Anticholinergics/Acetylcholinesterases

Question 1

Anticholinesterase (Clinical Uses)

Answer 1

Reverse NMBD effects, antagonism of CNS effects of other drugs (overdose atropine), treatment of MG or glaucoma

Question 2

Anticholinesterase (Mechanism of Action)

Answer 2

Acetylcholinesterase inhibitor (increase ACh in NMJ and everywhere else), NMJ effects

Question 3

Classification of antichoinesterase drugs

Answer 3

Reversible inhibition, Formation of carbamyl esters, Irreversible inactivation of acetylcholinesterase

Question 4

Reversible inhibition

Answer 4

Reversibly binds acetylcholinesterase

Edrophonium

Question 5

Edrophonium

Answer 5

Reversible inhibition
Short onset (1-2 min)
Quaternary amine
Myasthenia gravis

Question 6

Formation of carbamyl esters

Answer 6

Ester linkage to enzyme
Intermediate onset
Neostigmine, Physostigmine, and Pyridostigmine

Question 7

Neostigmine

Answer 7

Formation of carbamyl esters
Quaternary amine
Onset 7 min

Question 8

Physostigmine

Answer 8

Formation of carbamyl esters
Tertiary amine
Crosses BBB

Question 9

Pyridostigmine

Answer 9

Formation of carbamyl esters
Quaternary amine
Onset = 12 min

Question 10

Irreversible inactivation of acetylcholinesterase

Answer 10

Echothiophate

Question 11

Echothiophate

Answer 11

Pesticides/insectisides form irreversible covalent bond with enzyme
Must make new enzyme to overcome

Question 12

Duration of anticholinesterase drugs

Answer 12

Edrophonium shortest duration
Neostigmine duration ~80 min
Pyrdiostigmine duration ~2 hours

Question 13

Clearance of anticholinesterase drugs

Answer 13

Renal clearance accounts for 50-75% of elimination (prolonged duration in renal failure, but ok bc roc will last longer too and no active metabolites)
Hepatic function becomes important in renal failure patients (50% eliminated by liver if pt has ESRD)

Question 14

Age effects on anticholinesterase drugs

Answer 14

Kids: Lower dose needed and faster onset,
Elderly: Decrease blood flow to kidney = increased duration

Question 15

Which drugs cause BBLUDS?

Answer 15

anticholinesterase drugs

Question 16

BBLUDS

Answer 16

Bradycardia, Bronchoconstriction, Lactation, Urination, Defecation, Salivation

Question 17

Anticholinesterase and Myasthenia gravis

Answer 17

Diagnostic and Theraputic

Edrophonium

Question 18

Anticholinesterase overdose

Answer 18

Predominantly a pesticide issue
Effects are the BBLUDS response at muscarinic receptors and at nicotinic receptors (skeletal muscle) there is weak muscles (breathing muscles).
Most often due to organophosphates

Question 19

Anticholinesterase overdose treatment

Answer 19

Atropine and Pralidoxime (causes reactivation of acetylcholinesterase enzyme)

Question 20

Neostigmine (Dose)

Answer 20

0.04-0.07 mg/kg

Question 21

Neostigmine (Recovery)

Answer 21

Need at least 1 twitch to use
The absence of any palpable single twitches following 5 seconds of tetanic stimulation at 50 Hz implies very intense blockade that cannot be reversed
Excessive doses of cholinesterase inhibitors may actually prolong the recovery

Question 22

Anticholinergics (Drugs)

Answer 22

atropine, glycopyrrolate, and scopolamine

Question 23

Atropine

Answer 23

Naturally occurring, tertiary amine, crosses BBB

Question 24

Glycopyrrolate

Answer 24

Quarternary structure, synthetic, doesn’t cross BBB

Question 25

Scopolamine

Answer 25

Naturally occurring, tertiary amine, crosses BBB

Question 26

Scopolamine (Mechanism)

Answer 26

Prevent ACh binding at the muscarinic receptors

Can be overcome with increased ACh

Question 27

Anticholinergic effects

Answer 27

Sedation (atropine/scopolamine-cross BBB), antisialagogue, increase HR, relax smooth muscle, mydriasis (dilate pupil), prevention of motion sickness (reticular system in brain-scopolamine), decrease gastric ion secretion

Question 28

Anticholinergics (onset and duration)

Answer 28

Onset: atropine (1-2 min), glycopyrrolate (2-3 min)
Duration: both last 30-60 min

Question 29

Anticholinergics (absorption and clearance)

Answer 29

Absorption: lipid solubility. Atropine and scopolamine are tertiary amines and cross the BBB to have CNS effects (sedation)
Clearance: glycopyrrolate has faster clearance. All cleared by the kidneys, but renal failure is not a contraindication

Question 30

Clinical uses of anticholinergics

Answer 30

Important uses include: preop meds, tx of bradycardia, and NDNMB reversal
Less common uses include: bronchodilation, smooth muscle relaxant (biliary and uretal), antagonism of gastric acid secretion, prevent N/V
Caution: glaucoma and parturients

Question 31

Anticholinergics (Premed)

Answer 31

Anticholinergics can be used as premeds for sedation, antisialogogue, bradycardia treatment

Question 32

Sedation (Scopolamine, Atropine, Glycopyrrolate)

Answer 32

Scopolamine (0.4 mg IV) is the most potent. Works at the reticular activating system in the brain. Amnesia.
Atropine has memory deficit and delayed arousal. Not as much amnesia properties as scopolamine.
Glycopyrrolate has no sedation effects (quaternary amine)
CNS effects: atropine and scopolamine because cross BBB

Question 33

Antisailaogogue (Scopolamine, Atropine, Glycopyrrolate)

Answer 33

Scopolamine most potent, but it also has sedative properties so be cautious. 3x more potent than atropine. Less HR changes.
Glycopyrrolate (0.2 mg IM = more potent antisailagogue effect than IV and doesn’t increase HR as much). 2x more potent than atropine. Used when sedative properties not wanted

Question 34

Bradycardia Treatment (Scopolamine, Atropine, Glycopyrrolate)

Answer 34

Blocks ACh at the SA node, decreased parasympathetic effects, works on cardiac muscarinic receptors
Glycopyrrolate = atropine in effectiveness, but the onset of glycopyrrolate is slower
Good for vagal response in eye sx (ocularocardio reflex) and colon resections (peritoneal stretch response = decreased HR)

Question 35

Anticholinergics and bronchodilation (Mechanism)

Answer 35

Works on muscarinic receptors on the smooth muscle of medium and large airways→ decreased AW resistance and increased deadspace.

Question 36

Anticholinergics and bronchodilation (Drugs)

Answer 36

Ipratroprium (atrovent)—anticholinergic- inhaled so works directly on the airways.
Albuterol + ipratroprium = combivent → 2 methods to achieve same goal.

Question 37

Other uses of anticholinergics

Answer 37

Biliary/ureteral relaxation, mydriasis/cycloplegia (dilate pupils), gastric acid cessation (GERD), motion induced N/V prevention (scopolamine patch- put on night before sx because long duration and onset)

Question 38

Central anticholinergic syndrome

Answer 38

Too much anticholinergic
Symptoms: restlessness/hallucinations, somnolence/ unconsciousness
Treatment: physostigmine- crosses BBB (tertiary amine)
Who: children and elderly are most sensitive to this syndrome

Question 39

Anticholinergic OD

Answer 39

rapid onset of
Symptoms: dry mouth, blurred vision, tachycardia, increased temp, flushing, irritability
Effects: seizures, coma, ventilatory paralysis (central). Treatment: physostigmine

Question 40

Reversal criteria to extubate a patient

Answer 40

TOF ratio >0.7 (up to 80% receptors still blocked)
tetanus with 100 hz stimulation (50% receptors can still be blocked)
grip strength (difficult to quantify)
negative inspiratory pressure > 20 cmH20 (can still be 50% blocked)
sustained head lift for 5 seconds (GOLD STANDARD- but 33% of receptors can still be blocked)

Question 41

Where do we monitor

Answer 41

Ulnar nerve (adduct thumb), posterior tibial nerve (plantar flex big toe), peroneal nerve (dorsiflex foot), facial nerve (most closely corresponds to the vocal cords→ will stimulate the orbicularis oculi or the buccinator muscle)

Question 42

Sugammadex

Answer 42

Binds to muscle relaxant itself. Can still reverse even with no twichtes. New frontier in NDNMB reversal. Independent of Ach level in the NMJ…So….a PROFOUND block (no twitches) can be reversed. Cleared renally, but speed of reversal is independent of renal function. No need for a muscarinic antagonist. Awaiting approval from the FDA. Some evidence of anaphylactic reaction.