General anesthetics are drugs that produce reversible loss of sensation and consciousness. They work by depressing brain function from the cortex down to the medulla. There are two main types - inhalational anesthetics which are gases or vapors inhaled, and intravenous anesthetics which are injected. Both work by inhibiting excitatory neurotransmitters like glutamate while enhancing inhibitory neurotransmitters like GABA. This raises the threshold for electrical signals in the brain and lowers responsiveness to stimuli. While very effective at inducing unconsciousness, general anesthetics must be carefully monitored as the line between surgical anesthesia and respiratory/circulatory failure is narrow.

1. GENERAL ANESTHESIA

2. INDEX
 Definition
 Classification
 Components
 Mechanism of action
 Complications &
interactions

3. DEFINITION
GENERAL ANESTHETICS [GAs] ARE DRUGS
WHICH PRODUCE REVERSIBLE LOSS OF ALL
SENSATION AND CONSCIOUSNESS SO IT CAN BE
DIFFERENTIATED FROM SLEEP,HEAD
INJURY,HYPNOSIS,DRUG POISONING AND COMA.

4. • Definition : Anesthesia (an =without, aisthesis =
sensation )
• Anesthesia is medication that attempts to eliminate
pain impulse from reaching the brain.
• In general anesthesia this is accomplished by putting
the patient asleep.
STREPTOKINASESTREPTOKINASEStreptokinaseANAESTHESIA

5. CLASSIFICATION
*INHALATIONAL
*INTRAVENOUS

6. inhalationAL
GASES VOLATILE
LIQUIDS
NO ETHER
HALOTHANE
ENFLURANE
ISOFLURANE
DESFLURANE
SEVOFLURANE

7. •INTRAVENOUS
INDUSING AGENTS SLOWER ACTING DRUGS
THIOPENTONE SODIUM *BENZODIZAPINES
METHOHEXITONE SOD. DIAZEPAM
PROPOFOL LORAZEPAM
ETOMIDATE MIDAZOLAM
*DISSOSIATVE ANESTHETICS
KETAMINES
*OPIOID ANALGESIA
FENTANYL

8. COMPONENTS
THE FAMOUS COMPONENTS OF G.A ARE
UNCONSCIOUSNESS
ANALGESIA
MUSCLE RELAXATION

9. 1.WHERE UNCONSCIOUSNESS IS REPLACED BY AMNESIA OR
LOSS OF AWARENESS
2.ANALGESIA IS REPLACED BY NO STRESS AUTONOMIC
RESPONSE
3. MUSCLE RELAXATION IS REPLACED BY NO MOVEMENT IN
RESPONSE TO SURGICAL STIMULI

10. The empirical approach to anaesthetic
drug administration consists of selecting an
initial anesthetic dose {or drug} and then
titrating subsequent dose based on the clinical
responses of patients, without reaching toxic
doses.
The ability of anaesthesiologist to predict clinical
response and hence to select optimal doses is
the art of anaesthesia

11. HOW CAN WE ACHIEVE
G.A?

12. (a).INHALATIONAL ANAESTHESIA
- Inhalational anesthesia is achieved through
airway tract by facemask, laryngeal mask or
endotracheal tube.
- The agent used is a gas like nitrous oxide or
volatile vapor like chloroform, ether, or
flothane.
- Inhalational anesthesia depresses the brain
from up [cortex] to down [the medulla] by
increasing dose.

15. INTRVENOUS ANAESTHESIA
-Very rapid: 10 seconds, for 10 minutes
-Irreversible dose
-It is used in short operation or in induction
of anesthesia and anesthesia maintained by
inhalational route
-New agent now can be used in maintenance by
infusion

16. The relationship between anaesthetic activity
and lipid solubility has been repeatedly
confirmed. Anaesthetic potency in humans is
usually expressed as the minimal alveolar
concentration (MAC) required to abolish the
response to surgical incision in 50% of
subjects. Figure 36.1 shows the correlation
between MAC (inversely proportional to
potency) and lipid solubility, expressed as
oil:water partition coefficient, for a wide range
of inhalation anaesthetics. The Overton-Meyer
studies did not suggest any particular
mechanism, but revealed an impressive
correlation, for which any theory of
anaesthesia needs to account. Oil:water
partition was assumed to predict partition into
membrane lipids, consistent with the
suggestion that anaesthesia results from an
alteration of membrane function.

17. How the simple introduction of inert foreign
molecules into the lipid bilayer could cause a
functional disturbance is not explained by the
lipid theory. Two possible mechanisms, namely
volume expansion and increased membrane
fluidity, have been suggested and tested
experimentally, but both are now largely
discredited (see Halsey, 1989; Little, 1996), and
attention has swung from lipids to proteins,
the correlation of potency with lipid solubility
being explained by the effect of lipid solubility
on the concentration of anaesthetic adjacent
to its supposed protein target in the
hydrophobic region of neuronal cell
membranes

18. EFFECTS ON ION CHANNELS
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Following early studies that showed that
anaesthetics can bind to various proteins as
well as lipids, it was found that anaesthetics
affect many ligand-gated ion channels (see
Franks & Lieb 1994; Rudolph & Antkowiak,
2004). Many anaesthetic agents are able, at
concentrations reached during anaesthesia, to
inhibit the function of excitatory receptors,
such as the ionotropic glutamate, acetylcholine
or 5-hydroxytryptamine receptors, as well as
enhancing the function of inhibitory receptors
such as GABAA and glycine. The GABAA

19. receptor is the sole target for benzodiazepines
(see Ch. 37) and also appears to be a major
target for intravenous anaesthetics, such as
thiopental, propofol and etomidate (see
below), that act at a site on the receptor
different from the benzodiazepine binding site.
Studies of experimentally mutated receptors
(see Rudolph & Antkowiak, 2004) have
confirmed this and succeeded in identifying
the specific 'modulatory sites' through which
the anaesthetic drugs exert their effects on
channel function. The 'two-pore domain'
potassium channel known as TREK (see Ch. 4)
is another specifically anaesthetic-sensitive
channel. It is activated, thus reducing
membrane excitability, by low concentrations
of volatile anaesthetics (see Franks & Lieb,
1999).

20. In summary, general anaesthetics inhibit
excitatory channels (especially glutamate
receptors) and facilitate inhibitory channels
(particularly GABAA but also glycine and
certain potassium channels), and these
interactions are targeted at specific
hydrophobic domains of the channel proteins.
This is probably a serious oversimplification: as
Little (1996) emphasises, individual
anaesthetics differ in their actions and affect
cellular function in several different ways, so a
unitary theory is unlikely to be sufficient, but it
does provide a useful starting point.

21. EFFECTS OF ANAESTHETICS ON THE NERVOUS
SYSTEM
At the cellular level, the effect of anaesthetics
is mainly to inhibit synaptic transmission, any
effects on axonal conduction probably being
relatively unimportant
Inhibition of synaptic transmission could be
due to reduction of transmitter release,
inhibition of the action of the transmitter, or
reduction of the excitability of the postsynaptic
cell. Although all three effects have been
described, most studies suggest that reduced
transmitter release and reduced postsynaptic
response are the main factors. Reduced
acetylcholine release occurs at peripheral
synapses, and reduced sensitivity to excitatory
transmitters (due to inhibition of ligand-gated
ion channels; see above) occurs at both
peripheral and central synapses.

22. Inhibitory synaptic transmission is usually
potentiated by general anaesthetics,
particularly barbiturates, volatile anaesthetics
having similar but less strong actions (see
Rudolph & Antkowiak, 2004

23. The anaesthetic state comprises several
components, including unconsciousness, loss
of reflexes (muscle relaxation) and analgesia.
Much effort has gone into identifying the brain
regions on which anaesthetics act to produce
these effects. The most sensitive regions
appear to be the midbrain reticular formation
and thalamic sensory relay nuclei, inhibition of
which results in unconsciousness and
analgesia, respectively. Some anaesthetics
cause inhibition at spinal level, producing a
loss of reflex responses to painful stimuli,
although, in practice, neuromuscular-blocking
drugs (Ch. 10) are used to produce muscle
relaxation rather than relying on the
anaesthetic alone. Anaesthetics, even in low
concentrations, cause short-term amnesia, i.e.
experiences occurring during the influence of
the drug are not recalled later, even though
the subject was responsive at the time.2 It is
likely that interference with hippocampal
function produces this effect, because the
hippocampus is involved in short-term
memory, and certain hippocampal synapses
are highly susceptible to inhibition by

24. As the anaesthetic concentration is increased,
all brain functions are affected, including
motor control and reflex activity, respiration
and autonomic regulation. Therefore it is not
possible to identify a critical 'target site' in the
brain responsible for all the phenomena of
anaesthesia.
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High concentrations of any general anaesthetic
affect all parts of the CNS, causing complete
shut-down and, in the absence of artificial
respiration, death from respiratory failure. The
margin between surgical anaesthesia and
potentially fatal respiratory and circulatory
depression is quite narrow, requiring careful
monitoring by the anaesthetist and rapid
adjustment of the level of anaesthesia, as
required.

25. Clinical uses of general anaesthetics
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•Intravenous anaesthetics are used for:
• induction of anaesthesia (e.g. thiopental, etomidate)
• maintenance of anaesthesia throughout surgery ('total
intravenous anaesthesia', e.g. propofol given in combination
with muscle relaxants and analgesics).
•Inhalational anaesthetics (gases or volatile liquids) are used for
maintenance of anaesthesia. Points to note are that:
• volatile liquids (e.g. halothane, sevoflurane) are vaporised
with air, oxygen or oxygen-nitrous oxide mixtures as the carrier
gas
• halothane hepatotoxicity (see Ch. 53) occurs more often after
repeated exposure
• all inhalational anaesthetics can trigger malignant
hyperthermia in susceptible individuals (Ch. 10).

27. METABOLISM AND TOXICITY OF INHALATION
ANAESTHETICS
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Metabolism, although not quantitatively
important as a route of elimination of
inhalation anaesthetics, can generate toxic
metabolites. Chloroform (now obsolete)
causes hepatotoxicity associated with free
radical formation in liver cells. Methoxyflurane,
a halogenated ether, is no longer used because
about 50% is metabolised to fluoride and
oxalate, which cause renal toxicity. Enflurane
and sevoflurane also generate fluoride, but at
much lower (non-toxic) concentrations (Table
36.1). Halothane is the only volatile
anaesthetic in current use that undergoes
substantial metabolism, about 30% being
converted to bromide, trifluoroacetic acid and
other metabolites that are implicated in rare
instances of liver toxicity (see below).

28. The problem of toxicity of low concentrations
of anaesthetics inhaled over long periods by
operating theatre staff causes much concern,
following the demonstration that such chronic
low-level exposure (and associated metabolite
formation) leads to liver toxicity in
experimental animals. Epidemiological studies
of operating theatre staff have shown
increased incidence of liver disease and of
certain types of leukaemia, and of
spontaneous abortion and congenital
malformations, compared with control groups
not exposed to anaesthetic agents. Although
causation has not been clearly established,
strict measures are used to minimise the
escape of anaesthetics into the air of operating
theatres

30. •Pharmacological effects
of anaesthetic agents
• Anaesthesia involves three main neurophysiological
changes: unconsciousness, loss of response to painful
stimulation and loss of reflexes.
• At supra-anaesthetic doses, all anaesthetic agents can
cause death by loss of cardiovascular reflexes and
respiratory paralysis.
• .
• At the cellular level, anaesthetic agents affect
synaptic transmission rather than axonal conduction.
The release of excitatory transmitters and the
response of the postsynaptic receptors are both
inhibited. GABA-mediated inhibitory transmission is
enhanced by most anaesthetics

31. • diacAlthough all parts of the nervous system are
affected by anaesthetic agents, the main targets
appear to be the thalamus, cortex and hippocampus.
• Most anaesthetic agents (with exceptions, such as
ketamine and benzodiazepines) produce similar
neurophysiological effects and differ mainly in respect
of their pharmacokinetic properties and toxicity.
• Most anaesthetic agents cause cardiovascular
depression by effects on the myocardium and blood
vessels, as well as on the nervous system. Halogenated
anaesthetic agents are likely to cause car dysrhythmias,
accentuated by circulating catecholamines

34. Commonly used in children, where preoperative placement if an iv catheter
can be difficult.
Anesthesia is produced at end –tidal concentration of 0.7 -1%.
.
CLINICAL USES
SIDE EFFECTS