1. Anti-Cholinergics
Asmah Nasser, M.D.

2. 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

4. 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
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

5. WHAT ARE THE DRUG TARGETS?
Block/Antagonize Muscuranic Receptors
Prevent the release of acetylcholine
Prevent formation of acetylcholine
Deplete acetyl choline storage

6. Muscarinic receptor blockers
1.Natural alkaloids:
Atropine, Scopolamine
2.Semi synthetic drugs :
Homoatropine, tropicamide, (short acting)
Benztropine, ipratropium glycopyrrolate, Dicyclomaine

7. Atropine Muscarinic receptor blocker
Not hydrolyzed by cholinesterase, long duration of action
Actions of Atropine:
Decreased salivary, bronchial and sweat secretion
Mydriasis and cyloplegia (loss of accommodation reflex)
Tachycardia
Constipation
Urinary retention
Excitation /hallucinations

8. 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

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

10. 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

11. 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

12. 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

14. 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.

15. Nicotinic receptor blockers
Ganglionic blocking drugs: Trimethaphen
Neuromuscular blockers :
Nondepolarizing: D-tubocurarine , Atracurium
Depolarizing: Succinylcholine

16. 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

17. 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…)

19. Hemicholinium Indirect Cholinergic Antagonist
Blocks reuptake/recycle of Choline from the synapse to the pre-synaptic neuron
Not in clinical use

20. Skeletal Muscle Relaxants
Asmah Nasser, M.D.

21. Neuromuscular blockers
Nm blockers blocks acetylcholine at the Nm receptor. Used in Surgery for skeletal muscle relaxation
Non-depolarizing
Long acting: Tubocurarine, Pancuronium, Doxacuraium
Intermediate acting: Atracurium
Short acting: Miyacurium
Depolarizing: Succinylcholine (shorting acting)

22. 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

23. 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)

24. 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)

25. 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

26. 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.

27. 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

28. 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).

29. Treatment of Malignant Hyperthermia
Dantrolene :
MOA: Prevents calcium release from the sarcoplasmic reticulum

30. 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

31. 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

32. 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

33. 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

34. 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

35. 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

36. Pretest Question

37. Practice Question
Competitive Antagonists at the Nm junction include which of the following?
A. Dantrolene
B. Atracurium
C. Mecamylamine
D. Isoflurophate
E. Succinylcholine

38. Practice Question
Hereditary deficiency in what enzyme can lead to prolonged side effects of Succinylcholine?
G6PD
Plasma Cholinesterase
Pseudocholinesterase
Cytochrome Oxidase
Liver transaminase

39. Practice Question
Dantrolene is the drug of treament for Malignant hypertherma because:
Dantrolene blocks Ca2+ release from the SR
Dantrolene induces contraction of skeletal muscle
Dantrene increases the rate of succinylcholine metabolism
Succinylcholine binding to the Nicotinic receptor is blocked by dantrolene
Dantrolene acts centrally to reduce fever

40. Practice Questions
Which of the following agents, when applied topically to the eye, would induce both mydriasis and cycloplegia?
Phenylephrine
Carbachol
Prazosin
Atropine

41. Practice Question
Neostigmine would be expected to reverse which one of the following conditions?
Paralysis of skeletal muscle by a competitive (non-depolarizing) muscle relaxant
Paralysis of skeletal muscle by depolarizing muscle relaxant
Cardiac slowing induced by stimulation of the vagus nerve
Pupillary miosis induced by bright light