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GENERAL ANESTHETICS
Presentation by
Dr. Prerana B. Jadhav
Sanjivani College of Pharmaceutical Education & Research, Kopargaon
INTRODUCTION
• Agents that produces loss of consciousness.
• Depress CNS
• Absolute loss of sensation is anesthesia
• Controlled and reversible depression of central activity
• Used in surgical procedures
IDEAL CHARACTERISTICS
• Induce smooth and rapid effect for limited period
• Skeletal muscle relaxation
• Potent at low dose
• Wide therapeutic index and high safety
• Non irritating and easy to administer
• Not show any interaction
• Non toxic
• Non inflammable
STAGES OF ANESTHESIA
• STAGE I: Analgesia (Onset of drowsiness to loss of eyelash reflex) Patient is
unconscious at the end of stage I
• STAGE II: Excitement (Agitation & Delirium) Salivation, Irregular heart rate and
respiration. Induction agents are used to move patient through this stage.
• SATGE III: Surgical Anesthesia (Target depth for procedure) Painful stimuli will
not elicit somatic reflux.
• STAGE IV: Impending Death (Onset of apnea to failure of circulation and
respiration and ends in death.)
CLASSIFICATION
• INHALATION ANESTHETICS
Halothane, Methoxyflurane, Enflurane, Sevoflurane,
Isoflurane, Desflurane
• ULTRA SHORT ACTING BARBITURATES
Methohexital sodium, Thiamylal sodium, Thiopental
sodium
• DISSOCIATIVE ANESTHETICS
Ketamine Hydrochloride
INHALATION ANESTHETICS
• Structure Activity Relationship
Alkane:
 Potency of alkanes, cycloalkanes and aromatic hydrocarbons increases with
number of carbon atoms
 In n-alkane cut off number is 10 (except n-decane), cycloalkane cut off is 8
(except cyclooctane)
Alkanol:
 Increase in potency with increase in carbon length
 N-alkanol with given number of carbon is more potent than n-alkane with
same chain length.
INHALATION ANESTHETICS
Effect of Halogenation:
 Halogenating ether decreases flammability, enhanced stability, increased
potency
 Higher atomic mass of halogen increases potency
 Ex. Replacing F in desflurane with chlorine to form isoflurane increases
potency more than fourfold.
 When 2 to 4 carbons, highest potency was seen when terminal carbon
contains one hydrogen.
F
F
F
O H
H
F
F
F
F
F
F
O H
H
Cl
F
F
Desflurane Isoflurane
INHALATION ANESTHETICS
H
Cl
F
O H
F
F
F
F
Enflurane
F
F
F
O F
H
CF3
H
H
Sevoflurane
F
F
F
H
Br
Cl
Halothane
H
Cl
Cl
O H
F
F
H
H
Methoxyflurane
MOA of INHALATION ANESTHETICS
Acts on Receptors:
Inhibitory : GABA , glycine
Excitatory : NMDA
 Acts on GABA A receptor, Enhance chloride ion conductance into the cell and
hyperpolarize the cell membrane and prevent impulse transmission
 suppress excitatory synaptic channel activity of neuronal nicotinic Ach receptor,
glutamate receptors N-methyl D-aspartate (NMDA) receptors
 Hypnosis/sedation and amnesia are produced through effect sites in the brain.
 Immobility is produced by actions within the spinal cord.
MOA of INHALATION ANESTHETICS
Halothane
• Potent anesthetic, slow induction and recovery
• Weak analgesic, weak skeletal muscle relaxant.
• Metabolized to toxic metabolites (trifluroethanol)
hepatotoxic.
• CVS depression
– Hypotension, bradycardia (vagomimetic action)
–  Myocardial contractility,  Cardiac output
Adverse Effects
1. Hepatotoxicity (repeated use).
2. Malignant hyperthermia.
3. Cardiac arrhythmias.
4. Sensitizes heart to action of catechalamines 
arrhythmias.
Enflurane
• Less potent than halothane.
• Better muscle relaxation, Better analgesic properties.
• is metabolized to fluoride (8%), excreted in the kidney
• More rapid induction and recovery than halothane.
Disadvantages
• Pungent (Less induction -Not for pediatrics).
• CNS stimulation (Epilepsy-like seizure- abnormal
EEG).
Contraindication
• patients with seizure disorders.
• Not for renal failures.
Isoflurane (Forane)
 More rapid induction & recovery than halothane
 Stable compound (2%).
 Low biotransformation (Less fluoride).
 No nephrotoxicity - No hepatotoxicity.
 Good analgesic action.
 No sensitization of the heart.
 No cardiac arrythmias.
Disadvantages
Pungent (Not for pediatrics).
Desflurane
 Less potent than halothane.
 Pungent odor (irritation - Cough)
 Rapid induction & fast recovery (Low
solubility).
 Less metabolized (0.05 %).
 Low boiling point (special equipment).
Sevoflurane
• Better smell
• Less potent than halothane
• Rapid onset and recovery (Low solubility)
• Less metabolized (3- 5% fluoride)
• Little effect on HR
• No airway irritation (preferable for
children)
4/11/2024
Characters
Anesthetic
drugs
For veterinary use only
Methoxyflurane
Non irritant - Potent anesthetic, Weak analgesic.
Can be used in children
Halothane
Stable compound (2%), Low biotransformation (Less fluoride).
No nephrotoxicity - No hepatotoxicity.
Isoflurane
is metabolized to fluoride (8%)
Contraindicated in patients with seizure disorders.
Not for renal failures.
Enflurane
Less metabolized (0.05 %), low boiling point (special equipment)
Desflurane
Better smell, little effect on HR, No airway irritation (children)
Sevoflurane
Potent analgesics, weak anesthetic, Minimal CVS adverse effects,
contraindicated in pregnancy
Nitrous oxide
Side effects
Anesthetic
drugs
Slow induction, nephrotoxicity
Methoxyflurane
Slow induction and recovery
Sensitization of heart to catecholamines
Hepatotoxicity, Malignant hyperthermia
Halothane
Pungent odor, Airway irritation
Desflurane
Pungent (less induction -Not for pediatrics).
Airway irritation
CNS stimulation (Epilepsy-like seizure- abnormal EEG).
Enflurane
Weak anesthetic (low potency, combined).
Diffusion hypoxia, Nausea and vomiting.
Inactivation of B 12  megaloblastic anemia, congenital
anomalies
Nitrous oxide
Ultra Short Acting Barbiturates
• Methohexital sodium
• Thiamylal sodium
• Thiopental sodium
They shows rapid entry into the CNS, followed by
rapid redistribution of the drug
Uses:
Useful as induction agent
Supplementary drugs, when surgery requires
increased depth of anaesthesia
Methohexital
• Also known as Methohexitone.
• It is Barbiturate derivative.
• Has rapid onset of action.
MOA
• Binds to chloride ionophore site of GABAA and Cl- ionophore
receptor complex and enhances inhibitory actions of GABAA in the
brain.
• Leads to synaptic inhibition, decreases neuronal excitability, and
induces anesthesia.
USES
• Used to induce anesthesia
• Used to induce anesthesia for surgery and dental
procedure.
N
N
H
O
O
O
CH3
C
H3
CH3
CH2
Synthesis of Methohexital
Thiamylal
• Invented in 1950
• Member of class of barbiturates that is 2-
thioxodihydropyrimidinedione.
• It is thiobarbiturate analogue of Secobarbital.
• It is used for induction of surgical anesthesia or as an
anticonvulsant to counteract side effects from other
anesthetics.
NH
N
H
O
S
O
C
H3
C
H2
C
H3
• MOA
• Thiamylal binds at a distinct binding site associated with Cl-
ionophore at the GABAA receptor, increasing the duration of
time for which the Cl- ionophore is open.
• The post synaptic inhibitory effect of GABA in the thalamus is
increased.
• Uses
• Used in combination with acetaminophen or aspirin for its
sedative and relaxant effect in the treatment of headache,
migraine and pain.
Thiopental sodium
• Discovered in 1930
• First used in human beings in 1934
• It is rapid onset short acting barbiturate general
anesthetic.
• It is thiobarbiturate analog of Pentobarbital and
analogue of thiobarbital.
NH
N S
-
O
O
CH3
C
H3
C
H3
Na
+
• MOA
• Thiopental binds at distinct binding sites associated
with chloride ionophore at the GABAA receptor,
increasing the duration of time for which the Cl-
ionophore is open.
• The post synaptic inhibitory effect of GABA in the
thalamus is prolonged.
• Uses
• Thiopentone sodium solution administered
intravenously to produce anesthesia.
• Also used to control convulsions.
Synthesis of Thiopental sodium
DISSOCIATIVE ANESTHETIC
• Dissociative anaesthetics are a group of drugs
that can produce a trance-like state,
characterised by dissociation from reality.
• This state can be used to relieve pain and
anxiety, or to facilitate surgery.
• The first dissociative anaesthetic, ketamine, was
discovered in 1962. It
 These agents block the N-methyl-D-aspartate in the brain by producing
anaesthesia.
 Ketamine is a rapid-onset, short-duration agent used primarily for induction of
anaesthesia. Therefore, it is used primarily for the maintenance of anaesthesia.
 Dissociative anaesthetics produce anaesthesia by blocking N-methyl-D-
aspartate (NMDA) receptors in the brain.
 Dissociative anaesthetics are sometimes used in people who need to be sedated
for a short period, such as during surgery.
Ketamine HCl
Synthesis of Ketamine HCl

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Presentation on General Anesthetics pdf.

  • 1. GENERAL ANESTHETICS Presentation by Dr. Prerana B. Jadhav Sanjivani College of Pharmaceutical Education & Research, Kopargaon
  • 2. INTRODUCTION • Agents that produces loss of consciousness. • Depress CNS • Absolute loss of sensation is anesthesia • Controlled and reversible depression of central activity • Used in surgical procedures
  • 3. IDEAL CHARACTERISTICS • Induce smooth and rapid effect for limited period • Skeletal muscle relaxation • Potent at low dose • Wide therapeutic index and high safety • Non irritating and easy to administer • Not show any interaction • Non toxic • Non inflammable
  • 4. STAGES OF ANESTHESIA • STAGE I: Analgesia (Onset of drowsiness to loss of eyelash reflex) Patient is unconscious at the end of stage I • STAGE II: Excitement (Agitation & Delirium) Salivation, Irregular heart rate and respiration. Induction agents are used to move patient through this stage. • SATGE III: Surgical Anesthesia (Target depth for procedure) Painful stimuli will not elicit somatic reflux. • STAGE IV: Impending Death (Onset of apnea to failure of circulation and respiration and ends in death.)
  • 5.
  • 6. CLASSIFICATION • INHALATION ANESTHETICS Halothane, Methoxyflurane, Enflurane, Sevoflurane, Isoflurane, Desflurane • ULTRA SHORT ACTING BARBITURATES Methohexital sodium, Thiamylal sodium, Thiopental sodium • DISSOCIATIVE ANESTHETICS Ketamine Hydrochloride
  • 7. INHALATION ANESTHETICS • Structure Activity Relationship Alkane:  Potency of alkanes, cycloalkanes and aromatic hydrocarbons increases with number of carbon atoms  In n-alkane cut off number is 10 (except n-decane), cycloalkane cut off is 8 (except cyclooctane) Alkanol:  Increase in potency with increase in carbon length  N-alkanol with given number of carbon is more potent than n-alkane with same chain length.
  • 8. INHALATION ANESTHETICS Effect of Halogenation:  Halogenating ether decreases flammability, enhanced stability, increased potency  Higher atomic mass of halogen increases potency  Ex. Replacing F in desflurane with chlorine to form isoflurane increases potency more than fourfold.  When 2 to 4 carbons, highest potency was seen when terminal carbon contains one hydrogen. F F F O H H F F F F F F O H H Cl F F Desflurane Isoflurane
  • 9. INHALATION ANESTHETICS H Cl F O H F F F F Enflurane F F F O F H CF3 H H Sevoflurane F F F H Br Cl Halothane H Cl Cl O H F F H H Methoxyflurane
  • 10. MOA of INHALATION ANESTHETICS Acts on Receptors: Inhibitory : GABA , glycine Excitatory : NMDA  Acts on GABA A receptor, Enhance chloride ion conductance into the cell and hyperpolarize the cell membrane and prevent impulse transmission  suppress excitatory synaptic channel activity of neuronal nicotinic Ach receptor, glutamate receptors N-methyl D-aspartate (NMDA) receptors  Hypnosis/sedation and amnesia are produced through effect sites in the brain.  Immobility is produced by actions within the spinal cord.
  • 11. MOA of INHALATION ANESTHETICS
  • 12.
  • 13. Halothane • Potent anesthetic, slow induction and recovery • Weak analgesic, weak skeletal muscle relaxant. • Metabolized to toxic metabolites (trifluroethanol) hepatotoxic. • CVS depression – Hypotension, bradycardia (vagomimetic action) –  Myocardial contractility,  Cardiac output Adverse Effects 1. Hepatotoxicity (repeated use). 2. Malignant hyperthermia. 3. Cardiac arrhythmias. 4. Sensitizes heart to action of catechalamines  arrhythmias.
  • 14. Enflurane • Less potent than halothane. • Better muscle relaxation, Better analgesic properties. • is metabolized to fluoride (8%), excreted in the kidney • More rapid induction and recovery than halothane. Disadvantages • Pungent (Less induction -Not for pediatrics). • CNS stimulation (Epilepsy-like seizure- abnormal EEG). Contraindication • patients with seizure disorders. • Not for renal failures.
  • 15. Isoflurane (Forane)  More rapid induction & recovery than halothane  Stable compound (2%).  Low biotransformation (Less fluoride).  No nephrotoxicity - No hepatotoxicity.  Good analgesic action.  No sensitization of the heart.  No cardiac arrythmias. Disadvantages Pungent (Not for pediatrics).
  • 16. Desflurane  Less potent than halothane.  Pungent odor (irritation - Cough)  Rapid induction & fast recovery (Low solubility).  Less metabolized (0.05 %).  Low boiling point (special equipment).
  • 17. Sevoflurane • Better smell • Less potent than halothane • Rapid onset and recovery (Low solubility) • Less metabolized (3- 5% fluoride) • Little effect on HR • No airway irritation (preferable for children)
  • 18. 4/11/2024 Characters Anesthetic drugs For veterinary use only Methoxyflurane Non irritant - Potent anesthetic, Weak analgesic. Can be used in children Halothane Stable compound (2%), Low biotransformation (Less fluoride). No nephrotoxicity - No hepatotoxicity. Isoflurane is metabolized to fluoride (8%) Contraindicated in patients with seizure disorders. Not for renal failures. Enflurane Less metabolized (0.05 %), low boiling point (special equipment) Desflurane Better smell, little effect on HR, No airway irritation (children) Sevoflurane Potent analgesics, weak anesthetic, Minimal CVS adverse effects, contraindicated in pregnancy Nitrous oxide
  • 19. Side effects Anesthetic drugs Slow induction, nephrotoxicity Methoxyflurane Slow induction and recovery Sensitization of heart to catecholamines Hepatotoxicity, Malignant hyperthermia Halothane Pungent odor, Airway irritation Desflurane Pungent (less induction -Not for pediatrics). Airway irritation CNS stimulation (Epilepsy-like seizure- abnormal EEG). Enflurane Weak anesthetic (low potency, combined). Diffusion hypoxia, Nausea and vomiting. Inactivation of B 12  megaloblastic anemia, congenital anomalies Nitrous oxide
  • 20. Ultra Short Acting Barbiturates • Methohexital sodium • Thiamylal sodium • Thiopental sodium They shows rapid entry into the CNS, followed by rapid redistribution of the drug Uses: Useful as induction agent Supplementary drugs, when surgery requires increased depth of anaesthesia
  • 21. Methohexital • Also known as Methohexitone. • It is Barbiturate derivative. • Has rapid onset of action. MOA • Binds to chloride ionophore site of GABAA and Cl- ionophore receptor complex and enhances inhibitory actions of GABAA in the brain. • Leads to synaptic inhibition, decreases neuronal excitability, and induces anesthesia. USES • Used to induce anesthesia • Used to induce anesthesia for surgery and dental procedure. N N H O O O CH3 C H3 CH3 CH2
  • 23. Thiamylal • Invented in 1950 • Member of class of barbiturates that is 2- thioxodihydropyrimidinedione. • It is thiobarbiturate analogue of Secobarbital. • It is used for induction of surgical anesthesia or as an anticonvulsant to counteract side effects from other anesthetics. NH N H O S O C H3 C H2 C H3
  • 24. • MOA • Thiamylal binds at a distinct binding site associated with Cl- ionophore at the GABAA receptor, increasing the duration of time for which the Cl- ionophore is open. • The post synaptic inhibitory effect of GABA in the thalamus is increased. • Uses • Used in combination with acetaminophen or aspirin for its sedative and relaxant effect in the treatment of headache, migraine and pain.
  • 25. Thiopental sodium • Discovered in 1930 • First used in human beings in 1934 • It is rapid onset short acting barbiturate general anesthetic. • It is thiobarbiturate analog of Pentobarbital and analogue of thiobarbital. NH N S - O O CH3 C H3 C H3 Na +
  • 26. • MOA • Thiopental binds at distinct binding sites associated with chloride ionophore at the GABAA receptor, increasing the duration of time for which the Cl- ionophore is open. • The post synaptic inhibitory effect of GABA in the thalamus is prolonged. • Uses • Thiopentone sodium solution administered intravenously to produce anesthesia. • Also used to control convulsions.
  • 28. DISSOCIATIVE ANESTHETIC • Dissociative anaesthetics are a group of drugs that can produce a trance-like state, characterised by dissociation from reality. • This state can be used to relieve pain and anxiety, or to facilitate surgery. • The first dissociative anaesthetic, ketamine, was discovered in 1962. It
  • 29.  These agents block the N-methyl-D-aspartate in the brain by producing anaesthesia.  Ketamine is a rapid-onset, short-duration agent used primarily for induction of anaesthesia. Therefore, it is used primarily for the maintenance of anaesthesia.  Dissociative anaesthetics produce anaesthesia by blocking N-methyl-D- aspartate (NMDA) receptors in the brain.  Dissociative anaesthetics are sometimes used in people who need to be sedated for a short period, such as during surgery. Ketamine HCl