Drugs Affecting Autonomic

Nervous System (ANS)

I. Cholinergic Drugs
II. Adrenergic Drugs
Drugs affecting the
Autonomic I. Cholinergic Drugs:
Nervous System Cholinergic drugs are classified into 2 types

Autonomic drugs are classified into 2 main classes: A) Cholinergic agonists [Parasympathomimetic - Cholinomimetics]
I. Cholinergic Drugs: These are drugs that activate the cholinergic receptors, so produce pharmacological
Cholinergic drugs are drugs that act on the effects similar to that produced by parasympathetic stimulation.
cholinergic receptors (receptors that are activated
by Ach).
II. Adrenergic Drugs:
Adrenergic drugs are drugs that act on the
adrenergic receptors (receptors that are activated
by NE or EP).
B) Cholinergic antagonists [Parasympatholytic - Cholinergic blockers - Anticholinergic
drugs]
These are drugs that bind to cholinergic receptors and prevent Ach from interacting
with those receptors, so produce pharmacological effects opposite to that produced
by parasympathetic stimulation.
 A) Cholinergic agonists [Parasympathomimetic - Cholinomimetics]
Cholinergic agonists are classified into 2 groups :
Drugs affecting the
1- Direct acting cholinergic agonists (Direct acting parasympathomimetic):
Autonomic • They act by direct stimulation of the cholinergic receptors (Muscarinic and Nicotinic).
Nervous System 1A- Direct acting on muscarinic receptors (Muscarinic agonists):
Examples: Acetylcholine, Bethanechol, Carbachol, Pilocarpine
Autonomic drugs are classified into 2 main classes:
I. Cholinergic Drugs: 1B- Direct acting on nicotinic receptors (Nicotinic agonists):
Cholinergic drugs are drugs that act on the
Examples: Nicotine, Lobeline
cholinergic receptors (receptors that are activated
by Ach).
II. Adrenergic Drugs:
2- Indirect acting cholinergic agonists (Indirect acting parasympathomimetics)
Adrenergic drugs are drugs that act on the • They act by inactivation of cholinesterase enzyme leading to accumulation of Ach at the
adrenergic receptors (receptors that are activated cholinergic receptors.
by NE or EP).
• Since they inhibit cholinesterase enzyme they also named as cholinesterase inhibitors or
anticholinesterases.

These are drugs which inhibit the Ach Esterase enzyme so prolong the muscarinic and
nicotinic actions of Ach.

i- Reversible anticholinesterases

ii- Irreversible anticholinesterases

Drugs affecting the Acetylcholine
Autonomic Ach is one of many neurotransmitters in the autonomic nervous system.
Nervous System It is the neurotransmitter of the cholinergic nerves.
Ach acts on the muscarinic and nicotinic receptors so it has 2 types of
Direct acting on muscarinic receptors (Muscarinic
agonists) actions:
• Muscarinic action.
Acetylcholine
• Nicotinic action.
Bethanechol
Carbachol
Pilocarpine

Muscarinic Action Nicotinic Action

It is the action of Ach on the muscarinic receptors which It is the action of Ach on the nicotinic receptors which
present on cardiac muscles, smooth muscles and exocrine present on skeletal muscles, autonomic ganglia and
glands. adrenal medulla

The action of Ach on these receptors is similar to that The action of Ach on these receptors is similar to that
produced by muscarine which produces stimulation produced by nicotine which produces stimulation in
on small or large doses. small dose and inhibition in large dose

This action can be blocked by atropine. This action can be blocked on skeletal muscle by gallamine
and tubocurarine
 Acetylcholine

Drugs affecting the Muscarinic

Action
Autonomic Eyes Ach binds and activates the muscarinic receptors (M3) in the constrictor

Nervous System pupillae muscle producing contraction of the muscle which leads to
constriction of eye pupil (miosis).

Contraction of the constrictor pupillae muscle opens the canal of Schlemm

Direct acting on muscarinic receptors (Muscarinic so, improves the drainage of aqueous humor and reduces the intra-ocular
agonists) pressure (IOP)

Acetylcholine It binds to M3 in the ciliary muscle producing contraction of the muscle

leading to loss of accommodation. In this case, the lens become more
Bethanechol convex, so the vision becomes fixed at the nearest point, making it
impossible to focus (accommodation for near vision).
Carbachol
Ach also increases the lacrimal secretions.
Pilocarpine

Respiratory Ach binds to muscarinic receptors in the smooth muscle of the bronchioles
system (M3) producing bronchoconstriction (bronchial asthma).

It also increases respiratory tract secretions.

GIT Ach binds to muscarinic receptors in the GI smooth muscle leading to

increase in GI motility which may lead to spasms, vomiting or diarrhea.

It also increases the salivary, gastric and intestinal secretions.

 Acetylcholine

Drugs affecting the Muscarinic

Action
Autonomic CVS - Heart Ach binds to M2 receptors in SA node so decreases the heart rate
(bradycardia).
Nervous System It slightly decreases the force of contraction because M2 receptors are
located more in heart atriums

Direct acting on muscarinic receptors (Muscarinic CVS - Blood Ach binds to the muscarinic receptors (M3) in the smooth muscle of blood
Vessels vessels so induces vasodilatation.
agonists)
Note: Blood vessels have no parasympathetic supply so M3 of blood
Acetylcholine vessels
are normally silent (non innervated receptors).
Bethanechol
CVS - BP Ach causes lowering of blood pressure (hypotension) due to bradycardia
and vasodilatation.
Carbachol
Urinary Ach increases the contraction of the bladder muscle and relaxes the
Pilocarpine Tract sphincter leading to increased frequency of urination.
Exocrine Ach increases secretion of exocrine glands by acting on M3 receptors. It
glands increases lacrimal, bronchial, salivary and sweat secretions.
Note: The secretion of sweat is a sympathetic response but is mediated
via
the release of Ach onto muscarinic receptors.

Uses of Acetylcholine
Ach can't be used clinically for two reasons.

1- It is nonselective (its multiplicity of actions lead to diffuse effects).

2- Its rapid inactivation and short duration.

• When given orally, it is rapidly hydrolyzed in the digestive tract
• When given by injections, it is rapidly metabolized by plasma
cholinesterase enzyme.
Drugs affecting the
Bethanechol
Autonomic • It is a synthetic drug, structurally related to Ach, in which the acetate is replaced
Nervous System by carbamate, and the choline is methylated
• It is resistant to hydrolysis by cholinesterase enzyme (due to the addition of
Direct acting on muscarinic receptors (Muscarinic carbamic acid), so produces a prolonged duration of action as compared to Ach.
agonists) • It is inactivated slowly through hydrolysis by other esterases.
Acetylcholine
Bethanechol
Carbachol
Muscarinic Major effects on blood vessels (smooth muscle), GIT and UT.
Pilocarpine Action

Nicotinic Action It lacks nicotinic actions due to the addition of the methyl group.

Uses of Bethanechol (indications - applications)

1- Urinary retention particularly in postpartum or postoperative, non-obstructive cases.

2- Paralytic ileus following surgery

Note: Bethanechol is contraindicated in urinary retention due to obstruction as in case
of enlarged prostate, tumor or stone.
Drugs affecting the Carbachol (Carbamylcholine)
Autonomic • It is a synthetic drug, structurally related to Ach, in which the acetate is replaced
Nervous System by carbamate.
• It is resistant to hydrolysis by cholinesterase enzyme, so produces a prolonged
duration of action than Ach.
Direct acting on muscarinic receptors (Muscarinic
agonists) • It is inactivated slowly through hydrolysis by other esterases.
Acetylcholine
• It is non-selective in action.
Bethanechol
Carbachol
Muscarinic Major effects on CVS and GIT.
Pilocarpine Action

Nicotinic Action Yes. since there is no methyl group that is present in Bethanechol

Uses of Bethanechol (indications - applications)

• Carbachol is rarely used therapeutically due t. its high potency, non-selectivity,
and relatively long duration of action.
• Used topically in the eye for Glaucoma to reduce intraocular pressure in
glaucoma, particularly in patients who have become tolerant to pilocarpine.
Drugs affecting the Pilocarpine
Autonomic • It is a naturally occurring alkaloid obtained from Jaborandi leaves.
• Its structure has no relation with the structure of Ach, but it found to acts as
Nervous System muscarinic agonist.
• Not inactivated by cholinesterase enzyme, so produces a prolonged duration of
Direct acting on muscarinic receptors (Muscarinic
agonists) action than Ach.
Acetylcholine
• Compared with Ach and its derivatives, it is less potent.
Bethanechol Muscarinic Major effects on Eye and Exocrine glands.
Action
Carbachol
Pilocarpine Uses of Pilocarpine (indications - applications)
When applied topically to the eye, pilocarpine produces
• contraction of constrictor pupillae muscle producing rapid miosis,
•contraction of the ciliary muscle producing loss of accommodation. Pilocarpine
is used to treat glaucoma and is the drug of choice in the emergency lowering
of intraocular pressure. It causes an immediate drop in intraocular pressure as a
result of the increased drainage of aqueous humor.
Pilocarpine is one of the most potent stimulators of secretions (secretagogue)
such
as sweat (diaphoretic) used to remove edema, and saliva (sialagogue) to treat
xerostomia.
Note: Xerostomia is a condition of dry mouth due to reduced saliva secretion.
Many factors are responsible for this condition including radiation therapy of
head
and neck, and uses of several medication such as atropine, and
 Nicotine
Drugs affecting the • Nicotine is a stimulant and potent parasympathomimetic alkaloid that is naturally
Autonomic produced in the nightshade family of plants.
• It is used for smoking cessation to relieve withdrawal symptoms
Nervous System
• Nicotine acts as a receptor agonist at most nicotinic acetylcholine receptors (nAChRs),
Direct acting on nicotinic receptors (Nicotinic except at two nicotinic receptor subunits (nAChRα9 and nAChRα10) where it acts as a
agonists) receptor antagonist.
Nicotine
• Nicotine constitutes approximately 0.6–3.0% of the dry weight of tobacco
Lobeline

Nicotinic actions Major nicotinic actions.

Action

Lobeline
• Available as tablet form, for use as a smoking cessation aid
• application in the treatment of other drug addictions such as addiction to amphetamines,
cocaine, or alcohol. However, there is limited clinical evidence of any efficacy.

Drugs affecting the
Autonomic
Nervous System
Indirect acting cholinergic agonists
These are drugs which inhibit the Ach
Esterase enzyme to prolong the muscarinic
and nicotinic actions of Ach.
i- Reversible anticholinesterase
Physostigmine, Neostigmine
Edrophonium
Donepezil
ii- Irreversible anticholinesterase
• They reversible bind with cholinesterase
enzyme and impair hydrolysis of Ach. This
results in the accumulation of endogenous
Ach at the cholinergic nerve endings
(including both muscarinic and nicotinic
receptors).
• The result is stimulation of cholinergic
receptors (M and N) throughout the body.
Physostigmine
Pyridostigmine Intermediate acting
(Carbamates esters)
Neostigmine
Edrophonium Short acting (Alcohols)

Donepezil
Tacrine
Galantamine
 Muscarinic actions Nicotinic actions
CNS Excitation, convulsion, respiratory failure, coma only for lipid soluble
anticholinesterases physostigmine & phosphate ester except Ecothiophate.

Muscarinic
Eye Contraction of circular muscle of iris
(miosis)(M3)
Contraction of ciliary muscles for near
Vs. Nicotinic vision (M3)
Decrease in intraocular pressure
Actions
Heart bradycardia ( heart rate ) (M2)

endothelium Release of NO (EDRF)

Lung Constriction of bronchial smooth

muscles
Increase bronchial secretion M3
GIT Increased motility (peristalsis)
Increased secretion
Relaxation of sphincter M3

Urinary bladder Contraction of muscles

Relaxation of sphincter M3
Exocrine glands Increase of sweat, saliva, lacrimal,
bronchial, intestinal secretions M3

Neuromuscular Therapeutic dose: muscle contraction

junction Toxic dose: relaxation or paralysis.

Ganglia stimulation of sympathetic and

parasympathetic ganglia

Adrenal medulla release of catecholamines (EP & NEp).

 Physostigmine
Source Natural Alkaloid obtained from the
seeds of Calabar beans
Physostigmine Chemistry Has tertiary ammonium structure so it
is nonpolar
Vs. Neostigmine
Vs Absorption Completely absorbed from GIT
Pyridostigmine Distribution Cross BBB
Increase Ach peripherally and centrally
(Generalized action)
i- Reversible anticholinesterase
Carbamate esters Duration Duration of action 30-60 minutes
Action Muscarinic-> Mainly eye
Physostigmine, Neostigmine Nicotinic -> Muscle twitches
CNS effect because it crosses BBB and
Pyridostigmine: Similar to Neostigmine, But more increase Ach in the brain
selective, it increases the Ach at the motor end
plate (Neuromuscular junction) Phys may induce headache,
nervousness and convulsion (CNS
Excitatory effect)
binds to two sites of cholinesterase enzyme
Uses 1 Glaucoma
It is more selective on muscarinic
receptors. So it is used topically in the
form of eye drops, but pilocarpine is
more effective and potent
2Treatment of anticholinergic
overdose (like Atropine)
Neostigmine
Synthetic
Has quaternary ammonium structure so
it is more polar
Poorly absorbed from GIT
Do not Cross BBB
Increase Ach peripherally only
Duration of action 60-120 minutes
Muscarinic-> Mainly GIT and Urinary
tract
Nicotinic -> Muscle twitches
Neo may have greater effect on skeletal
muscle
No CNS effects
1- Myasthenia gravis
It is more selective to nicotinic receptors
2- Given with Atropine to block
muscarinic action
3- Used in non-obstructive urinary
retention and paralytic ileus
Note: Not used for the treatment of
anticholinergic overdose (like Atropine)
Glaucom
a
 Drug Actions Kinetics Uses
Physostigmine Physostigmine Nicotinic muscarinic
CNS
0.5-2 hours
Lipid soluble
Glaucoma
atropine toxicity
Vs. Neostigmine
Vs Neostigmine Nicotinic muscarinic 0.5-2 hours
polar
Myasthenia gravis
treatment
Pyridostigmine Paralytic ileus
i- Reversible anticholinesterase Urinary retention
Curare toxicity
Carbamate esters

Pyridostigmine Nicotinic muscarinic 3-6 hours Myasthenia gravis

Physostigmine, Neostigmine (more selective than polar treatment (without
Neostigmine) the need to use of
Pyridostigmine: Similar to Neostigmine, But more atropine)
selective, it increases the Ach at the motor end
plate (Neuromuscular junction)

binds to two sites of cholinesterase enzyme

 • Short-acting (20-30 min) reversible
anticholinesterase
• Polar (Alcohol) compound because it is
Edrophonium rapidly eliminated renally
• Available as I.V. only since it is not
absorbed
i- Reversible anticholinesterase orally
Alcohols • It is quaternary ammonium compound o, it
increases the level of Ach peripherally only
Edrophoniu
(More selective)
m
• Attach mainly to anionic site of cholinesterase
by weak hydrogen bond.

• Used for diagnosis of myasthenia gravis in

which rapid increase in muscle strength after
I.V. dose confirm the disease
• This test called (Tensilon test)

Please: Note that care must be taken since

excess drug induce cholinergic crisis. Atropine is
the antidote for it
 Donepezil
Drugs affecting the
Autonomic Anticholinesterase drugs.
Nervous System Given orally.
Used for treatment of dementia of Alzheimer’s disease.
i- Reversible anticholinesterase
n-benzylpiperidines Alzheimer’s Disease -> Neurodegeneration -> Neuronal loss -> Loss of
Donepezil Cholinergic fibers -> Dementia

Improve dementia by improving neuronal transmission -> increase Ach

levels in the synaptic cleft in muscarinic receptor of the cortex
Drugs affecting the
Autonomic
Nervous System
Indirect acting cholinergic agonists
These are drugs which inhibit the AchE
enzyme so prolong the muscarinic and
nicotinic actions of Ach.
ii- Irreversible anticholinesterase
Organophosphate
Phosphate esters
• Diazenone, Parathion, Malathion, Asuntol
• Ecothiophate – Isoflurophate
• Nerve gases as Sarin
All are synthetic compounds
• Very long duration of action
• Rapidly absorbed from all sites, even the intact skin
• Form very stable covalent bond with cholinesterase
• Widely distributed to all tissues including CNS (Cross BBB) causing
generalized cholinergic stimulation
• All phosphates are lipid soluble except Ecothiophate which is
polar.

Drugs affecting the
Autonomic
Nervous System
Indirect acting cholinergic agonists
These are drugs which inhibit the AchE
enzyme so prolong the muscarinic and
nicotinic actions of Ach.
ii- Irreversible anticholinesterase
Organophosphate
Mechanism of Action
• Organophosphate binds covalently
with cholinesterase enzyme forming
phosphorylated enzyme (PE)
• The PE slowly release an alkyl group
so, the bond between
organophosphate and the enzyme
become irreversible (This process
known as Aging)
• The enzyme is inactivated, and you
need a new enzyme so it can work
again
• Ach accumulate in the cholinergic
nerve endings (N and M) leading to
more activation of Ach receptor
• The result is potentiation of
cholinergic neurons throughout the
body

Drugs affecting the
Autonomic
Nervous System
Indirect acting cholinergic agonists
These are drugs which inhibit the AchE
enzyme so prolong the muscarinic and
nicotinic actions of Ach.
ii- Irreversible anticholinesterase
Organophosphate
Indication
• Some of them used as an insecticide
like; Diazenone, Parathion,
Malathion, Asuntol
• Ecothiophate and Isoflurophate
cause powerful miosis. So, it is used
in chronic glaucoma and other eye
condition like Accommodative
esotropia
• Binds to cholinesterase by strong
covalent bond
• Ecothiophate is not the first line
treatment since it has many side
effects mainly the risk of developing
cataracts

Drugs affecting the
Autonomic
Nervous System
Indirect acting cholinergic agonists
These are drugs which inhibit the AchE
enzyme so prolong the muscarinic and
nicotinic actions of Ach.
ii- Irreversible anticholinesterase
Organophosphate
Organophosphate toxicity
Organophosphates’ toxicity occurs when the body is exposed
to a toxic amount of them.
The patient is showing muscarinic and nicotinic symptoms:
• Muscarinic symptoms
Lacrimation, salivation, sweating
Miosis, bronchospasm, Increased GIT motility leading to
cramps, vomiting and diarrhea.
Sever bradycardia, hypotension.
• Nicotinic symptoms
Initial twitching of skeletal muscles, followed by muscle
weakness and paralysis.
• CNS effects
Convulsion, coma and respiratory failure.

Drugs affecting the
Autonomic
Nervous System
Indirect acting cholinergic agonists
These are drugs which inhibit the AchE
enzyme so prolong the muscarinic and
nicotinic actions of Ach.
ii- Irreversible anticholinesterase
Organophosphate
Organophosphate toxicity treatment and antidote
A- Atropine
To block muscarinic receptors actions (peripherally and
centrally)
Given I.V. or I.M. ( 2 mg /10 min) until pupil eye
dilation,
dry mouth, and pulse and the systolic BP are over 80.
B- Be Supportive to the patient
Support respiration by maintain patient airway, oxygen
supply and artificial respirator. Skin wash or Gastric
lavage to reduce exposure.
C- Cholinesterase reactivators (Oximes)
Pralidoxime (PAM) and Diacetyl Monoxime (DAM) they
act as cholinesterase reactivator. So, they can reactivate
the phosphorylated enzyme.
Effective in early stages only (within 12 hour of
exposure) given as I.V over 30 minutes
Act peripherally only, can not penetrate CNS
D- Diazepam
To reduce CNS effects (like convulsant)
 Side effects of ALL Cholinergic Agonists
Drugs affecting the
Autonomic Lacrimation, salivation, sweating
Nervous System Miosis, bronchospasm, Increased GIT motility
leading to cramps, vomiting and diarrhea.
Sever bradycardia, hypotension.
Direct cholinergic agonists

Indirect acting cholinergic Contraindication of ALL Cholinergic Agonists

agonists
These are drugs which inhibit the AchE • Bronchial asthma
enzyme so prolong the muscarinic and
nicotinic actions of Ach. • Peptic ulcer
i. Reversible anticholinesterase
• Obstruction of Urinary tract or GIT (tumor,
inflammation..etc.)
ii. Irreversible anticholinesterase • Bradycardia and hypotension
 Cholinergic Antagonists
Drugs affecting the • Drugs that binds to cholinergic receptors and prevent Ach from interacting on
these receptors. So, they produce an effect opposite to the effect produced by
Autonomic parasympathetic stimulation
Nervous System
• Called (Parasympatholytics, Cholinergic blockers, or Anticholinergic drugs)
Cholinergic Antagonists
Atropine
Scopolamine • Classified into:

A. Antimuscarinic agents: Drugs that selectively block muscarinic receptors to

prevent Ach from binding to these receptors (inhibit muscarinic action)

B. Ganglionic blocker: Drugs that selectively blocks nicotinic receptor on the

autonomic ganglia. Not that important clinically.

C. Neuromuscular-blocking agent: Interfere with the transmission of the

impulses to the skeletal muscle. These agents are used as skeletal muscle
relaxants and will be discussed later.
 Actions
• Block muscarinic receptors so, inhibit all
muscarinic actions
• Block some sympathetic nerves that are

Anti- cholinergic, such as those innervating sweat

glands
muscarinic • Do not block nicotinic receptors, the
agents antimuscarinic drugs have no action on the
skeletal muscles or autonomic ganglia

Examples: Atropine, Scopolamine

 Atropine
• It is a naturally occurring alkaloid obtained from Atropa
belladonna plant
• It binds muscarinic receptors and prevents Ach from binding

Atropin to those sites

• Tertiary amine, so it is relatively lipid - soluble and readily

e crosses membrane barriers

• Crosses the BBB so, it acts both centrally and peripherally
(Like atropine)

Actions:
CNS:
At higher than therapeutic doses, it causes CNS depression
characterized by:
• Sedation (by blocking the excitement effect of Ach in brain)
• Amnesia (by blocking the effect of Ach on M1 receptors that
are responsible for memory)
• Delirium and hallucination.
 Actions:
Peripheral:
General actions of atropine last about 4 hours, except when
placed topically in the eye, where the action may last for days.
1 - Eyes
Atropin • Atropine blocks M3 in the constrictor pupillae muscle of
the iris producing passive mydriasis (dilation of the pupil)
e and unresponsiveness to light.
• In addition, it increases the intra-ocular pressure (IOP).
• Atropine blocks M3 in ciliary muscles producing relaxation
and cycloplegia (inability to focus for near Vision).
• It also reduces the lacrimal secretion producing dryness of
the eyes (dry or sandy eyes).

Atropine may induce an acute attack of eye pain due to

sudden increases in eye pressure in individuals With
glaucoma
 Actions:
2 - Respiratory System
• Atropine blocks the muscarinic receptors in the smooth
muscle of the bronchioles (M3) producing
Atropin bronchodilatation.
• It reduces respiratory tract secretions (anti-secretory).

e 3 - GIT
• Blocks the muscarinic receptors in the GI smooth muscle
and relaxes the of stomach (anti-emetic) and intestine
(anti-spasmodic, spasmolytic) and constrict sphincters
• It reduces the salivary secretion leading to dryness of the
mouth (xerostomia).
• It also reduces the intestinal secretions (anti-secretory)
leading to constipation

HCl production is not significantly affected

 Actions:
4 - CVD
• Atropine produces contracting effects on the heart,
depending on the dose.
• Low doses of atropine block the presynaptic M1 receptors and
increases the release of Ach which decreases the heart rate
(bradycardia).
• High doses (1 mg or above) of atropine block M2 receptors on
Atropin the sinoatrial node and increases the heart rate (tachycardia)
No effect on blood pressure or blood vessels
e Atropine flushing occurs in atropine toxicity especially in children
because large dose of atropine induces direct vasodilation.
5 - Urinary tract
• Atropine blocks M3 and relaxes the smooth muscles and
constricts the sphincter of urinary bladder leading to urine
retention.
• Urine retention is disadvantage especially in elders With
benign prostatic hyperplasia.
6 – Sweat glands
• It blocks M3 and reduces sweating and increases body
temperature
• Inhibition of sweat secretions can elevate body
temperature,
which is dangerous in children and the elderly
(Atropine fever)
 Therapeutic Uses:
1- For eye examination :
• Used topically on the eye for eye examination (but causes
photophobia lasting for 7-10 days).
• Shorter-acting atropine substitutes; tropicamide and
Atropin cyclopentolate have largely replaced atropine because
their duration of action is shorter than that of atropine.
e Tropicamide and cyclopentolate:
• These agents are used similarly to atropine as
Ophthalmic solutions for mydriasis and cycloplegia.
• Their duration of action is shorter than that of
atropine.
• Tropicamide produces mydriasis for 6 hours, and
cyclopentolate for 24 hours.

NOTE:
Phenylephrine or similar alpha-adrenergic drugs are preferred
for pupillary dilation if cycloplegia is not required.
 Therapeutic Uses:
2- Bronchial asthma and chronic obstructive pulmonary
disease (COPD) :
• Atropine substitutes; ipratropium and tiotropium are
preferred than atropine for treatment of bronchial asthma
and COPD
Atropin Ipratropium and tiotropium:
• Both are quaternary derivatives of atropine used by
e inhalation
• Acts on M3 muscarinic receptors located in the airways
to produce smooth muscle relaxation and
bronchodilation
• They have very few anti-cholinergic effects outside the
lungs because they are poorly absorbed (Quaternary
amine) and rapidly metabolized
• The inhalation route of administration has the advantage
of maximal concentration at the bronchial target tissue
with reduced systemic effects.
• Tiotropium is administered once daily, a major advantage
over ipratropium, which requires dosing up to four times
daily.
 Therapeutic Uses:
3- Pre-operative medication (especially before volatile
anesthesia):
• To reduces salivary and respiratory tract secretions during
surgery, so avoid suffocation.
Atropin • To prevents nausea and vomiting during surgery
• To dilates the bronchi and bronchioles during surgery
• To blocks vagal stimulation during induction of anesthesia
e so protects against bronchoconstriction and bradycardia

Notes:
• Volatile irritant anesthetics markedly increased airway
secretions and were associated with occurrence of
laryngospasm
• Spasmodic colic (intestinal and renal colic)
• Hyoscine butyl bromide (Buscopan) is preferred than
atropine for treatment of spasmodic colic
• Used as antidote in case of toxicity by organophosphate
insecticides and some types of mushroom poisoning.
 Scopolamine (Hyoscine)
• It is an alkaloid from Solanaceae family of plants, such as
Datura
• Tertiary amine, so it is relatively lipid - soluble and readily

Scopolamin crosses membrane barriers

• Crosses the BBB so, it acts both centrally and peripherally
(Like atropine)
e Actions:
CNS:
MORE marked central effects with longer duration of action than
atropine.
• Like atropine, scopolamine produces sedation, but at higher
doses it can produces excitement instead
• produces significant amnesia (short-term loss of memory) for
the events associated with surgery and obstetric delivery, an
adverse effect that was considered desirable.
Peripheral:
Produces peripheral effects similar to those seen in atropine
 Therapeutic use of
Prevention of motion sickness (most effective anti-motion
sickness)

Scopolamin Sedation
To
e Notes:
blocking
•short-
As With all drugs used for motion sickness, scopolamine is
much more effective prophylactically than for treating
termmotion sickness once it occurs.
memory
• It can be given by injection or by mouth or as a trans-dermal
because
patch. The patch formulation produces significant blood
levels over 48-72 H
it blocks
• Useful doses by any route usually cause significant sedation
M1 and dry mouth.
receptor
• The amnesic action of scopolamine makes it an important
s adjunct drug in anesthetic procedures
• May produce euphoria and is susceptible to abuse
Side effects of
anti- cholinergic
drugs (Atropine - Side effects of anticholinergic agents:
Scopolamine) • Photophobia (due to dilated pupils)
• Dryness of the mouth (xerostomia)
• Urinary retention