Autonomic nervous system
Dr. Radhakrishna. L
Associate professor and Head
Department of Pharmacology
Nervous system
Central nervous system peripheral nervous
system
Autonomic nervous system
somatic nervous system
Sympathetic parasympathetic
Parasympathetic nervous system
Also called cholinergic system
Neurotransmitter - Acetyl choline
Parasympathetic nervous system
Receptors
Muscarinic nicotinic
M1, M2, M3 NM , N N
Location of receptors
Muscarinic
M1 - autonomic ganglia, gastric glands, CNS
M2 - heart, nerves, smooth muscles
M3 - exocrine glands, smooth muscles, eye
M4 - CNS
M5 - CNS
Nicotinic
NM - Neuromuscular junction
NN - autonomic ganglia, CNS, adrenal medulla
Parasympathomimetics
Also called as cholinomimetics
These are the drugs which imitate or mimic
the actions of acetyl choline (ACh) at
neuroeffcetor junction
Synthesis of acetylcholine
Acetylcholine is synthesized from acetyl CoA
and choline by the mediation of choline acetyl
transferase
Acetyl CoA + choline
choline acetyl transferase
Ach (Acetylcholine)
Storage and Release of acetylcholine
After synthesis ACh is stored in vesicles
ACh releases once the action potential
reaches nerve terminal
Metabolism of acetylcholine
Acetylcholine
acetyl cholinesterase
choline and acetic acid
Choline esterase is of 2 types
1. True cholinesterase : present at neurons, ganglia
and neuromuscular junction
2. Pseudo cholinesterase: present in liver, plasma and
other organs
Classification of drugs
Parasympathomimetics or Cholinomimetics
These are 2 types
Directly acting indirectly acting
1. Acetyl choline
2. Methacholine
3. Bethanechol
4. Carbachol
5. Pilocarpine Reversible irreversible
6. Muscarine
7. nicotine
Indirectly acting
Reversible
Neostigmine
Pyridostigmine
Physostigmine
Edrophonium
Ambenonium
Galantamine
Irreversible – organophosphorous
compounds (Insectisides)
Parathion
Malathion
Ecothiophate
Carbaryl
Propoxur
Mechanism of action
Directly acting drugs
These drugs directly bind with the receptors
(M/N) and produce the action
Indirectly acting drugs
(anticholinesterases)
These drugs act by inhibiting the enzyme
cholinesterase
Therefore increases the levels of ACh
Pharmacological actions
On eye- cause contraction of pupil called
miosis
GIT- causes secretion of gastric juice,
facilitates motility of intestine
On lungs- causes broncho constriction
Pharmacological actions
On Blood- causes
vasodilatation due to NO (nitric
oxide)
On heart- decreases heart
rate, force of contraction, and
conduction
On Urinary bladder-
facilitates voiding of urine
(constriction of detrusor muscle
and relaxation of sphincter)
On secretory glands
Increases the secretions of all glands- salivary,
lacrimal, nasopharyngeal, gastric, tracheobronchial
and intestinal secretions
Sweating also increases
Directly acting drugs - Therapeutic
uses
In treatment of Glaucoma (pilocarpine
is used)
To reverse mydriasis produced by
atropine
In the treatment of xerostomia (dry
mouth)
Used to get post operative urinary
retention
To treat GIT atony
Indirectly acting drugs- Therapeutic
uses
1. For treatment of Myasthenia
gravis
Myasthenia gravis:
Is an autoimmune disorder
Due to development of IgG antibodies that bind to
nicotinic receptors and inhibits the action of Ach
It causes weakness and easy fatiguability of
skeletal muscles
Symptoms- ptosis, diplopia, dysphagia, difficulty in
speaking, difficulty in chewing
Drugs used for Myasthenia gravis
Anticholinesterases like neostigmine,
pyridostigmine, physostigmine, edrophonium,
are used
These drugs act by increasing the levels of
ACh by inhibiting anticholiesterase
Glucocorticoids (steroids) are also used
2. Used in the treatment of glaucoma (Physostigmine
used)
3. To break the adhesion between iris and lens
4. To reverse the mydriasis produced by atropine
substituents
5. To treat atropine poisoning (Physostigmine used)
6. For post operative urinary retention
7. For the treatment of Alzheimers disease
Organophosphorous (OP) poisoning
These organophosphates used as insecticides
in agriculture and often causes poisoning
Symptoms-
Miosis,
Incresed sweating and salivation, gastric secrions
Vomting, abdominal cramps
Bronchospasm, hypotension
Muscle twiching, weakness, convulsions
Coma and death
Treatment of OP poisoning
Removing clothes and washing the skin with soap
Maintaining the ABC
Drugs
1. Cholinesterase reactivators- pralidoxime,
obidoxime (act by reactivating cholinesterase enzyme)-
1-2 gm iv can be given
2.
2. Atropine iv 2 mg
Adverse effects
Flushing of face
Salivation
Sweating
Bronchoconstriction
Muscle weakness
Tremors
Nausea
vomiting
If muscarinic side effects become prominent
(during the treatment with neostigmine or
physostigmine) treatment can done with
Atropine (0.5 mg S.C)
Atropine is the antidote for muscarinic
poisoning (physostigmine)
Anti muscarinic drugs
Also called as parasympatholytics or
anticholinergic drugs
These drugs blocks muscarinic receptors
Classification
Natural Semi synthetic Synthetic
Atropine Homatropine eucatropine
Scopalamine Atropine methionate cyclopentolate
Benztropine tropicamide
Ipatropium dicyclomine
Tiotropium pirenzepine
telenzepine
biperiden
trihexyphenidyl
glycopyrrolate
isopropamide
propantheline
methantheline
Classification
Natural alkaloids : Atropine, Scopalamine
Semi Synthetic and synthetic
a. Atropine derivatives used as mydriatics:
homatropine, cyclopentolate, tropicamide
b. Atropine derivatives used in respiratory disorders
ipatropium, tiotropium, oxytropium
c. Atropine derivatives used in peptic ulcers
pirenzepine, telenzepine
d. Atropine derivatives used as antispasmodic
dicyclomine, flavoxate, oxybutin
e. Atropine derivatives used as pre anaesthetic agents
gycopyrrolate
f. Atropine derivatives used in parkinsonism
trihexyphenidyl (benzhexol), benztropine
Mechanism of action
All the drugs act by blocking the muscarinic
receptors there by its actions
It is an competative antagonism
Pharmacological actions
On eye-causes dilatation of pupil called mydriasis
Is an indirect mydriasis (eye unresponsive to light)
GIT- reduces gastric acid secretions,
decreases the tone and motility of intestine
Reduces the spasm (as spasmolytics)
On lungs- causes broncho dilatation
On Blood- causes vasodilatation
High doses causes cutaneous vasodilatation and
hypotension
On heart-
initially decreases heart rate (bradycardia),
causes tachycardia
increases conduction
On Urinary bladder- facilitates urinary
retention (relaxation of detrusor muscle and
constriction of sphincter)
On CNS-
1. Low doses produce CNS
stimulant effect and in high
doses depressant effect
2. By reducing cholinergic 0ver
activity it produces anti
parkisons effect
3. It depresses the vomiting
centre (anti emetic effect)
4. Also causes drowsiness,
amnesia, fatigue, dreamless
sleep etc..
On secretory glands
decreases the secretions of all glands- salivary,
lacrimal, nasopharyngeal, gastric,
tracheobronchial and intestinal secretions
On sweat glands
Sweat glands have m3 receptors
These drugs decreases the sweat formation
Pharmacokinetics
Well absorbed orally
Well distributed in body, crosses BBB (Blood
Brain Barrier)
Metabolized in liver
Excreted in urine
Therapeutic uses
1. As mydriatic: used for examining
the eye
homatropine, tropicamide are used
2. As preanaesthetic medication: to
prevent the vagal bradycardia and
to reduce the secretions
atropine, scopalime, glycopyrrolate are
used
3. In treatment of Asthma and COPD
treatment
ipatropium, tiotropium are used
4. Used to relieve the excessive salivation
dicyclomine is used
5. Used as antispasmodic agents: to
relieve the spasm of GIT
Dicyclomine, glycopyrrolate are used
Therapeutic uses
6. Used in peptic ulcer and
diarrhoea: these drugs decreases
the acid secretions and reduces
the motility of intestine
pirenzepine, telenzepine are used
Therapeutic uses
7. Used in the treatment of motion
sickness
scopalamine is used
8. Used in the treatment of parkinsonism
trihexyphenidyl, biperiden are used
9. Used in treatment of primary and
secondary heart block
atropine is used
10. Used in renal and biliary colic
Therapeutic uses
11. Used in treatment of noctornal
enuresis
12. Used to treat hyperhydrosis (over
sweating)
13. Used in treatment of mushroom
poisoning
14. Used in treatment of OP poisoning
15. Used in treatment of curare
poisoning
Adverse effects
GIT: Dryness of mouth, throat, difficulty in
swallowing, constipation
EYE: blurred vision, photophobia
CNS: restlessness, excitement and hallucination
Urinary tract: difficulty in micturation
CVS: tachycardia, palpitation, hypotension
Atropine poisoning
Is due to atropine over dosage
Symptoms: dry skin, flushing of face (red
face), photophobia, dry mouth, hyperpyrexia,
slurred speech, restlessness, hallucination
Treatment:
Physostigmine is used as antidote.
Sympathomimetics
Drugs that mimic or imitate the action of sympathetic system are called as
sympathomimetics or adrenergic agonists
Neurotransmitters- nor adrenaline
Receptors
α receptors β receptors
α1 β1
α2 β2
β3
Receptors location
α1 receptors- present post synoptically
Present in most organs (bronchi, eye, uterus, )
Produces excitatory effect
α2 receptors- present pre synoptically
Produces reversal effect
Present in brain, gut etc..
β1 receptors- present post synoptically
Present in heart and kidney
β2 receptors- present post synoptically
Present in bronchi, blood vessels of skeletal muscles, myocardium
β3 receptors- present post synoptically
present in adipose tissues
Biosynthesis
Norepinephrine is the main neurotransmitter and
is synthesized from phenylalanine
Phenylalanine
Tyrosine
Tyrosine hydroxylase
DOPA
Dopamine
Norepinephrine
Epinephrine
Storage and release
The neurotransmitters stored in synaptic
vesicle
Action potential at the nerve terminal
releases the NE, E, DA
Metabolism
Metabolism mainly takes place by 2 mechanisms
1. Enzymatic transmission
2. Reuptake mechanism
3.
Enzymatic transmission
adrenaline/ noradrenaline
Catecholamine –O- methyltrasferase Monoamine oxidase
(COMT) (MAO)
Vanillylmandelic acid
Metanephrine
Nor metanephrine
Metabolism
2. Reuptake mechanism:
After release into the circulation most of the
NA (Noradrenaline) is taken back to the nerve
terminal
It is the main mechanism of termination of NA
Classification
Directly acting drugs Indirectly acting
Mixed
Adrenaline, Noradrenaline Tyramine Ephedrine
Dopamine, Dobutamine Amphetamine
α1 selective agonists Sibutramine
Phenylephrine
Oxymetazoline
Xylometazoline
α2 selective agonists
Clonidine
Methyldopa
β1 selective agonists
prenalterol
β2 selective agonists
Salbutamol
salmeterol
Terbutaline
formeterol
Mechanism of action
Directly acting drugs: act on pre and
post synaptic receptors and produce the
pharmacological effects
Indirectly acting drugs: act by
reuptake mechanism
Drugs displace the NA from stores and then
activates receptors
Mixed drugs: have both the mechanism
Pharmacological actions
On heart: By acting on β1 receptors
produces
Increase in heart rate
Increase in myocardial contractility
Increase in conductivity
Increase in cardiac output
Increase in automaticity
Increase the cardiac load (increases O2
requirement)
On blood vessels :
Increase the BP-. Adrenaline constrict skin and
mucous membrane blood vessels by acting on α1
receptors
But dilates the blood vessels of skeletal muscles
and coronary arteries
Adrenaline in normal therapeutic
doses produces biphasic
response
– initial rise in BP (α1 action ), later fall in
BP (β2 action) and this increased BP effect can
blocked by giving α1 blockers. This effect is called
DALES VASOMOTOR REVERSAL
PHENOMENA
Pharmacological actions
On eye-causes dilatation of pupil called mydriasis
Is an direct mydriasis .
GIT- reduces gastric acid secretions,
decreases the tone and motility of intestine
relaxes the gut muscles
On lungs- act on β2 receptors in lungs
causes broncho dilatation
decreases the secretions
On Urinary bladder- facilitates urinary
retention (relaxation of detrusor muscle and
constriction of sphincter)
On CNS:
Produces tremors, restlessness
Fall in BP (by acting on pre synaptic α2 receptors)
On secretions:
Produce thick saliva secretion
Sweating of palms and soles
On metabolism:
Hyperglycaemia due to glycogenolysis
Decreases the insulin release
Increase in free fatty acids
Increase in BMR
Therapeutic uses
Therapeutic uses of Adrenaline
1. In anaphylactic shock:
adrenaline is first choice drug in allergy
treatment (Type 1 hypersensitivity)
2. Used In bronchial asthma
3. Used to prolong the Local
anaesthetic action:
in dental practice adrenaline is added to
Lignocaine for dental prolonged anaesthesia
4. Used in cardiac arrest:
intra cardiac injection is given
5. As local haemostatic:
used to control bleeding after tooth
extraction, in nose and throat surgeries
Therapeutic uses of other directly acting drugs
1. Used in managing hypotensive
states
2. Used in bronchial asthma
3. Used as nasal decongestants – relieves
the nasal block
4. Used to treat hypertension (BP)
Clonidine and methyldopa due to its effect on
presynaptic receptors
5. Used to delay the premature
labour
6. Used to treat cardiogenic shock
Noradrenaline is uses
7. Used to treat low cardiac output
Dopamine is used
8. Used as Mydriatic for eye
examination (no cyclopegia)
Uses of indirectly acting drugs
These are popularly called as anorectics
(drugs reduces the food intake or reduces
body weight)
1. To treat Narcolepsy
2.
3.
4.
2. To treat ADHD (Attention deficit
hyperkinetic disorder)
3. To control obesity
Adverse effectsdirectly acting
drugs
Tachycardia, palpitation
Headache, restlessness
Tremors, rise in BP
Cardiac arrhythmias
Cerebral haemorrhage
hyperglycaemia, hallucinations
Hypokalaemia
Mixed acting drug- Ephidrine
Is an alkaloid from plant Ephidra
vulgaris
It act by direct (receptor) and indirect
(reuptake) mechanism
It used rarely in treating asthma and
hypotension
Sympatholytics
Also called sympathetic blockers
These are of 2 types
β blockers
α blockers
α blockers
Classification of drugs
-Non selective α blockers
Phentolamine
phenoxybenzamine
Selective α1 blockers
prazosin
terazosin
doxazosin
tamsulosin
Alfuzosin
Mechanism of action
Blocks the α receptors competitively
Is an competitive antagonism
Pharmacological properties
On eye- miosis
On heart and blood vessels-
vasodilatation ( due to α1 receptor block)
decrease in peripheral vascular resistance
fall in BP
On GIT- increases motility, increased gastric
acid secretion
On urinary bladder- facilitates voiding
of urine
Therapeutic uses
Used for treatment of
phaeochromacytoma
Used in the treatment of essential
hypertension
Used to treat hypertensive emergencies
In treatment of benign prostatic hypertension
Adverse effects
First dose phenomenon: selective alpha blockers
(Prazosin) with initial dose it produces severe postural
hypotension and syncopal attack. Hence initial dose should
start with small dose and should given at bed time
Nausea
Vomiting
Diarrhoea
Postural hypotension
Nasal congestion
Tachycardia
Palpitation
β blockers
Classification of drugs
Non selective β blockers
Propranolol
Sotalol
Nadolol
Pindolol
Selective β1 blockers
Atenolol
Metoprolol
Esmolol
Celiprolol
Acebutolol
Mixed blockers ( α β
blockers)
Labetalol
Carvedilol
Mechanism of action
Blocks the beta receptors competitively
Is a competitive antagonism
Pharmacological actions
On eye- reduces intra ocular pressure (IOP)
by reducing aqueous humour production
On heart-
Decreases Heart rate
Decreases Force of contraction
Decreases Cardiac output
Decreases Conductivity
Decreases automaticity
Decreases cardiac work
On blood vessels- decreases PVR
(peripheral vascular resistance)
On lungs- causes bronchoconstriction
Hence should be careful in Asthma and COPD
petients
Metabolic effects: inhibits
glycogenolysis and delay the recovery from
hypoglycaemia
Hence should be careful in diabetics
Decreases HDL and increases LDL
levels
Selective β1 blockers
Advantages
No severe bronchoconstriction and safer in
asthmatics
Safer in diabetics (cause less inhibition of
glycogenolysis)
Safer in old patients
Lipid profile is less worsened
Therapeutic effects
Used in hypertension
Used in treatment of cardiac arrhythmias
Used for heart failure
Used for angina
Used for myocardial infarction
Used in phaeochromacytoma
Used in migraine
Used to relieve anxiety (tensed)conditions
Used for glaucoma
Mixed blockers ( α β blockers)uses
Used to treat rebound hypertension
To treat essential hypertension
To treat hypertension in old peoples
Adverse effects
Bronchoconstriction
Hypoglycemia
Bradycardia
Bad dreams
Sleep disturbances
Muscle weakness
Fatigue
Hallucinations
Abrupt withdrawal symptoms: sudden
stoppage of beta blockers after chronic use causes
severe cardiac effects. Hence these drugs should
not be stopped suddenly
Glaucoma
Glaucoma can occur at any age but is more common in older adults.
It is one of the leading causes of blindness for people over the age
of 60.
Elevated eye pressure happens as the result of a buildup of
fluid(aqueous humor) that flows throughout the inside of the eye
Two types of glaucoma
1. Open angle glaucoma
2. Closed angle glaucoma
Drugs used for glaucoma
Mannitol
Glycerol
Acetazolamide
Timolol
Pilocarpine
Latanoprost
