2 contracts M3
muscles
G.I.T
Genitourinary
System
Bladder wall Relaxes β2 Contracts M3
Sweat glands
Thermoregualtory
Increases M
38
Metabolic Sympathetic Parasympat
hetic
Functions
-------- --------
Liver Gluconeo β2 / α
genesis
-------- --------
Liver Glycogeno β2 / α
lysis
-------- --------
Fat cells Lipolysis α 2/
β1/β3
-------- --------
Kidney Renin β1
release
39
FUNCTION OF
PARASYMPATHETIC
&
SYMPATHETIC
NEVOUS SYSTEM
40
Parasympathetic Nervous
System (PNS)
Rest & Digest situations.
The regulatory functions of PNS affect these sites
Heart rate
Gastric secretions
Bladder and bowel
Vision
Bronchial smooth muscle
41
Sympathetic Nervous System
Main functions of the SNS
Regulation of cardiovascular system
Regulation of body temperature
Implementation of “fight or flight” reaction
42
Opposing effects of parasympathetic and
sympathetic nerves.
43
ORGANS RECEIVING ONLY SYMPATHETIC
INNERVATION
Adrenal Medulla
Kidney
Pilomotor muscles
Sweat glands
Vessels
Metabolic processes
44
THREE MECHANISMS BY WHICH BINDING OF
NEUROTRANSMITTER LEADS TO A CELLULAR RESPONSE
AND EFFECT:
Ions
Adenylyl
PROTEIN PHOSPHORYLATION
INTRACELLULAR EFFECT 46
RECEPTORS COUPLED TO DIACYLGLYCEROL (DAG) & INOSITOL
TRIPHOSPHATE
Alpha-1 adrenoceptor
Cholinergic muscarinic receptor
DAG IP3
47
Intracellular effect
CHOLINERGIC AGONIST
CLASSIFICATION
48
Cholinergic agonists
Direct Acting
a. Alkaloids
muscarine, nicotine, pilocarpine
b. Choline Esters
ACh, methacholine, carbachol, bethanechol
In-direct Acting
Reversible
Edrophonium, neostigmine, physostigmine, demecarium
Irreversible
Ecothiophate, isoflurophate, Soman, parathion, malathion
Reactivator of acetylcholinesterase ---
Pralidoxime 49
Structural classification
Indirect acting drugs
1. Simple alcohols:
Edrophonium
50
51
24 years old ,married, beautiful female patient came in medical OPD
of Ghurki teaching hospital. 3rd year MBBS students were waiting for
their senior teacher to attend clinical class at OPD. When they got
medical history from married, beautiful lady. She told that she
remains hypertensive, remains hungry even after excessive food
intake, her body hairs raise when she listen any bad news at TV, and
she has problems of frequent micturation and increased sweating.
Medical students are discussing on ANS. Which group’s statement is
true:
f) Her problems are due to her crucial husband
g) She is in depression
h) She has no problem at all
i) Her complains related with kidney, adrenal medulla,
vessels, pilomotor muscles, sweat glands and metabolic
processes are due to sympathetic ANS stimulation
j) All her problems are related with histamine release 52
MOA
DIRECTLY ACTING CHOLINERGIC
AGONIST DRUGS ACT DIRECTLY
through RECEPTORS (affinity + intrinsic
activity of concerned receptors)
53
Mechanism of action
of
Indirect acting
Cholinergic agonist
54
Mechanism of Action
ACETATE
ACETYLCHOLINE ACETYLCHOLINESTERASE
Ach
ACETYLCHOLINESTERASE CHOLINE
INHIBITORS
H20
2. Acetylated Enzyme Acetate + Enzyme
55
Cholinergic Neurotransmitter
56
CHOLINERGIC
NEUROTRANSMITTER
ACETYLCHOLINE
59
Cholinergic receptors with locations and effects on
effector tissues
Receptor Typical location MOA
60
Synthesis & Transmission
of
Acetylcholine
61
Life cycle of Acetylcholine
62
Actions of cholinergic agonist
on
various systems
63
ACTIONS OF CHOLINERGIC AGONIST
CVS:
The action of Ach on heart mimic the effects of VAGAL stimulation.
The normal vagal activity regulates the heart by
release of Ach at SA node.
Vasodilatation
Decrease in heart rate ( -ve chronotropic effect).
Decrease in force of contraction ( -ve Inotropic
effect).
Decrease in rate of conduction in SA & AV
nodes ( -ve dromotropic effect).
64
G.I.T:
65
RESPIRATORY SYSTEM:
66
G.U SYSTEM:
67
EYE:
69
Therapeutic Uses
of
Cholinergic agonist
70
THERAPEUTIC USES OF CHOLINERGIC AGONIST
ACETYLCHOLINE:
No therapeutic use
BETHENECOL :
to stimulate atonic bladder
post partum or post operative non obstructive
urinary retention
PILOCARPINE:
Emergency lowering of I.O.P in glaucoma
71
PHYSOSTIGMINE
Rx of atony of bladder.
Rx of Glaucoma—to decrease I.O.P by miosis.
Antidote for anticholinergic overdosage (Atropine
Poisoning)
AMBENONIUM:
Rx of myasthenia gravis
D.O.A: 4-8 hours
72
PYRIDOSTIGMINE:
Chronic Rx of Myasthenia gravis
D.O.A: 3-6 hours
EDROPHONIUM
Diagnosis of Myasthenia gravis.
To reverse the neuromuscular blockage produced by
non depolarizing skeletal muscle relaxants.
NEOSTIGMINE
Antidote for Tubocurarine & other NMS blockers.
Symptomatic Rx of Myasthenia gravis
D.O.A: 0.5 TO 2 hour
73
Organophosphates
Ecothiophate
Rx of Glaucoma
74
Cholinergic Crises
Excessive
cholinergic (muscarinic) stimulation
Neuromuscular blockage.
Occurs because:
Irreversible anticholinesterases
78
Use of cholinergic agonist as
Antidote
Antidote
Neuromuscular blockage/ Neostigmine
Skeletal muscle paralysis Pyridostigmine
caused by non depolarizing Edrophonium
muscle relaxants
Atropine
81
CHOLINERGIC ANTAGONISTS
82
CHOLINERGIC ANTAGONIST
(PARASYMPATHOLYTICS)
ANTIMUSCARINIC AGENTS……..
Atropine
Ipratropium
Scopolamine/ Hyoscine
Pirenzipine.
GANGLIONINC BLOCKERS……...
Mecamylamine
Nicotine
Trimethaphan
83
NEUROMUSCULAR BLOCKERS..
1. Non - Depolarizing 2. Depolarizing
Tubocurarine
Succinylcholine
Atracurium
Doxacurium
Vecuronium
Mivacurium
Rocuronium 84
NICOTINIC RECEPTOR AGONIST & ANTAGONIST
87
Muscarinic Antagonist
Compound Clinical Uses Adverse effects
receptors in brain).
At low doses ------- mild restlessness
At higher doses ---- agitation,
disorientation.
91
Clinical Uses of Muscarinic antagonist
CVS: Rx of sinus bradycardia ------ Atropine.
Opthalmic: to dilate the pupil e.g tropicamide.
Neurological:Prevention of motion sickness e.g
hyoscine
Parkinson's: e.g Bentropine, Benhexol.
Respiratory: Asthma---- Ipratropium
Anesthetic Premedication: Atropine
Gastrointestinal:
Hyoscine ------- Antispasmodic action
Pirenzipine ----- Treatment of peptic ulcer disease
92
Neuromuscular
Blockers
93
NON-DEPOLARIZING (COMPETITIVE) BLOCKERS
TUBOCURARINE
M.O.A:
Ach
T
Nicotinic receptor
NMJ
Ion channel
94
PHASE-I
Muscle depolarizes resulting in an initial discharge which
produces transient fasiculation followed by flaccid
paralysis
Nicotinic receptor
depolarized
NMJ
Na
PHASE-II
Membrane repolarizes but receptor is desensitize to effect of Ach
97
Drug Onset Duration S.E
Dysrhythmias
( Plasma K+)
Post operative
muscle pain
98