Drugs Acting On Autonomic

Nervous System (ANS)

Group: 2nd
Submitted to : Mam
Bakhtawar muneer

Submitted by :
Abdullah khan
Taimoor Ali
Touqeer Husain
Junaid khan
Sharjeel hassan
 Neurotransmitters
 Sympathetic: noradrenaline
(norepinephrine)
 Parasympathetic :
acetylcholine
 Cholinergic receptors

 Muscarinic: M1 – M5
Activated by muscarine
 Nicotinic: NM, NN
Activated by nicotine
Overview
Drugs affecting the autonomic nervous
system (ANS) are divided into two groups
according to the types of neuron involved in
the mechanism of action

The cholinergic drugs, acts on receptors that

are activated by acetylcholine (ACh)

The adrenergic drugs, act on receptors

stimulated by norepinephrine or epinephrine
 Cholinergic system

The cholinergic system composed on nerve

cells that use the neurotransmitter
acetylcholine.

Acetylcholine estrase enzyme that catalyzes

the breakdown of acetylcholine
 Acetylcholinesterase

ACh is degraded to choline + Acetic acid by

enzyme acetylcholine (AChE).
There is two types of AChE.

1.True
2.Pseudo
 Cholinergic receptors

Cholinergic receptors are of two types.

1.Muscarinic
2.Nicotinic
Cholinergic receptors
•Muscarinic receptors are of five subtypes, i.e
M1,M2,M3,M4 and M5

•M1 receptor are present in autonomic ganglia ,

gastric glands and central nervous system
•M2 receptor are present in heart , smooth
muscle and nerve
•M3 receptor are present in exocrine glands,
smooth muscle and Eye
•M4 and M5 receptor are present in CNS
•Nm receptor are present in neuromuscular
junction (NMJ)
•Nn receptor are present in autonomic
ganglia,adrenal medulla and CNS
M1 Secretory salivation, stomach acid, sweating, lacrimation
glands

M2 Heart Decreases heart rate  bradycardia

M3 Smooth Contraction of smooth muscles (some) 

muscle diarrhea, urination, bronchospasm
(GI/GU/Resp)
M3 Pupil and Contracts  Miosis
ciliary Increased flow of aqueous humor
muscle
Nm Skeletal Contraction of skeletal muscle
muscle end
plate
Nn Autonomic Secretion of Epinephrine
ganglia, Controls ANS
Adrenal
Medulla
Actions of Ach
 Acetylcholine – major neurotransmitter
of PNS
 Actions of Ach
Characteristics M1 M2 M3
(neuronal) (cardiac) (glandular)
Location & •Ganglia – • SA node •Exocrine
impulse -Decreased rate glands-
Function of impulse secretion
transmission generation
•AV node – •Visceral
decreased smooth Muscle
conduction – contraction
velocity
•Atrium,
ventricle-
decreased
contractility
 Actions of Ach
Characteristics M1 M2 M3
(neuronal) (cardiac) (glandular)
Location & •Ganglia – • SA node •Exocrine
impulse -Decreased rate glands-
Function of impulse secretion
transmission generation
•AV node – •Visceral
decreased smooth Muscle
conduction – contraction
velocity
•Atrium,
ventricle-
decreased
contractility
 Actions of Ach
Characteristics M1 M2 M3
(neuronal) (cardiac) (glandular)
Location & •Ganglia – • SA node •Exocrine
impulse -Decreased rate glands-
Function of impulse secretion
transmission generation
•AV node – •Visceral
decreased smooth Muscle
conduction – contraction
velocity
•Atrium,
ventricle-
decreased
contractility
 Actions of Ach
Characteristics M1 M2 M3
(neuronal) (cardiac) (glandular)
Location & •Ganglia – • SA node •Exocrine
impulse -Decreased rate glands (salivary,
Function of impulse sweat)
transmission generation -secretion
•AV node –
decreased •Visceral
conduction smooth Muscle
velocity (bronchus,
•Atrium, bladder, GIT) –
ventricle- contraction
decreased
contractility
 Actions of Ach
Characteristics NM NN
(muscle type) (neuronal type)
Location &
Skeletal •Autonomic
neuromuscular ganglia– impulse
Function junction (NMJ) – transmission
contraction
 Choline-esters
Choline esters including Acetylcholine,carbachol ,bethanechol
Pharmacokinetics:-
 Quaternary ammonium compounds, charged,
 Highly water soluble.
 Poorly absorbed and poorly distributed into most tissues.
 Hydrolyzed in the GIT and not active by the oral route.
 They differ in their susceptibility to hydrolysis by cholinesterase.

Acetylchloline
 Prototype drug
 Not effective orally destroyed by HCl of stomache
 Produces muscarninc & nicotinic effects by interecting with respective
receptors on the effector cells
 Not effective parenterally- destroyed by choline esterase enzyme
Action:-
1.Muscarinic actions 2.Nicotinic actions
Drug Effects of Cholinergic
Agents
“SLUDGE”
• Salivation
• Lacrimation
• Urinary incontinence
• Diarrhea
• Gastrointestinal cramps
• Emesis
Actions of ACh on eye
Muscarinic:
 Eye:

-Circular muscle of iris (M3)- contraction-

miosis
-Ciliary muscle (M3) – contraction- eye’s
focus is accomodated for near vision
– spasm of accomodation
-Better drainage of aqueous humor – reduced
intraocular pressure
-Lacrimal glands (M3) - lacrimation
 Bronchi:-
M3 receptor

Ach

•Contracts bronchial smooth muscle(Bronchospasm)

•↑Tracheobronchial secretions
•Contraindicated – Asthma

CVS:-
Heart:- Inhibitory action in SA node–open K+ channel –
Hypepolarization
M2 receptor ↓ ↓ HR- negative chronotropic Effect
Ach ↓ ↓ FOC-Negative Inotropic effect
↓ ↓ A-V conduction-Negative dromotropic effect
 Blood Vessels:-
Ach stimulate M3 receptor in blood
vessels

Release of Nitrous Oxide

Vasodilatation ↓BP

Smooth Muscle:-
a. GIT:- stimulate M3 receptor
↑ Tone of the gut
↑ Peristaltic movements
↑ GI secretion
Relaxes the sphinter may cause defecation.
Urinary bladder:-
 Contracts the detrusor muscle (M3 receptor )
 Relaxes the trigonal sphinter( Causes
urination)

Exocrine gland:- (M3 receptor)

↑ salivation, lacrimation, sweat, bronchial , gastric &
other
gastrointestinal secretion
Nicotinic action:-
1. Autonomic ganglia:-
Higher dose causes dangerous muscarnic effect especialy on heart
High dose of Ach stimulate both the sympathetic as well as the
parasympathetic ganglia causing trachycardia & rise in bp.

2. Skeletal muscle :-
High dose – twitching ,fasciculation followed by prolong
depolarization of NMJ & paralysis

3. CNS:- no action as it poor penetration through the

BBB
 Acetylcholin
 No
e
therapeutic use because
i) Ultra short action: rapidly
hydrolyzed by cholinesterases
ii)Widespread and nonselective
activity: act on all receptors
 Drugs which mimic the actions of
Ach are called as cholinergic drugs
or parasympathomimetic drugs or
cholinomimetic or cholinergic
agonists
 Classification
1. Directly acting
Methacholine, bethanechol, pilocarpine

Act on muscarinic receptors

2. Indirectly acting (Anticholinesterases)
A. Reversible :
Physostigmine, neostigmine,
pyridostigmine, edrophonium
B. Irreversible:
Organophosphates: Parathion,
Malathion
 Bethanechol
 Not hydrolyzed by acetylcholinesterases
 It has strong Muscarinic action & no Nicotinic action

Actions
Directly stimulates M receptors causing increased intestinal
motility & tone
It stimulates detrusor muscle of the bladder while trigone &
sphincters are relaxed causing expulsion of urine

Therapeutic Uses:
Paralytic ileus
Urinary retentions-M3 receptor,
Neurogenic bladder
Gastroparesis
 Pilocarpine

An alkaloid, lipid soluble & is stable to hydrolysis by

cholinsterases It has Muscarinic activity only .
Actions-
When applied locally to cornea Produces rapid moisis &
contraction of ciliary muscle produces of spasm of
accommodation & vision is fixed at particular distance making it
impossible to focus for far situated objects

Therapeutic Use :-
In Glaucoma:-
It opens
trabecular
meshwork around
schlemm’s canal
 Mechanism of action of
Anticholinesterases
 Inhibit acetylcholinesterase (AChE) enzyme

 Ach ----------- Choline + acetate

AChE
_
_
Neostigmine

 Accumulation of Ach  Action

Therapeutic uses
 Ophthalmic use :
i) Glaucoma
ii)To counteract the effects of mydriatics
iii)To break adhesions between the iris and
lens or iris and cornea
 Myasthenia gravis : neostigmine
 Belladona(Atropine) poisoning :
Physostigmine – specific antidote
Irreversible AChE inhibitors

 Mainly used as insecticides and

pesticides
 Adverse effects of
anticholinesterases
 Diarrhea, urination, bronchoconstriction,
lacrimation, salivation, sweating,
bradycardia, fasciculation of skeletal
muscle
 Organophosphorus poisoning: treated
with an anticholinergic, atropine
Anticholinergic Drugs
Classification
 Natural alkaloids :
Atropine* (prototype), Scopolamine
(Hyoscine)
 Semisynthetic derivatives :
Homatropine*, ipratropium bromide,
tiotropium bromide
 Synthetic compounds :
i) Mydriatics – Cyclopentolate*,
tropicamide
ii) Antiparkinsonian – Benzhexol, Biperiden,
Benztropine
iii) Antisecretory- antispasmodics –
Dicyclomine
Pirenzepine
Glycopyrrolate

Semisynthetic and synthetic anticholinergics

- Atropine substitutes
Pharmacological actions of atropine

 CNS :

High doses – restlessness, delirium,

disorientation

 CVS :
Tachycardia
 Eye
m
: ydriasis : “Passive mydriasis”
Photophobia, abolition of light reflex
“Paralysis of accomodation or cycloplegia”
Rise in IOP
Decrease in lacrimation – dry eyes
 Respiratory system :
Bronchodilatation
Decreased secretions
 GIT :
Reduce gastric acid secretion
Reduced tone and motility of gut, constriction
of sphincters – constipation
 Genitourinary
Relaxation
tract : of ureter and urinary bladder –
urinary retention
 Glands :
Decreases sweat, salivary, tracheobronchial
and lacrimal secretion
 Body temperature :
Rise in body temperature
“Atropine fever”
Uses of atropine
 Preanaesthetic medication: to decrease
secretion
 Oraganophosphorous poisoning
Therapeutic uses
 Motion sickness : Scopolamine
 Parkinson’s disease :benzhexol,
benztropine etc.
 Bronchial asthma : ipratropium
and tiotropium bromide
 Preanaesthetic medication :
glycopyrrolate ,
 A s mydriatic during fundoscopy and
testing of refractive error – Tropicamide,
cyclopentolate
Side effects of atropine :
 Dry mouth
 Blurred vision and photophobia
 Urinary retention
 Constipation

 Dry, hot skin

 Precipitation of glaucoma
 Decreased sweating