Neuromuscular Blockade: Pathophysiologic Implications Flashcards
Factors associated with Resistance to Nondepolarizing NMB (decreases block)
Due to decrease activity of AChE, or induced cytochrome P-450 in the liver causes increased metabolism (?), or increased number of ACh receptor sites (increased amt. of NMB required)
Drugs and their resistance to non depolarizing NMB
Phenytoin – causes shorter duration
Rocuronium 20% of control
Vecuronium 37% of control
Pancuronium 40% of control
Chronic use of _____ cause increased resistance to steroidal relaxants like vecuronium
- corticosteriods
Corticosteriods often used as tx in what condition?
Myasthenia gravis
how do Aminophylline and Theophylline create resistance to NMBs?
inhibit phosphodiesterase - increase the cyclicAMP needed to synthesize and release ACh (greater dose of NMB to compete with more Ach)
how does furosemide increase resistance to NMBs
in large doses, 1-4 mg/kg, inhibits phosphodiesterase, increasing cAMP (same as azathioprine, Imuran
Resistance begins 10 days after ____ injuries
Burn
*peaks at 40 days, and declines after 60 days (463 days); requires 30% or more burned BSA;
Cannot give Sux 24-48 hrs after for burn victims due to risk of
hyperkalemia- extrajunctional receptors
Burn injures cause resistance to NMB due to
decreased sensitivity of the postjunctional receptors to either ACh or nondepolarizing NMB.
increased ______ receptors create resistance due to _____
*extrajunctional cholinergic receptors
*denervation
Example of patients that have increased extrajunctional receptors
hemiplegics or patients with paralyzed limbs
condition that causes resistance due to prolonged response due to co existing skeletal muscle weakness or having increased extrajunctional cholinergic receptors
multiple sclerosis
conditions that can lead to increased extrajunctional cholinergic receptors
*massive trauma
*immobilization
*chronic hyperkalemia
how does chronic hyperkalemia cause increased resistance
decreasing the resting potential of the membrane (moves it closer to depolarization), even partially depolarizes it (increases sensitivity to SCh)
How do volatile anesthetics increase Sensitivity to Nondepolarizing NMB?
decreases the skeletal muscle tone and decreases the sensitivity of muscle membranes to depolarization to lower the ED95; greatest impact on long-acting NMB
How do local anesthetics increase Sensitivity to Nondepolarizing NMB?
– interfere with the release of ACh from the prejunctional receptors (decrease competitor), block ion channels, and directly depress skeletal muscle tone. – makes pt more sensitive
ester LA compete with SCh for plasma cholinesterases which may result in prolonged SCh effect
How do antibiotics increase Sensitivity to Nondepolarizing NMB?
magnesium-type effect to decrease release of ACh to make reversal unreliable (can give calcium).
Antibiotics that have NO NEUROMUSCULAR EFFECT are
penicillins, cephalosporins (Ancef), and macrolides (erythromycin).
How does lidocaine increase Sensitivity to Nondepolarizing NMB?
when given to a patient who is recovering from a nondepolarizing NMB, the block is potentiated by the blockage of the prejunctional release of Ach
Blunts airway reflexes
How does Quinidine increase Sensitivity to Nondepolarizing NMB?
potentiates nondepolarizing NMB and SCh.
How does Lithium (cation) increase Sensitivity to Nondepolarizing NMB?
synergist(1+1=3 effect on nondepolarizing and additive effect(1+1=2) (prolonged onset and duration) on depolarizing
Lithium accumulates in nerve endings and decreases ACh synthesis- makes patient more sensitive to NMB
Similarity to sodium ion – the lithium influx intracellularly into the muscle - hypopolarizes the membrane and therefore potentiates depolarizing neuromuscular blockers (succ)
How does Lasix increase Sensitivity to Nondepolarizing NMB?
<1mg/kg – decreased cyclicAMP production
How does Cyclosporine increase Sensitivity to Nondepolarizing NMB?
Leg cramps, contractions
*Based on retrospective study of renal transplant patients who required postoperative ventilation – either atracurium or vecuronium
How does Succinylcholine increase Sensitivity to Nondepolarizing NMB?
– reduces dose required possibly due to membrane desensitization causing enhanced (not prolonged) blockade by the nondepolarizing NMB, succ makes pt more sensitive to NonDepolarizer
How does other non depolarizing NMBs increase Sensitivity to Nondepolarizing NMB?
synergistic effect with two drugs with different sites of action (pancuronium and metocurine) allowed smaller doses of each to minimize side effects – typically drugs from different classes.
How do calcium channel blockers increase Sensitivity to Nondepolarizing NMB?
- usual site of action is on the slow channels, not fast channels like the postjunctional receptors. Unpredictable effects have been reported.
How does hydrocortisone increase Sensitivity to Nondepolarizing NMB?
acute administration may potentiate nondepolarizing NMB, becomes sensitive to steroid class of drugs (ronium)
Development of critical illness myopathy
How do antihypertensives increase Sensitivity to Nondepolarizing NMB?
– ganglionic blockers – trimethaphan, hexamethonium – can decrease sensitivity of the muscle membrane to cause relaxation of its own and potentiate nondepolarizing NMB; they also inhibit plasma cholinesterase activity to cause prolongation of depolarizing block
How does hypothermia increase Sensitivity to Nondepolarizing NMB?
prolongs duration by slowing clearance via hepatic enzymes and renal pathways and via Hofmann elimination and ester hydrolysis
How does hypokalemia increase Sensitivity to Nondepolarizing NMB?
increases membrane potential (hyperpolarization, further from depolarization) and increases sensitivity to nondepolarizing NMB (resistant to SCh)
How does hypermagnesium increase Sensitivity to Nondepolarizing NMB?
decreased release of ACh from prejunctional receptors (enhanced block); pregnant women with toxemia being treated with magnesium should receive a reduced dose of relaxant- very sensitive to non depolarizer
How does hypernatremia increase Sensitivity to Nondepolarizing NMB?
dehydration causes decreased volume of distribution of NMB, thus more drug reaches the receptors (increased concentration of drug)
how does gender increase Sensitivity to Nondepolarizing NMB?
differences in muscle mass from men cause greater block in women with similar mg/kg dose.
Myasthenia gravis =
chronic autoimmune disorder caused by a decrease in functioning acetylcholine receptors at the NMJ (destroyed by IgG antibodies)
muscles that are first to show symptoms of fatigue, weakness (undiagnosed) with myasthenia gravis
Ocular, pharyngeal, laryngeal muscles
Myasthenia gravis treatment
anticholinesterases and immunosuppressive drugs which may cause resistance to non depolarizers
Myasthenia gravis shows a ____
sensitivity to nondepolarizing NMB due to ____ receptors for which to compete.
*increased
*fewer
- prolonged effect so NMB may need to be avoided with these patients
what is important/needed in order to determine the dose of myasthenia gravis patient?
baseline TOF-Titrate initial dose to response to peripheral nerve stimulator (reduce ½ to 1/3).
-No correlation between base TOF and clinical severity
Some correlation between base TOF and dose required
Myasthenic syndrome – Eaton Lambert=
Seen with oat cell carcinoma of the lung; autoimmune disease where presynaptic calcium channels are destroyed by antibodies. (vs. post synaptic channels in myasthenia gravis
*Think about possibility in known cancer patients and those having diagnostic or biopsy procedures for lung cancer.
what drugs are ineffective with Myasthenic syndrome – Eaton Lambert, which are sensitive?
Anticholinesterase drugs are ineffective.
Sensitive to both SCh and nondepolarizing NMB
diagnostic or biopsy procedure where Eaton Lamberts condition is discovered
Thoracoscopy
drug that HAs a black box warning to the pediatric population
SCh
-hyperkalemia and asystole potential similar response as with MH as with muscular dystrophy
What drug is contraindicated for muscular dystrophy
SCh
Sch may cause ____ ____ of NMB when muscle weakness and atrophy exists
prolonged duration
SCh causes ___ ____ in myotonia dystrophica
prolonged contraction
-give short acting that does not need to be reversed because ACH (ACH increased when giving anticholinesterase) will cause depolarization of the muscle membrane and contraction
Amyotrophic lateral Sclerosis (ALS) also known as
Lou Gehrig’s disease
ALS is a degenerative disease that affects the ___ ____ and spinal _____ tracts
- motor ganglia
- pyramidal tracts
ALS causes prolonged responses to
- non depolarizing NMB and Hyper K with SCh
- skeletal muscle atrophy
Giving a water soluble drug to a baby causes the drug to be
more diluted out since greater water amt in their bodies
Drug that causes a quicker onset in infants and children and why
Vecuronium due to faster circulation times
Vecuronium has prolonged recovery in ___ and ___ while children recover faster
- infants and neonates
Due to Atracuriums histamine release neonates required a 25% lower
- dose by weight due to increased sensitivity
Elderly have decreased ____ and ____ so doses will be more
body fluid and lean muscle mass
- concentrated
these 2 drugs shows a prolonged duration in the elderly
Vecuronium and Rocuronium
ELderly have decreased plasma ___,
proteins=so more unbound drug that can have an effect
- also have decreased cardiac output, kidney function, and hepatic blood flow
in the elderly, the priming technique resulted in decreased ____ ____ and ____
- pulmonary parameters,
- desaturation
drug that is age and organ independent so indicated for the elderly
Atracurium- however histamine release is greater
for Obese patients, SCh is dosed based on ___ body weight because?
total body weight, obese patients have more plasma cholinesterase so a bigger dose of drug is needed to prevent SCh from being “eaten up” and not enough of drug able to make it to the receptor sites
Blood flow matters!! increased cardiac output =
faster onset and vice versa
ephedrine- partial direct and indirect acting- affects alpha 1 receptors to cause ______ but also effects/stimulates beta 1 receptors to increase______
vasoconstriction
- HR and stroke volume
-given prior to administration of rocuronium, decreased onset time by 22%
Esmolol blocks beta 1 receptors which _____ onset time by 26%
increases
-application- someone on chronic beta blockers may have increased onset times during induction
