Download - Anti- Cholinergics
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ANTI-CHOLINERGICSAsmah Nasser, M.D.
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ANTI-CHOLINERGICS
Cholinergic blockers( Anti-cholinergics or parasympatholytics) - class of drugs that block the actions of acetylcholine in the PSNS
Cholinergic blockers allow the SNS to dominate and, therefore, have many of the same effects as the adrenergics.
Muscarinic receptor blockers
Nicotinic receptor blockers
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M1 Secretory glands
salivation, stomach acid, sweating, lacrimation
M2 Heart Decreases heart rate bradycardia
M3 Smooth muscle (GI/GU/Resp)
Contraction of smooth muscles (some) diarrhea, bronchospasm, urination
M3 Pupil and ciliary muscle
Contracts Miosis
Increased flow of aqueous humor
Nm Skeletal muscle end plate
Contraction of skeletal muscle
Nn Autonomic ganglia, Adrenal Medulla
Secretion of Epinephrine
Controls ANS
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WHAT ARE THE DRUG TARGETS?
Block/Antagonize Muscuranic Receptors Prevent the release of acetylcholine Prevent formation of acetylcholine Deplete acetyl choline storage
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MUSCARINIC RECEPTOR BLOCKERS
1.Natural alkaloids:
Atropine, Scopolamine
2.Semi synthetic drugs :
Homoatropine, tropicamide, (short
acting)
Benztropine, ipratropium
glycopyrrolate, Dicyclomaine
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ATROPINE
Muscarinic receptor blocker Not hydrolyzed by cholinesterase, long
duration of action Actions of Atropine:
1. Decreased salivary, bronchial and sweat secretion
2. Mydriasis and cyloplegia (loss of accommodation reflex)
3. Tachycardia
4. Constipation
5. Urinary retention
6. Excitation /hallucinations
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USES OF ATROPINE
Muscuranic Blocker
To produce mydriasis in refraction error
testing (short acting preparations of atropine
are preferred)
To treat Heart block, Bradycardia
To treat Cholinesterase inhibitors /
Oragnaophosphate (OP)pesticides poisoning
Anti-Diarrheal agent
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ATROPINE
Contrindications of Atropine: Glaucoma (closed angle) Urinary retention Benign prostatic hypertrophy Paralytic Ileus Myasthenia Gravis
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OTHER MUSCARINIC BLOCKERS
Tropicamide: which acts for 4 hours is
preferred to produce mydriasis and
cycloplegia in refraction error testing and
fundoscopy
Benztropine (drug of choice) for treatment
of drug-induced Parkinsonism
Ipratropium bromide: Bronchial asthama
Scopolamine: to prevent Motion sickness
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SCOPOLAMINE
Competitive Muscuranic receptor antagonist M1 > M2 and M3 Reduces Nausea Uses: Prevent sea sickness, used in motion
sickness, nausea, etc Used in a transdermal patch because of CNS
side effects
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IPRATROPIUM BROMIDE
Muscuranic Anatagnist Blocks M3 (for smooth muscle contraction) If used inhaled, will prevent bronchospams
bronchodilation Decreases the secretions made in the
respiratory mucosa Uses: Asthma
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NICOTINIC RECEPTOR BLOCKERS
There are 2 subtypes of Niotinic Receptors: Nn and Nm Nn is found in nerves, at the ganglion Nm is found on muscles.
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NICOTINIC RECEPTOR BLOCKERS
Ganglionic blocking drugs: Trimethaphen
Neuromuscular blockers :
A.Nondepolarizing: D-tubocurarine , Atracurium
B.Depolarizing: Succinylcholine
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GANGLIONIC BLOCKING DRUGS
Blocks the Sympathetic and Parasympathetic ANS.
Effects are dependant on the organ sympathetic or
parasympathetic activity in that organ is reduced
Side effects are combined with both Symapathetic
and Parasynmpathetic Symptoms (depends on what
tone that the organ is predominantly supplied by)
Hexamethonium : Not used
Trimethaphen: Used to treat severe hypertensive
crises
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GANGLIONIC BLOCKERS
Trimethaphen Nn receptor antagonist. Blocks sympathetic
and parasympathetic nervous system Uses: Hypertensive Crsis Side effects: Mixed loss of Sympathetic
(hypotension) and Parasympathetic Nervous System (tachycardia, constipation, urinary rentention, dry mouth, etc…)
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HEMICHOLINIUM
Indirect Cholinergic Antagonist Blocks reuptake/recycle of Choline from the
synapse to the pre-synaptic neuron Not in clinical use
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SKELETAL MUSCLE RELAXANTS
Asmah Nasser, M.D.
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NEUROMUSCULAR BLOCKERS
Nm blockers blocks acetylcholine at the Nm
receptor. Used in Surgery for skeletal muscle
relaxation
A. Non-depolarizing Long acting: Tubocurarine, Pancuronium,
Doxacuraium Intermediate acting: Atracurium Short acting: Miyacurium
B. Depolarizing: Succinylcholine (shorting acting)
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NON-DEPOLARIZING NM BLOCKER
Example: Turbocurarine (long acting) MOA: After blocking NM receptors, they
prevent depolarization of muscle membrane and muscle contraction
Halothene and Aminoglycosides increase the actions of Nm blockers
Affinity for Nm not much higher than Nn Side effects:
Ganglionic blocker hypotension Releases histamine Hypotension,
bronchospasm
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OTHER NON-DEPOLARIZING ANTAGONISTS
Atracurium Metabolism: By plasma Cholinesterase Safe in patients with Renal Failure Intermediate Duration of Action (15 minutes)
Miyacurium Short acting (minutes) Used in short procedures (intubations)
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DEPOLARIZING NM BLOCKERS: SUCCINYLCHOLINE
It stimulates the Nm receptor, similar to Ach
Persists at receptor at high concentration, because it is not destroyed by AChE at the Nm junction
“Desensitizes” the end plate by occupying the receptors and causing a “persistent depolarization” leads to flaccid paralysis of muscle
Rapid onset and short duration of action (4-5 minutes) than other Nm blockers
Used mostly in very short procedures (intubation)
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SIDE EFFECTS OF SUCCINYLCHOLINE
Is metabolized rapidly by plasma pseudocholinestrase.
Side effect: Therefore pts who have a congenital deficiency is
pseudocholinesterase can’t metabolize Succinylcholine toxicity “Succinylcholine Apnea”
Malignant hyperthermia Hyperkalemia Arrythmias
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ANTIDOTE?
Neostigmine is used to reserve the effects of Non-depolarizing agents.
It inhibits the cholinesterase enzyme, increasing the amount of acetylcholine in the synapse, displacing Nm antagonists from the post-synaptic receptor.
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MALIGNANT HYPERTHERMIA
Is an autosomal dominant genetic disorder of skeletal muscle
It is associated with mutations in the gene for the skeletal muscle ryanodine receptor (RYRl), the calcium release channel of the sarcoplasmic reticulum
The specific biochemical abnormality is an increase in free calcium concentration in skeletal muscle cells
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MALIGNANT HYPERTHERMIA
Rapid onset of hypertension and tachycardia, severe muscle rigidity, hyperthermia, hyperkalemia, and acid-base imbalance with acidosis, following exposure to a triggering agent.
Is a rare but important cause of anesthetic morbidity and mortality.
Occurs in susceptible individuals who undergoes general anesthesia with inhaled agents (halothene) and skeletal muscle relaxants( eg, succinylcholine).
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TREATMENT OF MALIGNANT HYPERTHERMIA
Dantrolene : MOA: Prevents calcium release from the
sarcoplasmic reticulum
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WHAT TO KNOW!
Know the different Cholinergic receptors! Uses of Atropine, Benztropine, Ipatropium Know about Ganglionic blockers, their side
effects (and why they get those side effects). Know about the use of Trimethaphan
Know the difference between Depolaring and Non-Depolaring Neuromuscular blockers
Know about Malignant Hyperthermia
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PRETEST QUESTION
Of the many types of adrenergic receptors found throughout the body, which is most likely responsible for the cardiac stimulation that is observed following an intravenous injection of epinephrine?
a. α1-adrenergic receptors b. α2-adrenergic receptors c. β1-adrenergic receptors d. β2-adrenergic receptors e. β3-adrenergic receptors
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PRETEST QUESTION
Applied to the skin in a transdermal patch (transdermal therapeutic delivery system), this drug is used to prevent or reduce the occurrence of nausea and vomiting that are associated with motion sickness.
a. Diphenhydramine b. Chlorpromazine c. Ondansetron d. Dimenhydrinate e. Scopolamine
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PRETEST QUESTION
Which of the following antimuscarinic drugs is used by inhalation in the treatment of bronchial asthma?
a. Dicyclomine hydrochloride b. Cyclopentolate hydrochloride c. Ipratropium bromide d. Methscopolamine bromide e. Trihexyphenidyl hydrochloride
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PRETEST QUESTION
A male patient is brought to the emergency department (ED) following ingestion of an unknown substance. He is found to have an elevated temperature, hot and flushed skin, dilated pupils, and tachycardia. Of the following, which would most likely cause these findings?
a. Propranolol b. Methylphenidate c. Prazosin d. Guanethidine e. Atropine
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PREEST QUESTION
Of the following, which will not be blocked by atropine and scopolamine?
a. Bradycardia b. Salivary secretion c. Bronchoconstriction d. Skeletal muscle contraction e. Miosis
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PRETEST QUESTION
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Practice Question
Competitive Antagonists at the Nm junction include which of the following?
A. DantroleneB. AtracuriumC. MecamylamineD. IsoflurophateE. Succinylcholine
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Practice Question
Hereditary deficiency in what enzyme can lead to prolonged side effects of Succinylcholine?
A. G6PDB. Plasma CholinesteraseC. PseudocholinesteraseD. Cytochrome OxidaseE. Liver transaminase
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Practice Question
Dantrolene is the drug of treament for Malignant hypertherma because:
A. Dantrolene blocks Ca2+ release from the SRB. Dantrolene induces contraction of skeletal
muscleC. Dantrene increases the rate of
succinylcholine metabolismD. Succinylcholine binding to the Nicotinic
receptor is blocked by dantroleneE. Dantrolene acts centrally to reduce fever
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Practice Questions
Which of the following agents, when applied topically to the eye, would induce both mydriasis and cycloplegia?
A. PhenylephrineB. CarbacholC. PrazosinD. Atropine
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Practice Question
Neostigmine would be expected to reverse which one of the following conditions?
A. Paralysis of skeletal muscle by a competitive (non-depolarizing) muscle relaxant
B. Paralysis of skeletal muscle by depolarizing muscle relaxant
C. Cardiac slowing induced by stimulation of the vagus nerve
D. Pupillary miosis induced by bright light