ANTI-CHOLINERGICSAsmah Nasser, M.D.

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

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

WHAT ARE THE DRUG TARGETS?

Block/Antagonize Muscuranic Receptors Prevent the release of acetylcholine Prevent formation of acetylcholine Deplete acetyl choline storage

MUSCARINIC RECEPTOR BLOCKERS

1.Natural alkaloids:

Atropine, Scopolamine

2.Semi synthetic drugs :

Homoatropine, tropicamide, (short

acting)

Benztropine, ipratropium

glycopyrrolate, Dicyclomaine

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

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

ATROPINE

Contrindications of Atropine: Glaucoma (closed angle) Urinary retention Benign prostatic hypertrophy Paralytic Ileus Myasthenia Gravis

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

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

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

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.

NICOTINIC RECEPTOR BLOCKERS

Ganglionic blocking drugs: Trimethaphen

Neuromuscular blockers :

A.Nondepolarizing: D-tubocurarine , Atracurium

B.Depolarizing: Succinylcholine

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

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…)

HEMICHOLINIUM

Indirect Cholinergic Antagonist Blocks reuptake/recycle of Choline from the

synapse to the pre-synaptic neuron Not in clinical use

SKELETAL MUSCLE RELAXANTS

Asmah Nasser, M.D.

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)

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

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)

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)

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

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.

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

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).

TREATMENT OF MALIGNANT HYPERTHERMIA

Dantrolene : MOA: Prevents calcium release from the

sarcoplasmic reticulum

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

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

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

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

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

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

PRETEST QUESTION

Practice Question

Competitive Antagonists at the Nm junction include which of the following?

A. DantroleneB. AtracuriumC. MecamylamineD. IsoflurophateE. Succinylcholine

Practice Question

Hereditary deficiency in what enzyme can lead to prolonged side effects of Succinylcholine?

A. G6PDB. Plasma CholinesteraseC. PseudocholinesteraseD. Cytochrome OxidaseE. Liver transaminase

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

Practice Questions

Which of the following agents, when applied topically to the eye, would induce both mydriasis and cycloplegia?

A. PhenylephrineB. CarbacholC. PrazosinD. Atropine

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