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Maninder Kaur M.Pharm (Pharmacology)
 The autonomic nervous system is the subdivision
of the peripheral nervous system that regulates
body activities that are generally not under
conscious control
 Visceral motor innervates non-skeletal (non-
somatic) muscles
 Visceral sensory will be covered later
2Maninder Kaur M.Pharm (Pharmacology)
3Maninder Kaur M.Pharm (Pharmacology)
4
Diagram of Autonomic nervous system
Diagram contrasts somatic (lower) and autonomic:
autonomic
somatic
this dorsal
root ganglion
is sensory
Maninder Kaur M.Pharm (Pharmacology)
 Neurotransmission in ANS occurs in 5 steps:
• Impulse conduction.
• Neurotransmitter release.
• Activity on pre- ganglionic neurons.
• Activity on post- ganglionic neurons.
• Termination of neurotransmitter release.
5
Maninder Kaur M.Pharm (Pharmacology)
 Parasympathetic division
 Sympathetic division
Parasympathetic: routine maintenance.
“rest &digest”
Sympathetic: mobilization & increased
metabolism.
“fight, flight or fright”
6Maninder Kaur M.Pharm (Pharmacology)
2 divisions:
 Sympathetic
▪ “Fight or flight”
▪ “E” division
▪ Exercise, excitement,
emergency, and
embarrassment
 Parasympathetic
▪ “Rest and digest”
▪ “D” division
▪ Digestion, defecation,
and diuresis
7Maninder Kaur M.Pharm (Pharmacology)
8
 Also called the craniosacral system because
all its preganglionic neurons are in the brain
stem or sacral levels of the spinal cord.
 Cranial nerves III,VII, IX and X
 In lateral horn of gray matter from S2-S4
 Only innervate internal organs (not skin).
 Acetylcholine is neurotransmitter at end
organ as well as at preganglionic synapse:
“cholinergic”.
Maninder Kaur M.Pharm (Pharmacology)
 Works to save energy, aids in digestion, and
supports restorative, resting body functions.
 Decrease in heart rate
 Increased gastro intestinal tract tone and
peristalsis
 Urinary sphincter relaxation
 Vasodilation – decrease in blood pressure
9Maninder Kaur M.Pharm (Pharmacology)
10Maninder Kaur M.Pharm (Pharmacology)
11Maninder Kaur M.Pharm (Pharmacology)
12Maninder Kaur M.Pharm (Pharmacology)
13Maninder Kaur M.Pharm (Pharmacology)
Location of cholinergic receptors-
1. Postganglionic parasympathetic neuroeffector junctions.
2. All autonomic ganglia.
3. At the neuromuscular endplate.
14Maninder Kaur M.Pharm (Pharmacology)
Two types of receptors are present-
 Muscarinic receptor.
 Nicotinic receptor.
15Maninder Kaur M.Pharm (Pharmacology)
M-cholinoceptors can be classified into subtypes
according to their molecular structure, signal
transduction, and ligand affinity in the M1, M2, M3
subtypes etc.
• M1-receptors are present on nerve cells, e.g., in
ganglia, where they mediate a facilitation of impulse
transmission from preganglionic axon terminals to
ganglion cells.
• M2-receptors mediate acetylcholine effects on the
heart. Opening of K+
channels leads to slowing of
diastolic depolarization in sinoatrial pacemaker cells
and a decrease in heart rate. 16Maninder Kaur M.Pharm (Pharmacology)
M3-receptors are found in the glandular epithelia
(which respond with activation of phospholipase
C and increases secretory activity) and in smooth
muscle.
17
Maninder Kaur M.Pharm (Pharmacology)
Muscarinic receptor (G protein-linked: 7 subunits)
18
Maninder Kaur M.Pharm (Pharmacology)
NM -cholinoceptors
Location: neuromuscular junction.
Function: depolarization of muscle end
plate and contraction of skeletal muscle.
NN -cholinoceptors
Location: autonomic ganglia.
Function: depolarization
postganglionic membrane (in adrenal medulla –
catecholamine release).
19Maninder Kaur M.Pharm (Pharmacology)
20
Maninder Kaur M.Pharm (Pharmacology)
(1) Choline ester (stimulants of M- and N-
receptors):
 Acetylcholine, Carbachol, etc.
(2) Alkaloids
 a) stimulants of M-receptors:
▪ Pilocarpine, Cevimeline (dry mouth),
▪ Bethanechole, Musacarine, Phalloidin
 b) stimulants of N-receptors:
▪ Nicotine, Cytisine (Tabex®
), Lobeline
21Maninder Kaur M.Pharm (Pharmacology)
(1) Reversible drugs (most are carbamates)
a) With N3+
(cross BBB)
Alkaloids: Galantamine, Physostigmine
Synthetic drugs: Donepezil, Rivastigmine,
Tacrine.
b) With N4+
(do not cross BBB)- Demecarium,
Edrophonium (Tensilon®
),Neostigmine,
Pyridostigmine.
22Maninder Kaur M.Pharm (Pharmacology)
(2) Irreversible anticholinesterase agents (most of
them are organophosphates)-
a) Thiophosphate insecticides
 Parathion
 Malathion (Pedilin®
– in pediculosis)
b) Nerve paralytic gases for chemical warfare
 Tabun
 Sarin
 Soman
23Maninder Kaur M.Pharm (Pharmacology)
 cardiac output M2: decreases
 SA node: heart rate (chronotropic) M2: decreases
 cardiac muscle: contractility (inotropic) M2: decreases (atria only)
 conduction at AV node M2: decreases
 smooth muscles of bronchioles M3: contracts
 pupil of eye M3: contracts
 ciliary muscle M3: contracts
 salivary glands: secretions stimulates watery secretions
 GI tract motility M1, M3: increases
 smooth muscles of GI tract M3: contracts
 sphincters of GI tract M3: relaxes
 glands of GI tract M3: secretes
24Maninder Kaur M.Pharm (Pharmacology)
 Myasthenia gravis.
 Belladonna poisoning.
 In glucoma
25Maninder Kaur M.Pharm (Pharmacology)
 These are drugs which oppose the
acetylcholine actions or block the cholinergic
receptors.
 Anti- cholinergics mainly block the
muscarinic receptor.
26Maninder Kaur M.Pharm (Pharmacology)
 Atropine, the prototype drug of this class, is a
highly selective blocking agent for pre and post
muscarinic receptors, but some of its synthetic
derivatives have significant nicotinic blocking
property as well.
27Maninder Kaur M.Pharm (Pharmacology)
1. Natural alkaloids: Atropine (spasmolytic, mydriatic),
 Hyoscine (Scopolamine), Scopoderm®
TTS (antiemetic)
2. Semisynthetic derivatives
• Mydriatics: Homatropine
• GI spasmolytics: Hyoscine butyl bromide (Buscolysin®
)
28Maninder Kaur M.Pharm (Pharmacology)
3. Synthetic compounds
• GI spasmolytics: Oxyphenonium
• Antiulcus drugs: Pirenzepine (M1-blockers)
• Antiasthmatics: Ipratropium and Tiotropium
• Antidisurics: Flavoxate, Oxybutynyne, Trospium
• Mydriatics: Tropicamide
• Antiparkinsonian (central M-cholinolytics):
▪ Benztropine, Biperiden, Trihexyphenidyl
29Maninder Kaur M.Pharm (Pharmacology)
30Maninder Kaur M.Pharm (Pharmacology)
Atropine
(-)
31Maninder Kaur M.Pharm (Pharmacology)
• CNS. Atropine has an overall stimulant action. Its
stimulant effects are not appreciable at low doses which
produce peripheral effects because of restricted entry into
the brain.
• Atropine stimulates many medullar centers- vagal,
respiratory, and vasоmotor.
• By blocking the relative cholinergic overactivity in basal
ganglia, it suppresses tremor and rigidity in
parkinsonism.
• High doses cause cortical excitation, rest- lessness,
disorientation, hallucinations.
32Maninder Kaur M.Pharm (Pharmacology)
 CVS. Atropine causes tachycardia, due to blockade of M2-
receptors on SA node through which vagal tone decreases
HR.
 Atropine does not influence BP. It blocks the
vasodepressor action of cholinergic agonists.
 Eye. Topical instillation of atropine (0.1%) causes
mydriasis, abolition of light reflex, and cycloplegia, lasting
7–10 days. This results in photophobia and blurring of near
vision. The intraocular tension rises, specially in narrow
angle glaucoma, but conventional systemic doses produce
minor ocular effects.
33Maninder Kaur M.Pharm (Pharmacology)
 Smooth muscles. All visceral smooth muscles with
parasympathetic inervation are relaxed (M3 blokade).Tone
and amplitude of GIT are reduced. Spasm may be
reduced, constipation may occur. Peristalsis is only
incompletely suppressed because it is primarily regulated
by local reflexes and other neurotransmitters (serotonin,
encephalin, etc.).
 Atropine causes bronchodilation and reduced airway
resistance, especially in asthma patients.
34Maninder Kaur M.Pharm (Pharmacology)
 Glands. Atropine decreases sweat, salivary, tracheo-
bronchial, and lacrimal secretion (M3-blockade). Skin and
eyes become dry, talking, and swallowing my be very
difficult. Atropine decreases less the secretion of acid and
pep-sin and more of the mucus in the stomach.
 Body temperature. Rise in body temperature occurs at
higher doses, and is due to both inhibition of sweating as
well as stimulation of the temperature regulating centre in
the hypothalamus.
35Maninder Kaur M.Pharm (Pharmacology)
saliva, sweat, bronchial secretion > eye >
bronchial muscles > heart > intestinal and
bladder smooth muscles > gastric glands
and gastric smooth muscles
36Maninder Kaur M.Pharm (Pharmacology)
NEUROMUSCULAR BLOCKING AGENTS:
Skeletal muscle relaxants act peripherally at neuromuscular
junction. According to their action they are divided into the
following groups.
•Nondepolarizing (competitive) agents or curare-like drugs
•Depolarizing (hyperdepolarazing) agents
37Maninder Kaur M.Pharm (Pharmacology)
 Also called thoracolumbar system: all its neurons
are in lateral horn of gray matter from T1-L2
 Lead to every part of the body
 Easy to remember that when nervous, you sweat; when
afraid, hair stands on end; when excited blood pressure
rises (vasoconstriction): these sympathetic only
 Also causes: dry mouth, pupils to dilate, increased heart &
respiratory rates to increase O2 to skeletal muscles, and
liver to release glucose
 Norepinephrine (noradrenaline) is neurotransmitter
released by most postganglionic fibers
(acetylcholine in preganglionic): “adrenergic”
38Maninder Kaur M.Pharm (Pharmacology)
 Helps the body cope with external stimuli and
functions during stress (triggers the flight or
fight response)
 Vasoconstriction – increase in blood pressure
 Increased heart rate
 Increased respiratory rate
 Cold, sweaty palms
 Pupil dilation
39Maninder Kaur M.Pharm (Pharmacology)
40Maninder Kaur M.Pharm (Pharmacology)
41Maninder Kaur M.Pharm (Pharmacology)
 Sympathetic and parasympathetic divisions typically
function in opposition to each other. But this opposition is
better termed complementary in nature rather than
antagonistic. For an analogy, one may think of the
sympathetic division as the accelerator and the
parasympathetic division as the brake. The sympathetic
division typically functions in actions requiring quick
responses. The parasympathetic division functions with
actions that do not require immediate reaction. Consider
sympathetic as "fight or flight" and parasympathetic as "rest
and digest".
42Maninder Kaur M.Pharm (Pharmacology)
END 43

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physiology of Autonomic nervous system

  • 1. 1 Maninder Kaur M.Pharm (Pharmacology)
  • 2.  The autonomic nervous system is the subdivision of the peripheral nervous system that regulates body activities that are generally not under conscious control  Visceral motor innervates non-skeletal (non- somatic) muscles  Visceral sensory will be covered later 2Maninder Kaur M.Pharm (Pharmacology)
  • 3. 3Maninder Kaur M.Pharm (Pharmacology)
  • 4. 4 Diagram of Autonomic nervous system Diagram contrasts somatic (lower) and autonomic: autonomic somatic this dorsal root ganglion is sensory Maninder Kaur M.Pharm (Pharmacology)
  • 5.  Neurotransmission in ANS occurs in 5 steps: • Impulse conduction. • Neurotransmitter release. • Activity on pre- ganglionic neurons. • Activity on post- ganglionic neurons. • Termination of neurotransmitter release. 5 Maninder Kaur M.Pharm (Pharmacology)
  • 6.  Parasympathetic division  Sympathetic division Parasympathetic: routine maintenance. “rest &digest” Sympathetic: mobilization & increased metabolism. “fight, flight or fright” 6Maninder Kaur M.Pharm (Pharmacology)
  • 7. 2 divisions:  Sympathetic ▪ “Fight or flight” ▪ “E” division ▪ Exercise, excitement, emergency, and embarrassment  Parasympathetic ▪ “Rest and digest” ▪ “D” division ▪ Digestion, defecation, and diuresis 7Maninder Kaur M.Pharm (Pharmacology)
  • 8. 8  Also called the craniosacral system because all its preganglionic neurons are in the brain stem or sacral levels of the spinal cord.  Cranial nerves III,VII, IX and X  In lateral horn of gray matter from S2-S4  Only innervate internal organs (not skin).  Acetylcholine is neurotransmitter at end organ as well as at preganglionic synapse: “cholinergic”. Maninder Kaur M.Pharm (Pharmacology)
  • 9.  Works to save energy, aids in digestion, and supports restorative, resting body functions.  Decrease in heart rate  Increased gastro intestinal tract tone and peristalsis  Urinary sphincter relaxation  Vasodilation – decrease in blood pressure 9Maninder Kaur M.Pharm (Pharmacology)
  • 10. 10Maninder Kaur M.Pharm (Pharmacology)
  • 11. 11Maninder Kaur M.Pharm (Pharmacology)
  • 12. 12Maninder Kaur M.Pharm (Pharmacology)
  • 13. 13Maninder Kaur M.Pharm (Pharmacology)
  • 14. Location of cholinergic receptors- 1. Postganglionic parasympathetic neuroeffector junctions. 2. All autonomic ganglia. 3. At the neuromuscular endplate. 14Maninder Kaur M.Pharm (Pharmacology)
  • 15. Two types of receptors are present-  Muscarinic receptor.  Nicotinic receptor. 15Maninder Kaur M.Pharm (Pharmacology)
  • 16. M-cholinoceptors can be classified into subtypes according to their molecular structure, signal transduction, and ligand affinity in the M1, M2, M3 subtypes etc. • M1-receptors are present on nerve cells, e.g., in ganglia, where they mediate a facilitation of impulse transmission from preganglionic axon terminals to ganglion cells. • M2-receptors mediate acetylcholine effects on the heart. Opening of K+ channels leads to slowing of diastolic depolarization in sinoatrial pacemaker cells and a decrease in heart rate. 16Maninder Kaur M.Pharm (Pharmacology)
  • 17. M3-receptors are found in the glandular epithelia (which respond with activation of phospholipase C and increases secretory activity) and in smooth muscle. 17 Maninder Kaur M.Pharm (Pharmacology)
  • 18. Muscarinic receptor (G protein-linked: 7 subunits) 18 Maninder Kaur M.Pharm (Pharmacology)
  • 19. NM -cholinoceptors Location: neuromuscular junction. Function: depolarization of muscle end plate and contraction of skeletal muscle. NN -cholinoceptors Location: autonomic ganglia. Function: depolarization postganglionic membrane (in adrenal medulla – catecholamine release). 19Maninder Kaur M.Pharm (Pharmacology)
  • 20. 20 Maninder Kaur M.Pharm (Pharmacology)
  • 21. (1) Choline ester (stimulants of M- and N- receptors):  Acetylcholine, Carbachol, etc. (2) Alkaloids  a) stimulants of M-receptors: ▪ Pilocarpine, Cevimeline (dry mouth), ▪ Bethanechole, Musacarine, Phalloidin  b) stimulants of N-receptors: ▪ Nicotine, Cytisine (Tabex® ), Lobeline 21Maninder Kaur M.Pharm (Pharmacology)
  • 22. (1) Reversible drugs (most are carbamates) a) With N3+ (cross BBB) Alkaloids: Galantamine, Physostigmine Synthetic drugs: Donepezil, Rivastigmine, Tacrine. b) With N4+ (do not cross BBB)- Demecarium, Edrophonium (Tensilon® ),Neostigmine, Pyridostigmine. 22Maninder Kaur M.Pharm (Pharmacology)
  • 23. (2) Irreversible anticholinesterase agents (most of them are organophosphates)- a) Thiophosphate insecticides  Parathion  Malathion (Pedilin® – in pediculosis) b) Nerve paralytic gases for chemical warfare  Tabun  Sarin  Soman 23Maninder Kaur M.Pharm (Pharmacology)
  • 24.  cardiac output M2: decreases  SA node: heart rate (chronotropic) M2: decreases  cardiac muscle: contractility (inotropic) M2: decreases (atria only)  conduction at AV node M2: decreases  smooth muscles of bronchioles M3: contracts  pupil of eye M3: contracts  ciliary muscle M3: contracts  salivary glands: secretions stimulates watery secretions  GI tract motility M1, M3: increases  smooth muscles of GI tract M3: contracts  sphincters of GI tract M3: relaxes  glands of GI tract M3: secretes 24Maninder Kaur M.Pharm (Pharmacology)
  • 25.  Myasthenia gravis.  Belladonna poisoning.  In glucoma 25Maninder Kaur M.Pharm (Pharmacology)
  • 26.  These are drugs which oppose the acetylcholine actions or block the cholinergic receptors.  Anti- cholinergics mainly block the muscarinic receptor. 26Maninder Kaur M.Pharm (Pharmacology)
  • 27.  Atropine, the prototype drug of this class, is a highly selective blocking agent for pre and post muscarinic receptors, but some of its synthetic derivatives have significant nicotinic blocking property as well. 27Maninder Kaur M.Pharm (Pharmacology)
  • 28. 1. Natural alkaloids: Atropine (spasmolytic, mydriatic),  Hyoscine (Scopolamine), Scopoderm® TTS (antiemetic) 2. Semisynthetic derivatives • Mydriatics: Homatropine • GI spasmolytics: Hyoscine butyl bromide (Buscolysin® ) 28Maninder Kaur M.Pharm (Pharmacology)
  • 29. 3. Synthetic compounds • GI spasmolytics: Oxyphenonium • Antiulcus drugs: Pirenzepine (M1-blockers) • Antiasthmatics: Ipratropium and Tiotropium • Antidisurics: Flavoxate, Oxybutynyne, Trospium • Mydriatics: Tropicamide • Antiparkinsonian (central M-cholinolytics): ▪ Benztropine, Biperiden, Trihexyphenidyl 29Maninder Kaur M.Pharm (Pharmacology)
  • 30. 30Maninder Kaur M.Pharm (Pharmacology)
  • 32. • CNS. Atropine has an overall stimulant action. Its stimulant effects are not appreciable at low doses which produce peripheral effects because of restricted entry into the brain. • Atropine stimulates many medullar centers- vagal, respiratory, and vasоmotor. • By blocking the relative cholinergic overactivity in basal ganglia, it suppresses tremor and rigidity in parkinsonism. • High doses cause cortical excitation, rest- lessness, disorientation, hallucinations. 32Maninder Kaur M.Pharm (Pharmacology)
  • 33.  CVS. Atropine causes tachycardia, due to blockade of M2- receptors on SA node through which vagal tone decreases HR.  Atropine does not influence BP. It blocks the vasodepressor action of cholinergic agonists.  Eye. Topical instillation of atropine (0.1%) causes mydriasis, abolition of light reflex, and cycloplegia, lasting 7–10 days. This results in photophobia and blurring of near vision. The intraocular tension rises, specially in narrow angle glaucoma, but conventional systemic doses produce minor ocular effects. 33Maninder Kaur M.Pharm (Pharmacology)
  • 34.  Smooth muscles. All visceral smooth muscles with parasympathetic inervation are relaxed (M3 blokade).Tone and amplitude of GIT are reduced. Spasm may be reduced, constipation may occur. Peristalsis is only incompletely suppressed because it is primarily regulated by local reflexes and other neurotransmitters (serotonin, encephalin, etc.).  Atropine causes bronchodilation and reduced airway resistance, especially in asthma patients. 34Maninder Kaur M.Pharm (Pharmacology)
  • 35.  Glands. Atropine decreases sweat, salivary, tracheo- bronchial, and lacrimal secretion (M3-blockade). Skin and eyes become dry, talking, and swallowing my be very difficult. Atropine decreases less the secretion of acid and pep-sin and more of the mucus in the stomach.  Body temperature. Rise in body temperature occurs at higher doses, and is due to both inhibition of sweating as well as stimulation of the temperature regulating centre in the hypothalamus. 35Maninder Kaur M.Pharm (Pharmacology)
  • 36. saliva, sweat, bronchial secretion > eye > bronchial muscles > heart > intestinal and bladder smooth muscles > gastric glands and gastric smooth muscles 36Maninder Kaur M.Pharm (Pharmacology)
  • 37. NEUROMUSCULAR BLOCKING AGENTS: Skeletal muscle relaxants act peripherally at neuromuscular junction. According to their action they are divided into the following groups. •Nondepolarizing (competitive) agents or curare-like drugs •Depolarizing (hyperdepolarazing) agents 37Maninder Kaur M.Pharm (Pharmacology)
  • 38.  Also called thoracolumbar system: all its neurons are in lateral horn of gray matter from T1-L2  Lead to every part of the body  Easy to remember that when nervous, you sweat; when afraid, hair stands on end; when excited blood pressure rises (vasoconstriction): these sympathetic only  Also causes: dry mouth, pupils to dilate, increased heart & respiratory rates to increase O2 to skeletal muscles, and liver to release glucose  Norepinephrine (noradrenaline) is neurotransmitter released by most postganglionic fibers (acetylcholine in preganglionic): “adrenergic” 38Maninder Kaur M.Pharm (Pharmacology)
  • 39.  Helps the body cope with external stimuli and functions during stress (triggers the flight or fight response)  Vasoconstriction – increase in blood pressure  Increased heart rate  Increased respiratory rate  Cold, sweaty palms  Pupil dilation 39Maninder Kaur M.Pharm (Pharmacology)
  • 40. 40Maninder Kaur M.Pharm (Pharmacology)
  • 41. 41Maninder Kaur M.Pharm (Pharmacology)
  • 42.  Sympathetic and parasympathetic divisions typically function in opposition to each other. But this opposition is better termed complementary in nature rather than antagonistic. For an analogy, one may think of the sympathetic division as the accelerator and the parasympathetic division as the brake. The sympathetic division typically functions in actions requiring quick responses. The parasympathetic division functions with actions that do not require immediate reaction. Consider sympathetic as "fight or flight" and parasympathetic as "rest and digest". 42Maninder Kaur M.Pharm (Pharmacology)