Test 2: Reversal

Question 1

Reversal requires ___ nicotinic transmission with ____ muscarinic side effects.

Answer 1

Reversal requires maximal nicotinic transmission with minimal muscarinic side effects. (Blue box!)

Need anti-cholinesterase to stop break down of Ach so that we can have competition at the binding sites. However, want to avoid side effects from systemic increases in Ach (Muscarinic receptors).
-SLUDGE, parasympathomimetic symptoms.
-Extra Ach goes to any Ach site.
-Give anticholinergic with it to mitigate SEs (Glyco, Atropine, Scopolamine)

Question 2

What do you have to have before you can reverse (traditional)?

Answer 2

-Some spontaneous recovery (twitches, curare cleft, etc)
-May be disorganized, but at least patient is having some type of spontaneous recovery in the body and we’re ready to reverse.

Question 3

Why is Physostigmine not used to reverse muscle relaxants?

Answer 3

Physostigmine is not used to reverse muscle relaxants b/c the dose required is excessive.

Question 4

What is important to know regarding intrathecal administration of Neostigmine?

Answer 4

50mcg-100mcg has been used as an adjunct to intrathecal blockade, prolonging both sensory and motor blockade.
-Inhibits the breakdown of spinal cord acetylcholine.
-Side effects: pruritus, nausea, vomiting, fecal incontinence, delayed recovery room discharge and atropine resistant bradycardia (higher doses, approx 200mcg)

Question 5

What are the symptoms of Central Anticholinergic Toxicity?

Answer 5

-Sedation, stupor
-Anxiety, restlessness
-Disorientation, hallucination
-Delirium, coma
-Convulsions
-Respiratory failure

Question 6

T/F: Some evidence of spontaneous reversal MUST be present before pharmacological reversal is initiated or attempted.

Answer 6

True! (Blue Box!)

-Concern that Neostigmine could be metabolized and gone before the subsequent NMB. Have to have spontaneous recovery first to let you know that you’re on track with metabolizing and eliminating the NMB.
-If gave reversal, but there’s too much NMB, it’s called Recurarization.

Question 7

What is the MOA of Anticholinesterases (Cholinesterase Inhibitors)?

Answer 7

-Inhibits actions of Ach-E (inhibits breakdown of Ach).
-Decreases the amount of ACH-E available to hydrolyze Ach, leading to an INDIRECT increase in the amount of Ach available. Creates a scenario of competition.
-Ach competes with the NDMR for the nAchR (nicotinic receptor)
-Extends life of Ach in NMJ and everywhere else (systemic effects). Re-establishes normal muscle function

Question 8

T/F: ALL Patients should receive reversal, even if full recovery status is noted on clinical testing.

Answer 8

True (Blue Box!)
-4/4 Twitches could still have majority of receptors blocked (50-70% could still be blocked)
-Can reduce dose of reversal depending on # of twitches.

Question 9

Describe Edrophonium

Answer 9

-electrostatic attraction, hydrogen bond; short DOA
-DOA can be increased by increasing the dose
-Prejunctional effect: increases Ach release

Question 10

Describe Neostigmine

Answer 10

-Covalent Bond, Long DOA
-Used in tx of Myasthenia gravis
-interrupts plasma cholinesterase. Will have prolonged effects of Succinylcholine.
-Neostigmine is a weak agonist of Nicotinic Receptors: Pre-junctional receptor effects and Post-junctional receptor effects.
-Increased risk for PONV

Question 11

Describe the Organophosphates

Answer 11

-Form irreversible bonds to AchE
-Rapidly absorbed through the skin
-Used in opthamology (Ex. Echothiophate for treatment of glaucoma)
-prolongs the Sux block secondary to decreased Pseudo-AchE
-Commonly used in pesticides and chemical warfare (nerve gases)
-Tertiary (!) compounds that cross the BBB, GI tract, placenta.

Question 12

What are the cardiovascular effects of Anticholinesterase administration?

Answer 12

-Vagal-like bradycardia that can progress into sinus arrest (Possible in the denervated heart)
-Slowing of conduction through the AV node = Decreased HR (!!!)
-Nodal and ventricular escape beats
-Decreased BP and SVR
-Need anticholinergic with it to combat CV related SEs.

Question 13

What are the pulmonary effects of Anticholinesterase administration?

Answer 13

-Bronchoconstriction/ Bronchospasm
-Increased respiratory tract secretions
-Increased airway resistance

Question 14

What are the cerebral effects of Anticholinesterase administration?

Answer 14

-Only with Physostigmine (crosses the BBB)
-Diffuse activation of the EEG

Question 15

What are the GI effects of Anticholinesterase administration?

Answer 15

-Increases peristalsis (Esophageal, gastric and intestinal)
-Increased glandular secretions (Enhanced gastric fluid secretion by parietal cells. Parietal cells are the stomach epithelium cells that secrete gastric acid and intrinsic factor in response to Ach.)
-Potential for bowel anastomotic leakage (for the pt s/p colectomy)
-N&V
-Fecal incontinence

Question 16

What is the Max Dose of Neostigmine?

Answer 16

5 mg (!)

Question 17

What is the dose of Neostigmine?

Answer 17

0.04 - 0.08 mg/kg (up to 5 mg)

Question 18

What is the onset and DOA of Neostigmine?

Answer 18

Onset: 5 - 11 min
DOA: 65 - 80 min

Question 19

What are special considerations to note with Neostigmine?

Answer 19

-decreases P-AchE and will prolong a succ block
-Peds/elderly are more sensitive (rapid onset, require a smaller dose)

Question 20

What anticholinergic is paired with Neostigmine?

Answer 20

-Glycopyrrolate (onset is similar, and less tachycardia than atropine)
-0.2 mg per 1 mg of Neostigmine
-Use Atropine in pregnant patients (fetal bradycardia)

Question 21

What is important to know regarding Neostigmine and pregnant patients?

Answer 21

It crosses the placenta, and can cause fetal bradycardia.
-Use atropine in pregnant patients.

Question 22

What is the structure of Pyridostigmine?

Answer 22

-Quaternary
-20% as potent as Neostigmine
-Paired with Glycopyrrolate

Question 23

What is important to know regarding Edrophonium?

Answer 23

-Less than 10% as potent as Neostigmine
-Onset is fast (1-2 min) so it’s paired with Atropine
-Less muscarinic effects than Neo or Pyrido

Question 24

What is important to know regarding Physostigmine?

Answer 24

-Prototype drug (not used for reversal)
-Tertiary: crosses BB Barrier
-Used in tx of Central Anticholinergic Toxicity (OD of Atropine or Scopolamine)

Question 25

In high doses, cholinesterase inhibitors will ____ a DMR.

Answer 25

In HIGH doses, cholinesterase inhibitors potentiate a DMR.
-Prolongs a depolarizing block (inhibits P-AchE and regular Ach-E, increasing DOA of Succ)
-Increases motor end plate depolarization secondary to increased Ach (Augmentation)
-Also get non-therapeutic increased levels of Ach
-Particularly with Neostigmine (Pyrido has less effect and Edro has no effect)
-Use cautiously in patients with C/I to succ (patients with extrajunctional receptors that can lead to hyperK+ = myotonia, muscular dystrophy, spinal cord transection, extensive burns)

Question 26

How are Anticholinesterases eliminated?

Answer 26

-Hepatic metabolism
-Renal excretion
-Mixtures of anticholinesterase drugs have no clinical advantage over the use of the individual drugs alone

Question 27

What is important to know regarding anticholinesterases and renal failure?

Answer 27

-elimination is prolonged with renal failure. Use Roc & Sugammadex and avoid use of Neostigmine with renal patients
-Prolongation of a NDMR from renal or hepatic insufficiency will be accompanied by a corresponding increase in DOA of a cholinesterase inhibitor

Question 28

What is the MOA of Anticholinergics?

Answer 28

Highly selective, competitive antagonist at all muscarinic receptors.
-Competitively blocks binding by Ach and prevents receptor activation
-Cellular effects of Ach are inhibited
-Only Muscarinic receptors are blocked
-Well absorbed and distributed throughout the body

Question 29

Do NOT administer an Anticholinesterase without also giving an _____________.

Answer 29

DO NOT ADMINISTER AN ANTICHOLINESTERASE WITHOUT ALSO GIVING AN ANTICHOLINERGIC
(Blue Box)

Question 30

What are the CV effects associated with anti-cholinergics?

Answer 30

-Tachycardia
-Atrial arrhythmias and nodal (junctional) rhythms occasionally occur
-Presynaptic muscarinic receptors on adrenergic nerve terminals are known to inhibit NE release
-Blocking this receptor may enhance SNS activity by increasing available NE
-Large doses result in dilation of cutaneous vessels (atropine flush)

Question 31

What are the Respiratory effects associated with anti-cholinergics?

Answer 31

-Inhibit secretions from the mucosa (nose to bronchi)
-Bronchodilation: Relaxation of the bronchial smooth musculature reduces airway resistance and increases anatomic dead space
-Issues for pts with COPD, RAD, and asthma

Question 32

What are the Cerebral effects associated with anti-cholinergics?

Answer 32

-Stimulation or depression depending on the drug
-Stimulation = excitation, restlessness, hallucinations
-Depression = sedation, amnesia

Question 33

What are the GI effects associated with anti-cholinergics?

Answer 33

-Decreased salivary secretions
-Decreased intestinal motility = prolonged gastric emptying time
-Decreased lower esophageal sphincter tone (Increased risk for aspiration pneumonia)

Question 34

Describe Atropine

Answer 34

A tertiary amine (Crosses BB Barrier)
-TACHYCARDIA

Question 35

Describe Scopolamine

Answer 35

-Tertiary Amine
-Most potent antisialagogue
-Sedation, Antisialagogue, Amnesia

Has to be within 4 hrs of surgery. Can wear for 72 hours through post op
-Don’t touch eyes (dilation)

Question 36

Describe Glycopyrrolate

Answer 36

-Quaternary
-Dries up secretions and causes tachycardia, but not to the same degree as the other two

Question 37

What is the dose of Glyco?

Answer 37

0.1 - 0.2 mg IV/IM

Question 38

What is the onset and DOA of Glyco?

Answer 38

Onset: 2-3 min
DOA: 2-4 hours

Question 39

T/F: you need to reverse a defasciculating dose.

Answer 39

False

Question 40

When is Sugammadex used?

Answer 40

-Only on steroids (roc/vec)
-Wait times vary for re-admin of a NDMR (roc or vec) after admin of Bridion from 5 min to 24 hours depending on dose given and patient renal function
-Use a non-steroidal muscle relaxant and expect longer onset times
-Pregnancy category unknown
-No safety data in peds

Question 41

What is the dosing of Sugammadex based on # of twitches?

Answer 41

2/4 twitches in TOF = 2 mg/kg

0/4 twitches in TOF with 1-2 post tetanic twitches = 4 mg/kg

Clinical need to reverse a 1.2 mg/kg dose of Roc within 3 minutes of administration = 16 mg/kg

Question 42

What is the metabolism of Sugammadex?

Answer 42

-No metabolites
-Not metabolized/excreted in liver
-95% excreted unchanged in urine

Question 43

What is the MOA of Sugammadex?

Answer 43

-Modified gamma cyclodextrin
-Forms a complex with Roc/Vec and reduces the amount of NDMR available to bind to the nicotinic receptor in the NMJ

Question 44

What are the side effects associated with Sugammadex?

Answer 44

-Marked bradycardia
-Hypotension
-HA, N/V, pain

Question 45

How does the 1/2 life of Sugammadex alter with renal impairment?

Answer 45

½ life is 2 hours - 19 hours depending on renal impairment. Can hang around for a long time if renal impairment.

Question 46

What are the contraindications for Sugammadex?

Answer 46

-Hypersensitivity reactions (Skin irritation to anaphylaxis)
-Severe renal impairment to include dialysis
-Marked bradycardia

Question 47

What are the misc effects associated with Sugammadex?

Answer 47

-Interferes with hormonal contraceptive users. Need to use another form of birth control for at least 7 days (also true with Abx administration)
-Incompatible with Zofran (in the same line). Don’t give at the same time. Flush good after giving Zofran.
-No dosage adjustment required for mild/moderate renal impairment
-Recovery prolonged with Toremifene (breast cancer drug with high binding affinity for sugammadex)