Hall Ch. 3: Pharmacology and Pharmacokinetics of IV Drugs

Question 1

Name 4 acetylcholinesterase inhibitors / anticholinesterases:

Of them,

a) which cross the BBB and why?*
b) which do not cross the BBB and why?

*Therefore, can treat what? And what is another name for that?

Answer 1

Neostigmine, edrophonium, pyridostigmine and physostigmine.

a) Only physostigmine can cross the BBB, because it is a tertiary amine.*
b) Neostigmine, edrophonium and pyridostigmine do not cross the BBB because they are quaternary ammonium compounds.

*Physostigmine is therefore useful for treating Central Anticholinergic Syndrome. Aka “ atropine toxicity”.

Question 2

What are the signs and symptoms of anticholinergic toxicity (aka central anticholinergic syndrome)?

Answer 2

Flushing (red as a beet)

Dry skin and dry mucous membranes (dry as a bone)

Mydriasis

Altered mental status (mad as a hatter)

Fever (hot as a hare)

Additional manifestations include the following:

Sinus tachycardia

Decreased bowel sounds

Functional ileus

Urinary retention (full as a flask)

Hypertension

Tremulousness

Myoclonic jerking

Question 3

According to ASRA, neuraxial anesthesia placement should be delayed for how long after:

a) a therapeutic dose of LMWH?
b) a prophylactic dose of LMWH?
c) a prophylactic dose of UFH?
d) higher than prophylactic doses of UFH? How do these vary for pregnant patients?

Answer 3

a) 24 hrs (eg. enoxaparin 1mg/kg SC BID or 1.5mg/kg SC daily)
b) 10 to 12 hrs (eg. enox 0.5 mg/kg daily)
c) for heparin 5000 units SC BID, there is no contraindication
d) for higher doses of heparin, there are no existing recommendations

*No changes to any of these guidelines for pregnant patients.*

Question 4

Name 4 opioid-receptor antagonists.

Which one can/cannot cross the BBB and why? What does this mean clinically?

Answer 4

Naloxone

Naltrexone - used mainly for EtOh dependence.

Nalmefene - More expensive than naloxone. Longer half-life (better for methadone?). Used in Europe for EtOh dependence.

Methylnaltrexone - Cannot cross the BBB. The other 3 can. This means it only antagonizes peripheral opioid receptors and can treat SEs (eg. constipation) without reversing analgesia. For that reason, also not used to treat addiction. Only available IV, not absorbed PO.

The first 3 reverse central and peripheral opioid effects.

Question 5

Aprepitant

Half-life

What are its analgesic effects?

Effect on QT interval

Besides antiemetic effects, it also has these beneficial effects:

Answer 5

Aprepitant

Half-life: 9 to 13 hours

Analgesia: It doesn’t have any

Effect on QT interval: None

Besides antiemetic effects, it also has these beneficial effects: Anxiolysis and mild antidepressant effects

Question 6

Train of four correlates well with _______________ suppression, measured at _____________.

Answer 6

Train of four correlates well with single twitch height suppression, measured at the adductor pollicis.

Question 7

At what ED (eg. 25, 50, 90, etc) of non-depolarizing NMBD are there good conditions for intubating and intra-abdominal surgery?

What reduction in single-twitch height does that correspond to?

Answer 7

ED₉₀ to ED₉₅ represents good conditions for intubating and intra-abdominal surgery.

That corresponds to a 90 to 95% reduction in single-twitch height.

Question 8

Based on the following # of TOF twitches remaining, how much is single twitch height depressed by?

1 twitch:

2 to 4 twitches:

Answer 8

Based on the following # of TOF twitches remaining, how much is single twitch height depressed by?

1 twitch: at least 85% depressed

2 to 4 twitches: 70% to 85% depressed

Question 9

A significant number of receptors may still be occupied by non-depolarizing NMBDs at ___ number of twitches.

Answer 9

Even at 4 twitches, a significant number of receptors may still be occupied and blockade may not be recovered.

Question 10

What are the 3 mechanisms that NMBDs can cause cardiovascular effects?

Answer 10

1. Histamine release
2. By affecting the cardiac muscarinic receptors
3. By affecting the nicotinic receptors at autonomic ganglia

Question 11

How much histamine release do the following NMBDs have?

1. Aminosteroids?
2. D-tubocurarine?
3. Mivacurium?
4. Atracurium?
5. Cisatracurium?
6. Sux?

Answer 11

1. Aminosteroids : None
2. D-tubocurarine : Moderate
3. Mivacurium : Slight
4. Atracurium : Slight
5. Cisatracurium : None
6. Sux : Slight

Question 12

Effects of NMBDs on cardiac muscarinic receptors:

• Sux:
• Roc:
• Vec:
• Benzylisoquinoliniums:
• Pancuronium:

Answer 12

Effects of NMBDs on cardiac muscarinic receptors:

• Sux: Simulates - acts on the SA node directly causing bradycardia
• Roc: Blocks weakly causing tachycardia
• Vec: No effect
• Benzylisoquinoliniums: No effect
• Pancuronium: Blocks moderately causing tachycardia

Question 13

Effects of NMBDs on nicotinic receptors at autonomic ganglia:

• Sux:
• D-tubocurarine:
• All others:

Answer 13

Effects of NMBDs on nicotinic receptors at autonomic ganglia:

• Sux: Stimulates (increases HR)
• D-tubocurarine: Blocks (decreases HR)
• All others: Do nothing

Question 14

Describe the effect of Sux on HR…

Answer 14

• Variable
• Dependent on the predominant nervous system; parasympathetic in kids so tend to get brady, sympathetic in adults so sometimes see tachycardia

Question 15

What is the ED₉₅ and intubating dose of the following (mg/kg)?:

Cisatracurium

Pancuronium

Vecuronium

Mivacurium

Atracurium

Rocuronium

Answer 15

Typically, the ED₉₅ is doubled to get the intubating dose.

Question 16

Onset to maximum twitch depression:

Rocuronium:

Mivacurium:

Vecuronium:

Pancuronium:

Atracurium:

Cisatracurium:

Answer 16

Onset to maximum twitch depression:

Rocuronium: 1 - 2 mins

Mivacurium: 2 - 3 mins

Vecuronium: 3 - 5 mins

Pancuronium: 3 - 5 mins

Atracurium: 3 - 5 mins

Cisatracurium: 3 - 5 mins

Question 17

Duration to return to single twitch height (at least 25%):

• Mivacurium:
• Rocuronium:
• Vecuronium:
• Atracurium:
• Cisatracurium:
• Pancuronium:

Answer 17

Duration to return to single twitch height (at least 25%):

• Mivacurium: 12 to 20 mins
• Rocuronium: 20 to 35 mins
• Vecuronium: 20 to 35 mins
• Atracurium: 20 to 35 mins
• Cisatracurium: 20 to 35 mins
• Pancuronium: 60 to 90 mins