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Nonvolatile anesthetic agents

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Title: Interesting Case Author: User Last modified by: Anes04_ Created Date: 8/1/2007 6:14:53 AM Document presentation format ... – PowerPoint PPT presentation

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Title: Nonvolatile anesthetic agents


1
Nonvolatile anesthetic agents
2
?????????? ?????????? anesthesia gas
3
?????????????????????
  1. ?????????????????????????
  2. ??????????????????????????????????????
  3. ????????????????????????????????????????????????

4
Nonvolatile anesthetic agents
  • Opioids
  • Non-opioid
  • Barbiturates
  • Benzodiazepine
  • Ketamine
  • Etomidate
  • Propofol

5
Nonvolatile anesthetic agents
  • Induction agent for GA
  • Sedation
  • Analgesia

6
Barbiturate
  • Properties
  • Sodium salt water soluble
  • Markedly alkaline

7
Barbiturate
  • Mechanism of action
  • Depress RAS
  • Suppresstion transmission of excitatory
    neurotransmitters (Ach)
  • Enhance transmission of inhibitory
    neurotransmitters (GABA)

8
Phamacokinetics
  • Distribution
  • High protein binding ,great lipid solubility
  • Duration redistribution
  • Maximal brain uptake in 30 s
  • (one arm to brain circulation)
  • Biotransformation Hepatic oxidation
  • Excretion renal

9
Effect on organ system
  • Cardiovascular
  • Decrease BP Depression of the medullary
    vasomotor center
  • Increase HR Central vagolytic effect
  • Maintained CO compensate baroreceptor reflex
  • Except in hypovolemia ,CHF , ß-block, old age

10
Effect on organ system
  • Respiratory
  • Decrease ventilatory response to hypercapnia
    hypoxia depress the medullary ventilatory
    center
  • Not complete depress noxious airway reflex
  • Bronchospasm histamine release ,cholinergic n.
    stimulation

11
Effect on organ system
  • Cerebral
  • Decrease CBF ICP
  • Renal
  • Decrease RBF GFR depend on BP
  • Hepatic
  • Decrease HBF

12
Clinical use
  • Dose 3-5 mg/kg
  • Side effect
  • Urticarial rash
  • Pain on injection
  • Laryngospasm, hiccup

13
Propofol
  • Properties
  • Oil in water emulsion
  • Containing soybean oil ,glycerol ,egg lecithin
    (egg yolk)
  • Pain on injection decrease by lidocaine

14
Propofol
  • Mechanism
  • Activation of inhibitory neurotransmitter (GABA)

15
Pharmacokinetics
  • Absorption IV
  • Distribution
  • High lipid solubility (one-arm-to-brain
    circulation time)
  • Awakening redistribution (2-8 min)
  • Less hangover than other drug
  • Biotransformation
  • Hepatic extrahepatic metabolism
  • Excretion renal

16
Effect on organ system
  • Cardiovascular
  • Decrease BP decrease SVR ,cardiac contractility
    ,preload
  • Decrease HR Impair arterial baroreflex response
    to hypotension
  • Transient change in HR CO but severe in extreme
    aged ,on negative chronotropic medication

17
Effect on organ system
  • Respiratory
  • Depress ventilatory drive like the barbiturates
  • Depress upper airway reflexs
  • Less incidence of bronchospasm
  • Cerebral
  • Decrease CBF ICP
  • Other
  • Anti-emetic effect preferred for outpatient
    anesthesia
  • Anticonvulsant properties

18
Clinical use
  • Dose
  • Induction Dose 1-2 mg/kg
  • Sedation 10-50 µg/kg/min
  • Side effect
  • Pain on injection
  • Anaphylactoid reaction
  • Propofol infusion syndrome

19
Ketamine
  • Properties
  • Analogue of phencyclidine
  • Cause hallucinogenic effect

20
Ketamine
  • Mechanism of action
  • Multiple effect on CNS
  • Dissociative anesthesia
  • Effect on thalamus limbic cortex
  • Appear conscious
  • (eye opening ,swallowing ,muscle contracture)
    but unable to process sensory input

21
Pharmacokinetics
  • Absorption IV ,IM ,oral, rectum
  • Distribution
  • More lipid soluble less protein bound than
    thiopental
  • Awakening due to redistribution to peripheral
    compartment
  • (10-15 min)
  • Biotransformation
  • liver
  • Norketamine retain anesthetic activity
  • Excretion renal

22
Effect on organ system
  • Cardiovascular
  • Increase BP ,HR ,CO
  • stimulation of the sympathetic system
    inhibition of the reuptake of NE
  • Increase myocardial work
  • Avoid in pt. with CAD ,HT ,CHF ,arterial aneurysm
  • Beneficial to pt. with acute hypovolemic shock

23
Effect on organ system
  • Respiratory
  • Minimal effect to ventilatory drive
  • Potent bronchodilator (good for asthmatic pt.)
  • Remain upper airway reflex
  • Increase salivation

24
Effect on organ system
  • Cerebral
  • Increase CBF ,ICP
  • Avoid in pt. with space-occupying intracranial
    lesion
  • Undesirable psychotomimetic S/E (eg. Illusion
    ,disturbing dream delirium)
  • Analgesia

25
Contraindication
  • Increase ICP
  • Open eye injury
  • MI
  • Vascular aneurysm
  • Psychomimetic patient

26
Clinical use
  • Dose
  • Induction Dose 1-2 mg/kg
  • Sedation 0.2-0.8 mg/kg
  • Side effect
  • Emergence reaction (adult 10-30)

27
Benzodiazepine
  • Mechanism of action
  • Interact with specific receptor in CNS
  • enhance the inhibitory neurotransmitter (GABA)
  • Properties
  • Midazolam water solubility
  • Diazepam water insolubility

28
Pharmacokinetics
  • Absorption Oral ,IV ,IM
  • Distribution
  • Imidazole ring increase lipid solubility of
    midazolam at physiologic pH
  • Biotransformation liver
  • Excretion Urine

29
Benzodiazepines
Agent Duration Potency
Midazolam Short 3
Diazepam Intermediate 1
Lorazepam Long 5
30
Effect on organ system
  • Cardiovascular
  • Minimal CVS depressant effect
  • BP ,CO ,PVR slightly decline
  • Respiratory
  • Slightly depress the ventilatory response to CO2
  • Increasing when use with other respiratory
    depressant drug
  • Cerebral
  • Slightly reduce CMRO2 ICP
  • Anti-anxiety
  • Anterograde amnesia

31
Clinical use
Agent Use Route Dose (mg/kg)
Diazepam Premedication Sedation Induction Oral IV IV 0.2-0.5 0.04-0.2 0.3-0.6
Midazolam Premedication Sedation Induction IM IV IV 0,07-0.15 0.01-0.1 0.1-0.4
Lorazepam Premedication Sedation Oral IM IV 0.053 0.03-0.05 0.03-0.04
32
Agent CVS CVS RS RS CNS CNS
Agent HR MAP Ventilatory drive Brochodilatation CBF ICP
1.Barbiturates - - - - - - - - - - - -
2.Propofol 0 - - - - - - 0 - - - - - -
3.Ketamine -
4.Benzodiazepines 0/ - - - 0 - - - -
5.Etomidate 0 - - 0 - - - - - -
6.Opioids -Meperidine -Morphine -Fentanyl - - - - - - - - - - - - - - - - 0 - - - - - -
33
Question ?
34
Test
35
?????????? underlying HT ??????????????
appendectomy ????????????????????????
  1. Propofol
  2. Ketamine
  3. Thiopental

36
??????????? ?????????????????? ?????????????????
?????????????????????????????????
  1. Propofol
  2. Ketamine
  3. Thiopental

37
?????????? ?????????????????? ??????????????????
BP 80/50 mmHg PR 105 mmHg ????????????? Explore
abdomen ??????????????????
  1. Propofol
  2. Ketamine
  3. Thiopental

38
?????????? 66 ?? underlying HT,IHD,DM
?????????????? total gastrectomy
???????????????????????
  1. Propofol
  2. Ketamine
  3. Thiopental

39
??????????? underlying severe asthma
?????????????? LC ??????????????????????????????
  1. Propofol
  2. Ketamine
  3. Thiopental

40
Neuromuscular blocking agents
41
Neuromuscular transmission
42
NMJ 1.Nerve terminal 2.Synaptic
cleft 3.Motor endplate
Neuromuscular junction
Ach
Nicotinic
43
Na
Depolarization
Muscle action potential
Muscle contraction
44
Acetylcholinesterase (cholinesterase)
Acetate, choline
Ach
45
Muscle relaxant
  • Depolarizing
  • Succinylcholine
  • Nondepolarizing

46
depolarizing drug
Not metabolized by acetylcholinesterase Prolong
depolarization
Na
Ach agonist
Sch
Fasciculation
Nicotinic
47
Succinylcholine
  • Rapid onset (30-60 s)
  • Short duration (less than 10 min)
  • Metabolized by pseudocholinesterase

48
Indication
  • Rapid sequent induction
  • Suspected difficult airway

49
Side effect
  • Contraindication
  • Burn injury
  • Spinal cord injury
  • Bed ridden
  • Muscular disease
  • CVS sinus bradycardia ,asystole
  • Fasciculations(60 90)
  • Hyperkalemia
  • Increase 0.5 1.0 mEq/L
  • Muscle pain (1.5 89)
  • 24 48 hr. after Sch
  • Increase pressure
  • IOP
  • ICP
  • Contraindication
  • Rupture eye globe
  • Brain tumor, ICP?

50
Side effect
  • Malignant hyperthermia (MH)
  • Prolong paralysis
  • Phase II block
  • Dose 7-10 mg/kg
  • Like a nondepolariazing block but unprediction
    the result of antgonization

51
Non depolarizing agent
52
Non-depolarizing drug
Na
Ach antagonist
No muscle contraction
Sch
Nicotinic
53
Nondepomuscle relaxants
Aminosteroid Vecuronium Pancuronium
Benzylisoquinolines Atracurium Cisatracurium
54
Aminosteroid
Generic name class Trade name Excretion Comments
Short - None Intermediate (35-40 min) - Vecuronium - Rocuronium Long (45-60 min) - Pancuronium Norcuron Zemuron Pavulon Hepatic (80) Hepatic (70) Renal (80) Vagolytic effect Recuralization
55
Nondepomuscle relaxants
Generic name class Trade name Excretion Comments
Benzylisoquinolines Short - Mivacurium Intermediate - Atracurium - Cisatracurium Long - Doxacurium Mivacuron Tracrium Nimbex Nuromax Plasma pseudocholinesterase Hoffman elimination esterase Renal (80) Histamine release Histamine release No histamine release
56
?????????????
  • ????????????????????
  • ???? ??????? HT ????????? pavulon
  • ????????????????????
  • ???? ?????? ET ??? rapid sequence induction
    ?????? Sch
  • ?????????????????
  • ???? ?????????????????????? ?????????????
    short-intermediate acting
  • ????
  • ?????????????????

57
Interaction
Drug Result
Anesthetic agents Antibiotic (clindamycin, gentamycin) Anticonvulsant Cardiovascular drug -
Condition
Myasthenia gravis Magnesium, calcium Hypokalemia Hypothermia
58
Monitoring
  • Nerve electrical stimulator

59
?????????? underlying asthma ?????????????? LC
???????????????????????????????????
  1. Vecuronium
  2. Pancuronium
  3. Atracurium
  4. Cisatracurium
  5. Succinylcholine

60
?????????? underlying ESRD ??????????????
herniorrhaphy ????????????????????????????
  1. Vecuronium
  2. Pancuronium
  3. Atracurium
  4. Cisatracurium
  5. Succinylcholine

61
??????????? underlying HT ?????????????????????
rupture ovarion cyst ?????????????? Explore lap
???????????????? 3 ??. ??????????????????
????????????????????????????????????????????????
  1. Vecuronium
  2. Pancuronium
  3. Atracurium
  4. Cisatracurium
  5. Succinylcholine

62
?????????? underlying hepatic cirrhosis childB
?????????????? Rt.hemicolectomy
????????????????????????????????????????????
  1. Vecuronium
  2. Pancuronium
  3. Atracurium
  4. Cisatracurium
  5. Succinylcholine

63
?????????? underlying HT ??????????????
appendectomy ?????????????????????????????
  1. Vecuronium
  2. Pancuronium
  3. Atracurium
  4. Cisatracurium
  5. Succinylcholine

64
Antagonism of neuromuscular block
65
Reversal agent
  • Inhibit acetylcholinesterase

Increase Ach
66
Acetylcholine effect
  • Muscarinic effect
  • Bradycardia
  • Bronchodilatation
  • Miosis
  • Hypersecretion
  • Increase bowel movement
  • Nicotinic effect
  • NMJ

67
Reversal agent
Peak onset (min) Dose (mg/kg)
Neostigmine 3-5 0.04-0.07
Edrophonium 10-20 0.2-0.3
Pyridostigmine 1-2 0.5-1
68
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69
Anticholinergic agent
Agents Tachycardia Bronchodilatation Sedation Secretion
Atropine Scopolamine Glycopyrrolate 0 - - - - - - - -
70
Adrenergic agonist antagonists
71
Autonomic nervous system
parasympathetic
sympathetic
72
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73
(No Transcript)
74
Adrenoceptor physiology
  • Neurotransmitter Norepinephrine (noradrenaline)
    ?????? sweat gland some bl. vv.

75
Adrenergic receptor
Locate Action
a1 Smooth m. (eye ,lung ,vv ,uterus ,GI) Vasoconstriction ,increase PVR ,bronchoconstriction ,mydriasis
a2 Presynaptic n. termimal Reduce sympathetic outflow ,peripheral vasodilate
ß1 Heart Increase HR ,conduction contractility
ß2 Smooth m. gland cells Vasodilate ,bronchodilate ,relax of uterus bladder gut ,glycogenolysis ,gluconeogenesis
76
Adrenergic agonists drug
  • Epinephrine
  • Ephedrine
  • Norepinephrine (Levophed)
  • DPM

77
Epinephrine
  • Mechanism
  • ß1 increase contractility HR
  • a1 decrease splanchnic RBF ,increase SBP
  • increase coronary CPP
  • ß2 vasodilate may lower DBP

78
Dose
  • Emergency situation
  • IV bolus 0.05-1 mg
  • Continuous infusion 2-20 µg/min

79
Ephedrine
  • Mechanism
  • Increase BP ,HR ,CO ,contractility
  • Compare with epinephrine
  • Longer duration
  • Less potent
  • Indirect direct action
  • tachyphylaxis

80
Clinical use
  • Commonly use in anesthesia
  • Most obstetric use
  • Dose
  • IV bolus 2.5-10 mg
  • IV blolus in children 0.1 mg/kg

81
Norepinephrine
  • a1 intense vasocon. of arterial venous vv.
  • ß1 increase contractility HR
  • Consideration
  • Reflex bradycardia
  • Decrease tissue perfusion

82
Clinical use
  • Septic shock
  • Dose
  • IV bolus 0.1 µg/kg
  • Continuous infusion 2-20 µg/min

83
Dopamine
  • Mechanism vary with dose
  • Small (lt2 µg/kg/min)
  • Activate DA vasodilate of renal vv.
  • Moderate (2-10 µg/kg/min)
  • ß1 stimulation increase HR ,CO ,myocardial
    contractility
  • High (10-20 µg/kg/min)
  • a1 effect increase PVR fall in RBF

84
Clinical use
  • Treatment of shock to improve CO ,support BP
    maintain renal function
  • Dose
  • Continuous infusion 2-20 µg/kg/min

85
Dobutamine
  • Relatively selective ß1 agonist
  • Slight decline in PVR from ß2 stimulation
  • Decerase LV pressure Increase coronary BF

86
Clinical use
  • Good choice for Pt. combine with CHF CAD
  • Dose
  • Continuous infusion 2-20 µg/kg/min

87
Receptor selectivity of adrenergic agonists
Drug a1 a2 ß1 ß2 DA1 DA2
Epinephrine 0 0
Ephedrine ? 0 0
Norepinephrine 0 0 0
Dobutamine 0 0 0 0
Dopamine
88
Effect of adrenergic agonist on organ systems
Drug HR MAP CO PVR Bronchodi. RBF
Epinephrine /- --
Ephedrine --
Norepi . - /- 0 ---
DBT - 0
DPM 0
89
????????????????????????? SB 5 ???? ?????????????
?????????? PR ?????????40 bpm BP 80/40 mmHg
??????????????????????????????????
  1. Levophed
  2. Atropine
  3. Ephedrine
  4. Adrenaline

90
?????????? underlying HT ,IHD ????????????????????
???????????? ?????? 10 ???? ????????????????
75/45 mmHg PR 118 bpm ????????????????????????????
??????
  1. Levophed
  2. Atropine
  3. Ephedrine
  4. Adrenaline

91
??????????? ??????????????? SB ????????????????
85/45 mmHg PR 80 bpm ?????????????????????????????
?????
  1. Levophed
  2. Atropine
  3. Ephedrine
  4. Adrenaline

92
??????????? ??????????????? SB ????????????????
85/45 mmHg PR 80 bpm ??????? ephedrine ?? 30 mg
??????????????????? ??? PR ????????? 120 bpm
??????????????????????????????????
  1. Levophed
  2. Atropine
  3. Ephedrine
  4. Adrenaline

93
??????????? underlying DM,HT?????????????????????
NF with Sepsis shock ????????????? DB
????????????????????????? ???????????????? 50/20
mmHg PR 0 bpm ??????????????????????????????????
  1. Levophed
  2. Atropine
  3. Ephedrine
  4. Adrenaline

94
Question ?
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