Antagonis Kolinergik 7 April 14

5/24/2018 Antagonis Kolinergik 7 April 14

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Antagonis

KolinergikHerni Suprapti


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cholinergic antagonists

O Drugs that bind to cholinergic receptors

(muscarinic and/or nicotinic), but do nottrigger the usual intracellular response


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3 subclasses of cholinergic antagonists

1. Muscarinic blockers

2. Neuromuscular blocking agentsO 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 andsympathetic ganglia


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MUSCARINIC ANTAGONISTS

O 1. Atropine (prototype)

O 2. ScopolamineO 3. Homatropine

O 4. Cyclopentolate

O 5. Tropicamide

O 6. Pirenzepine


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other drugs that exhibit

antimuscarinic properties

O anti-Parkinsons (benztropine),

O anti- depressants (Thorazine),O antihistamines (diphenhydramine),

O anti-asthmatics (ipratropium)


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atropine

O Atropine comes from the plant Atropabelladonna and is known as a belladonna

alkaloid.

O Belladonna in Latin means pretty lady.

O During the Roman era the plant was used todilate women's pupils, which was consideredto be attractive.


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atropineO 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.
http://en.wikipedia.org/wiki/Tropane_alkaloidhttp://en.wikipedia.org/wiki/Deadly_nightshadehttp://en.wikipedia.org/wiki/Datura_stramoniumhttp://en.wikipedia.org/wiki/Mandrake_(plant)http://en.wikipedia.org/wiki/Solanaceaehttp://en.wikipedia.org/wiki/Solanaceaehttp://en.wikipedia.org/wiki/Mandrake_(plant)http://en.wikipedia.org/wiki/Datura_stramoniumhttp://en.wikipedia.org/wiki/Deadly_nightshadehttp://en.wikipedia.org/wiki/Tropane_alkaloidhttp://en.wikipedia.org/wiki/Tropane_alkaloidhttp://en.wikipedia.org/wiki/Tropane_alkaloid


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atropineO It is a competitive antagonistfor the

muscarinic acetylcholine receptortypes

M1, M2, M3, M4 and M5.

O It is classified as an anticholinergic drug

(parasympatholytic).
http://en.wikipedia.org/wiki/Competitive_antagonisthttp://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptorhttp://en.wikipedia.org/wiki/Anticholinergic_drughttp://en.wikipedia.org/wiki/Parasympatholytichttp://en.wikipedia.org/wiki/Parasympatholytichttp://en.wikipedia.org/wiki/Anticholinergic_drughttp://en.wikipedia.org/wiki/Anticholinergic_drughttp://en.wikipedia.org/wiki/Anticholinergic_drughttp://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptorhttp://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptorhttp://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptorhttp://en.wikipedia.org/wiki/Competitive_antagonist


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O mechanism of action

O It causes reversible, nonselective blockadeof 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.


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What are the pharmacologic

actions of atropine?O CNS

O Cardiovascular system

O Gastrointestinal system

O Pulmonary systemO Urinary system

O Eye

O Sweat glands

O You will more readily remember the actions ofatropine if you recognize that blockedcholinergic receptors result in an unopposedsympathetic response.


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O CNSO At toxic doses can cause restlessness,

hallucinations, and delusions

O Cardiovascular systemO 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 inducestachycardia.

O Gastrointestinal systemO Reduces salivary gland secretion and GI

motilityO Pulmonary system

O Reduces bronchial secretions and stimulatesbronchodilation


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O

Urinary systemO 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 glandsO Suppresses sweating, especially in

children


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therapeutic uses of atropine

O Bradycardia

O Mydriasis and cycloplegiaO beneficial when a thorough fundus

examination or an accurate refraction is

required

O Gastrointestinal and bladder spasmsO Organophosphate poisoning


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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.


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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.


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the toxic effects of this drug

Toxic Effect: Mnemonic:

O Dry mouth

O Inhibition of sweating,especially in youngchildren

O Tachycardia andcutaneous vasodilation

O Blurring of vision

O Hallucinations anddelirium

O "Dry as a boneO "Hot as a hare"

O "Red as a beet

O "Blind as a bat

O "Mad as a hatter"


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SCOPOLAMINE


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O What is the classification of scopolamine?

O Like atropine, this drug is a belladonnaalkaloid.

O What is its mechanism of action?

O Nonselective competitive blockade ofmuscarinic receptors

O How is scopolamine used therapeutically?

O Prevention of motion sickness"lotion for

motion"


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O How does this drug differ from atropine?

O It has a longer duration of action and morepotent 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."


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HOMATROPINE,CYCLOPENTOLATE, AND

TROPICAMIDE


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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


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PIRENZEPINEO 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


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NEUROMUSCULAR

BLOCKING AGENTS


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2 major subdivisions of

neuromuscular agents

O 1. Nondepolarizing blocking agents

O 2. Depolarizing blocking agents


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NONDEPOLARIZING

BLOCKING AGENTS

O 1. Tubocurarineprototype

O 2. Pancuronium

O longer duration of action than tubocurarine

O 3. Atracurium

O 4. Vecuronium


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O What is their mechanism of action?

O These drugs competitively block cholinergictransmission at the nicotinic receptors bypreventing the binding of acetylcholine to itsreceptor.

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 areaffected first, whereas the respiratory musclesare affected last.


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O What is the route of administration?

O All neuromuscular junction blockers must begiven IV because oral absorption is poor.


O Bronchoconstriction and hypotension, caused

by histamine release

O What can be used to counteract the effects ofthese drugs?

O Because neuromuscular junction blockers are

competitive inhibitors, their actions can bereversed with edrophonium or neostigmine.


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DEPOLARIZINGNEUROMUSCULAR

BLOCKING AGENTS

Succinylcholine


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mechanism of actionO Phase 1

O Succinylcholine binds to the nicotinic receptor, opensthe Na+ channels, and causes membranedepolarization, which results in transient fasciculations.

Flaccid paralysis will follow in a few minutes, becausesuccinylcholine is resistant to acetylcholinesterase andwill cause prolonged depolarization of the membrane.

O Phase IIO Eventually the membrane will at least partially

repolarize. However, the receptor is now desensitized to

acetylcholine, thus preventing the formation of furtheraction potentials. In other words, succinylcholine is nowacting in a manner similar to tubocurarine .


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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


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adverse effects

O Bronchoconstriction caused by histamine

releaseO Hypotension

O Arrhythmias

O Apnea due to respiratory paralysis

O Malignant hyperthermia


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O How is malignant hyperthermia treated?

O Dantrolene is used. It blocks the release of

Ca2+ from the sarcoplasmic reticulum,

which subsequently reduces skeletalmuscle contraction.


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O

Do neuromuscular blocking agents blockautonomic 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.


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GANGLIONIC BLOCKERS

O 1. Nicotine

O 2. HexamethoniumO 3. Mecamylamine

O 4. Trimethaphan


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O What exactly do these drugs do?

O Ganglionic inhibitors compete with

acetylcholine to bind with nicotinicreceptors of both parasympathetic and

sympathetic ganglia.


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mechanism of actionO Ganglionic blockers can be divided into two

groups:

O 1. Drugs such as nicotine, which initiallystimulate the ganglia and then block thembecause of a persistent depolarization

O

2. Drugs such as hexamethonium,mecamylamine, and trimethaphan, whichblock ganglia without any prior stimulation


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the physiologic effectsThe physiologic effects of ganglionic blockerscan be predicted if you remember which

division of the autonomic nervous systemexercises dominant control of the organ inquestion:

O Heart

O Arterioles and veins

O Eye

O GI system

O Urinary system

O Sweat glands


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O HeartO Tachycardia results because the parasympathetic

system is normally dominant on the heart.O Arterioles and veins

O Vasodilation, increased peripheral blood (sympatheticnormally dominant)

O EyeO Cycloplegia, mydriasis (parasympathetic normally

dominant)O GI system

O Reduced motility; diminished gastric and pancreatic -secretions (parasympathetic normally dominant)

O Urinary systemO Urinary retention (parasympathetic normally dominant)

O

Sweat glandsO Reduced sweating (sympathetic normally dominant)


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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 The toxicities of ganglionic blockers are

identical to their physiologic effects, which

have been described above.


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Describe the effects ofatropine on the major organ

systems (CNS, eye, heart,vessels, bronchi, gut,genitourinary tract, exocrine

glands, skeletal muscle).


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atropineO is a naturally occurring tropane alkaloidextracted from

O deadly nightshade(Atropa belladonna),

O Jimson weed(Datura stramonium),

O mandrake(Mandragora officinarum) and other plants of the familySolanaceae.

O It is a secondary metaboliteof these plants and serves as a drugwith a wide variety of effects.

O It is a competitive antagonistfor the muscarinic acetylcholinereceptortypes 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 ofdeadly nightshade as a way of dilating women's pupils to makethem beautiful.

O Bothatropineand the genus name for deadly nightshade derivefromAtropos, one of the three Fateswho, according to Greekmythology, chose how a person was to die.
http://en.wikipedia.org/wiki/Tropane_alkaloidhttp://en.wikipedia.org/wiki/Deadly_nightshadehttp://en.wikipedia.org/wiki/Datura_stramoniumhttp://en.wikipedia.org/wiki/Solanaceaehttp://en.wikipedia.org/wiki/Solanaceaehttp://en.wikipedia.org/wiki/Solanaceaehttp://en.wikipedia.org/wiki/Secondary_metabolitehttp://en.wikipedia.org/wiki/Drughttp://en.wikipedia.org/wiki/Competitive_antagonisthttp://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptorhttp://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptorhttp://en.wikipedia.org/wiki/Anticholinergic_drughttp://en.wikipedia.org/wiki/Parasympatholytichttp://en.wikipedia.org/wiki/Atroposhttp://en.wikipedia.org/wiki/Moiraihttp://en.wikipedia.org/wiki/Atroposhttp://en.wikipedia.org/wiki/Moiraihttp://en.wikipedia.org/wiki/Moiraihttp://en.wikipedia.org/wiki/Atroposhttp://en.wikipedia.org/wiki/Parasympatholytichttp://en.wikipedia.org/wiki/Anticholinergic_drughttp://en.wikipedia.org/wiki/Anticholinergic_drughttp://en.wikipedia.org/wiki/Anticholinergic_drughttp://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptorhttp://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptorhttp://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptorhttp://en.wikipedia.org/wiki/Muscarinic_acetylcholine_receptorhttp://en.wikipedia.org/wiki/Competitive_antagonisthttp://en.wikipedia.org/wiki/Drughttp://en.wikipedia.org/wiki/Secondary_metabolitehttp://en.wikipedia.org/wiki/Solanaceaehttp://en.wikipedia.org/wiki/Mandrake_(plant)http://en.wikipedia.org/wiki/Datura_stramoniumhttp://en.wikipedia.org/wiki/Deadly_nightshadehttp://en.wikipedia.org/wiki/Tropane_alkaloidhttp://en.wikipedia.org/wiki/Tropane_alkaloidhttp://en.wikipedia.org/wiki/Tropane_alkaloid

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Antagonis Kolinergik 7 April 14