Pharm Quiz#6

Question 1

What is the definition of postoperative residual neuromuscular blockade

Answer 1

Train of four < 0.9 after reversal

Clinical weakness

Question 2

What is recurarization?

Answer 2

Not “re-paralysis” but residual paralysis

Residual paralysis may persist up to 4 hours after rocuronium/vecuronium/cisatracurium

Question 3

When do you reverse a patient?

Answer 3

TOFR > 0.9, statistical reduction in morbidity

Question 4

What does the ability to reverse depend on

Answer 4

Ability to revere depends on amount of spontaneous recovery before reversing

Question 5

How much time should be given for anticholinesterases to antagonize block?

Answer 5

at least 15 to 30 minutes

Question 6

What is the safest approach for residual paralysis?

Answer 6

Sedation/mechanical ventilation

“Keep the tube in”

Question 7

List qualitative monitoring for paralysis

Answer 7

Train of four, single twitch, tetanus

Question 8

List quantitative monitoring for paralysis

Answer 8

Electromyography

Question 9

What will potentiate neuromuscular blockers?

Answer 9

inhalation agents

Question 10

What are metabolic issues related to paralysis?

Answer 10

Acidosis, hypercarbia, hypoxia, hypothermia

Question 11

What class of antibiotic will potentiate NMBs?

Answer 11

Aminoglycosides

Question 12

What is the most common cholinesterase inhibitor?

Answer 12

Neostigmine

Question 13

Cholinesterase inhibitors hydrolyze ___ molecules of acetylcholine per minute.

Answer 13

300,000

Question 14

Acetylcholine is a protein with molecular weight of approximately ___

Answer 14

320,000

Question 15

Explain the ionized centers of cholinesterase inhibitors. List three cholinesterase inhibitors.

Answer 15

Cholinesterase inhibitors have ionized centers that combine at AChE active center or site removed from active center of AChE.

Neostigmine
Pyridostigmine
Edrophonium

Question 16

List the three mechanisms of action for cholinesterase inhibitors

Answer 16

Direct influences on neuromuscular transmission along with enzyme inhibition.

MOA

• weak agonist action
• formation for desensitized receptor complex intermediates
• alteration of conductance properties of active channels

Question 17

All cholinesterase inhibitors act by the same mechanism, what is it?

Answer 17

They prevent the hydrolysis of acetylcholine in the neuromuscular junction

Question 18

What is the class of cholinesterase inhibitors? How lipid soluble is it?

Answer 18

Quaternary ammonium compounds

Poorly lipid soluble

Question 19

Neostigmine and pyridostigmine, describe the structure and function of these drugs

Answer 19

Carbamic acid esters of alcohols containing quarternary or tertiary ammonium groups

Form carbamyl-ester complexes at esteratic sites of cholinesterase

Question 20

Neostigmine and pyridostigmine increase ACh ___ and ___ by changing the agonist-antagonist ratio and amount of free ACh available.

Answer 20

concentration, duration of effect

Question 21

Neostigmine and pyridostigmine form ___ bonds with AChE resulting in carbamylated enzyme. Carbamylated AChE won’t work.

Answer 21

covalent

Question 22

Give details for Neostigmine

Answer 22

Onset IV - 4 to 8 minutes
Duration - 0.5 to 2 hr
50% glomerular filtration excretion
50% hydrolyzed by plasma esterases and hepatic metabolism
- 3-hydroxyphenyltrimethyl ammonium
- conjugated 3-OH PPM
Metabolites 1/10 activity of neostigmine

Question 23

How are metabolites of neostigmine eliminated?

Answer 23

Renal elimination

• Elimination 1/2 of neostigmine 70 to 80 min. Increase to 181 to 183 min in anephric patients
• Vd of 0.7 L/kg in healthy patients increases to 0.8 L/kg with renal failure

Question 24

Pyridostigmine, give details

Answer 24

Longest onset and duration
Onset - 2 to 5 min
Duration - 90 min to 3 to 6 hours
75% renal elimination
25% metabolized by hepatic microsomal enzymes 
- 3-hydroxy-methyl pyridinium
- six others

Question 25

How are pyridostigmine metabolites eliminated?

Answer 25

Urine excretion | Elimination 1/2 time - 113 minutes, Vd 1.1 L/kg

Question 26

Edrophonium, explain how it works

Answer 26

Binds reversibly with negatively charged enzyme sites by electrostatic attraction of positively charged nitrogen. Prevents catalytic binding with ACh for the short time that edrophonium occupies binding sites.

Question 27

What is the chemical composition of edrophonium

Answer 27

Simple alcohol containing quarternary ammonium group Electorstatically attaches to anionic site of AChE, stabilized with hydrogen bones. True chemical bond not formed.

Question 28

Edrophonium, give chemical information

Answer 28

Competitive inhibition for binding sites with ACh Short duration - 5 to 10 min Onset - 30 to 60 seconds IM onset 2 to 10 min

Question 29

Edrophonium, how is it eliminated?

Answer 29

75% renal elimination Without renal function - hepatic metabolism inactivates 30% of the dose via conjugation to edrophonium glucuronide 1/2 life 110 min with Vd 1.1 L/kg 1/2 life 304 min in anephric patient with Vd 0.7 L/kg

Question 30

List clinical signs of NMB recovery

Answer 30

``` Adequate tidal volume and rate Respirations smooth and unlabored Opens eyes widely on command No diplopia Tongue protrusion and purposeful movement Effective swallowing and sustained bite Sustained head or leg lift for 5 seconds Arm lift and touch opposite shoulder Strong, constant hand grip Effective cough Adequate vital capacity of at least 15 ml/kg Adequate inspiratory force of at least 25 to 30 cm H2O negative pressure Sustained tetanic response Train of four ratio greater than 0.9 No fade to double burst stimulation ```

Question 31

Factors prolonging paralysis

Answer 31

``` Acid maltase deficiency Adrenocortical dysfunction Acute intermittent porphyria Amyotrophic lateral sclerosis Anoxia and ischemia Carcinomatous polyneuropathy Cholinesterase deficiency of genetic variance Compressive neuropathy Critical illness polyneuropathy Diphtheria Eaton-Lambert syndrome Guillain-Barre syndrome ```

Question 32

Electrolyte imbalances associated with factors prolonging paralysis

Answer 32

``` Hypokalemia Hypocalcemia Hypomagnesemia Hypophosphatemia Hypothermia Motor neuron disease ```

Question 33

More factors prolonging paralysis

Answer 33

``` multiple sclerosis muscular dystrophy myasthenia gravis myotonic syndromes neurofibromatosis nonspecific nutritional deficiency Poliomyelitis Pyridoxine abuse Polymyositis Renal failure Respiratory acidosis Sepsis Thiamine deficiency Tike bite Trauma Vitamin E deficiency Wound botulism ```

Question 34

Pharmacologic causes of prolonged paralysis

Answer 34

``` Aminoglycoside toxicity Penicillin toxicity Steroid myopathy Antihypertensives - Calcium channel blockers - beta blockers - Furosemide ```

Question 35

Continued pharmacologic causes of prolonged paralysis (antidysrhthmics, aminoglycosides)

Answer 35

Quinidine Porcainamide Local anesthetics in large doses Polymyxin B Clindamycin Tetracycline

Question 36

Continued pharmacologic causes of prolonged paralysis (miscellaneous drugs)

Answer 36

``` Cyclosporine Steroids Volatile anesthetics Dantrolene Magnesium - OB Lithium Azathioprine Organophosphate (Poisoning) *** ```

Question 37

Typical doses and duration of Neostigmine

Answer 37

``` Neostigmine Dose - 25-75 mcg/kg Onset - 5-15 min Duration - 45-90 min Side effects - +PONV ```

Question 38

Typical doses and side effects of Pyridostigmine

Answer 38

Dose - 100-300 mcg/kg Onset - 10-20 min Duration - 60-120 min Side effects - slow onset, long duration

Question 39

Typical doses and side effects to Edrophonium

Answer 39

Dose - 50-1,000 mcg/kg Onset - 5-10 min Duration - 30-60 min Side effects - Not for deep block, rapid