Antagonis

Kolinergik
Herni Suprapti
cholinergic antagonists

O 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
O inhibit the efferent impulses to skeletal
muscle via the nicotinic muscle receptor
(NM)
3. Ganglionic blockers
O inhibit the nicotinic neuronal receptor
(NN) of both parasympathetic and
sympathetic ganglia

MUSCARINIC ANTAGONISTS

O 1. Atropine (prototype)
O 2. Scopolamine
O 3. Homatropine
O 4. Cyclopentolate
O 5. Tropicamide
O 6. Pirenzepine

other drugs that exhibit
antimuscarinic properties

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

atropine

O Atropine comes from the plant Atropa
belladonna and is known as a belladonna
alkaloid.

O Belladonna in Latin means pretty lady.

O During the Roman era the plant was used to
dilate women's pupils, which was considered
to be attractive.

atropine
O is a naturally occurring tropane alkaloid
extracted from
O deadly nightshade (Atropa belladonna),
O Jimson weed (Datura stramonium),
O mandrake (Mandragora officinarum) and
O other plants of the family Solanaceae.

atropine
O It is a competitive antagonist for the
muscarinic acetylcholine receptor types
M1, M2, M3, M4 and M5.

O It is classified as an anticholinergic drug
(parasympatholytic).
O mechanism of action
O It causes reversible, nonselective blockade
of muscarinic receptors.

O What agent can be used to counteract the
effects of atropine?
O High concentrations of acetylcholine or an
equivalent muscarinic agonist

O Does this drug cross the blood-brain
barrier?
O No. Atropine does not readily cross the
blood-brain barrier.

What are the pharmacologic
actions of atropine?
O CNS
O Cardiovascular system
O Gastrointestinal system
O Pulmonary system
O Urinary system
O Eye
O Sweat glands
O You will more readily remember the actions of
atropine if you recognize that blocked
cholinergic receptors result in an unopposed
sympathetic response.

O CNS
O At toxic doses can cause restlessness,
hallucinations, and delusions
O Cardiovascular system
O At low doses, atropine reduces heart rate
through central stimulation of the vagus
nucleus.
O At high doses, atropine blocks muscarinic
receptors of the heart and thus induces
tachycardia.
O Gastrointestinal system
O Reduces salivary gland secretion and GI
motility
O Pulmonary system
O Reduces bronchial secretions and stimulates
bronchodilation

O Urinary system
O Blocks muscarinic receptors in the bladder
wall, which results in bladder wall
relaxation
O Eye
O Causes paralysis of the sphincter muscle
of the iris and ciliary muscle of the lens,
resulting in mydriasis and cycloplegia.
O Mydriasis = dilation
O Sweat glands
O Suppresses sweating, especially in
children
therapeutic uses of atropine

O Bradycardia
O Mydriasis and cycloplegia
O beneficial when a thorough fundus
examination or an accurate refraction is
required
O Gastrointestinal and bladder spasms
O Organophosphate poisoning


O When is the use of atropine to effect
mydriasis and cycloplegia
contraindicated?

O 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.

O How long is atropine's duration of action?
O Approximately 4 hours, except when it is
placed in the eye, where it usually lasts
about 14 days

O How is atropine absorbed and excreted?
O 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:
O Dry mouth

O Inhibition of sweating,
especially in young
children
O Tachycardia and
cutaneous vasodilation
O Blurring of vision
O Hallucinations and
delirium

O "Dry as a bone
O "Hot as a hare"

O "Red as a beet

O "Blind as a bat
O "Mad as a hatter"

SCOPOLAMINE
O What is the classification of scopolamine?
O Like atropine, this drug is a belladonna
alkaloid.

O What is its mechanism of action?
O Nonselective competitive blockade of
muscarinic receptors

O How is scopolamine used therapeutically?
O Prevention of motion sickness "lotion for
motion"



O How does this drug differ from atropine?
O It has a longer duration of action and more
potent CNS effects.

O What is scopolamine's route of
administration?
O It is often given transdermally.

O Are there any adverse effects?
O Yessimilar to those of atropine:
O "Dry as a bone, red as a beet, hot as a hare,
blind as a bat, mad as a hatter."
HOMATROPINE,
CYCLOPENTOLATE, AND
TROPICAMIDE

O What are these drugs used for?
O In ophthalmology, they are given topically
for mydriasis and cycloplegia

O What are the adverse effects?
O Similar to those for atropine but much
milder

PIRENZEPINE
O What is it?
O A selective M1 muscarinic inhibitor

O How is this drug used?
O For treating gastric ulcers

O What are the adverse effects?
O Similar to those for atropine

NEUROMUSCULAR
BLOCKING AGENTS
2 major subdivisions of
neuromuscular agents


O 1. Nondepolarizing blocking agents

O 2. Depolarizing blocking agents

NONDEPOLARIZING
BLOCKING AGENTS

O 1. Tubocurarineprototype

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

O 4. Vecuronium

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

O What is the therapeutic use of these agents?
O They are used as adjuvant drugs for
anesthesiathey promote muscle relaxation.

O Are all muscles equally affected?
O No. The muscles of the eye and face are
affected first, whereas the respiratory muscles
are affected last.

O What is the route of administration?
O All neuromuscular junction blockers must be
given IV because oral absorption is poor.

O What are the adverse effects?
O Bronchoconstriction and hypotension, caused
by histamine release

O What can be used to counteract the effects of
these drugs?
O Because neuromuscular junction blockers are
competitive inhibitors, their actions can be
reversed with edrophonium or neostigmine.

DEPOLARIZING
NEUROMUSCULAR
BLOCKING AGENTS

Succinylcholine

mechanism of action
O Phase 1
O 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.

O Phase II
O 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 .

O What is the duration of action?
O 3 to 6 minutes if given as a single dose

O What substance metabolizes
succinylcholine?
O Plasma cholinesterase

O How is succinylcholine used clinically?
O As an adjuvant to general anesthesia
O To facilitate rapid intubation

adverse effects

O Bronchoconstriction caused by histamine
release
O Hypotension
O Arrhythmias
O Apnea due to respiratory paralysis
O Malignant hyperthermia


O How is malignant hyperthermia treated?

O Dantrolene is used. It blocks the release of
Ca2+ from the sarcoplasmic reticulum,
which subsequently reduces skeletal
muscle contraction.

O Do neuromuscular blocking agents block
autonomic ganglia as well?

O In general, no. The skeletal muscle end
plate and autonomic ganglia use different
subtypes of nicotinic receptors.
O Tubocurarine can, however, produce a
small amount of ganglionic blockade.

GANGLIONIC BLOCKERS

O 1. Nicotine
O 2. Hexamethonium
O 3. Mecamylamine
O 4. Trimethaphan


O What exactly do these drugs do?

O Ganglionic inhibitors compete with
acetylcholine to bind with nicotinic
receptors of both parasympathetic and
sympathetic ganglia.

mechanism of action

O Ganglionic blockers can be divided into two
groups:

O 1. Drugs such as nicotine, which initially
stimulate the ganglia and then block them
because of a persistent depolarization

O 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:
O Heart
O Arterioles and veins
O Eye
O GI system
O Urinary system
O Sweat glands
O Heart
O Tachycardia results because the parasympathetic
system is normally dominant on the heart.
O Arterioles and veins
O Vasodilation, increased peripheral blood (sympathetic
normally dominant)
O Eye
O Cycloplegia, mydriasis (parasympathetic normally
dominant)
O GI system
O Reduced motility; diminished gastric and pancreatic -
secretions (parasympathetic normally dominant)
O Urinary system
O Urinary retention (parasympathetic normally dominant)
O Sweat glands
O Reduced sweating (sympathetic normally dominant)

O What is the therapeutic use?
O Because they lack selectivity, the
ganglionic blockers are very rarely used
clinically. In the past, these drugs were
used in hypertensive emergencies.

O What are the adverse effects?
O 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
O is a naturally occurring tropane alkaloid extracted from
O deadly nightshade (Atropa belladonna),
O Jimson weed (Datura stramonium),
O mandrake (Mandragora officinarum) and other plants of the family
Solanaceae.
O It is a secondary metabolite of these plants and serves as a drug
with a wide variety of effects.
O It is a competitive antagonist for the muscarinic acetylcholine
receptor types M1, M2, M3, M4 and M5.

O It is classified as an anticholinergic drug (parasympatholytic).
O The species name "belladonna" comes from the original use of
deadly nightshade as a way of dilating women's pupils to make
them beautiful.
O 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.