General anaesthetics

GAs
– block conduction of pain impulses to the sensory
cortex
Gas
Classification
 Inhalation anaesthetics
• Non halogenated
– Nitrous oxide
• Halogenated
– Halothane, desflurane, enflurane, isoflurane, sevoflurane
 Parenteral
– Ketamine, mildazolam, fentanyl, thiopental, propofol
GAs
Inhalation
MOA-interact with hydrophobic regions of proteins in
neuronal membranes
• Non-halogenated-NO
– ↑analgesia, ↓loss of consciousness
• Halogenated-Halothane
– Rapid induction + recovery
– S/E-dose dependent resp./cardiac depression
– Uterine relaxation → C/I in pregnancy
Parenteral
– Barbiturates/benzodiazepines/opioids
– Pre anaesthetic sedation, analgesia+ anaesthesia for
major/minor surgery
Ketamine
• Blocks receptors for excitatory amino acids e.g.
glutamate
• A/E-may cause unpleasant effects during recovery stage
Mildazolam
• Short acting benzodiazepine
– Preoperative sedation/endoscopy
• Effects reversed by flumazenil
Propofol /Thiopental
• Potentiate GABA
• Rapid onset/short duration of action
– Induction of anaesthesia
Fentanyl
 Inhalational anaesthetics
• Rationale for the use inhalational anesthetics
– Provide hypnosis
– Enhance or provide analgesia
– Provide muscle relaxation
– Reduce visceral reflex responses
– Enable lower doses of inhalational agent to
be used
 Nitrous Oxide
• Weak anesthetic, by itself is not suitable or safe as a sole
anesthetic agent
• Effective analgesic
• Minimal skeletal muscle relaxation
• No significant effects on the liver, kidney, or GI tract
• Very rapid onset and recovery
• Little toxicity
• Use as an adjunct to other inhalational agents allows
reduction in their dosage
 Halothane
• Loss of consciousness; but does not provide adequate analgesia;
reversible reduction in glomerular filtration rates (GFR)
Advantages:
• Relatively potent and nonflammable
• Relatively rapid induction & recovery from anesthesia
Indications
• Mainly used in pediatric anesthesia
• Infrequently used in adults due to the availability of other agents
which exhibit relatively more favourable pharmacological properties
e.g. isoflurane, enflurane, sevoflurane and  desflurane
A/Effects
– Hepatitis occurrences
– Causes significant myocardial depression
– Associated with malignant hyperthermia
Halothane A/E contd
• Sensitizes the myocardium to catecholamines, and may
induce arrhythmias in patients with phaechromocytoma (high
circulating levels of epinephrine and norepinephrine ) and
pre-existing cardiac disease
 Enflurane
• Rapid induction with limited effects on pulse or respiration
• Less arrhythmias, nausea, post-operative shivering and
vomiting compared to halothane
• Adequate muscle relaxation greater than halothane
• Reversible reduction of GRF
Uses:
• Mainly in adults. Not widely used in pediatric cases
A/Effects
– Not recommended for use in patients with seizure
disorders. Avoided in epileptic patients because it
occasionally induces CNS excitatory effects
– May cause malignant hyperthermia
 Isoflurane
• Rapid induction of anesthesia with limited effects on pulse or
respiration
• No hepatic and renal toxicity
• Provides adequate muscle relaxation greater than halothane
• Reversible reduction of GRF
Uses
• Isoflurane is the most widely used inhalational agent
 A/Effects:
• May cause malignant hyperthermia (as with halothane & enflurane)
• May cause arrhythmias in patients with phaechromocytoma and pre-
existing cardiac disease as halothane

 
 Desflurane
• Rapid onset and recovery , recovery twice as rapid as for isoflurane
• Causes laryngospasm and coughing
• Does not provide adequate muscle relaxation
• Circulatory effects similar to isoflurane
• Reversible reduction of GRF
• Seizure-like activity is not observed
• A/E: Malignant hyperthermia, coughing and laryngospasm
Sevoflurane
• Low blood solubility & high potency
• Pharmacological properties as of desflurane
• Commonly used
• Increase fluoride levels rarely associated with kidney or renal damage
• Compared to desflurane,  sevoflurane is more extensively metabolized,
releasing more fluoride
 Type of general anaesthetics
• I. V. Benzodiazepines
• I. V. Barbiturates
• I.V. Opioids
• Ketamine
• Propofol
• Combinations
 Intravenous drugs used in anaesthesia
Barbiturates – thiopental, methohexital sodium,
thiamylal sodium
Benzodiazepines - Diazepam,mildazolam, lorazepam
Opioids - Morphine, meperidine , fentanyl , sufentanil ,
alfentanil , remifentanil
Propofol
Ketamine
 Intravenous barbiturates used in Anesthesia
• Thiopental, methohexital sodium, thiamylal sodium
Thiopental
 Pharmacological properties:
• Rapid induction and fast recovery
• Rapid recovery (20-30 min) due to redistribution from brain to peripheral
tissues
• Little postoperative excitement or vomiting
• A/Effects
• Cough, laryngospasm, bronchospasm & histamine release
• Dose-related respiratory depression; Limited cardiovascular effects
• Crosses the placental barrier and depresses the fetus
Contraindications:
• Variegate porphyria or acute intermittant porphyria. Barbiturates can
cause nerve demyelination and CNS lesions which may result in pain,
weakness and life-threatening paralysis
 Benzodiazepines
 Intravenous benzodiazepines used in anesthesia
–  Diazepam (prototype), mildazolam, lorazepam
• Benzodiazepines are effective in promoting sedation and reducing
anxiety
• Midazolam has the most rapid onset of action and a shorter duration
• Benzodiazepines are not analgesic
• Amnesic in most patients
• Used alone benzodiazepines have limited depressant effects on the
cardiovascular/respiratory system.
• CNS depression can be reversed by the specific anatagonist
flumazenil
• When administered in combination with opioids, significant
cardiovascular and respiratory depression may occur
Uses
• Used alone for procedures not requiring analgesia, such as
endoscopy, cardiac catherization & certain radiological
procedures
• Used in combination with other drugs for "balanced
anesthesia"- which include opioids, muscle relaxants &
thiopental for induction and an inhalational agent
 Intravenous opioids used in anesthesia
 Morphine, meperidine , fentanyl , sufentanil , alfentanil ,
remifentanil
• Opioids are used to supplement inhalational or i.v.
anesthetics
• Morphine-nitrous oxide combination has been used in
cardiovascular surgery
A/Effects
• Respiratory depression, hypotension, post-operative nausea
or vomiting are associated with opioid use
• Respiratory depression caused by opioids is reversed by using
specific narcotic antagonists – Naloxone, naltrexone,
nalmefene
 Fentanyl and related agents
Fentanyl
• I.V. fentanyl causes analgesia and unconsciousness
• Compared to morphine, fentanyl is:
—  More amnestic
—  Less likely to provoke hypotensive or hypertensive responses
—  Shortened duration of respiratory depression
—  Fentanyl and related agents therefore preferrred to
morphine
Uses
• Fentanyl is often combined with a muscle relaxant and nitrous
oxide or low doses inhalational agent for anesthesia
A/E – may cause muscle rigidity
Alfentanil and sufentanil
• Alfentanil and sufentanil are more potent than fentanyl and
produce analgesia, and at higher concentrations- anesthesia
• Remifentanil - a new potent agent which produces analgesia very
rapidly
– Readily metabolized resulting in rapid recovery time
Propofol
• I.V.  propofol rapidly induces anesthesia, similar to thiopental; with
minimal postoperative confusion
• Duration of anesthesia can be increased by combination with
inhalational agents, nitrous oxide, or opioids
• Does not adversely affect hepatic or renal function
• Postoperative GI upset occur at a similar frequency to that of
thiopental
Uses: In ambulatory surgery settings
 Ketamine
• Produces a state that is characterized by sedation, amnesia,
analgesia and immobility
• This type of anesthesia has been termed "dissociative anesthesia"
because of patient's subjective impression of being dissociated from
the environment
• Significant amnesia and analgesia rapidly follow injection
• Recovery is slower than with barbiturates
 A/Effects
• Awakening may be associated with bad dreams and hallucinations
•  These A/E uncommon in children and can be reduced by concurrent
administration with benzodiazepines
Uses
•  In conjunction with diazepam, in emergency surgery, trauma,
dressing changes and certain pediatric radiological procedures