INTRODUCTION TO

AUTONOMIC NERVOUS SYSTEM (ANS)

PHARMACOLOGY

Basic Pharmacology - 2016

dr. Agung Nova Mahendra, M.Sc.

Department of Pharmacology
Faculty of Medicine, Udayana University
Curriculum Vitae
Full Name : Agung Nova Mahendra
P/DoB : Tabanan/November 14, 1986
Research Areas:
Antioxidant pharmacology
Experimental neuropsychopharmacology

Level of Education Alma mater Degree / Awards

Senior High School SMAN 1 Singaraja Silver Medal in National
Biology Olympiad - 2003
Undergraduate (S1) Fakultas Kedokteran dr.; S.Ked.
UNUD

Postgraduate (S2) in Fakultas Kedokteran M.Sc. / Certificate of

Pharmacology UGM Summa Cum laude

Postmaster Research Yakko Kaiseki Gaku, Certificate of Excellence

Fellowship Yakko Gakubu, in Neuropharmacology
Okayama Daigaku,
Okayama, Japan
The importance of comprehending
ANS pharmacology

ANS controls nearly all bodily functions

ANS pathophysiology is involved in many

disorders/diseases

Many drugs may affect ANS (therapeutic,

side, & toxic effect)

Serves as a basis for higher medical

education

Basic Pharmacology - 2016

 List of Terms

Sympathomimetics/Adrenomimetics
Sympatholytics /Antiadrenergics or
Adrenoceptor antagonists
Cholinomimetics/Cholinergics
Cholinesterase regenerators
Parasympatholytics/Anticholinergics or
Cholinoceptor antagonists
Dopaminergics

Basic Pharmacology - 2016

Anatomic aspect of the ANS
Spinal root of origin & ganglia
location
Division Origin Ganglia
Location
Parasympathet Cranial nerve Lateral
ic ANS (PANS) nuclei III, VII, aspects of
IX, & X & spinal collumn
Sacral (except
segments of prevertebral
spinal cord ganglia)

Sympathetic Thoracic & Near the

ANS (SANS) lumbar innervated
segments of organs
spinal cords- 2016
Basic Pharmacology
Basic Pharmacology - 2016 (Mathias, 2003)
Creative thinking.

SANS: Flight or Fight Response

PANS: Rest & Digest (Spit-Pee-Shit)

Basic Pharmacology - 2016

Neurotransmitter aspects of the ANS

NOREPINEPHRINE
: primary
transmitter of SANS
adrenoceptor &
noradrenergic
neuron/synapse
ACETYLCHOLINE:
primary
COTRANSMITTE
transmitter of
RS: ATP, VIP, NPY,
PANS
substance P,
cholinoceptor &
somatostatin, etc.
cholinergic
neuron/synapse

Basic Pharmacology - 2016

Neurotransmitters involved in the ANS
pathways

Basic Pharmacology - 2016 (Mathias, 2003)

 Many drugs exert their effects by
working at different steps of autonomic
transmission:

Synthesis

Uptake &
Metaboli Storage
sm

Receptor
Interacti Release
on
Basic Pharmacology - 2016
 Presynapse CHOLINERGIC NEURON

1. Drugs affecting
Acetyl-CoA + Choline cholinergic activity:
Choline
1. Hemicholinium
2. Vesamicol
2. 3. Botox
ACh-containing
breakdown of
vesicle
SNAP25
Ca2+
+

3. Vesicle
docking &
fusion;
ACh ACh release
AChE
Cholinoceptor
Acetate & Choline
Postsynapse
Basic Pharmacology - 2016
 Presynapse NORADRENERGIC NEURON
Tyrosine Tyrosine
Mt TH 1.
(with DOPA
MAO)
AT II R
DA* Drugs affecting
2. M1 R noradrenergic
NE-containing activity:
2 R
vesicle
1. Metyrosine
++
Ca2+ 2. Reserpine
NE
uptake 3.
3. Vesicle
4. docking & Guanethidine,
fusion; Amphetamine
NE NE *(& DA)
release
4. Cocaine,
Adrenoceptor TCAs
Diffusion & Metabolism
Postsynapse
Basic Pharmacology - 2016
Receptor characteristics
Cholinocept
ors:
Muscarinic &
Nicotinic
Major ANS Adrenocept
receptor ors: Alpha &
systems Beta
Dopamine
receptors (D
or DA
receptors)
Basic Pharmacology - 2016
 Cholinoceptors

Type Mechanism Location

M1 Gq increases IP3 & DAG Nerve endings

M2 Gi decreases cAMP, Heart, some nerve

activates K+ channels endings

M3 Gq Effector cells: SM,

glands,
endothelium

NN Ion channel ANS ganglia

depolarization
NM Ion channel NMJ
depolarization
Basic Pharmacology - 2016
 Adrenoceptors & Dopaminergic Receptors
Type Mechanism Function Location

1 Gq Increases Ca2+ Effector tissues:

contraction & SM, glands
secretion

2 Gi Reduces transmitter Nerve endings

release contraction & some SM

1 Gs Inotropic & Cardiac muscle

chronotropic (+); & JGA
increases renin
release

2 Gs Inotropic & Heart, liver, &

chronotropic (+); SM
increases
glycogenolysis; relax
SM

Basic Pharmacology - 2016

Gs Increases lipolysis Adipocytes
 Effects of autonomic nerves
activation

E.g.: Pupil is both

Each ANS division has innervated by SANS &
specific effects on PANS fibers (with -
organ systems adrenoceptors & M
receptors, respectively)

Basic Pharmacology - 2016

Sympathetic innervation of the pupil: Example of
autonomic nerves activation

SANS
Pupil

1
receptor

Radial
muscle of
the iris (m.
dilator
pupillae)

Mydriasi
s

Basic Pharmacology - 2016

Parasympathetic innervation of the pupil: Example
of autonomic nerves activation

PANS Pupil

M
receptor

Circular muscle
of the iris (m.
constrictor
pupillae)

Miosis

Basic Pharmacology - 2016

Sites of autonomic drug
action
The sites include CNS
centers, ganglia,
There are many sites postganglionic nerve
of drug action (e.c. terminals, effector cell
multistep nature of receptors, & steps of
ANS transmission) autonomic
transmission
Selectivity is mostly
achieved by drugs
acting @ receptors
with very specific
actions

Basic Pharmacology - 2016

Functional integration of
the ANS
Mainly based on negative feedback
Two levels of integration

Local Modulatory pre- &

integration postsynaptic receptors
Autonomic
integration
Systemic Systemic homeostatic
reflexes
integration

Basic Pharmacology - 2016

Systemic integration: symphony of
autonomic & hormonal feedback
loop
Increased blood
pressure to
Increase
normal level
Decreas d HR &
ed PANS CO
Vasomot (vagal)
or center tone &
Barorecept increas
ors ed
increase SANS
tone
Reducedfiring
blood RAAS
pressure Increases renin activati
release AT II on
increases PVR;
aldosterone causes
salt & water
Basic Pharmacology - 2016
retention
 Conclusions
The ANS (PANS & SANS) involves various
types of neurotransmitter to regulate bodily
functions, with ACh & NE as primary
neurotransmitters

Cholinergic & Adrenergic systems mainly

work to counterbalance one another

Autonomic drugs exert their effects on

various components of autonomic
transmission, from the CNS centers to
neurotransmitters reuptake or metabolism
Both local & systemic integration have
important contribution on the functional
integrity of ANS

Basic Pharmacology - 2016

 References
Trevor AJ, Katzung BG, Masters SB. Katzung & Trevors
Pharmacology Examination & Board Review seventh
edition. The McGraw-Hill Companies. 2005: 43-53.
Mathias CJ. Autonomic Diseases: Clinical Features and
Laboratory Evaluation. J Neurol Neurosurg Psychiatry.
2003(74): 31-41.

Basic Pharmacology - 2016

A N S P H A R M A C O LO G Y
(2):
D R U G S A C TIN G O N
PA N S
dr. Agung Nova Mahendra, S.Ked., M.Sc.

Department of Pharmacology
Faculty of Medicine, Udayana University
2016
Postganglionic parasym pathetic
neurotransm ission

Decker, 2012
M uscarinic (M ) Receptor Subtypes:

M1: brain, autonomic ganglia, presynaptic

neuronal endings

M2: heart (>>)

M3: glands (>>)

M4 & M5: CNS (>>)

Rem inder

Decker, 2012
 C H O LIN ER G IC S
CHOLINERGICS
 Basic concepts ofcholinergics

Most cases: cholinergics specificity

for muscarinic receptor > nicotinic
receptor hence the term
MUSCARINICS

Cholinergic activity can be

stimulated at the
CONCEPT cholinoceptors (direct
S: action) or
Increased by inhibiting
AChE (indirect action)
ClinicalU ses

Cholinergics:
Pilocarpine: muscarinic agent used as
miotics (treatment of glaucoma) & as
antixerostomia
Cevimeline: muscarinic agent (at M3)
approved for xerostomia
ClinicalU ses

Cholinesterase inhibitors:
Pyridostigmine: for myasthenia gravis
Neostigmine: neuromuscular blockade
reversal
Donepezil: for Alzheimer dementia
ANTICHOLINERGICS

ANTICHOLINERGICS
 Basic concepts ofanticholinergics

Anticholinergics: antagonists
at M receptors
Note: cholinergic synapses are
prevalent in brain (excitatoric
effect)
Anticholinergics sedation,
antiemetic, worsening of
dementias symptoms
Clinicaluses

Atropine: mydriatic &

antibradycardia
Scopolamine: antisialagogues
(sedative & psychotomimetic)
Glycopyrrolate: antisialagogues
(water-soluble does not cross BBB)
Trihexyphenidyl: antiparkinsonism
Benztropine: antiparkinsonism
All drugs with anticholinergic
properties should be avoided
in patients with:
Constipation
Urinary retention
Alzheimers dementia
Other dementias
 Sum m ary

Cholinergics mainly act at M receptors

Cholinergic activity can be stimulated

through direct action (cholinoceptors
agonims) & indirect action (AChE inhibition)
Anticholinergics act as antagonists at M
receptors. These agents are used to
counteract disease- or drug-induced PANS
overactivity
 Reference

Becker, D.E., 2012. Basic and Clinical

Pharmacology of Autonomic Drugs.
Anesth Prog. 59: 159 169.
ANS PHARMACOLOGY (3):
DRUGS ACTING ON SANS

dr. Agung Nova Mahendra, S.Ked., M.Sc.

Department of Pharmacology
Faculty of Medicine, Udayana University
2016
Introduction

Korakuen, Okayama-shi, Okayama, Japan

Sympathetic Neurotransmission
Very prominent roles in
cardiovascular system
Transmitters: NE (& E)
Inactivation: Reuptake mechanism
>>
Receptors: &
 SYMPATHOMIMETICS

Tsus
hima
Cam
pus,
Kita-
ku, O
kaya
ma-s
hi, O
kaya
ma,
Japa
n
SYMPATHOMIMETICS
Drugs that mimic the action of NE &/or E
(stimulate adrenergic activities)
Pharmacodynamics:
Direct : Adrenoceptor agonists of
effector cells
Indirect : Act in presynaptic neuron, dependent
on endogenous catecholamines release
Displace stored catecholamines
Inhibit catecholamines reuptake
Agonists of 1:

Phenylephrine: used intranasally

as decongestant
Midodrine: used PO as a prodrug to
treat orthostatic hypotension
Agonists of 2:
Clonidine: used PO as hypertension tx
-Methyldopa: safe choice for
hypertension in pregnancy
Agonist of 1:

Dobutamine: positive inotropic

effect (IV use to treat cardiogenic
shock & acute heart failure)
Agonist of 2:

Albuterol: dilates bronchi (for asthma)

with 4 6 hrs duration little 1
activity
SYMPATHETIC
ANTAGONISTS

Fuyu sakura in Tsuyama-jo, Okayama, Japan

 Sympathetic
Antagonists
Drugs that block catecholamine receptors
activation
Antagonist of -adrenoceptors:
Phenoxybenzamine: irreversible
blocks of both subtype of -
adrenoceptors pheochromocytoma
tx.
Antagonist of 1-adrenoceptors:

Tamsulosin: HT & benign prostatic

hyperplasia (BPH) tx.
Antagonist of 2-adrenoceptors:

Yohimbine: 2 blockade increased

NE release; male erectile dysfunction
& hipotension tx.
Antagonist of -adrenoceptors:

Propranolol: 1 & 2 blockade; HT,

angina pectoris, arrhythmias,
migraine, hyperthyroidism tx.
 Summary
Drugs acting on SANS can be classified
as sympathomimetics & sympathetic
blockers

SANS neurotransmission modulation

(i.e., adrenoceptors activation) can be
established directly or indirectly
Reference
 THE END OF
PRESENTATION

Shikata Campus, Shikata-cho, Okayama-shi, Okayama, Japan

TERIMAKASIH

MATUR SUKSMA

MATUR NUWUN

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