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NEUROMUSCULAR BLOCKING AGENTS

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Title: NEUROMUSCULAR BLOCKING AGENTS


1
NEUROMUSCULAR BLOCKING AGENTS
2
NEUROMUSCULAR TRANSMISSION
3
??
  • Neuromuscular junction
  • Motor neuron? muscle cell ??? region of
    approximation
  • Cell membrane of neuron ? muscle ??? ? 20nm ?
    narrow gap ? synaptic cleft
  • Nerve ? action potential ? terminal ?
    depolarizing ? calcium ion ? voltage-gated
    clacium chnnel ? ?? influx ? cytoplasm? storage
    vesicles ? terminal membrane ? ?? ? release their
    contents (Ach)
  • Ach molecule ? synaptic cleft? ?? diffusion ??
    muscle membrane ? nicoticinc receptor ? ??
    (mortor end plate)

4
??
  • ??? neuromuscular junction ? ? 500 ??? Ach
    receptor? ??? ???, ?? ? 500,000 ?? activation
    ???, normal muscle contracture ???
  • ??? Ach receptor ? ?? 5?? subunit
  • 2?? alpha, ?? ? ? ?? beta, delta, epsilon
    subunits
  • ?? 2?? alpha subunit ?? Ach molecule ? ??
  • 2?? alpha subunit , ? binding site ? ?? occupy
    ??, receptor ? conformational change ? ???,
    receptor core ? ion channel ? open
  • Ach receptor channel ? ?? sodium ? calcium ?
    influx, potassium ? outflux ? end-plate
    potential ??
  • ??? single vesicle ? ?? Ach quantum (100,000 ??
    ) ? miniature end-plate potential ? ?? ? ???
    nerve impulse ? ?? 200?? Ach quantum ? release ?
    ??? extracellular calcium? ??? ???? ??, ?
    calcium ??? ?? ?? , relasese ?? quantum ? ?? ??

5
??
  • ??? ?? recepor ? Ach? ????, end-plate potential
    ? perijunctional membrane ? ??? ?? ??? ????
  • ? ??? sodium channel ? threshold voltage ? across
    ??? ??? ?

6
??
  • Muscle ? perijunctional area ? ?? ?? sodium
    channel ? ??
  • Action potential ? muscle membrane ? ??
    propagation ??, T-tubule systme? ?? ?? ?? sodium
    channel ? open ?? sarcoplasmic reticulum ?? ??
    cytoplasm ?? calcium ion ??
  • Intracelluar calcium ? action ? myosin ? ??? ????
    ??? ??
  • Ach ? ??? hydrolize ? ? into acetate, choline
  • By the acetylcholineesterase in motor end-plate
  • Receptors ion channel ? close ? repolarize
  • Action potential ? cease , calcium ion ? ??
    sarcoplasmic reticulum ?? ??

7
DISTICTIONS BETWEEN DEPOLARIZING
NONDEPOLARIZING BLOCKCADE
8
(No Transcript)
9
MECHANISM OF ACTION
  • Ach ? ???? ?? neuromuscular blocking agents ?
    quaternary ammonium compound? ??
  • ???? ?? 2?? quaternary ammonium compound, ?? ???
    1?? ??
  • Depolarizing agent ? Ach ? ?? ??? ??? ??
  • ?? Ach receptor ? ???? action potential ??
  • ???, ? agent ? acetylcholinesterase ? ?? ??
    ????,synaptic cleft ? ?? ??? ?? ?? ?? ??
  • Prolonged depolarization ??
  • Continuous end-plate depolarization ? muscle
    relax ?? ? ?? sodium channel ? lower gate ? open
    ?? (time limited) ? initial excitation opening
    ? ??? ??? upper gate ? close , ? closing ?
    repolarization ? ???? ??? open ?? ???.

10
MECHANISM OF ACTION
11
MECHANISM OF ACTION
  • ?? ??? depolarizing muscle relaxant ? Ach
    receptor ? ??? ????? end-plate ? repolarizing ??
    ??
  • Phase I block
  • ?? ??? ???, prolonged end-plate depolarization ?
    Ach receptor ? ionic and conformational change ?
    ??
  • Phase II block
  • ??? nondepolarizing mescle relaxant ? ??? ??
  • Nondepolarizing muscle relaxant
  • Ach receptor ? ?????, depolarizing agent ? ??
    chonformational change ? ???? ??
  • Ach ? receptor ? ??? ?? ?? end-plate potential ?
    ??? ??

12
MECHANISM OF ACTION
  • Depolarizing agent ? Ach receptor agonist ? ???
    ??? ???, nondepolarzing agent ? competitive
    antagonist ? ??
  • Chronic decrease in Ach release (eg, muscle
    denervation injury)
  • ??? ??, ????? ?? Ach receptor ? ?? ??
  • Immature isoform of the Ach receptor ? induction
  • ??? ?? depolarzing agent ? ??? ??,nondepolarzing
    agent? ?? resistance ? ??
  • Fewer Ach receptors
  • Down-regulation in Myasthenia gravis
  • Nondepolarzing agent ? ??? ??

13
NONCLASSICAL MECHANISMS OF NEUROMUSCULAR BLOCKADE
  • ??? drug ? agonist ? antagonist effect ?? Ach
    receptor ? ??? ??
  • Receptor binding site, receptor channel? closing,
    opening ? function? ??
  • ?????, ?????, ketamine
  • Channel blocking agent
  • Neostigmine, antibiotics, cocaine, quinidine

14
REVERSAL OF NEUROMUSCULAR BLOCKADE
  • Depolarizing agent ? acetylcholinesterase ? ??
    hydrolyzed ?? ???, NM junction ?? diffuse ??,
    plasma ? liver ?? Pseudocholinesterase ? ??
    hydrolyzed
  • ??? ??? ?? ??? ???? ??? reverse agent ? ?? ????
    ??
  • Mivacurium ? ????, nodepolarzing agent ? ? ?? ??
    ?? ???, reversal ? redistribution, gradual
    metabolism, excretion ? ??
  • ??? ??? reversal agent (cholinesterase
    inhibitors)??
  • Acetylcholinesterase ? ?? ??, NM junction ???
    Ach ?? ???? nondepolarizing agent ? ????? ????
  • ??? depolarizing agent ? ??? prolong, ??
    pseudocholinesterase ? ?? ?? ?? ??? ??

15
RESPONSE TO PERIPHERAL NERVE STIMULATION
  • Pph nerve stimulator ?neuromuscular function
    monitor
  • Tetany sustained stimulus of 50-100 Hz, lasting
    5s.
  • Twitch A single pulse 0.2ms duration
  • Train-of-four A series of four twitches in 2s
    (2Hz frequency, ??? duration ? 0.2 ms
  • Double burst stimulation (DBS) Three short (0.2
    ms) highfrequency (50Hz) and followed 750 ms
    later by two or three additional impulse
  • Polonged or repeated nerve stimulation ? ?? Fade,
    gradual diminution of evoked response ?
    nondepolarizing block
  • Fade ??? nondepolarizing agent ? prejunctional
    effect ? ?? ???, ?? nerve terminal ?? available
    for release Ach amount ? ????? ??

16
RESPONSE TO PERIPHERAL NERVE STIMULATION
  • Adequate clinical revery ? fade ? ??? ??
  • Fade ? TOF ? repeated twitch ?? sustained tetanic
    stimulation. DBS ?? ??? ?? ??
  • ??? sustained tetacic stimulation, DBS ???
    adequacy of recovery ? ??
  • Posttetanic potentiation
  • Partial nondepolarizing block ??, tetanic
    stimulation ?, twitch ? ?? ???, increased evoked
    potential ? ??? ??
  • Transient increase in Ach mobilization
  • Phase I depolarization block ? ??, tetanus, TOF,
    ? fade ??? ??? ??
  • Posttetanic potentiation ? ??? ??
  • ??? ??? ?? dose ? ??? ?? phase II blockade ?
    ????, ?? nondepolarizing agent ? ??? ??? ??

17
RESPONSE TO PERIPHERAL NERVE STIMULATION
18
DEPOLARIZING MUSCLE RELAXANT
19
SUCINYLCHOLINE
Physical Structure
  • Diacetylcholine or suxamethonium
  • Two joined Ach molecule ? ??

20
SUCINYLCHOLINE
21
SUCINYLCHOLINE
Metabolism Excretion
  • Rapid onset of action(30-60s), short duration of
    action
  • Low lipid solubility
  • Circulation ?? ??? ?? (pseudocholinesterase)
  • Succynylmonocholine ?? ???
  • ? ?? ? ?? small fraction of the injected dose ?
    ????, NM junction ? ??
  • ?? ??? ???? succinylcholine ? NM junction ??
    blood stream ?? diffuse

22
SUCINYLCHOLINE
Metabolism Excretion
  • Duration of action ? ?? ?? ??
  • High dose
  • Abnormal metabolism
  • Hypothermia decrease hydrolysis
  • Low level of pseudocholinesterase (modest
    prolongation2-20 min)
  • ??, liver dz, renal failure, certain drug therapy
  • Pseudocholinesterase gene defect
  • Dibucaine number
  • proportional to pseudocholinesterase function
  • Abnormal pseudocholinesterase ? ?? prolonged
    paralysis ? continued mechanical ventilation ??
    ??

23
SUCINYLCHOLINE
Metabolism Excretion
24
SUCINYLCHOLINE
Drug interactions
  • Cholinesterase inhibitors
  • Markdly prolong a depolarizing phase I block
  • Acetylcholinesterase inhibition ? nerve terminal
    ?? Ach ??? ??, depolarization
  • Pseudocholinesterase inhibition ? hydrolysis ??
  • Eg, organophosphate ?? ?????? acetylcholinesterase
    activity ???? ? succinylcholine ? action ?
    prolongation
  • Nondepolarizing relaxants
  • Small dose ? phase I block ? antagonize
  • Same Ach receptor ? ?? (pancuronium? ??)
  • Intubation dose ? succinylcholine? rocuronium,
    atracurium ? dose ?? ??? ??

25
SUCINYLCHOLINE
Drug interactions
26
SUCINYLCHOLINE
Dosage
  • Good choice for routine intubation
  • Rapid onset, short duration, low cost
  • Usual intubation dose 1-1.5mg/kg iv
  • ?? 0.5 mg / kg ? dose ?? acceptable ? intubation
    ??? defasciculating dose ? nondepolarizer ? ???
    ?? ??
  • Intense ? paralysis ? ??? ?? repeated small dose
    ? bolus ? drip ? ??
  • ??? ??, overdosing ?? phase II block ? ?? ?? ??
    nerve stimulator ? ??? monitoring ? ??
  • ??? technique ? short acting nondepolarizing
    agent (mivacurium ?) ? ?? ???? ??
  • Distribution lipid solubility ? ?? ???, ?? ECF
    ? ??
  • ECF ? ??? ????? ? infant ? neonate ? ?? dosage ?
    ???

27
SUCINYLCHOLINE
Side Effects Clinical Consideration
  • Relatively safe drug
  • ?? potential complication ? ??? ??? , ??? ??? ???
    ??? ?? ??? ??
  • Hyperkalemia, rhabdomyolysis, cardiac arrest in
    children
  • Routine management of children and adolescent pt
    ?? ??
  • ?? ?? clinician ?? difficult intubation ?? full
    stomach ?? ??? ?????, adult ?? ???? routine use
    ? ??? ??
  • ??? ??? nondepolarizing agnet? succinylcholine ?
    rapid onset ? short duration ? ???? ?? ??

28
SUCINYLCHOLINE
Side Effects Clinical Consideration
  • Cardiovascular
  • Ach? ??? ?? NM junction ? cholinergic receptor
    ? ??
  • ?Ach ? ?? parasympathetic n. ? sympathetic gg,
    adrenal medulla, sweat gl ??? neurotransmitter ?
    ??
  • Succinylacholine ? NM junction ? nicotinic
    receptor ?? ????? ????? ??
  • ??? ??? nicotinic receptor, ?????, SA node ?
    muscarinic receptor ?? ?? ? BP ? HR ? ?? ?? ????
  • Low dose ? negative chronotropic, inotropic
    effects
  • High dose ??? circulating catecholamine ? level ?
    ????
  • ? HR ? contractility ??
  • Children ? ?? bradycardia ??? ????
  • Adult first dose ? 3-8? ?? 2nd dose?, brady
    cardia ??
  • ??? first dose ? ??? metabolite ? SA node ?
    muscarinic receptor ? sensitization

29
SUCINYLCHOLINE
Side Effects Clinical Consideration
  • Fasciculation
  • Onset of paralysis ? ???? visible muscle
    contraction
  • ???? ????? small dose pretreatment? ????
  • Pretreatment ?, depolarizing ? antagonize, ? ??
    ?? succinylcholine ?? (1.5mg/kg)
  • Fasciculation ? children ?? elderly ??? ?? ?? ??
  • Hyperkalemia
  • Succinylcholine induced depolarization ? normal
    m. ? pottasium? ?? ? serum level ? 0.5 mEq/l ??
  • ??? ??? normal baseline level ? ???? ???? ???,
    preexisting hyperkalemia, burn, massive trauma,
    neurological disorder ??? life threatening

30
SUCINYLCHOLINE
Side Effects Clinical Consideration
  • Hyperkalemia
  • ??? severe hyperkalemia ? routine CPR ?? ??,
    calcium, insulin, glucose, bicarbonate,
    cation-exchange resins, dantrolene ?? ??
  • Dennervation injury ?, immature isoform of Ach
    receptor ? NM junction ?? ??? ? ?? site ?? induce
    ?? (up-regulation) wide spread depolarization ?
    ??, extensive potassium release
  • ??? life-threatening potassium release ? ????
    ????? pretreatment ? ??? ??

31
SUCINYLCHOLINE
Side Effects Clinical Consideration
  • Muscle Pains
  • Unsynchronized muscle contraction
  • Increase incidence of postoperative myalgia
  • M/C in female and outpatient, ??, ????? ?? ??? ??
  • ???? ????? pretreatment ? controversial
  • Rocuronium 0.06-0.1 mg/kg ???, fasciculation? ??
    ?? postoperative myalgia ? ?????? report
  • Perioperative NSAIDs reduce the incidence and
    severity
  • Intragastric pressure elevation
  • Abdominal wall muscle ? fasciculation ? ??
    intragastric pressure ? ?????, lower esophageal
    sphincter tone? ?? ?? ? aspiration, reflux ? ???
    ??

32
SUCINYLCHOLINE
Side Effects Clinical Consideration
  • Intraocular Pressure Elevation
  • Extraocular m. ? ?? striated m. ? ?? multiple
    end-plate ? ?? ???? ???? ??? ??? ?? intraocular
    pressure ??
  • ???? ????? ???? ?? ??? ??? ??
  • Masseter Muscle Rigidity
  • Masster m. tone ? ??
  • Intubation ? mouth openning ? difficult
  • Marked increase in masster m. tone ? laryngoscope
    use difficult ??? ??? malignant hyperthermia ?
    premonitory sign ??? ??
  • Malignant hyperthermia
  • Hypermetabolic disorder of skeletal m.
  • NMS (neuroleptic malignant syndrome)
  • Malignant hyperthermia ? ??? ??, ??? pathogenesis
    ? ??? ??? succinylcholine ? ??? ??

33
SUCINYLCHOLINE
Side Effects Clinical Consideration
  • Prolonged paralysis
  • Intracranial pressure
  • Slight increase in cerebral blood flow
  • Muscle fasciculation ? stretch receptor ? ?? ??
    cerebral activity ??
  • ICP ??? good airway control, hyperventilation ??
    ??
  • ???? ????? ??? ? lidocaine iv ??? preventing
  • Histamine release

34
NONDEPOLARIZING MUSCLE RELAXANT
35
UNIQUE PHARMACOLOGICAL CHARACTERISTICS
36
UNIQUE PHARMACOLOGICAL CHARACTERISTICS
Suitability For Intubation
  • Succcinylcholine ? rapid onset, short duration ?
    ???? ????? ????? ??
  • Rapid onset ? ??, large dose ??
  • ED 95 ? 1-2 ?? ??? intubation dose? ??
  • Larger intubation dose ? onset speed ? ?? ???,
    prolonged blockade, side effect ? ??? ??
  • ??? large dose ? duration of action ? ????,
    completely reversing ? ??? ??, postoperative
    pulmonary complication ? ?? (?? ???? ?? ?? ?)
  • More potent drug ? onset speed ? ??
  • Priming dose short or intermediate acting
    agent, usual intubating dose ? 10-15 ??
    (induction 5??)
  • Rocuronium ? ??, ? 60? ?, intubation ? suitable

37
UNIQUE PHARMACOLOGICAL CHARACTERISTICS
Suitability For Intubation
  • Priming dose
  • priming dose ? ???, clinically significant
    paralysis ? ???? ???, ?? ??? ??, distressing
    dyspnea, diplopia, dysphagia ??
  • ??? ???? ??? ?????, ?? induction ? ??
  • Priming ? ?? significant deteriotaion in
    respiratory function ? ??

38
UNIQUE PHARMACOLOGICAL CHARACTERISTICS
Suitability For Preventing Fasciculation
  • Intubationg dose ? 10-15 ? succinylcholine ??
    5? ? ???, fasciculation ? ?? (?? tubocurarine,
    rocuronium)

39
UNIQUE PHARMACOLOGICAL CHARACTERISTICS
Maintenance relaxation
  • Intubation ???, muscle paralysis ? ??? ??? ?? ??
  • Abd. Surgery, anesthetic management for
    mechanical ventilation
  • Nerve stimulator monitoring ?, clinical sign ?
    ????, ??? ??? ??

40
UNIQUE PHARMACOLOGICAL CHARACTERISTICS
Potentiation By Other Nondepolarizer
  • Some combination (eq, mivacurium pancuronium)
  • Greater potency? ??
  • ??? ??? ??, ??? potency ? ??? ??
  • ?? ?? mechanism? ?? drug ? ???? ? ?? potency ? ??

41
UNIQUE PHARMACOLOGICAL CHARACTERISTICS
Autonomic Side Effects
  • ???? ??, clinical dose ???, nicotinic or
    muscarinic Ach receptor? ?? effect ? ?? ??? ??
  • ?? older agent (eg, tubocurarine, metocurarine )
    ?? autonomic ganglia ? block, sympathetic
    nervous system ? compromise
  • Hypotension, intraoperative steress ? ?? ???? ??
  • Pancuronium ? SA node ? vagal muscarinic receptor
    ? block ? tachycardia
  • Atracurium, cisatracurium, mivacurium, vecuronium
    ?? newer agent ?? ??? dosage ??? significant ?
    autonomic side effects ? ?? ??

42
UNIQUE PHARMACOLOGICAL CHARACTERISTICS
Hepatic clearance
  • Pancuronium ? vecuronium ? significantly
    metabolized in liver
  • Active metabolite ? clinical effect ? ??
  • Vecuronium ? rocuronium ? bile ? ???? excretion
  • Liver cirrhosis ? blockade effect ? ??
  • Atracurium, cisatracurium depend on extrahepatic
    mechanism
  • ??? ?? liver disease ??? ?? ?? ??

43
UNIQUE PHARMACOLOGICAL CHARACTERISTICS
Renal Excretion
  • Doxacurium, pancuronium, vecuronium, pipecuronium
    ?? kidney ?? partially excreted
  • Renal failure ? prolonged action

44
GENERAL PHARMACOLOGICAL CHARACTERISTICS
  • Temperature
  • Hypotermia prolongs blockade by decreasing
    metabolism (mivacurium, atracurium,
    cisatacurium), and delaying excretion (
    pancuronium, vecuronium)
  • Acid-base balance
  • Respiratory acidosis ???? ???? ????? potency ?
    ????? reversal ? antagonize
  • ?? hypoventilating postoperative ????? ????
  • Electrolyte abnormality
  • Hypokalemia, hypocalcemia ? ???? ???? ????? block
    effect ? ??
  • Preeclampsia pt ? ??, magnesium sulfate ???
    magnesium ? ??, motor end-plate ?? calcium ?
    ????? ???? blockade ??? ??

45
GENERAL PHARMACOLOGICAL CHARACTERISTICS
  • AGE
  • Neonate ? ??, immature NM junction ? ??? ?? ????
    ????? ?? sensitivity ? ??, ??? ECF ? volume ? ??
    ??? Vd ? ?? ? drug ? ??? ?? ??
  • Drug interactions

46
GENERAL PHARMACOLOGICAL CHARACTERISTICS
  • Concurrent disease
  • LC, CRF ? ?? Vd ?? ? water soluble drug ? ??
    plasma conc. ? ?? (dosage ?? )
  • ?? hepatic clearance ? renal excretion ? ???
    drug? ?? ? prolonged effects ( dosage ?? )
  • ??? ??? ??, greater initial dose, smaller
    maintenece dose ? ?? ?? ?? ???

47
GENERAL PHARMACOLOGICAL CHARACTERISTICS
  • Muscle Groups
  • Muscle group ? ??, onset ? intensity of blockade
    ? ??
  • Blood flow, distance, different fiber types
  • Choice of m. relaxant ? ?? m. group ? sensitivity
    ? ??
  • ???, diaphragm, jaw, larynx, facial muscle ?
    thumb m. ?? recover ? ??
  • Glottic m. ? blockade ? ???? ??? ??
  • Laryngeal m. ? ED95 ? adductor pollicis ? ? 2?
  • orbicularis oculi m. ? twitch response ? ????
  • ?? good intubation condition
  • ????? duration ? magnitude ? ?? ??? ?? ????, ???
    response ? ??? ??
  • Text ? ??? dosage recommend ? indibidual Pt ? ??
    modification ??? ?

48
ATRACURIUM
  • Physical Structure
  • Quaternary group, benzylisoquinoline
  • 10 stereoisomer ? ??
  • Metabolism Excretion
  • Extensively metabolized, independent of renal,
    hepatic function
  • Ester hydrolysis nonspecific esterase
  • Hofmann elimination physiologic ? pH ? ????
    ???? nonenzymatic chemical breakdown
  • Dosage
  • For intubation 0.5 mg/kg iv (30-60 ?? inject)
  • Intraoperative relaxation initial 0.25 mg/kg, ?
    10-20 ??? 0.1mg/kg iv, infusion ? 5-10 microgram
    /kg/min
  • Age insignificant effects, ??, ?? ? ?? short
    acting

49
ATRACURIUM
  • Side effects clinical considerations
  • Dose dependent histamine release 0.5mg/kg ??
    ???
  • Hypotension and tachycardia
  • 0.5mg/kg ??? dose ??? ?? ???? ??
  • Transient drop in systemic vascular resistance,
    increase acrdiac index
  • Slow rateof injection ? minimize this effects
  • Bronchospasm
  • Avoided in asthmatic pt
  • Severe bronchospasm ? asthma Hx ?? ????? ??
  • Laudanosine toxicity
  • Atracurium ? Hofmann elimination ? product
  • MAC ? ??, CNS excitation

50
CISATRACURIUM
  • Hofmann elimination end product ? no intrinsic
    neuromuscular blocking effect
  • Laudanosine ??? aracurium ? ?? ??
  • Age ? ?? pharmacokinetic change ? ?? ??
  • Dosage
  • 0.1-0.15 mg/kg ??? ? 2??? good intubataion
    condition
  • Average infusion rate 1.0-2.0 microgram/kg
  • Atracurium ? cisatracurium ? 2-8 ?? ???? ??, ???
    14? (atracurium) 21?(cisatracurium) ?? ?? ??? ?
  • Side effects clinical consideration
  • Dose not produce histamine release
  • Dose not affect HR, BP, autonomic effects
  • Ph, temperature, chemical incompatibility ??
    atracurium ? ??

51
PANCURONIUM
  • Physical structure
  • Bisquaternary relaxant (tow modified Ach molecule
    steroid ring)
  • Metabolism Excretion
  • Liver ?? ??? ?? ??? (deacetylated)
  • ?? ??? some blocking effect ? ??
  • 40 ??? kidney ? excretion
  • Renal failure ? prolonged action
  • Liver cirrhosis ?, Vd ? ???? ???, initial dose ?
    ?? ??? ??, plasma clearance ? ?? ?? ???,
    maintenance dose ? ??

52
PANCURONIUM
  • Dosage
  • Intubation dose 0.08-0.12 mg/kg , 2-3? ??
  • Intraoperative relaxation dose 0.04 mg/kg ?? ?,
    20-40? ?? 0.01 mg/kg injection
  • ??? ?? moderately higher dose
  • 2-8 ? ?? ????, 6?? ?? ???? stable
  • Side effects clinical considerations
  • Hypertension tachycardia
  • Vagal blockade
  • Sympathetic stimulation ganglionic stimulation,
    catecholamine release from adrenergic nerve
    endings, decreased catecholamine reuptake
  • Increased HR ? ?? (coronary aretery dz,
    idiopathic hypertrophic subaortic stenosis ?) ???
    ?? ?? monitoring

53
PANCURONIUM
  • Side effects clinical considerations
  • Arrhythmias
  • Atrioventricular conduction ? ??, catecholamine
    release ?? ? predisposed pt ??? ventricular
    dysfunction ? ??
  • Pancuronium ? TCA, halothane ?? ?? ??? ??
    arrhythmogenic
  • Allergic reactions
  • Bromide ? hypersensitive ??? ??? ?? allergic
    reaction ?? ? ?? (eg, pancuronium bromide)

54
PIPECURONIUM
  • Physical structure
  • Bisquaternary steroidal structure, pancuronium ?
    ??
  • Metabolism excretion
  • Metabolism ? minor role, elimination ? excretion
    ? ?? ??
  • Renal 70, biliary 20
  • Renal failure ? duration ?? , ??? hepatic
    insufficiency ??? ?? ?? ??
  • Dosage
  • Pancuronium ?? slightly potent
  • Intubating dose 0.06-0.1 mg/kg
  • Maintenance relaxation dose ? pancuronium ? ?? ?
    20 ??
  • Infants ? ??, kg ? dose ? ??, ??? ?? ?? ??

55
PIPECURONIUM
  • Side effects Clinical considerations
  • Principal advantage over pancuronium lack of
    cardiovascular side effects (cardiac muscarine
    receptor binding ? ??)
  • Onset of action ? duration ? pancuronium ? ??

56
VECURONIUM
  • Physical structure
  • Pancuronium ?? quaternary methyl group ? ? ??
  • ??? ??? ??? pnacuronium ? potency ? ?? ? ?, side
    effects? ????
  • Metabolism Excretion
  • ??? small extent, ?? biliary excretion, 25 ?
    renal excretion
  • Renal failure ???? ???, satisfactory, ??? ???
    duration??? ??
  • Pancuronium ? ??, brief duration, rapid
    clearance, due to shorter elimination half life
  • ICU ?? long term administration ? ?? ?? ????
    prolonged blockade ? ????, ?? active metabolite ?
    accumulation, drug clearance ? ??,
    polyneuropathy? ??
  • female, renal failure, high dose , long term
    steroid therapy, sepsis ?? risk factor

57
VECURONIUM
  • Metabolism Excretion
  • Long-term relaxant ??? prolonged lack of Ach
    binding at the post synaptic nicotinic Ach
    receptors ? chr. Denervation state ?lasting
    receptor dysfunction, paralysis
  • Long term use of nondepolarizing m. relaxant ?
    toleranace ?? ??
  • Dosage
  • Pancuronium ? ?? potent
  • Intubating dose 0.08-0.12 mg/kg
  • Intraoperative relaxation dose 0.04 mg/kg
    (initial)
  • ?? 15-20 ? ?? ? 0.01 mg/kg ? ?? ?? ??
  • Infusion 1-2 micro grams/kg/min
  • Age initial dose? not affected , subsequent
    dose ? neonate ? infant ? ?? less frequent

58
VECURONIUM
  • Dosage
  • ??? ??? ?? ? 30 sensitive (blockade ???
    duration ? ??)
  • Fat muscle mass, protein binding,Vd ? ??? ??
  • Postpartum pt ? ?? duration of action ? ??
  • Liver uptake ? hepatic blood flow ? ??
  • 10mg of powder 5-10 ml ? water ? ?? ? ??
  • ?? ??? 24 ??? ??
  • Thiopental ? ?? line ?? ?? ?, ?? ??

59
VECURONIUM
  • Side effects clinical considerations
  • Cardiovascular 0.28 mg/kg ? ????? significant
    ?cardiovacular effects ? ??? ??
  • ?? ??, opioid induced bradycardia ? potentiation
  • Liver failure
  • 0.15 mg ??? dose ??? cirrhosis ??? ????, ??? ???
    prolongation ? ??? ??
  • Liver transplantation ? anhepatic phase ??? ???
    ??? ?

60
ROCURONIUM
  • Physical structure
  • Vecuronium analogue ?? rapid onset of action ? ??
    ??
  • Metabolism Excretion
  • No metabolism, liver ?? ?? excretion
  • Renal dz ?, duration ? ???? ?? ??? ???, severe
    hepatic failure? pregnancy ? , modest
    prolongation ? ??
  • Prolonged infusion ?, rocuronium ? , active
    metabolite ? ???? ?? ??? vecuronium ?? ???
  • ?? ??? ??,liver mass ? ?? ??? duration ? ??? ??

61
ROCURONIUM
  • Dosage
  • Induction dose (0.9-1.2 mg /kg ) ? onset of
    action ? succinycholine ? ?? (60-90s)
  • Rapid-sequence induction ? ?? ???, ??? ??, ?? ??
    dose ? ?? duration ??
  • ?? clinician ? ??? rocuronium ? longer action
    (succinylcholine ? ??? ) ? ?? ?? ??, pofol ??
    thiopental ?? 20? ??, rocuronium ?? timing
    principle
  • ??? ??? ??? induction agent ? delayed
    administration ? ??? ??? ??? ?? ????? paralyzed
  • Rocuronium ? 0.1mg/kg ? ??? succinylcholine ?? ?
    precurarization ? ????
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