Autonomic Cholinergic Drugs And Toxins

Front 1

Bethanechol -- MOA

Back 1

1. Direct AGONIST for all types of MUSCARINIC receptors
2. Dose NOT cross BBB; NO CNS ACTION
3. Stimulates GI, bladder, eye, sweating
4. Lowers HR & dilates blood vessels via endothelium

Front 2

Bethanechol -- Clinical Uses

Back 2

1. GI stimulation in case of
2. Post-surgical gastric atony
3. Paralytic ileus
4. Stimulate bladder to reduce urinary retention

Front 3

Bethanechol -- Side Effects

Back 3

1. Decreased HR, cardiac contractility, conduction velocity
2. Bronchoconstriction & bronchosecretion
3. Excessive GI symptoms -- nausea, vomiting, cramps, defecation
4. Miosis (pupil constriction)

Front 4

Bethanechol -- Breakdown/Excretion

Back 4

1. RESISTS hydrolysis by cholinesterase or buterylcholinesterase
2. Excreted in URINE

Front 5

Pilocarpine -- MOA

Back 5

1. Direct AGONIST at MUSCARINIC receptors (all types)
2. Stimulates GI, bladder, eye, lung, sweating
3. Lowers HR & dilates blood vessels via endothelium
4. CNS arousal: hallucination, delerium

Front 6

Pilocarpine -- Clinical Uses

Back 6

1. GLAUCOMA
- effective in narrow or wide-angle glaucoma
- drug of choice in emergency INCREASE in intraoccular pressure
- causes miosis, which helps open Schlemm's canal. Also improves tone & thus INCREASE flow through the canal itself
2. Can be used to INCREASE secretion following head/neck irradiation

Front 7

Pilocarpine -- Side Effects

Back 7

Systemic effects usually minimal in occular use, but might include nausea, vomiting, diarrhea, salivation, sweating, hypotension, bronchoconstriction

Front 8

Pilocarpine -- Breakdown/Excretion

Back 8

1. NOT degraded by cholinesterases

Front 9

Atropine -- MOA

Back 9

1. Direct ANTAGONIST for all types of muscarinic receptor
2. Higher doses effect eye (mydriasis & cycloplegia), increase HR, inhibit bladder function, GI activity
2. TERTIARY amine -- crosses BBB; CNS effects include excitation, irritability, delirium, coma

Front 10

Atropine -- Clinical Uses

Back 10

1. Rapid treatment of BRADYCARDIA (possible due to vagal overstimulation)
2. Overcoming effects of cholinesterase block following anesthetic OR poisoning
3. Decreasing bladder spasm

Front 11

Atropine -- Side Effects

Back 11

1. Flushed dry skin, dry mouth, tachycardia, dilated pupil, urinary retention, constipation, CNS disturbances
2. Children are particularly sensitive. Can have strong reaction to atropine in occular preparations.
3. Can exacerbate narrow-angle glaucoma

Front 12

Atropine -- Breakdown/Excretion

Back 12

1. Partially metabolized in liver
2. Excreted in URINE

Front 13

What do you treat atropine poisoning with?

Back 13

1. Physostigmine -- which blocks the cholineresterase enzyme (CNS & peripheral)

Front 14

Scopolamine -- MOA

Back 14

1. Direct ANTAGONIST for all types of MUSCARINIC receptor
2. Action like atropine but LONGER lasting
3. Effect eye (mydriasis & cycloplegia), INCREASE HR, inhibit bladder function, GI activity
4. TERTIARY amine -- readily crosses BBB; low dose CNS effects include inhibition of MOTION SICKNESS & induction of amnesia ( short term memory).
-- CNS effects at HIGHER DOSE include excitation, irritability, delirium, coma

Front 15

Scopolamine -- Clinical Uses

Back 15

1. Decrease motion sickness (transdermal patch behind ears)
2. Decrease in secretions. Amnesia during surgical procedures

Front 16

Scopolamine -- Side Effects

Back 16

1. Flushed dry skin, dry mouth, tachycardia, dilated pupil, urinary retention, constipation, CNS disturbances

Front 17

Ipratropium -- MOA

Back 17

1. Direct ANTAGONIST for all types of MUSCARINIC receptor
2. QUATERINARY amine relative of atropine
3. DOES NOT cross membranes, BBB

Front 18

Ipratropium -- Clinical Uses

Back 18

1. Treatment of BRONCHOSPASM (wheezing or difficulty breathing) caused by chronic obstructive pulmonary disease, associated w/ chronic bronchitis & emphysema
2. Treatment of allergic or non allergic rhinits

Front 19

Ipratropium -- Side Effects

Back 19

1. Minimal side effects when used as an inhaler because it is POORLY absorbed.
2. Dry mouth can sometimes occur

Front 20

Nicotine -- MOA >> Ganglionic Actions

Back 20

1. Direct AGONIST for nicotinicholinergic receptors (CNS, autonomic ganglia, neuromuscular junction)
2. Ganglionic Actions
-- LOW doses: Ganglionic stimulation (final effect depends on sympathetic vs parasympathetic dominance) >>> vasoconstriction, INC GI motility & secretion, INC epinephrine from adrenal medulla, INC HR & BP

-- High Doses: Ganglionic blockade, nausea, vomiting, CNS stimulation

Front 21

Nicotine -- MOA >> NMJ Actions

Back 21

1. Direct AGONIST for nicotinicholinergic receptors (CNS, autonomic ganglia, neuromuscular junction)
2. NMJ actions
-- LOW doses: fasciculations & spasms
-- HIGH doses: depolarizing blockage

Front 22

Nicotine -- Clinical Uses

Back 22

1. Smoking cessation aid; short term relief of TOURETTE's Syndrome symptoms

Front 23

Nicotine -- Side Effects

Back 23

1. Use in cigarettes INCREASES HR, BP, altered blood lipoprotein profile. Can INCREASE risk for arthroschlerotic disease
2. See MOA for other side effects

Front 24

Nicotine -- Breakdown/Excretions

Back 24

1. Oxidized in liver, kidneys, lungs
2. Excreted in URINE

Front 25

What happen when there is a frequent use of Nicotine?

Back 25

1. Frequent use can lead to receptor desenitization/downregulation. Leads to dependency.

Front 26

Succinylcholine -- MOA

Back 26

1. Depolarizing ANTAGONIST of neuromuscular nicotinic receptors
2. Binds to & weakly opens receptors (partial agonist). Leads to two phases of block
-- Phase I: DEPOL of the muscle due to receptor/channel opening. Causes inactivation of Na channels preventing excitation of the muscle
-- Phase II: Continued binding to the receptor/channel causes it to desensitize. Muscle repolarizes but block continues because of receptor DYSFUNCTION
3. NOT reversed by cholinesterase inhibitors

Front 27

Succinylcholine --- Onset time and duration

Back 27

1. RAPID (30-60s)
2. VERY SHORT duration of action (<10 min)

Front 28

Succinylcholine -- Clinical Uses

Back 28

1. Induction of short-term paralysis during anesthesia & surgical procedures
2. Paralysis of skeletal muscles prior to shock therapy for depression

Front 29

Succinylcholine -- Side Effects

Back 29

1. Arrhythmias & Bradycardia
2. INCREASED intraoccular pressure
3. Induction of MALIGNANT HYPERTHERMIA

Front 30

Succinylcholine -- Breakdown/Excretion

Back 30

1. Hydrolyzed quickly by plasma and liver BUTERYLcholinesterases

Front 31

Does Succinylcholine induce loss of consciousness or anesthesia?

Back 31

1. NO
2. Still preferred over most non-depolarizing antagonists due to very short duration of action. Respiration can begin again quickly in case of difficulties in intubation

Front 32

Rocuronium -- MOA

Back 32

1. NON-depolarizing Antagonist of neuromuscular nicotinic receptors
2. Produce flacid paralysis of skeletal muscle
3. No ganglionic blockade
4. Very Rapid onset (1 min), rapid reversal (~15 min)
5. DOES NOT stimulate histamine release

Front 33

Rocuronium -- Clinical Uses

Back 33

1. VERY rapid induction of paralysis during anesthetic & surgical procedures e.g. when vomiting of gastric contents during intubation is a threat
2. Lacks most of the side effects of succinylcholine

Front 34

Rocuronium -- Side Effects

Back 34

1. Low safety margin: QUICKLY induces respiratory paralysis. Requires ventilation of patient.
2. Activity lasts for at least 30 minutes. Danger of respiratory emergerncy inc ase intubation fails
3. COMPLETE paralysis without loss of consciousness or anethesia

Front 35

Mivacurium -- MOA

Back 35

1. NON-depolarizing ANTAGONIST of neuromuscular nicotinic receptors
2. Produces flaccid paralysis of skeletal muscle
3. No ganglionic blockade
4. Rapid onset (2 min), rapid reversal (~15 min)
5. DOES NOT stimulate histamine release

Front 36

Mivacurium -- Clinical Uses

Back 36

1. Temporary induction of paralysis during anethetic & surgical procedures
2. Lacks most of the side effects of succinylcholine

Front 37

Mivacurium -- Side Effects

Back 37

1. Low safety margin: quickly induces respiratory paralysis. Requires ventilation of patient.
2. COMPLETE paralysis without loss of consciousness or anethesia

Front 38

Mivacurium -- Breakdown/Excretion

Back 38

1. Hydrolyzed quickly by plasma and liver BUTERYLcholinesterases

Front 39

Trimethaphan -- MOA

Back 39

1. Direct ANTAGONIST for GANGLIONIC nicotinic receptors
2. DOES NOT cross BBB
3. Produces dysautonomia due to ganglionic block
-- DEC blood pressure (vaso- and venodilation)
-- DEC GI motility and secretions

Front 40

Trimethaphan -- Clinical Uses

Back 40

1. NO LONGER on market in US (replaced by mecamylamine)
2. Previously used for deliberate induction of hypotension
-- Initial BP lowering with accute dissecting aortic aneurysm
-- Hypertensive crisis
-- Decrease loss of blood during surgery

Front 41

Trimethaphan -- Side Effects

Back 41

1. Profound HYPOtension
2. Histamine release
3. Loss of other autonomic function e.g. atony of bladder and GI, dry mouth, no sweating

Front 42

Which one release histamine?
A. Trimethaphan
B. Mivacurium
C. Rocuronium
D. Succinylcholine

Back 42

Answer: Trimethaphan

Front 43

Which drug induce malignant hyperthermia (Side Effect) ?

Back 43

Succinylcholine

Front 44

Edrophonium -- MOA

Back 44

1. Fast REVERSIBLE inhibitor of acetylcholineresterase enzyme
2. Onset & duration of actions w/in minutes
3. Causes a transient INCREASE of Ach actions at NMJ & autonomic synapses

Front 45

Edrophonium -- Clinical Uses

Back 45

1. Diagnosis of Myesthenia Gravis
2. Transient INCREASE in NMJ Ach levels overcomes loss of active nicotinic receptors
3. Decreasing HR in paroxysmal atrial bradycardia

Front 46

Edrophonium -- Side Effects

Back 46

1. As for muscarinic overstimulation: DECREASEED HR, BP, and bronchoconstriction etc.
2. Atropine is an effect antidote

Front 47

What is an effective antidote for Edrophonium overdose?

Back 47

Answer: ATROPINE

Front 48

Neostigmine -- MOA

Back 48

1. Moderately LONG ACTING inhibitor of the acetylcholinesterase enzyme
2. QUARTINARY amine, does NOT cross the BBB. Strong affinity for the NMJ

Front 49

Neostigmine -- MOA -- Two sites of Action

Back 49

1. NMJ: initial stimulus, followed by paralysis
2. ANS: muscarine-like sitmulation
3. Hydrolyzed at the active site like Ach, but carbomolates reactive OH
4. Reverses over the course 2-4 hours

Front 50

Neostigmine -- Clinical Uses

Back 50

1. Reversal of NON-depolarizing NMJ antagonists (CANNOT reverse depolarizing antagonists)
2. Treatment of Myasthinia Gravia
3. Creases intestinal & bladder motility in cases of atony

Front 51

Neostigmine -- Side Effects

Back 51

1. As for muscarinic overstimulation: DEC HR, BP and bronchoconstriction etc

Front 52

What do you use to reverse CNS effects of atropine?

Back 52

Answer: Physotigmine because Neostigmine CANNOT reverse CNS effects of atropine due to low BBB permeability

Front 53

Physostigmine -- MOA

Back 53

1. Moderately LONG ACTING inhibitor of acetylcholinesterase enzyme
2. TERTIARY amine -- CROSSES the BBB
3. Hydrolyzed at the active site like Ach, but carbamolates reactive OH
4. Reverses over the course of 2-4 hours

Front 54

Physostigmine -- MOA -- Three sites of action

Back 54

1. NMJ: initial stimulus, followed by paralysis
2. ANS: muscarinic-like stimulation
3. CNS: stimulation, convulsion

Front 55

Physostigmine -- Clinical Uses

Back 55

1. Increases intestinal & bladder motility in cases of atony
2. Treatment of GLAUCOMA by causing miosis (however, pilocarpine is more effective)
3. Compensation for atropine or especially scopolamine overdose.

Front 56

Physostigmine -- Side Effects

Back 56

1. Muscarinic overstimulation: DEC HR, BP and bronchoconstriction etc.
2. Atropine or scopolamine are effective antidotes

Front 57

Which two can be used for physostigmine overdose?

Back 57

1. Atropine OR scopolamine

Front 58

Which two can be used to treat Glaucoma? Out of the two, which one is better for the treatment of Glaucoma?

Back 58

Answer: physostigmine and pilocarpine BUT Pilocarpine is MORE effective.

Isoflurophate and Echothiphate can also be used in the treatment of glaucoma

Front 59

Isoflurophate -- MOA

Back 59

1. Long-acting INHIBITOR of acetylcholinesterase
2. Phosphorylates the OH group of the active site serine. Covalent bond >> essentially IRREVERSIBLE

Front 60

Isoflurophate -- MOA -- Three sites of action

Back 60

1. NMJ: stimulation then paralysis due to excess of ACh
2. ANS: stimulation of ganglia & muscarinic receptors
3. CNS: crosses BBB, stimulating cholinergic systems

Front 61

Isoflurophate -- Clinical Uses

Back 61

1. Can be used in treatment of wide-angle glaucoma via intense miosis

Front 62

Isoflurophate -- Side Effects

Back 62

1. Extremely potent as toxin. Prototype of insecticides and nerve gases
2. CNS: coma, respiratory depression, seizures
3. ANS: nausea, vomiting, diarrhea, vision disturbances, sweating, salivation, DEC HR, bronchoconstriction/secretion
4. Muscle twitching, weakness, paralysis

Front 63

Pralidoxine -- MOA

Back 63

1. Regenerates acetylcholinesterase enzyme following "irreversible" organophosphate poisoning
2. Molecular structure has a higher affinity for the phosphorus than the enzyme
3. CANNOT act on "aged" inhibitors that have lost one of their side chains
4. CANNOT act on carbamolated form of the enzyme (e.g. neostigmine and physostigmine)

Front 64

Pralidoxine -- Clinical Uses

Back 64

1. Restoration of AChase function following nerve gas or insecticide

Front 65

Echothiophate

Back 65

Very potent AChE inhibitor used in the treatment of glaucoma

Front 66

What is used to diagnose myasthenia gravis?

Back 66

Answer: Edrophonium

Front 67

What is used to treat myasthenia gravis?

Back 67

Neostigmine OR physostigmine

Front 68

What is the most common cause of death by organophosphates?

Back 68

Answer: respiratory failure

Front 69

What are the ganglionic blockers mentioned in this class? And it's clinical uses?

Back 69

1. Ganglionic blockers are used for treatment of dissecting aneurysm or to lower blood pressure during surgery.
2. Hexamethhonium is the obsolete prototype in this drug class
3. ONLY mecamylamine & trimethaphan remain in clinical use

Front 70

Name two MUSCARINIC Receptor AGONISTS

Back 70

1. Bethanechol
2. Pilocarpine

Front 71

Name three MUSCARINIC receptor ANTAGONISTS

Back 71

1. Atropine
2. Scopolamine
3. Ipratroprium

Front 72

Name three NICOTINIC receptor ANTAGONISTs

Back 72

1. Succinylcholine
2. Rocuronium
3. Mivicurium

Front 73

Name three Acetylcholinesterase INHIBITORS

Back 73

1. Edrophonium
2. Neostigmine/Physostigmine
3. Organophosphates (Sarin)