ANS (1).pdf of pharmacology 1 second year 4th sem

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1. UNIT II
AUTONOMIC NERVOUS SYSTEM (ANS)
BY
HARSHA M
ASSISTANT PROFESSOR
MVM COLLEGE OF PHARMACY

2. NERVOUS SYSTEM
Central Nervous system Peripheral nervous system
Autonomic nervous system Somatic nervous system
(Involuntary) (Voluntary)
Sympathetic system(adrenaline) Parasympathetic system(Ach)
Agonist Antagonist Agonist Antagonist
(Sympathomimetic) (sympatholytic)
Autonomic nervous system
Auto-Self Nomos-Governing
This system is involuntary and maintains homeostasis

3. ANS controls Heart, Eye, GIT, Uterus, Urinary system , blood vessels, glands.
The prime function of the sympathetic system is to help a person to adjust the
stress and prepare the body for fight or flight reaction.
While parasympathetic mainly participate in tissue building reaction.
Body indications during sympathetic
responses
Body indications during parasympathetic
responses
Heart rate increases Heart rate decreases
Liver release glucose Liver produces bile
Bronchioles will dilate Bronchioles will constrict
Pupils dilate Pupils constrict
Adrenal glands secrete epinephrine and
norepinephrine
Adrenal glands stop secreting
epinephrine and norepinephrine
Digestion is inhibited Digestion is stimulated
Bladder is relaxed Bladder constricts

4. NEUROTRANSMITTERS
•For the transmission of an impulse across a synapse , a neurohumoral transmitter
substances is released into the synaptic cleft.
•In the ANS the neurotransmitters released are acetylcholine, Noradrenaline ,
dopamine
•Neurotransmitters released in adrenal medulla is adrenaline and noradrenaline

5. PERIPHERAL NERVOUS SYSTEM
RECEPTORS:
PNS uses Acetylcholine (Ach) as its neurotransmitter.
Ach acts on 2 type of receptor
I.Muscarinic
II.Nicotinic
Cholinergic receptor / Cholinoreceptor
(Nerves, receptor or drug that mimic the action of Ach)
Nicotinic Muscarinic
N
m(N
1) N
n(N
2) M
1 , M
3, M
5 M
2, M
4
(activation of (Inhibit adenyl
phospholipase) cyclase)

6. Muscarinic:
These receptors are selectively stimulated by muscarine and blocked by atropine
They are primary located on autonomic effector cells in heart , blood vessels , eye
, smooth muscle and glands of gastrointestinal, respiratory, urinary tracts, and
sweat glands etc.
Subtype of muscarinic receptor are
M
1, M
2, M
3, M
4 , M
5
M
1 M
2 M
3
Location Autonomic ganglia,
gastric glands and CNS
Heart and CNS SMs of visceral eye,
endocrine glands and
endothelium
Functions Histamine release and
acid secretion with
CNS learning and
motor function
Less impulse generation, less
velocity of conduction,
Ach release
Visceral SM
contraction,
constriction of pupil,
ciliary muscle and
vasodilation
Agonist Oxotremorine Methacholine Bethanechol
Antagonist Pinenzepine Methoctramine &
Triptramine
Darifenacin

7. Nicotinic Receptor
These receptors are selectively activated by nicotine and blocked by
tubocurarine or hexamethonium
Which encloses the ligand gated cation channel, their activation causes opening
of channel & rapid flow of cation resulting in depolarization and an action
potential.
Subtype of Nicotinic receptor
I.N
m(N
1)
II.N
n(N
2)
N
m
: Primary for somatic motor neurons
•These are present at skeletal muscle endplate
•Stimulated by Phenyl trimethyl ammonium(PTMA) & blocked by Tubocurarine.
N
n : Primaryfor Autonomic neurons
•
These are present in ganglionic cells and adrenal medullary cells, spinal chord and certain
areas of brain
•
This are stimulated by Dimethyl Phenyl Piperazinium (DMPP) & blocked by Hexamethonium

8. CHOLINERGIC SYSTEM (Parasympathomimetic)
Acetylcholine is an excitatory neurotransmitter
Synthesis and storage of Ach
Ach is synthesized locally from
(ATP + acetate + co enzyme A)
Acetyl Co enzyme A
choline transferase
Acetylcholine + Co enzyme A (Free)
Ach is stored in Synaptic vesicle

9. Transmission of an impulse
•When an action potential reaches the presynaptic membrane, Ach is
released into the synaptic cleft
•The Ach binds and activates the cholinergic receptor on the postsynaptic
membrane leading to depolarization of the membrane. Thus, the impulse
is transmitted across the synapse
•Ach released into the synaptic cleft is rapidly destroyed by the enzyme
acetylcholinesterase (AchE) .Then the post synaptic membrane is
repolarized

10. Cholinergic drugs
I.Directly acting
a)Esters of choline
e.g. : Acetylchone, Methacholine, Carbachol , Bethanechol
b)Cholinomimetic Alkaloid
e.g. : Pilocarpine , Muscatine , Arecoline
II.Indirectly acting (Anticholinesterase)
a)Reversible(Carbamates)
e.g. : Neostigmine , Physiostigmine , Pyridostigmine, Ambenonium,
Edrophonium , Galantamine
b)Irreversible
•Organophosphorus compounds
e.g. : Ecothiophate , Malathion , Parathion , Sumithion , Dyflos ,
Diazinon
•Carbamates insecticides
e.g. : Carbaryl , Propoxur ( Baygon) , Aldicarb

11. Cholinergic drug:
These are chemicals that act as same site as acetylcholine and there by mimic its
action , they are therefore called parasympathomimetic or cholinomimetic
Directly acting cholinergic drug
Pharmacological actions
A.Muscarinic actions
i.Heart : It depress the SA node and thereby reduces the heart rate and force of
contraction
•In larger doses AV conduction is depressed .
ii.Blood vessels : Ach releases vascular smooth muscle and dilates the blood
vessels of skin , muscle.
•The BP fall due to fall in TRP ( total peripheral resistance)

12. iii.Smooth Muscle : Bronchial smooth muscle contracts resulting in bronchospasm
•Ach increases the tone of all other smooth muscle.
iv.Secretory gland : Ach enhances the secretion of all glands, saliva secretion ,
lacrimal secretion, nasopharyngeal , Tracheobronchial , gastric and intestinal
secretions are increased.
•Sweating is also increased.
v. Eye : constriction of pupil (miosis)

13. B. Nicotinic Action
i.Autonomic ganglia : Ach Stimulates the sympathetic and
parasympathetic ganglia and adrenal medulla.
ii.CNS : Ach is a neurotransmitter at several sites in CNs . Ach injected IV
cannot cross the BBB and has no effect.
iii.NMJ : Ach brings about contraction of skeletal muscle by stimulating Nm
receptor present in the neuromuscular junction. Large doses causes
persistent depolarization of skeletal muscle resulting in paralysis.

14. Effect of cholinergic stimulations or actions of acetylcholine
Uses
•Ach therapeutically not used because it is non selective agonist
•Carbacol used in glaucoma (eye drop)
•Bethanechol used for urinary retention
CVS Vasodilation , BP , AV conduction, force of
cardiac contraction
Non vascular smooth
muscle
Contraction , gut peristalsis , bronchospasm.
Glands Secretion
Eye Miosis , IOP
NMJ Muscle contraction
Ganglia Stimulation

15. CHOLINOMIMETIC ALKALOID
Pilocarpine: it is an alkaloid obtained from the leaves of Pilocarpus microphylls
•It stimulates the cholinergic receptor but the muscarinic actions are prominent
•It cross BBB and cause CNS effect .
Action
•Its action on eye are important.
•When applied on eye it causes miosis, contraction and fall in intraocular tension.
•It also increases sweat (Diaphoretic) & salivary gland (Sialagogue)
ADR
•Burning sensation & painful spasm of accommodation corneal edema can occur
•Long term can cause retinal detachment
•Fallowing systemic use, salivation, sweating, bradycardia, diarrhoea, and bronchospasm
can occur

16. INDIRECTLY ACTING CHOLINERGIC DRUGS
Anticholinesterase / cholinesterase inhibitors
•Which inhibit the enzyme cholinesterase.
•They primarily inhibit acetyl chE but also target butyryl chE.
•Anticholinesterase are either esters of carbamic acid (carbamates) or derivative
of phosphoric acid(organophosphates)
Mechanism of action
Acetylcholine
Ach esterase Acetyl choline esterase
Choline + acetic acid

17. Reversible Anticholinesterase
Physostigmine
•It is an alkaloid obtained from the plant physostigma venenosum (Calabar
bean)
•It is lipid soluble, tertiary ammonium compound, hence has a better penetration
into the tissue and also cross BBB.
•It is available for IV injection, as 0.1-1% eye drops.
Uses
•Used in glaucoma(eye disease that can cause vision loss)
•Atropine and tricyclic antidepressant poisoning

18. Neostigmine
•Synthetic quaternary ammonium compounds
•Poorly absorbed from gut
•Does not cross BBB
•Used in myasthenia gravis, post operative paralytic ileus
Uses
•In glaucoma
•Myasthenia gravis
•Cobra bite , Alzheimer's disease
•Urinary retention
•Beladona poisoning
•Curare poisoning

19. Pharmacological actions
a.CVS : cardiovascular effects of anti-chEs are complex , where as muscarinic
actions would produce bradycardia and hypotension
•Ganglionic stimulation would tend to increase BP and HR
b.CNS : Lipophilic anti chEs which penetrate into brain produce a generalized
alerting response. Cognitive functions may be improved in Alzheimer's disease
•In higher dose produce excitement, mental confusion, tremors and convulsion
fallowed by coma

20. Irreversible anticholinesterase
Organophosphorus(OP) compounds are powerful inhibitors of AchE Enzyme
•All organophosphates except Echothiopate are lipid soluble and hence are absorbed from
all the routes including intact skin , this make OP poisoning possible even while insecticides
are used for spraying the plants.
Uses : Glaucoma-Echothiopate eye drop are sometime used in glaucoma.
Organophosphorus poisoning
Acute toxicity
As organophosphates are used as agricultural and domestic insecticides, poisoning them is
quite common.
•While spraying insecticides, accidental / suicidal symptoms result from muscarinic, nicotinic
and central effects like vomiting, abdominal cramp, diarrhea, sweating, increased salivary,
tracheobronchial and gastric secretions,
•bronchospasm: hypotension, muscular twitching, weakness, convulsion and coma.
•Death is due to respiratory paralysis

21. Treatment
1.If poisoning is through skin, remove clothing and wash the skin, with soap and
water, if consumed by oral route through gastric lavage must be given(the
process of cleaning out the contents of stomach using a tube).
2.Patient should be in prone position to avoid aspiration of secretion.
3.Maintain BP and patient airway.
4.Drug of choice Atropine IV 2mg every 10min till pupil dilates. Maximum dose
can be from 50-100mg or much more depending on the severity of the
poisoning.
5.Treatment should be carefully monitored because of the risk of reappearance
of symptoms due to delayed absorption of OP compounds.
6.Cholinesterase reactivator : Pralidoxime, Obidoxime, Diacetylmonoxime.

22. Pralidoxime(oximes)
Binds to cholinesterase organophosphate complex
Release cholinesterase
Cholinesterase degrades Ach
Recovers all symptoms

23. Anticholinergic drugs / cholinergic blocking / parasympatholytic drugs.
•Anticholinergic drugs are agents which block the effect of acetylcholine on
cholinergic receptors.
•Drugs that block the nicotinic receptors are ganglionic blocking and
neuromuscular blockers.
Anticholinergic drugs
Muscarinic blockers Nicotinic blockers
e.g. : Atropine
Scopolamine Neuromuscular Ganglionic
blocker blocker
e.g. : Pancuronium, Trimethaphan
Tubocurarine hexamethonium

24. Classification
I.Natural alkaloids
e.g. : Atropine, Hyoscine(scopolamine)
II.Semisynthetic derivative
e.g. : Homatropine, Atropine methonitrate, Ipratropium bromide,
Tiotropium bromide
III.Synthetic substitutes
a)Mydriatics : Cyclopentolate, Tropicamide
b)Antispasmodic-antisecretory : Propantheline, Methantheline, Dicyclomine
c)Antiparkinsonian : Benzhexol, benztropine, Biperiden
d)Vasicoselective : Oxybutynin, Tolterodine, Flavoxate

25. BELLADONA ALKALOIDS
Atropine
•Atropine is a prototype drug
•It is obtained from plant Atropa belladonna
•Atropine and scopolamine are belladonna alkaloids
•They are muscarinic antagonist.
MOA
Atropine and scopolamine binds to muscarinic receptors and block the effect of Ach
•Atropine and scopolamine are non-selective antagonist and block all the subtype
(M
1to M
5) of muscarinic receptors.

26. Pharmacological actions
1.CVS : atropine increases the heart rate. In case of high dose, vasodilation and
hypotension occur.
2.Secretion Atropine reduces all secretion except milk
•Decrease in salivation result in dry mouth and difficulty in swallowing.
3.Smooth muscle :
•GIT: Decreases tone, motility and relieves spasm.
•Bronchi : Atropine causes bronchodilation.
•Genitourinary tract: Atropine relaxes uterus and urinary bladder.
4.Eye : Atropine produce mydriasis by blocking muscarinic receptor.
5.CNS : In higher doses atropine stimulates CNS resulting in restlessness,
hallucination.
•Scopolamine produce sedation and drowsiness it also causes Euphoria.

27. Pharmacokinetics
•Well absorbed
•Cross BBB
•Metabolized in liver
•Excreted via urine
Uses ADR
•Motion sickness Blur vision
•Antispasmodic (diarrhea, dysentery) Dry mouth
•Motion sickness Dysphagia(difficulty in swallowing)
•Mydriatic Dry skin
•Parkinsonism Fever
•Preanesthetic medication Constipation
•Op poisoning Skin rashes
•Urinary disorder Palpitation
•Bronchial asthma Restlessness
•Peptic ulcer Coma, Psychosis, Hallucination

28. Belladona poisoning
•Overdose of atropine / belladonna alkaloids can be fetal
•High doses causes hyperthermia(abnormally high body
temp),palpitation(irregular heart beat) flushing(skin, face become red and
hot), restlessness, delirium(mental state in which confused, disoriented)
hallucinations, psychosis, convulsion and coma.
•In toxic doses, CNS stimulation is fallowed by depression with circulatory
collapse and respiratory failure.

29. Treatment
•If the poison is taken orally, gastric lavage should be done, hyperthermia
should be controlled, cold water sponging, respiratory support may be
needed.
•Physostigmine 1-3mg slow IV (repeated after 1-2hr) can reverse both central
and peripheral effects.
•Diazepam may be used to control seizures.

30. Sympathetic system
Adrenergic system and sympathomimetic
•Nerve cell in which adrenaline, NA act as neurotransmitter
Adrenergic transmission
•The prime function of the adrenergic or sympathetic nervous system is to help the
human being for fight or flight reaction.
•When exposed to stress, the heart rate and stroke volume increases with the
resultant increase in cardiac output.
•The body is shifted from the skin, gut, kidney, and glands to heart, skeletal
muscle, brain and lungs as these organ need more stress.
•Pupils and bronchi are dilated and sweating is increased.
•Blood glucose increases by glycogenolysis.

31. Neurotransmitter.
Neurotransmitter of the sympathetic system are noradrenaline (NA,
norepinephrine) and dopamine.
•Adrenaline(epinephrine) is the major hormone secreted by the adrenal
medulla which consist of 85% adrenaline and 15% NA.
Synthesis and storage of catecholamine
Catecholamines are adrenaline, NA, dopamine.
Storage: stored in granules of sympathetic vesicle in the adrenergic nerve
terminals.

32. Synthesis
Tyrosine
Tyrosine hydroxylase
DOPA
DOPA decarboxylase
Dopamine
DA beta hydroxylase
Noradrenaline
N-methyl transferase
Adrenaline

33. Metabolism of catecholamine
MAO MAO
Adrenaline 3,4 dihydroxy mandelic acid NA
COMT COMT COMT
MAO MAO
Meta-nephrine 3 methoxy, 4-hydroxy non meta nephrine
mandelic acid
MAO: Monoamine oxidase
COMT: catechol-o-methyl transferase

34. Adrenergic receptors(2types)
1.αreceptors : Produce excitatory effect.
Subtypes α
1and α
2
α
1a α
2a
α
1b α
2b
α
1c α
2c
2. βreceptors : it produce inhibitory effect
Subtypes are β
1, β
2, β
3

35. Classification of adrenergic drugs/ adrenomimetics / sympathomimetics
Sympathomimetics are the drugs which acts by mimicking the action of
sympathetic stimulations.
Classification
I.Depending upon mode of action
a.Direct acting : e.g. Adrenaline, Noradrenaline, Dopamine, Isoprenaline
b.Indirectly acting : e.g. Amphetamine, Tyramine
c.Mixed actions : e.g. Ephedrine, Pseudoephedrine, Phenylpropanolamine
II.Based on chemical nature
a.Catecholamines : e.g. Noradrenaline, Adrenaline, DA, synthetic-Isoprenaline,
Dobutamine, Dopexamine
b.Non-catecholamines : e.g. Epidrine, Amphetamine

36. III.Based on therapeutic effect
a.Vasopressors –NA, DA, Phenylephrine, Methoxamine
b.Cardiac stimulant-Adrenaline, DA, Dopexamine, Ephedrine, Dobutamine,
Isoprenaline
c.CNS stimulant-Amphetamine, Ephedrine, Dexamphetamine
d.Bronchodilators –Adrenaline, Isoprenaline, Salbutamol, Terbutaline,
Salmeterol, Fenoterol
e.Appetite suppressant (anorectics)-Fenfluramine, Dexfluramine,
Sibutramine(banned)
f.Uterine relaxant-Salbutamol, Terbutaline
g.Nasal decongestant-Ephedrine, Pseudoephedrine

37. Adrenaline (prototype)
MOA
Adrenaline binds to adrenergic receptor
It activates adenyl cyclase enzyme and converts to 3
1
5
1
CAMP
And produce their action

38. Pharmacological actions
1.CVS :
a.Heart: Adrenaline increases the HR and force of contraction, cardiac output
also increases oxygen consumption
b.Blood vessel and BP : Vasoconstriction (α) and dilation (β) occurs.
BP: NA –both systolic and diastolic BP increases.
Adrenaline-increases systolic BP and decreases diastolic BP
Isoprenaline-increases systolic , decreases diastolic BP
2.Respiration –Adrenaline is bronchodilators and weak respiratory stimulant.
They dilates bronchial smooth muscle and causes anti-inflammatory effect.

39. 3.Eye –Adrenaline causes mydriasis due to constriction of radial muscle of iris
and decreases intraocular pressure
4.Metabolic effect –Adrenaline increases blood sugar level by enhancing the
hepatic glycogenolysis and inhibit the insulin resistance.
5.Skeletal muscle –Catecholamines facilitate neuromuscular transmission by
acting on both αand βreceptor and enhances the amount of Ach release.
Pharmacokinetic
•Catecholamines are rapidly inactive in gut and liver they are not given orally
•SC/IM given
•Adrenaline and NA are metabolized by COMT and MAO
•Excreted via urine
•Ophthalmic solutions are available.

40. Adrenaline NA
COMT COMT
Metanephrine Nor-metanephrine
MAO MAO
venyl mandelic acid (VMA)
excreted in urine

41. ADR
Anxiety, palpitation, weakness, tremors, dizziness, restlessness, throbbing
headache, anginal pain, arrhythmia.
Uses
•Anaphylatic shock
•Cardiac arrest
•Control of hemorrhage
•Local anesthetics
•Acute bronchial asthma
•Glaucoma

42. Adrenergic antagonist / Antiadrenergic drug / Sympatholytic /
Adrenolytic / Adrenergic blockers
These are the drugs that blocks the action of adrenaline by binding to adrenergic
receptors.
CLASSIFICATION
Alpha-adrenergic blockers
I.Selective
a.α
1blocker-Prazosin, Doxazosin, Terazosin, Trimazosin, Tamsulosin
b.α
2 blocker-Yohimbine, Idazoxam
II.Non selective
a.Non-competitive blocker-Phenoxybenzamine
b.Competitive blockers-Ergot alkaloids()ergotamine), Tolazoline, Phentolamine,
Chlorpromazine