Antagonis Kolinergik

HERNI SUPRAPTI
cholinergic antagonists

Drugs that bind to cholinergic receptors (muscarinic

and/or nicotinic), but do not trigger the usual
intracellular response
3 subclasses of cholinergic antagonists

1. Muscarinic blockers
2. Neuromuscular blocking agents
inhibit the efferent impulses to skeletal muscle via the
nicotinic muscle receptor (NM)
3. Ganglionic blockers
inhibit the nicotinic neuronal receptor (NN) of both
parasympathetic and sympathetic ganglia
MUSCARINIC ANTAGONISTS

1. Atropine (prototype)
2. Scopolamine
3. Homatropine
4. Cyclopentolate
5. Tropicamide
6. Pirenzepine
other drugs that exhibit antimuscarinic properties

anti-Parkinsons (benztropine),
anti- depressants (Thorazine),
antihistamines (diphenhydramine),
anti-asthmatics (ipratropium)
atropine

Atropine comes from the plant Atropa belladonna

and is known as a belladonna alkaloid.

Belladonna in Latin means pretty lady.

During the Roman era the plant was used to dilate

women's pupils, which was considered to be
attractive.
atropine

is a naturally occurring tropane alkaloid extracted

from

deadly nightshade (Atropa belladonna),

Jimson weed (Datura stramonium),
mandrake (Mandragora officinarum) and
other plants of the family Solanaceae.
atropine

It is a competitive antagonist for the muscarinic

acetylcholine receptor types M1, M2, M3, M4 and
M5.

It is classified as an anticholinergic drug (

parasympatholytic).
mechanism of action
It causes reversible, nonselective blockade of muscarinic
receptors.

What agent can be used to counteract the effects of

atropine?
High concentrations of acetylcholine or an equivalent
muscarinic agonist

Does this drug cross the blood-brain barrier?

No. Atropine does not readily cross the blood-brain barrier.
What are the pharmacologic actions of atropine?

CNS
Cardiovascular system
Gastrointestinal system
Pulmonary system
Urinary system
Eye
Sweat glands
You will more readily remember the actions of atropine
if you recognize that blocked cholinergic receptors
result in an unopposed sympathetic response.
CNS
At toxic doses can cause restlessness, hallucinations, and delusions
Cardiovascular system
At low doses, atropine reduces heart rate through central
stimulation of the vagus nucleus.
At high doses, atropine blocks muscarinic receptors of the heart
and thus induces tachycardia.
Gastrointestinal system
Reduces salivary gland secretion and GI motility
Pulmonary system
Reduces bronchial secretions and stimulates bronchodilation
Urinary system
Blocks muscarinic receptors in the bladder wall, which results
in bladder wall relaxation
Eye
Causes paralysis of the sphincter muscle of the iris and ciliary
muscle of the lens, resulting in mydriasis and cycloplegia.
Mydriasis = dilation
Sweat glands
Suppresses sweating, especially in children
therapeutic uses of atropine

Bradycardia
Mydriasis and cycloplegia
beneficial when a thorough fundus examination or an accurate
refraction is required
Gastrointestinal and bladder spasms
Organophosphate poisoning
When is the use of atropine to effect mydriasis and
cycloplegia contraindicated?

Do not dilate the eyes of a patient who has narrow-angle

glaucoma, because this may result in an acute crisis due to
closure of the canal of Schlemm.
How long is atropine's duration of action?
Approximately 4 hours, except when it is placed in the eye,
where it usually lasts about 14 days

How is atropine absorbed and excreted?

It is well absorbed from the gastrointestinal system and
conjunctival membrane. It is excreted through both hepatic
metabolism and renal filtration.
 the toxic effects of this drug

Toxic Effect: Mnemonic:

Dry mouth
Inhibition of sweating, especially in young "Dry as a bone
children
Tachycardia and cutaneous vasodilation "Hot as a hare"
Blurring of vision
Hallucinations and delirium

"Red as a beet

"Blind as a bat
"Mad as a hatter"
SCOPOLAMINE
What is the classification of scopolamine?
Like atropine, this drug is a belladonna alkaloid.

What is its mechanism of action?

Nonselective competitive blockade of muscarinic receptors

How is scopolamine used therapeutically?

Prevention of motion sickness "lotion for motion"
How does this drug differ from atropine?
It has a longer duration of action and more potent CNS effects.

What is scopolamine's route of administration?

It is often given transdermally.

Are there any adverse effects?

Yessimilar to those of atropine:
"Dry as a bone, red as a beet, hot as a hare, blind as a bat, mad as a
hatter."
 HOMATROPINE,
CYCLOPENTOLATE, AND
TROPICAMIDE
What are these drugs used for?
In ophthalmology, they are given topically for mydriasis and
cycloplegia

What are the adverse effects?

Similar to those for atropine but much milder
PIRENZEPINE

What is it?
A selective M1 muscarinic inhibitor

How is this drug used?

For treating gastric ulcers

What are the adverse effects?

Similar to those for atropine
NEUROMUSCULAR
BLOCKING AGENTS
2 major subdivisions of neuromuscular agents.

1. Nondepolarizing blocking agents

2. Depolarizing blocking agents

NONDEPOLARIZING BLOCKING AGENTS

1. Tubocurarineprototype

2. Pancuronium
longer duration of action than tubocurarine
3. Atracurium

4. Vecuronium
What is their mechanism of action?
These drugs competitively block cholinergic transmission at the
nicotinic receptors by preventing the binding of acetylcholine to its
receptor.

What is the therapeutic use of these agents?

They are used as adjuvant drugs for anesthesiathey promote
muscle relaxation.

Are all muscles equally affected?

No. The muscles of the eye and face are affected first, whereas the
respiratory muscles are affected last.
What is the route of administration?
All neuromuscular junction blockers must be given IV because oral
absorption is poor.

What are the adverse effects?

Bronchoconstriction and hypotension, caused by histamine release

What can be used to counteract the effects of these

drugs?
Because neuromuscular junction blockers are competitive inhibitors,
their actions can be reversed with edrophonium or neostigmine.
DEPOLARIZING NEUROMUSCULAR
BLOCKING AGENTS

SUCCINYLCHOLINE
mechanism of action

Phase 1
Succinylcholine binds to the nicotinic receptor, opens the Na+
channels, and causes membrane depolarization, which results in
transient fasciculations. Flaccid paralysis will follow in a few
minutes, because succinylcholine is resistant to acetylcholinesterase
and will cause prolonged depolarization of the membrane.

Phase II
Eventually the membrane will at least partially repolarize. However,
the receptor is now desensitized to acetylcholine, thus preventing
the formation of further action potentials. In other words,
succinylcholine is now acting in a manner similar to tubocurarine .
What is the duration of action?
3 to 6 minutes if given as a single dose

What substance metabolizes succinylcholine?

Plasma cholinesterase

How is succinylcholine used clinically?

As an adjuvant to general anesthesia
To facilitate rapid intubation
adverse effects

Bronchoconstriction caused by histamine release

Hypotension
Arrhythmias
Apnea due to respiratory paralysis
Malignant hyperthermia
How is malignant hyperthermia treated?

Dantrolene is used. It blocks the release of Ca2+ from the

sarcoplasmic reticulum, which subsequently reduces skeletal
muscle contraction.
Do neuromuscular blocking agents block autonomic
ganglia as well?

In general, no. The skeletal muscle end plate and autonomic

ganglia use different subtypes of nicotinic receptors.
Tubocurarine can, however, produce a small amount of
ganglionic blockade.
GANGLIONIC BLOCKERS

1. Nicotine
2. Hexamethonium
3. Mecamylamine
4. Trimethaphan
What exactly do these drugs do?

Ganglionic inhibitors compete with acetylcholine to bind with

nicotinic receptors of both parasympathetic and sympathetic
ganglia.
mechanism of action

Ganglionic blockers can be divided into two groups:

1. Drugs such as nicotine, which initially stimulate

the ganglia and then block them because of a
persistent depolarization

2. Drugs such as hexamethonium, mecamylamine,

and trimethaphan, which block ganglia without any
prior stimulation
the physiologic effects

The physiologic effects of ganglionic blockers can be

predicted if you remember which division of the autonomic
nervous system exercises dominant control of the organ in
question:
Heart
Arterioles and veins
Eye
GI system
Urinary system
Sweat glands
Heart
Tachycardia results because the parasympathetic system is normally dominant on
the heart.
Arterioles and veins
Vasodilation, increased peripheral blood (sympathetic normally dominant)
Eye
Cycloplegia, mydriasis (parasympathetic normally dominant)
GI system
Reduced motility; diminished gastric and pancreatic - secretions (parasympathetic
normally dominant)
Urinary system
Urinary retention (parasympathetic normally dominant)
Sweat glands
Reduced sweating (sympathetic normally dominant)
What is the therapeutic use?
Because they lack selectivity, the ganglionic blockers are very
rarely used clinically. In the past, these drugs were used in
hypertensive emergencies.

What are the adverse effects?

The toxicities of ganglionic blockers are identical to their
physiologic effects, which have been described above.
Describe the effects of atropine on the
major organ systems (CNS, eye, heart,
vessels, bronchi, gut, genitourinary tract,
exocrine glands, skeletal muscle).
atropine

is a naturally occurring tropane alkaloid extracted from

deadly nightshade (Atropa belladonna),

Jimson weed (Datura stramonium),

mandrake (Mandragora officinarum) and other plants of the family Solanaceae.

It is a secondary metabolite of these plants and serves as a drug with a

wide variety of effects.
It is a competitive antagonist for the muscarinic acetylcholine receptor
types M1, M2, M3, M4 and M5.
It is classified as an anticholinergic drug (parasympatholytic).
The species name "belladonna" comes from the original use of deadly
nightshade as a way of dilating women's pupils to make them beautiful.
Both atropine and the genus name for deadly nightshade derive from
Atropos, one of the three Fates who, according to Greek mythology, chose
how a person was to die.