7..intravenous anaesthesia 2
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INTRAVENOUS ANAESTHESIA
E OMONGE
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Anaesthetic drugs - qualities Readily controllable
Induction and recovery rapid
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General anaesthesiaAdjunct to surgery renders the patient
unaware or unresponsive to pain stimuli
Systemic
effect on the CNS
Intravenous agents act more rapidlyproducing unconsciousness in
20sec.thiopental, etomidate andpropofol are used in induction ofanaesthesia
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Other induction drugs Benzodiazepines diazepam,
midazolam( less rapid action)
Propofol and Ketamine can be used forshort operations . Most of the otheragents need maintenance with other
drugs Droperidol causes deep sedation and
analgesia
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GENERAL ANAESTHESIA PARENTERAL( INTRAVENOUS )
INHALATIONAL
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PHARMAKOKINETICS Small, hydrophobic, substituted
aromatic or heterocyclic compounds
Hydrophobic
preferential partition inperfused and lipophilic brain and spinalcord anaesthesia
Blood level fall and back diffusion inthe less well perfused muscle ,visceraand at slower rate in hydrophobic
adipose
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KINETICS Termination redistribution out of CNS
Blood level fall , metabolism and lipophilicity
of drug in peripheral compartment Half-life dependent hydrophobicity ,
metabolic clearance , and time
t initial redistribution and subsequentmetabolism take minutes and hoursrespectively with awakening level in between
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VARIABILITY Cardiac output
Septic shock
Cardiomyopathy
Age
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CONTEXT SENSITIVE HALF-TIME Modest for etomidate, propofol and
ketamine
Increase with infusion time fordiazepam, thiopental
Determined by redistribution from
active site
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BARBITURATES Derivatives of barbituric acid Sodium thiopental ,thiomylal
,methohexital
Racemic mixtures withenantioselectivity
Sodium salts
Stability post reconstitution
1 weekand 6 weeks respectively for thiopentaland thiomylal
Precipitates when mixed with more
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KINETICS Duration of action dependent on
redistribution- very high lipid solubility
makes thiopental rapid acting Clearance influence duration following
multiple doses
Methohexital much rapid clearance
Prolonged use of thiopental andthiomylal can cause long duration
coma due to slow elimination and large
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KINETICS Methohexital outpatient, rapid return
to consciousness where propofol is
unavailable Elimination hepatic metabolism and
renal excretion
Inactive metabolites Plasma protein binding is high- Vd
decrease in hepatic disease andcondition that decrease protein
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INDICATIONS Induction of anaesthesia- rapid
unconsciousness in seconds, peak in 1
minute, duration of 5-8 minutes (thiopent-al )
Higher doses for neonates and infants
Smaller doses for elderly and inpregnancy
Reduce doses after diazepam premed
Thyomylal equipotent andmethohexital is 3x more potent
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INDICATIONS Methohexital produces pain on injection
Pain reduction by using large veins orLA
Avoid intra-aterial injection
Dygeusia with thiopental
Excitement e.g tremors, hypertonus,hiccoughs with methohexital
Rectal route x10
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SIDE EFFECTS Cerebral metabolic rate reduction
Reduced intraocular pressure
Dose dependent decrease BP due tovasodilatation
Myocardial contraction reduced
Compensatory HR rise
Care in patients with heart disease and
b- adrenoceptor blockers
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SIDE EFFECTS
Respiratory depression
Care with opiods but can be used in
asthmatics due to little effect onbronchomotor response
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PROPOFOL
I V
Kinetics similar to thiopental
Rapid recovery due to high clearance
Metabolites from liver less active andloss via kidney
PPB high
Used in induction and maintanance of
GA in short procedures
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ETOMIDATE
Large margin of dose that causeanaesthetic effect and that which
causes respiratory depression More rapidly metabolised than
thiopental
Less likely to cause prolonged hangover
More involuntary movement duringinduction
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Etomidate
Adrenocortical suppression seen
Useful in day case surgery
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KETAMINE
Resembles phencyclidine
Produce anaesthesia like state and
profound analgesia
Less euphoria and sensory distortion cf.phencyclidine
Block activation of NMDA-receptor(excitatory receptor)
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Ketamine
IV
Slow effect 2-5 min.
Dissociative anaesthesia
Sensory loss ,analgesia and amnesiaand paralysis of movement withoutactual loss of consciousnessinvoluntarymovement during induction andrecovery
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Ketamine
BP and HR increases
Respiration unaffected with effective
anaesthetic doses
Hallucinations, delirium, and irrationalbehaviour common during recovery
Less adverse effects in children
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Midazolam
Benzodiazepene
Slower onset and offset of action
Respiratory and cardiovasculardepression
Perioperative sedative in endoscopy