GENERALANAESTHETICS
BAJGIRE KRUSHNA BALIRAM
Department of Pharmacology and Toxicology
National Institute Of Pharmaceutical Education And Research
S.A.S. Nagar
FLOW OF PRESENTATION
1. DEFINITION
2. CARDINAL FEATURES GENERAL ANAESTHESIA
3. STAGES OF GENERAL ANAESTHESIA
4. DIFFERENCE BETWEEN GENERAL AND LOCAL
ANAESTHETICS
5. MECHANISM OF GGENERAL ANAESTHETICS
6. CLASSIFICATION OF GENERAL ANAESTHETICS
7. INHALATIONALANAESTHETICS
8. INTRAVENOUS ANAESTHETICS
WHAT ARE GENERAL ANAESTHETICS ?
 Definition : Anesthesia (an =without, aisthesis = sensation )
 The drugs which produce reversible loss of all sensations
and consciousness
Generally administered by an anaesthesiologist in order to
induce or maintain general anaesthesia to facilitate surgery.
THE CARDINAL FEATURES OF GENERAL
ANAESTHETICS
Loss of all sensation, especially pain
Sleep (unconsciousness) and amnesia
Abolition of somatic and autonomic reflexes
Immobility and muscle relaxation
STAGES OF GENERAL ANAESTHESIA
Stage-1
• Analgesia : Start from beginning of anaesthesia
administration and last upto loss of consciousness,
feels a dream like state, reflexes and respiration
remains normal
Stage-2
• Stage of delirium : From loss of consciousness
to beginning of irregular respiration. Apparent
excitement is seen. Muscle tone increases. Jaws are
tightly closed. Heart rate and blood pressure may
rise.
Stage-3
• Surgical anaesthesia : Extends from onset of irregular
respiration to cessation of spontaneous breathing. This has been
divided into 4 planes
• Plane1:This plane ends when eyes become fixed
• Plane 2: Loss of corneal and laryngeal reflexes
• Plane 3:Pupil start dilating and light reflexe
• Plane 4: Dilated pupil, decrease muscle tone ,BP
• falls
Stage-4
• Medullary paralysis : Respiratory and vasomotor control
ceases
DIFFERENCE BETWEEN GENERAL AND
LOCALANAESTHETICS
CLASSIFICATION OF GENERAL
ANAESTHETICS
General
anaesthetics
Inhalational
Gas:
Nitrous oxide
Volatile
liquids:
Halothane
Desflurane
Sevoflurane
Isoflurane
Enflurane
Intravenous
Thiopentone
sod.
Etomidate
Ketamine
Propofol
Methohexiton
e sod.
MECHANISM OF ACTION OF GENERAL
ANAESTHETICS
 GABA –A receptor : Potentiated by Halothane,
Propofol, Etomidate ,Enflurane,
isoflurane, Desflurane,
sevoflurane
 NMDA receptors : Inhibited by Ketamine,
nitrous oxide and xenon
 Glycine receptors : Potentiated by Halothane,
Propofol, ,Enflurane,
isoflurane, Desflurane,
sevoflurane
Also has effect on neuronal nicotinic receptors and
5-HT3 receptors
INHALATIONAL ANAESTHETICS
Inhalational anaesthesia refers to the delivery of gases or
vapours to the respiratory system to produce anaesthesia
It is explosive
Irritant to respiratory tract
High incidence of nausea and vomiting during
induction and post-surgical emergence
Ether
Colourless, odourless gas at room temperature.
Very insoluble in blood and other tissues (quick recovery)
Rapid induction of anaesthesia and rapid emergence
following discontinuation of administration.
Completely eliminated by the lungs.
It is weak anaesthetic and powerful analgesic.
The mac value is 105%.
Causes megaloblastic anaemia.
Used as adjunct to supplement other inhalationals.
Nitrous oxide
Volatile liquid at room temperature.
Light sensitive
High fat solubility => slow induction & recovery
Eliminated unchange via lungs
Commonly used in children, where preoperative
placement of an iv catheter can be difficult
It is marketed in amber bottles with thymol added as a
preservative
Metabolised in liver by Cyt-P450
Halothane
 Side effects of halothane :
CVS : Cardiac arrhythmia, depression of myocardial contraction.
Respiratory system : Depression of respiration
Muscles : Malignant hyperthermia
Kidney : Decrease renal blood flow and g.f.r
Liver and GIT: Cause halothane induced hepatitis & nausia and
vomitting
 DRUG INTERACTION : Halothane + adrenaline, theophylline => arrhythmia
may be precipitated.
 CONTRAINDICATION : Hepatic dysfunction and/or jaundice.
 Pleasant smell , non irritant and bronchodilation makes it agent of choice
for
paediatric anaesthesia.
 2nd agent of choice for
Neuro anaesthesia.
Cardiac anaesthesia .
Asthmatics.
 Sevoflurane reacts with soda lime used in anaesthetic circuit to form
“compound A” which acts as renal toxin (nephrotoxic).
 Agents that should not be given with soda lime.
1) Trielene.(trichloro ethylene)
2) Sevoflurane.
3) Desflurane
Sevoflurane
MEASURMENT OF INHALATIONAL
ANAESTHETIC POTENCY
 Minimum alveolar concentration
 MAC is the Concentration at which 50% of subjects have no
response (movement) to surgical stimulus (skin incision).
 Different for each inhaled agent
 Increase MAC
i. Hyperthermia
ii. Hypernatraemia
iii. Drug induced elevation of CNS catecholamine stores
iv. Chronic alcohol abuse
v. Increases in ambient pressure (experimental)
MAC
 Decrease MAC
i. hypothermia
ii. hyponatraemia
iii. increasing age
iv. hypotension
v . anaemia
vi. CNS depressant drugs
 No Change in MAC
i. sex
ii. weight,
iii. type of stimulus
iv. duration of anaesthesia
v. hypo/hyperkalaemia
Two important characteristics of Inhalational
anaesthetics which govern the anaesthesia are :
1. Solubility in the fat
(oil : gas partition coefficient)
2. Solubility in the blood (blood : gas
partition coefficient)
 Oil-gas partition coefficients :
It indicates the amount of gas that is soluble in oil phase
It is a measure of lipid solubility of anaesthetic
It a measure of anaesthetic potency
Higher the solubility of general anaesthetics in oil greater
is the anaesthetics action
 Blood-gas partition coefficients :
The ratio of the concentration in blood to the
concentration in the gas phase
Lower the blood : gas coefficient faster the
induction and the faster the recovery
Anaesthetic Blood/Gas Oil/gas
Nitrous oxide 0.47 1.4
Halothane 2.4 224
Isoflurane 1.4 97
Sevoflurane .65 42
Desflurane .42 18.7
INTRAVENOUS ANAESTHETICS
 Ultrashort acting barbiturate
 High lipid solubility rapid entry into the brain
 Rapid onset (20 sec) , short duration
 Effect terminated not by metabolism but by redistribution
 Risk of sever vasospasm if accidently injected into artery
 Depress cerebral blood flow
 Decrease intracranial pressure
 Tissue necrosis—gangrene, Tissue stores, hypotension, apnea
 Build-up in adipose tissue = very long emergence from anaesthesia
THIOPENTAL
 Rapid onset and have a short duration of action
 Highly protein bound in vivo and is metabolised by conjugation
in the liver
 Very good anesthetic for induction and maintaince of anesthesia
with no accumulation effect
 Side-effects are pain on injection, hypotension and transient
apnea following induction
 Used for the induction, maintenance of GA and sedation
 Useful for day-case surgery
Propofol
 Dissociative anaesthetic
 NMDA Receptor Antagonist
 Cardiovascular stimulant
 Catatonia, analgesia, and amnesia without loss of consciousness
 Useful for anesthetizing patients at risk for hypotension and
bronchospasm and for certain paediatric procedures
Ketamine
 Rapid induction
 Minimal change in cardiac function and respiratory rate
 Not analgesic
 Cause pain on injection and nausea postoperatively
 Prolonged administration may cause adrenal suppression
Etomidate
General anaesthetics

General anaesthetics

  • 1.
    GENERALANAESTHETICS BAJGIRE KRUSHNA BALIRAM Departmentof Pharmacology and Toxicology National Institute Of Pharmaceutical Education And Research S.A.S. Nagar
  • 2.
    FLOW OF PRESENTATION 1.DEFINITION 2. CARDINAL FEATURES GENERAL ANAESTHESIA 3. STAGES OF GENERAL ANAESTHESIA 4. DIFFERENCE BETWEEN GENERAL AND LOCAL ANAESTHETICS 5. MECHANISM OF GGENERAL ANAESTHETICS 6. CLASSIFICATION OF GENERAL ANAESTHETICS 7. INHALATIONALANAESTHETICS 8. INTRAVENOUS ANAESTHETICS
  • 3.
    WHAT ARE GENERALANAESTHETICS ?  Definition : Anesthesia (an =without, aisthesis = sensation )  The drugs which produce reversible loss of all sensations and consciousness Generally administered by an anaesthesiologist in order to induce or maintain general anaesthesia to facilitate surgery.
  • 4.
    THE CARDINAL FEATURESOF GENERAL ANAESTHETICS Loss of all sensation, especially pain Sleep (unconsciousness) and amnesia Abolition of somatic and autonomic reflexes Immobility and muscle relaxation
  • 5.
    STAGES OF GENERALANAESTHESIA Stage-1 • Analgesia : Start from beginning of anaesthesia administration and last upto loss of consciousness, feels a dream like state, reflexes and respiration remains normal Stage-2 • Stage of delirium : From loss of consciousness to beginning of irregular respiration. Apparent excitement is seen. Muscle tone increases. Jaws are tightly closed. Heart rate and blood pressure may rise.
  • 6.
    Stage-3 • Surgical anaesthesia: Extends from onset of irregular respiration to cessation of spontaneous breathing. This has been divided into 4 planes • Plane1:This plane ends when eyes become fixed • Plane 2: Loss of corneal and laryngeal reflexes • Plane 3:Pupil start dilating and light reflexe • Plane 4: Dilated pupil, decrease muscle tone ,BP • falls Stage-4 • Medullary paralysis : Respiratory and vasomotor control ceases
  • 7.
    DIFFERENCE BETWEEN GENERALAND LOCALANAESTHETICS
  • 8.
    CLASSIFICATION OF GENERAL ANAESTHETICS General anaesthetics Inhalational Gas: Nitrousoxide Volatile liquids: Halothane Desflurane Sevoflurane Isoflurane Enflurane Intravenous Thiopentone sod. Etomidate Ketamine Propofol Methohexiton e sod.
  • 9.
    MECHANISM OF ACTIONOF GENERAL ANAESTHETICS  GABA –A receptor : Potentiated by Halothane, Propofol, Etomidate ,Enflurane, isoflurane, Desflurane, sevoflurane  NMDA receptors : Inhibited by Ketamine, nitrous oxide and xenon  Glycine receptors : Potentiated by Halothane, Propofol, ,Enflurane, isoflurane, Desflurane, sevoflurane Also has effect on neuronal nicotinic receptors and 5-HT3 receptors
  • 10.
    INHALATIONAL ANAESTHETICS Inhalational anaesthesiarefers to the delivery of gases or vapours to the respiratory system to produce anaesthesia It is explosive Irritant to respiratory tract High incidence of nausea and vomiting during induction and post-surgical emergence Ether
  • 11.
    Colourless, odourless gasat room temperature. Very insoluble in blood and other tissues (quick recovery) Rapid induction of anaesthesia and rapid emergence following discontinuation of administration. Completely eliminated by the lungs. It is weak anaesthetic and powerful analgesic. The mac value is 105%. Causes megaloblastic anaemia. Used as adjunct to supplement other inhalationals. Nitrous oxide
  • 12.
    Volatile liquid atroom temperature. Light sensitive High fat solubility => slow induction & recovery Eliminated unchange via lungs Commonly used in children, where preoperative placement of an iv catheter can be difficult It is marketed in amber bottles with thymol added as a preservative Metabolised in liver by Cyt-P450 Halothane
  • 13.
     Side effectsof halothane : CVS : Cardiac arrhythmia, depression of myocardial contraction. Respiratory system : Depression of respiration Muscles : Malignant hyperthermia Kidney : Decrease renal blood flow and g.f.r Liver and GIT: Cause halothane induced hepatitis & nausia and vomitting  DRUG INTERACTION : Halothane + adrenaline, theophylline => arrhythmia may be precipitated.  CONTRAINDICATION : Hepatic dysfunction and/or jaundice.
  • 14.
     Pleasant smell, non irritant and bronchodilation makes it agent of choice for paediatric anaesthesia.  2nd agent of choice for Neuro anaesthesia. Cardiac anaesthesia . Asthmatics.  Sevoflurane reacts with soda lime used in anaesthetic circuit to form “compound A” which acts as renal toxin (nephrotoxic).  Agents that should not be given with soda lime. 1) Trielene.(trichloro ethylene) 2) Sevoflurane. 3) Desflurane Sevoflurane
  • 15.
    MEASURMENT OF INHALATIONAL ANAESTHETICPOTENCY  Minimum alveolar concentration  MAC is the Concentration at which 50% of subjects have no response (movement) to surgical stimulus (skin incision).  Different for each inhaled agent  Increase MAC i. Hyperthermia ii. Hypernatraemia iii. Drug induced elevation of CNS catecholamine stores iv. Chronic alcohol abuse v. Increases in ambient pressure (experimental) MAC
  • 16.
     Decrease MAC i.hypothermia ii. hyponatraemia iii. increasing age iv. hypotension v . anaemia vi. CNS depressant drugs  No Change in MAC i. sex ii. weight, iii. type of stimulus iv. duration of anaesthesia v. hypo/hyperkalaemia
  • 17.
    Two important characteristicsof Inhalational anaesthetics which govern the anaesthesia are : 1. Solubility in the fat (oil : gas partition coefficient) 2. Solubility in the blood (blood : gas partition coefficient)
  • 18.
     Oil-gas partitioncoefficients : It indicates the amount of gas that is soluble in oil phase It is a measure of lipid solubility of anaesthetic It a measure of anaesthetic potency Higher the solubility of general anaesthetics in oil greater is the anaesthetics action  Blood-gas partition coefficients : The ratio of the concentration in blood to the concentration in the gas phase Lower the blood : gas coefficient faster the induction and the faster the recovery
  • 19.
    Anaesthetic Blood/Gas Oil/gas Nitrousoxide 0.47 1.4 Halothane 2.4 224 Isoflurane 1.4 97 Sevoflurane .65 42 Desflurane .42 18.7
  • 20.
    INTRAVENOUS ANAESTHETICS  Ultrashortacting barbiturate  High lipid solubility rapid entry into the brain  Rapid onset (20 sec) , short duration  Effect terminated not by metabolism but by redistribution  Risk of sever vasospasm if accidently injected into artery  Depress cerebral blood flow  Decrease intracranial pressure  Tissue necrosis—gangrene, Tissue stores, hypotension, apnea  Build-up in adipose tissue = very long emergence from anaesthesia THIOPENTAL
  • 21.
     Rapid onsetand have a short duration of action  Highly protein bound in vivo and is metabolised by conjugation in the liver  Very good anesthetic for induction and maintaince of anesthesia with no accumulation effect  Side-effects are pain on injection, hypotension and transient apnea following induction  Used for the induction, maintenance of GA and sedation  Useful for day-case surgery Propofol
  • 22.
     Dissociative anaesthetic NMDA Receptor Antagonist  Cardiovascular stimulant  Catatonia, analgesia, and amnesia without loss of consciousness  Useful for anesthetizing patients at risk for hypotension and bronchospasm and for certain paediatric procedures Ketamine
  • 23.
     Rapid induction Minimal change in cardiac function and respiratory rate  Not analgesic  Cause pain on injection and nausea postoperatively  Prolonged administration may cause adrenal suppression Etomidate