General anesthesia

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General anesthesia

• General anesthesia was not known until the
  mid-1800s
• Diethylether was the first general anesthetic
  used for surgery
• General Anesthetics are divided into two
  classes
• Inhaled anesthetics (usually halogenated
  compounds)
• Intravenous anesthetics or induction agents

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Modern Anesthesia

• It combines the following
• Analgesia
• Sleep (loss of consciousness)
• Skeletal Muscle relaxation
• amnesia
• Abolition sensory autonomic reflexes
• No single drug can produce all these effects

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Ideal anesthesia is

• Induce loss of consciousness smoothly and rapidly
• Allow for prompt recovery of cognitive function
  after its administration is discontinued
• Possess wide margin of safety
• Have no side effects
• No single drug can produce all these effects

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Stages of anesthesia

• Stage 1analgesia
• Decreased pain awareness, sometimes with amnesia
  ,conscious may be impaired but not lost
• Stage 2disinhibition
• Delirium, excitation, amnesia, enhanced reflexes,
  irregular respiration and incontinence
• Stage 3surgical anesthesia
• Unconsciousness ,no pain reflex, regular
  respiration and maintained blood pressure
• Stage 4medullary depression
• Severe CVS and respiratory depression and the
  patient require pharmacological and ventilatory
  support

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Anesthesia protocols

• For minor procedure, conscious sedation conscious
  sedation techniques that combine IV agent with
  local anesthetics are often used these can
  provide profound analgesia, with retention of the
  patient ability to maintain a patent airway and
  response to verbal commands
• For extensive surgical procedure protocol
  commonly includes IV drug for induction, inhaled
  agent(with or without IV)for maintenance and
  neuromuscular junction blockers to cause muscle
  relaxation

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General Anesthetics

• Absence of sensation associated with a reversible
  loss of consciousness, skeletal muscle
  relaxation, and loss of reflexes.
• Drugs used for anesthesia are CNS depressants
  with action that can be induced and terminated
  more rabidly than conventional sedative and
  hypnotics
• Most sensitive site of action for general
  anesthetics is the reticular activating system of
  the brainstem (RAS)
• Anesthetic dose does not cause depression of
  cardiac, vasomotor or respiratory centers
• Has a small margin of safety

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Inhaled Anesthetics

• Include
• Nitrous oxide
• Halothane
• Enflurane
• Isoflurane
• Desflurane

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Intravenous Anesthetics

• Include
• Barbiturates
• Thiopental Methohexital
• Opioids
• Alfentanil, Meperidine, Fentanyl, Sufentanil
  (agonists)
• Naloxone (antagonist)
• Benzodiazepines
• Diazepam, Midazolam
• Flumazenil (antagonist)

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Intravenous Anesthetics

• Miscellaneous Agents
• Etomidate non-barbiturate hypnotic agent
  without analgesic properties
• Droperidol - Neuroleptic (similar to Haloperidol)
  - combined with Fentanyl and is used for
  neuroleptanalgesia (state of analgesia and
  amnesia)
• Ketamine - dissociative anesthetic
• Propofol

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General Uses of IV Anesthetics

• Primary Use induction of general anesthesia
• Supplement general anesthesia
• maintain general anesthesia
• provide sedation
• control Blood Pressure

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Intravenous agents

• Mechanism of action
• Act at cell surface receptors
• Barbiturates and benzodiazepine act at GABA-A
  receptors to increase Cl- influx
• Opioids act on m and other subtypes
• Ketamine antagonizes PCP site on NMDA receptors
  (prevent excitation)
• Pharmacokinetics
• Rapid induction shorter acting
• Duration of effect proportional to redistribution
  from brain to other tissue

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Barbiturates Thiopentone

• Ultra-short acting hypnotic with no analgesic
  action
• High lipid solubility promotes rapid entry to the
  brain
• Eliminated by the liver
• Has rapid onset of action and recovery
• M.O.A. potentiates GABA, decrease glutamate
  activity, increase chloride ion conductance
• Adverse reactions decreased myocardial and
  respiratory activity

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Etomidate

• Imidazole derivative that provide induction with
  minimal change in cardiac function and
  respiratory rate and has short duration of action
  
• It is not analgesic , and its primary advantage
  is in anesthesia for patient with limited
  respiratory and cardiac reserve
• Activates GABA receptors
• Uses
• Induction of anesthesia
• Side effects
• Myoclonus
• Post-operative nausea and vomiting

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Ketamine

• This drug produce dissociative state in which the
  patient is patient remains conscious but has
  marked catatonia, analgesia, and amnesia
• It is a chemical congener of the psychotomimetic
  agent, phencyclidine (PCP)
• It is a cardiovascular stimulant drug and this
  action may cause increase ICP
• Emergency reactions include disorientation
  ,excitation and hallucination which can be
  reduced by preoperative administration of
  benzodiazepines

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• Uses- Induction of anesthesia
• in children
• in severely hypovolemic patients
• Contraindications
• Increased intracranial pressure
• Ischemic heart disease
• Psychological disorders
• Effects
• Analgesic with dissociative anesth. properties
• Dreaming in children

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Propofol

• Uses
• Induction and maintenance of anesthesia
• As anesthetic agent at outpatient surgery
• Also effective in producing prolog sedation in
  patient in critical care setting
• Contraindications
• Cardiovascular instability due to marked
  reduction in the peripheral resistance
• Effects
• Hypnosis ,Antiemetic
• Fast acting, short duration. Fewer peripheral
  side effects compared to barbiturates

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Opiates

• Potent analgesics
• Fentanyl -Potency 50-100X gtMorph
• Alfentanil -Potency 25-30X gt Morph
• Sufentanil -Potency 5-10X gtFentanyl
• Meperidine
• Uses
• Supplementation of general anesthesia or
  analgesia
• Effects
• respiratory depression
• nausea and vomiting
• muscle rigidity

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• INHALATION ANESTHETICS

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MAC(minimal alveolar concentration)

• MAC of anaesthetic measures potency of
  anaesthetic vapour. High MAC means low potency
• Defined as the concentration of anesthetic that
  prevents movement induced by a painful stimulus
  in 50 of subjects.

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Mechanism of Action

• Potency is correlated with lipid solubility
• Olive oilgas partition coefficient
• The greater the number, the more potent the
  anesthetic Methoxyfluranegthalothanegtisoflurane
  etc.

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Theories for Mechanism of Action

• Theory 1
• Gas movement into lipid membrane disrupting ion
  channels and action potential propagation
• Increased Atmospheric pressure will reverse
  effects
• Theory 2
• Binding theory anesthetics bind to hydrophobic
  portion of the ion channel
• Theory 3
• Neuromodulator theory anesthetics bind to
  cell-surface receptors.
• increased Cl- flux (possible GABA mediation)

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Pharmacokinetics of Inhaled Anesthetics

• Factors influencing the effects of inhaled
  anesthetics
• Amount that reaches the brain
• Indicated by oilgas ratio (lipid solubility)
• Partial pressure of anesthetic
• 5 anesthetic 38 mmHg (10 76 mmHg)
• Solubility of gas into blood
• The lower the bloodgas ratio, the more
  anesthetic will arrive at the brain
• Cardiac Output
• Increased CO greater Induction time

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Rate of Entry into the Brain Influence of Blood
and Lipid Solubility
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General Actions of Inhaled Anesthetics

• Respiration
• Depressed respiration
• Kidney
• Depression of renal blood flow and urine output
• Muscle
• High enough concentrations will relax skeletal
  muscle

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General Actions of Inhaled Anesthetics

• Cardiovascular System
• Generalized reduction in arterial pressure and
  peripheral vascular resistance. Isoflurane
  maintains CO and coronary function better than
  other agents
• Central Nervous System
• Increased cerebral blood flow and decreased
  cerebral metabolism

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Toxicity and Side Effects

• Depression of respiratory drive
• Depressed cardiovascular drive
• Fluoride-ion toxicity from methoxyflurane
• Metabolized in liver release of Fluoride ions
• Decreased renal function allows fluoride to
  accumulate nephrotoxicity
• Malignant hyperthermia
• To treat this, rapidly cool the individual and
  administer Dantrolene to block release of Calcium
  from muscle sarcoplasmic reticulum

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Advantages and Disadvantages of Selected Inhaled
Anesthetics

• Isoflurane
• Cardiac output is maintained
• Arrhythmias are uncommon
• Potentiates the actions of muscle relaxants
• Minimally metabolized and no reports of heptato-
  or nephrotoxicity
• most widely used agent
• MAY CAUSE MALIGNANT HYPERTHERMIA

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Advantages and Disadvantages of Selected Inhaled
Anesthetics

• Desflurane
• More irritating to airways than other agents
• Rapid recovery
• No reports of malignant hyperthermia

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Preanaesthetic Medication
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Focus Points

• Induction of anesthesia is through use of any of
  the IV agents (Barbiturates Thiopental, Opiate
  Fentanyl, Benzodiazepines Midazolam,
  Dissociative Ketamine, Others Propofol,
  Etomidate and Droperidol)
• Majntenance of anesthesia is through use of any
  of the ihalation agents
• -N2O (70 in oxygen) is not suitable alone
• - N2O is usually combined with another
  inhalation agent or with opioids e.g. fentanyl

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A comparison

• halothane
  N2O
• Speed of induction intermediate fast
• Potency v.potent
  weak
• MAC2
  MAC 80
• Muscle relaxation some
  none
• Cardiac arrhythmia yes
  no
• Liver damage yes
  no
• Recovery slow
  rapid

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• NOTES
• Enflurane releases flouride ions which may cause
  renal failure
• All inhalation anesthetics can cause resp.
  depression, myocardial depression, cardiac
  arrhythmias, hypotension and PONV
• A mixture of N2O(50-70) and haothane 1 is
  usually used in anesthesia.

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Nitrous Oxide

• Characterized by inert nature with minimal
  metabolism
• Colorless, odorless, tasteless, and does not burn

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• Simple linear compound
• Only anesthetic agent that is inorganic
• Major difference is low potency
• MAC value is 80 - 105
• Weak anesthetic, powerful analgesic
• Needs other agents for surgical anesthesia
• Low blood solubility (quick recovery)

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• GOOD LUCK