Quiz 7 Flashcards
Which receptor does NMB work on? how do the normally work?
Nicotinic
- ACH binds to both alpha channels (ligand gated)
- Na moves through
What part of ACH reacts with subunit at receptor?
N+
ACH deactivated by? made of?
Acetylcholinesterase
choline and acetate
ACH facts
can activate rest/digest or fight/flight response b/c activates both parasympathetic/sympathetic pathways
receptor that activates fight/flight
nicotinic
receptor that activates rest/digest
muscarinic
how much twitch response suppression adequate for surgery?
90%
tracheal intubation dose = ?
2x ED95 dose
how are muscles effected by NMB
small muscles first (eyes, fingers)
large muscles last (abdomen, diaphragm)
More rapid/ less intense at _______ muscles than ________ muscles. Whats a good predictor?
laryngeal
peripheral
(Adductor pollicis response poor indicator of laryngeal relaxation
Orbicularis oculi better prediction)
which type NDMNB has a higher incidence of histamine release? whats the other type of NDNMB?
- Benzylisoquinolinium
- Aminosteroid
(different reversals b/w the 2)
does albumin levels effect NMB action?
No bc not highly protein bound
CYP interference is what type of interaction?
Pharmacokinetic
membrane stabilization or receptor site action is what type of interaction?
Pharmacodynamic
Long acting NDNMB and class? (3)
Pancuronium (A)
Doxacurium (B)
Pipecuronium (A)
Intermediate acting NDNMB and class? (4)
Atracurium (B)
Vecuronium (A)
Rocuronium (A)
Cisatracurium (B)
Short acting NDNMB and class? (1)
Mivacurium (B)
Succ action on receptor site?
Succ specific on formulary level?
- only needs to bind to 1 site (nicotinic receptor)
- two N+ in chemical formula
Why does Succ. have a longer duration than ACH?
Slower hydrolysis
any pre or post synaptic effects in Succ?
Pre - minor effects
Post - leakage of K+ out of cell for increase serum K+ of 0.5 mEq/L
Phase I Blockade:
- Depolarizing block- receptor stimulation
- Decreased contraction in response to single twitch stimulation
- Decreased amplitude by sustained response to continuous stimulation
- TOF ratio >0.7
- Absence of posttetanic facilitation
- Augmentation of neuromuscular blockade after reversal agent
- Accompanied by fasiculations at onset
Phase II Blockade:
- Desensitization: Similar to non-depolarizers
- May be antagonized by a reversal agent
- Manifests as tachyphylaxis
Metabolites of Succ? what breaks Succ. down?
- succinic acid and choline
- Plasma Cholinesterase
(Must diffuse away from the NMJ to plasma to be metabolized)
what reduces amounts of plasma cholinesterase? what increases?
- Severe liver disease
- neostigmine
- high estrogen levels
- Reglan (inhibits enzyme)
-Obesity
What tests for atypical pseudocholinesterase?
Dibucaine test
how to reduce Succ side effects?
treat with NDNMB
doesn’t treat s/e of hyperkalemia
what increases arrhythmia risk in Succ use? What to do for arrythmias?
- 2nd dose within 5 minutes
- Atropine will not work, need B1 agonist (epi, dopamine)
What arrythmias can you get with Succ?
- Sinus bradycardia
- junctional rhythm
- sinus arrest
- May increase heart rate and BP due to ANS ganglia stimulation
increased risk pts for hyperkalemia? VERY high risk? How long can last?
- Muscular dystrophy
- Third degree burns
- Skeletal muscle atrophy or severe trauma
- Upper motor neuron lesions
VERY HIGH RISK - male children with undiagnosed myopathy
-May develop within 96 hours, last up to 6 months or more
Succ s/e of increased pressure - most common? biggest risk?
- increased intragastric pressure
- aspiration
NDNMB characteristics:
- Antagonism by anticholinesterases
- Decreased twitch response to single stimulus
- TOF ratio <0.7
- Unsustained response during continuous stimulation
- Posttetanic potentiation
- Potentiation of other nondepolarizers
NDNMB cardiac effects
- Histamine release (Atracurium, Mivacurium)* vasodilation, drops bp
- Cardiac muscarinic receptors (Pancuronium)
- Nicotinic autonomic ganglia (mostly SCh)
what type of receptor competition for NDNMB?
Competitive antagonist
who has higher risk of allergic reaction to NDNMB
women
what enhances NMBs
- Volatile anesthetics
- Aminoglycosides ( tobramycin, gentamicin, and amikacin)
- Local anesthetics
- Antiarrhythmics
- Diuretics
- Mg++, Li+ (Ca inhibition with too much Mg. Li tricking body believe its Na)
- hypothermia
Temp and NMB
Every degree C in each direction can delay/quicken response by 5-15 mins
Pancuronium:
- Renal failure: clearance reduced up to 50%
- Metabolite: 3-desacetylpancuronium Half as potent as pancuronium
- Total billiary obstruction, hepatic cirrhosis - prolonged half life d/t fluid dynamic changes (larger vD) bc hydrophilic
- Enhanced by respiratory acidosis
Pancuronium cardiovascular effects:
Increase heart rate
Increased MAP
Increased cardiac output
Mechanism: vagal blockade; SNS activation; muscarinic interference (block)
Dysrhythmias, esp. in combo with Digoxin
NMB with no CV changes
Doxacurium
pipecuronium
Infants: increased potency, shorter duration
pipecuronium
Priming Principle:
Alternative to SCh for intubation 1: Small dose binds spare receptors no clinical effect 2: 4 minutes later deliver the rest deepens the neuromuscular blockade rapidly
Which drug is protein bound?
Atracurium (higher effect in low albumin levels)
what effects Hoffmans elimination and what drugs effected?
- Accelerated by alkalosis, slowed by acidosis
- Atracurium and Cisatracurium
(Independent of renal and hepatic function)
What NMB good for pts with organ issues?
-Atracurium and Cisatracurium
what metabolite of Hoffman elimination that can increase MAC values?
Laudanosine
Atracurium CV s/e?
- Histamine release (H1 and H2 blockers help (combo))
- long term H2 blocker use may exacerbate CV effects due to histamine
cisatricurium difference?
NO HISTAMINE release
Vecuronium:
- Both hepatic metabolism and renal clearance
- Higher lipid solubility to enter hepatocytes
- Lipid solubility for billiary excretion (40% unchanged in the bile)
- Exaggerated response with hepatic cirrhosis
- 30% unchanged in the urine (Half life prolonged in renal failure)
what enhances vecuronium?
-Hypercarbia post injection enhances effects (avoid hypoventilation post-op)
Vecuronium - Pediatric:
- Onset more rapid for infants
- Duration longest in infants shortest in children
NDNMB with quickest onset?
Rocuronium
NDNMB with shortest duration?
Mivacurium
NMB with 1 N+ base?
Rocuronium
Vecuronium
most potent NMB
Doxacurium
