Pharm Quiz#6 Flashcards
What is the definition of postoperative residual neuromuscular blockade
Train of four < 0.9 after reversal
Clinical weakness
What is recurarization?
Not “re-paralysis” but residual paralysis
Residual paralysis may persist up to 4 hours after rocuronium/vecuronium/cisatracurium
When do you reverse a patient?
TOFR > 0.9, statistical reduction in morbidity
What does the ability to reverse depend on
Ability to revere depends on amount of spontaneous recovery before reversing
How much time should be given for anticholinesterases to antagonize block?
at least 15 to 30 minutes
What is the safest approach for residual paralysis?
Sedation/mechanical ventilation
“Keep the tube in”
List qualitative monitoring for paralysis
Train of four, single twitch, tetanus
List quantitative monitoring for paralysis
Electromyography
What will potentiate neuromuscular blockers?
inhalation agents
What are metabolic issues related to paralysis?
Acidosis, hypercarbia, hypoxia, hypothermia
What class of antibiotic will potentiate NMBs?
Aminoglycosides
What is the most common cholinesterase inhibitor?
Neostigmine
Cholinesterase inhibitors hydrolyze ___ molecules of acetylcholine per minute.
300,000
Acetylcholine is a protein with molecular weight of approximately ___
320,000
Explain the ionized centers of cholinesterase inhibitors. List three cholinesterase inhibitors.
Cholinesterase inhibitors have ionized centers that combine at AChE active center or site removed from active center of AChE.
Neostigmine
Pyridostigmine
Edrophonium
List the three mechanisms of action for cholinesterase inhibitors
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
All cholinesterase inhibitors act by the same mechanism, what is it?
They prevent the hydrolysis of acetylcholine in the neuromuscular junction
What is the class of cholinesterase inhibitors? How lipid soluble is it?
Quaternary ammonium compounds
Poorly lipid soluble
Neostigmine and pyridostigmine, describe the structure and function of these drugs
Carbamic acid esters of alcohols containing quarternary or tertiary ammonium groups
Form carbamyl-ester complexes at esteratic sites of cholinesterase
Neostigmine and pyridostigmine increase ACh ___ and ___ by changing the agonist-antagonist ratio and amount of free ACh available.
concentration, duration of effect
Neostigmine and pyridostigmine form ___ bonds with AChE resulting in carbamylated enzyme. Carbamylated AChE won’t work.
covalent
Give details for Neostigmine
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
How are metabolites of neostigmine eliminated?
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
Pyridostigmine, give details
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
How are pyridostigmine metabolites eliminated?
Urine excretion
Elimination 1/2 time - 113 minutes, Vd 1.1 L/kg
Edrophonium, explain how it works
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.
What is the chemical composition of edrophonium
Simple alcohol containing quarternary ammonium group
Electorstatically attaches to anionic site of AChE, stabilized with hydrogen bones.
True chemical bond not formed.
Edrophonium, give chemical information
Competitive inhibition for binding sites with ACh
Short duration - 5 to 10 min
Onset - 30 to 60 seconds
IM onset 2 to 10 min
Edrophonium, how is it eliminated?
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
List clinical signs of NMB recovery
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
Factors prolonging paralysis
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
Electrolyte imbalances associated with factors prolonging paralysis
Hypokalemia Hypocalcemia Hypomagnesemia Hypophosphatemia Hypothermia Motor neuron disease
More factors prolonging paralysis
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
Pharmacologic causes of prolonged paralysis
Aminoglycoside toxicity Penicillin toxicity Steroid myopathy Antihypertensives - Calcium channel blockers - beta blockers - Furosemide
Continued pharmacologic causes of prolonged paralysis (antidysrhthmics, aminoglycosides)
Quinidine
Porcainamide
Local anesthetics in large doses
Polymyxin B
Clindamycin
Tetracycline
Continued pharmacologic causes of prolonged paralysis (miscellaneous drugs)
Cyclosporine Steroids Volatile anesthetics Dantrolene Magnesium - OB Lithium Azathioprine Organophosphate (Poisoning) ***
Typical doses and duration of Neostigmine
Neostigmine Dose - 25-75 mcg/kg Onset - 5-15 min Duration - 45-90 min Side effects - +PONV
Typical doses and side effects of Pyridostigmine
Dose - 100-300 mcg/kg
Onset - 10-20 min
Duration - 60-120 min
Side effects - slow onset, long duration
Typical doses and side effects to Edrophonium
Dose - 50-1,000 mcg/kg
Onset - 5-10 min
Duration - 30-60 min
Side effects - Not for deep block, rapid
