Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
2
Introduction
Nervous System
Peripheral NS Central NS
Efferent Division Afferent Division
Autonomic Somatic
Sympathetic Parasympathetic
4
Feedback loop of the Feedback loop of the autonomic nervous system.autonomic nervous system.
5
Anatomy
ANATOMYANATOMY
1) SYMPATHETIC (THORACOLUMBAR) DIVISION. 2 ) PARASYMPATHETIC (CRANIOSACRAL) DIVISION.
7
EFFERENT NEURONSEFFERENT NEURONS
PREGANGLIONIC NEURONS
POSTGANGLIONIC NEURON
pregnanglionic neuron
ganglia
postganglionic neuron
effector organ
effector organ
1) SYMPATHETIC (THORACOLUMBAR) DIVISION. 2) PARASYMPATHETIC ( CRANIOSACRAL) DIVISION.
Brain stem or spinal cord
9
How neurons regulate other cells.How neurons regulate other cells. The basic steps in theThe basic steps in the process by which neurons elicit process by which neurons elicit
responses from other cells are responses from other cells are
(1) axonal conduction, (2) transmitter (T) release, and(1) axonal conduction, (2) transmitter (T) release, and (3) (3)
binding of transmitter to its receptor on the postsynaptic cell. binding of transmitter to its receptor on the postsynaptic cell.
10
The basic anatomy of the parasympathetic and sympathetic nervous systems and the somatic motor system.
11Transmitters employed at specific junctions of the peripheral nervous system
13
Steps of Synaptic Transmission
14
Steps in synaptic transmission.Steps in synaptic transmission. Step 1,Step 1, Synthesis of transmitter (T) from precursor molecules (Q, R, S Synthesis of transmitter (T) from precursor molecules (Q, R, SStep 2, Step 2, Storage of transmitter in vesicles. Storage of transmitter in vesicles. Step 3,Step 3, Release of transmitter: Release of transmitter: Step 4,Step 4, Action at receptor: Action at receptor: Step 5,Step 5, Termination of transmission: Termination of transmission:
15
AUTONOMIC
NEUROTRANSMITTERS
16
NEUROTRANSMITTERSNEUROTRANSMITTERS
Epinephrine Nor epinephrine Acetylcholine Dopamine
Each of these binds to specific family of receptors.
17
SITES OF RELEASE OF Ach
&
NOR EPINEPHRINE
18
Sites where Ach is releasedSites where Ach is released
All preganglionic efferent fibers
All parasympathetic postganglionic fibers
Few sympathetic postganglionic fibers
Somatic, Motor fibers
19
Sites where Nor epinephrine is Sites where Nor epinephrine is releasedreleased
Postganglionic sympathetic fibers
20
AUTONOMIC RECEPTORS
21
AUTONOMIC RECEPTORSAUTONOMIC RECEPTORSCHOLINERGIC RECEPTORS ----- 2 Types
– Muscarinic receptors– Nicotinic receptors
ADRENERGIC RECEPTORS------- 2 Types Alpha -1 (i) alpha adrenoceptor
Alpha -2 Beta -1 (ii) beta adrenoceptor Beta-2
22
Subtypes of Cholinergic and Subtypes of Cholinergic and Adrenergic ReceptorsAdrenergic Receptors
Cholinergic receptor– Nicotinic n– Nicotinic m– Muscarinic
Adrenergic receptor– Alpha1 and alpha2
– Beta1 and beta2
– Dopamine
23
24
25
26
27
28
FUNCTIONS OF AUTONOMIC RECEPTORS
29
Functions of Cholinergic Functions of Cholinergic Receptor SubtypesReceptor Subtypes
Nicotinic n (neuronal)– Promotes ganglia transmission– Promotes release of epinephrine
Nicotinic m (muscle) – Contraction of skeletal muscle
Muscarinic– Activates parasympathetic nervous system
30
Functions of Adrenergic Functions of Adrenergic Receptor SubtypesReceptor Subtypes
Alpha1 – Vasoconstriction– Ejaculation– Contraction of bladder neck and prostate
Alpha2
– Located in presynaptic junction– Minimal clinical significance
31
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
32
Functions of Adrenergic Functions of Adrenergic Receptor Subtypes (cont.)Receptor Subtypes (cont.)
Beta1
Heart
– Increases heart rate
force of contraction
velocity of conduction in AV node
Kidney
– Renin release
33
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
34
Functions of Adrenergic Receptor Functions of Adrenergic Receptor Subtypes (cont.)Subtypes (cont.)
Beta2 – Bronchial dilation– Relaxation of uterine muscle– Vasodilation– Glycogenolysis
Dopamine– Dilates renal blood vessels
35
OrganEffect of
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
36
Vascular Smooth Muscle
Sympathetic
Parasympathetic
Skin, Splanchnic vessels
Contract α -----
……
Skeletal Muscle vessels
Relaxes β2 --------- --------
Contract α ---------
--------
Relaxes M3 --------- …….
37
Bronchial smooth muscles
Relaxes β2 contracts M3
G.I.T
Walls Relaxes α 2, β2 Contracts M3
Sphincters Contracts α1 Relaxes M3
Secretion -------- ------- Increases M3
Myenteric plexus Activates M1
Genitourinary System
Bladder wall Relaxes β2 Contracts M3
Sphincter Contracts α1 Relaxes M3
38
Uterus, pregnant
Relaxes β2------- -------
Contracts α------- --------
Penis, Seminal Vesicles
Ejaculation α Erection M3
Skin
Pilomotor smooth muscles
Contract α ------- -------
Sweat glandsThermoregualtory
Increases
M
Apocrine (stress) Increases
α -------- --------
39
Metabolic Functions
Sympathetic
Parasympathetic
Liver Gluconeogenesis
β2 / α-------- --------
Liver Glycogenolysis
β2 / α-------- --------
Fat cells Lipolysis α 2/ β1/β3
-------- --------
Kidney Renin release
β1-------- --------
40
FUNCTION OF
PARASYMPATHETIC
&
SYMPATHETIC
NEVOUS SYSTEM
41
Parasympathetic Nervous Parasympathetic Nervous System (PNS)System (PNS)
Rest & Digest situations.The regulatory functions of PNS affect these sites Heart rate Gastric secretions Bladder and bowel Vision Bronchial smooth muscle
42
Sympathetic Nervous SystemSympathetic Nervous System
Main functions of the SNS Regulation of cardiovascular system Regulation of body temperature Implementation of “fight or flight” reaction
FIGHT OR FLIGHT RESPONSEStressful Situations ----
trauma, fear , hypoglycemia.
43
Opposing effects of parasympathetic and Opposing effects of parasympathetic and sympathetic nerves.sympathetic nerves.
44
ORGANS RECEIVING ONLY SYMPATHETIC ORGANS RECEIVING ONLY SYMPATHETIC INNERVATIONINNERVATION
Adrenal Medulla Kidney Pilomotor muscles Sweat glands Vessels Metabolic processes
45
THREE MECHANISMS BY WHICH BINDING OF THREE MECHANISMS BY WHICH BINDING OF NEUROTRANSMITTER LEADS TO A CELLULAR RESPONSE NEUROTRANSMITTER LEADS TO A CELLULAR RESPONSE
AND EFFECT:AND EFFECT:
RECEPTORS COUPLED TO A ION CHANNEL Cholinergic nicotinic receptors GABA receptors Ions
Change in membrane potential or ionic Concentration in cell. Ions
46
RECEPTORS COUPLED TO ADENYLYL CYCLASE Beta- adrenoceptors Alpha-2 adrenoceptors
Adenylyl
ATP cyclase cAMP
PROTEIN PHOSPHORYLATION INTRACELLULAR EFFECT
47
RECEPTORS COUPLED TO DIACYLGLYCEROL (DAG) & INOSITOL RECEPTORS COUPLED TO DIACYLGLYCEROL (DAG) & INOSITOL TRIPHOSPHATETRIPHOSPHATE
DAG IP3
Protein phosphorylation & increase in intracellular Ca
Intracellular effect
Alpha-1 adrenoceptor
Cholinergic muscarinic receptor
48
CHOLINERGIC AGONIST
CLASSIFICATION
49
Cholinergic agonistsCholinergic agonistsDirect 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
50
Structural classification Structural classification Indirect acting drugsIndirect acting drugs
1. Simple alcohols:Edrophonium
2. Carbamic acid esters of alcohols: Neostigmine
3. Organophosphates:
Isoflurophate
51
52
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:
a) Her problems are due to her crucial husbandb) She is in depressionc) She has no problem at alld) Her complains related with kidney, adrenal medulla,
vessels, pilomotor muscles, sweat glands and metabolic processes are due to sympathetic ANS stimulation
e) All her problems are related with histamine release
53
MOAMOA
DIRECTLY ACTING CHOLINERGIC AGONIST DRUGS ACT DIRECTLY through RECEPTORS (affinity + intrinsic activity of concerned receptors)
54
Mechanism of action of
Indirect acting Cholinergic agonist
55
Mechanism of ActionMechanism of Action
ACETATE
ACETYLCHOLINE ACETYLCHOLINESTERASE
Ach
CHOLINE
1.Choline + Acetylated Enzyme
H202. Acetylated Enzyme Acetate + Enzyme
ACETYLCHOLINESTERASE INHIBITORS
56
Cholinergic Neurotransmitter
57
CHOLINERGIC NEUROTRANSMITTER ACETYLCHOLINEACETYLCHOLINE
SITES WHERE Ach IS RELEASED AS TRANSMITTER:
The Preganglionic fibers to adrenal medulla.
The postganglionic fibers of parasympathetic
division.
The autonomic ganglia (both sympathetic
and parasympathetic)
58
Drug structure and receptor Drug structure and receptor selectivityselectivity
•The structure of Acetylcholine allows this transmitter to interact with both receptor subtypes.
•In contrast, because of their unique configurations,
Nicotine and Muscarine are selective for the cholinergic receptor subtypes whose structure complements their own.
59
Cholinergic Receptors
60
Cholinergic receptors with locations and effects on Cholinergic receptors with locations and effects on effector tissueseffector tissues
Receptor Typical location MOA
M1 CNS neurons,
Sympathetic postganglionic neurons,
Formation of IP3 & DAG, intracellualr Calcium
M2 Myocardium, smooth muscles Opening of potassium channels, inhibition of adenyl cyclase.
M3 Exocrine glands, vessels (smooth muscles & endothelium)
Formation of IP3 & DAG, intracellualr Calcium
Nn Post ganglionic neurons, Opening of Na, K channels, depolarization
Nm Skeletal muscle neuromuscular endplates
Opening of Na, K channels, depolarization
61
Synthesis & Transmission of
Acetylcholine
62
Life cycle of AcetylcholineLife cycle of Acetylcholine
63
Actions of cholinergic agonist on
various systems
64
ACTIONS OF CHOLINERGIC AGONISTACTIONS 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).
65
G.I.T:
Increase salivary secretions
Stimulates intestinal secretions
Stimulates intestinal motility.
66
RESPIRATORY SYSTEM: Stimulates bronchiolar secretions
67
G.U SYSTEM:
Increase tone of detrusor muscle
Relaxes sphincter and trigone.
68
EYE:
Contraction of sphincter pupillae muscle--- pupil constricts (Miosis).
Contraction of ciliary muscle----------- ---- accommodation of lens for
Near vision
69
26 years old patient came in hospital for his treatment. He complained about increased salivation, GIT cramps, diarrhea, increased sweating , frequent urination. Whatever the diagnosis of the problem is ,can you just guess that:
a) All symptoms are due to muscrinic receptors stimulation
b) All symptoms are due to sympathetic stimulation
c) All symptoms are due to his anxiety
d) All symptoms are due to dopaminergic inhibition
e) All symptoms are due to his abdominal pain
70
Therapeutic Uses
of
Cholinergic agonist
71
THERAPEUTIC USES OF CHOLINERGIC AGONISTTHERAPEUTIC 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
72
PHYSOSTIGMINE
Rx of atony of bladder.Rx of atony of bladder.
Rx of Glaucoma—to decrease I.O.P by miosis.Rx of Glaucoma—to decrease I.O.P by miosis.
AntidoteAntidote for anticholinergic overdosage (Atropine for anticholinergic overdosage (Atropine
Poisoning)Poisoning)
AMBENONIUM:AMBENONIUM:
Rx of Rx of myasthenia gravismyasthenia gravis
D.O.AD.O.A: 4-8 hours: 4-8 hours
73
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.
D.O.A: 5-15 minutes.
NEOSTIGMINENEOSTIGMINE AntidoteAntidote for Tubocurarine & other NMS blockers.for Tubocurarine & other NMS blockers.
Symptomatic Rx of Symptomatic Rx of Myasthenia gravis Myasthenia gravis
D.O.A:D.O.A: 0.5 TO 2 hour0.5 TO 2 hour
74
Organophosphates Organophosphates
Ecothiophate Rx of Glaucoma
D.O.A: 100 hours
75
Cholinergic CrisesCholinergic Crises
Excessive cholinergic (muscarinic) stimulation Neuromuscular blockage.
Occurs because: Irreversible anticholinesterases
(organophosphate insecticides or nerve gases)
binds the enzyme acetylcholinesterase and inactivates it.
76
Management of Cholinergic Management of Cholinergic CrisesCrises
DecontaminationActivated charcoalGastric Lavage.Atropine (to counter the muscarinic effects)Pralidoxime (Cholinesterase reactivator): to relieve neuromuscular blockage.Diazepam: to control seizuresMechanical Ventilation- resp paralysis
77
31 years old male patient was brought at HUJRA SHAH MUKEEM HOSPITAL, tehseel Debalpur. He had headache, excessive salivation, diarrhea, frequent urination. History revealed that he took powder kept in cupboard, to check, weather it is table salt or something else. Which statement is true to keep symptoms of the patient:
a) Powder might be table salt, he took
b) Powder was histamine, which was incidentally kept in house
c) Powder was basically old grinded sugar, which was contaminated
d) Powder was not the etiology of these symptoms, it was something else
e) Powder was insecticide
78
Cholinergic agonist
as
Anti dotes
79
Use of cholinergic agonist as Use of cholinergic agonist as AntidoteAntidote
AntidoteNeuromuscular blockage/ Skeletal muscle paralysis caused by non depolarizing muscle relaxants
Neostigmine
Pyridostigmine
Edrophonium
Anticholinergic poisoning (Atropine or TCA)
Physostigmine
80
29 years old patient was used to take antidepressant, TOFRANIL tablets (imipramine 25 mg) 1 X 8 hly since long time. One day he took 10 TOFRANIL tablets at once due to some disputed problem with his father. He was brought in casualty with symptoms like lethargy, drowsiness, headache, lower abdominal pain, and difficulty in urination. What should be the appropriate treatment:
a) Antidote for anticholinergic drug poisoning, like
physostigmine is the best treatment b) Gastric levage and atropine must be given by IV route
immediatelyc) Adrenaline s/c is sufficient treatment to relieve the
symptomsd) Psychological counseling is the best advise for the patiente) IV glucose may be given as infusion to relieve drowsiness,
PONSTON for headache and lower abdominal pain and LASIX may be given to start urination
81
Antidote for cholinergic drugAntidote for cholinergic drugoverdosageoverdosage
Atropine
82
CHOLINERGIC ANTAGONISTS
83
CHOLINERGIC ANTAGONISTCHOLINERGIC ANTAGONIST(PARASYMPATHOLYTICS)(PARASYMPATHOLYTICS)
ANTIMUSCARINIC AGENTS……..
Atropine IpratropiumScopolamine/ Hyoscine Pirenzipine.GANGLIONINC BLOCKERS……...MecamylamineNicotineTrimethaphan
84
NEUROMUSCULAR BLOCKERS.. 1. Non - Depolarizing 2. Depolarizing Tubocurarine
Succinylcholine Atracurium
Doxacurium
Vecuronium
Mivacurium
Rocuronium
85
NICOTINIC RECEPTOR AGONIST & ANTAGONISTNICOTINIC RECEPTOR AGONIST & ANTAGONIST
DRUGS MAIN SITE TYPE OF ACTION
NOTES
AGONISTS
Nicotine Autonomic ganglia, CNS
Stimulation then block
Stimulation
No clinical uses
Lobeline Autonomic ganglia,
Stimulation
Suxamethonium NMJ Depolarization block
Muscle relaxant
86
ANTAGONIST Main site Type of response
Notes
Hexamethonium Autonomic ganglia
Transmission block
no clinical use
Trimethaphan Autonomic ganglia
Transmission block
B.Pressure lowering in surgery (rare)
Tubocurarine Autonomic ganglia
Transmission block
Now rarely used
Pancuronium
Atracurium
Vecuronium
Autonomic ganglia
Transmission block
Widely used as muscle relaxant in anesthesia
87
Muscarinic Antagonist
88
Muscarinic AntagonistMuscarinic Antagonist
Compound Clinical Uses Adverse effects
Atropine Adjunct for anesthesia.Anticholinesterase poisining.Bradycardia.Antispasmodic.
Urinary
retention.Dry mouthBlurred vision.Hyperthermia.Constipation
Hyoscine Motion sickness Sedation(CNS
depressant)
89
Compound Clinical Uses Adverse effects
Ipratropium Asthma, Bronchitis
Rare
Tropicamide Ophthalmic use to produce mydriasis
& cycloplegia
Increase I.O.P
Pirenzipine Peptic Ulcer Selective for M1 receptors, fewer
side effects.
90
Effects of muscarinic antagonistsEffects of muscarinic antagonists Inhibition of secretion: Salivary, lacrimal, Bronchial & sweat glands
Heart rate: Tachycardia (Modest)
Eye: Mydriasis, pupil unresponsive to light, paralysis of accomodation (cycloplegia), impaird near vision,
increased I.O.P
91
G.I.T: Decrease motility, inhibition of gastric acid secretion
(Pirenzipine). smooth muscles: relaxation of bronchial, biliary,
and urinary tact
smooth musclesCNS: excitatory effect on CNS (block muscarinic
receptors in brain).
At low doses ------- mild restlessness
At higher doses ---- agitation, disorientation.
92
Clinical Uses of Muscarinic antagonistClinical 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
93
Neuromuscular Blockers
94
NON-DEPOLARIZINGNON-DEPOLARIZING (COMPETITIVE) (COMPETITIVE) BLOCKERSBLOCKERS
TUBOCURARINETUBOCURARINE
M.O.A:
Ion channel
Nicotinic receptorNMJ
TAch
95
PHASE-IMuscle depolarizes resulting in an initial discharge which
produces transient fasiculation followed by flaccid paralysis
Nicotinic receptorNMJ
NaPHASE-IIMembrane repolarizes but receptor is desensitize to effect of Ach
Nicotinic receptorNMJ
depolarized
repolarized
96
Neuromuscular blocking drugsNeuromuscular blocking drugs
Drug Onset Duration S.E
Tubocurarine Slow
(> 5 min)
Long (1-2h) Hypotension
(histamine release)
Bronchoconstriction
Gallamine Slow Long Tachycardia
Pancuronium Intermediate
(2-3 min)
Long Slight Tachycardia
Vecuronium Intermediate Intermed
(30-40 min)
Few side effects
97
Drug Onset Duration S.E
Atracurium Intermediate Intermediate
(< 30 min)
Transient hypotension
Mivacurium Fast (-2 min) Short (-15 min) Transient hypotension
98
Drug Onset Duration S.E
Suxamethonium Fast Short (-10 min) BradycardiaCardiac
Dysrhythmias
( Plasma K+)Post operative muscle pain
Related Documents
