for anaesthesia only

1. GENERAL ANAESTHETICS
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2. The state of General Anaesthesia usually
includes Analgesia; Amnesia; Loss of
consciousness and autonomic reflexes
and skeletal muscle relaxation.
No single anaesthetic drug is capable of
achieving all of these desirable effects
without some disadvantages when used
alone.
Thus the modern practice of anaesthesia
involves the use of a combination of
drugs.
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3. Balanced anaesthesia includes
the administration of
medications preoperatively for
sedation and analgesia;
The use of neuromuscular
blocking drugs
intraoperatively; and the use of
both intravenous and inhaled
anaesthetic drugs.
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4. TYPES OF GENERAL
ANAESTHETICS
Inhalational agents.
Intravenous agents.
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5. INHALATIONAL AGENTS
GASES:
 Nitrous oxide- important component of many
anaesthesia regimens.
 Cyclopropane – limited current use because of
potential inflammability closed circuit.
VOLATILE LIQUIDS:
 Halothane; Enflurane; Isoflurane and
Methoxyflurane are used commonly.
 Ether has limited use because it is potentially
inflammable.
 Chloroform has limited use because of organ
toxicity.
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6. DRUGS USED
Premedication:
(i) Anxiolytics and amnesia
Benzodiazepines e.g. Temazepam
10-20 mg for anxiolytics and amnesia.
(ii) Analgesia for patients who have
pain preoperatively or
 to cover postoperative pain.
Morphine, NSAIDs and paracetamol
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7. (ii) To prevent aspiration of gastric
contents:
Sodium citrate to neutralize
gastric acid, H2 receptor blockers
or a proton pump inhibitor will
reduce gastric secretion, volume
as well as acidity.
Metoclopramide hastens gastric
emptying, increases oesophageal
sphincter tone and is antiemetic.
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8. SIGNS AND STAGES OF ANAESTHESIA
These were described from observations on patients
who were being anaesthetized by Diethyl-ether
alone.
 The stages can be observed because Ether has
slow onset of central action due to its high
solubility in blood.
The signs are not readily seen with the more
rapidly acting Modern inhaled anaesthetic and
are unusual with intravenous agents.
Anaesthesia effects are divided into 4 stages of
increasing depth of CNS depression.
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9. STAGE OF ANALGESIA:
 Patient experiences Analgesia without
amnesia but later Amnesia ensues.
STAGE OF EXCITEMENT:
 Delirium; Excitement and
Amnesia….Respiration is irregular both in
volume and rate.
 Retching and vomiting may occur.
 Incontinence and struggling may occur.
 Stage ends with re-establishment of
regular breathing.
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10. STAGE OF SURGICAL ANAESTHESIA:
 Begins with regular respiration and extends to
complete cessation of spontaneous respiration.
 There are four planes representing signs of
increasing depth of anaesthesia.
STAGE OF MEDULLARY DEPRESSION:
 Begins with cessation of spontaneous
respiration.
 There is severe depression of the respiratory
centre in the medulla and vasomotor centre as
well .
 Without full circulatory and respiratory support-
coma and death ensue.
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11. Most reliable indications that
stage 111 (surgical
Anaesthesia ) has been
achieved are loss of the eye-
lash reflex and
establishment of a
respiratory pattern that is
regular in rate and depth.
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12. MECHANISM OF ACTION:
Increased the threshold of
cells to firing;
resulting in decreased activity.
Reduce the rate of rise of the
action potential by interfering
with Sodium influx.
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13. MECHANISM OF ACTION
Anaesthetics have specific anatomical,
physiological and molecular targets
(a) Anatomical sites of action
E.g. immobilization in response to
surgical incision results from inhalational
anaesthetic action in the spinal cord.
Inhalational anaesthetics depress the
excitability of the thalamic neurons
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14. The thalamus may be a potential locus
for sedative effects of inhalational
anaesthetics
Blockade of the thalamocortical
communication produces
unconsciousness.
Both iv and inhalational anaesthetics
depress hippocampal
neurotransmission (a probable locus
for amnesic effects of anaesthetics).
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15. Dexmedetomidine, an iv GA, and an
ά2 –adrenergic receptor agonist
produces unconsciousness via action
in the locus coeruleus.
It reduces the MAC % of inhalational
anaesthetics by as much as 90%
The sites of action at which other
inhalational and iv anaesthetics
produce unconsciousness have not
been identified.
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16. (b) PHYSIOLOGICAL MECHANISMS OF
ANAETHESIA:
Inhalational anaesthetics inhibit
excitatory synapses in various
preparations.
These effects may be produced both
in pre- and postsynaptic actions of the
agents.
Isoflurane can inhibit neurotransmitter
release.
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17. Inhalational anaesthetics can act
postsynaptically altering response to
released neurotransmitter.
Most iv agents act predominantly by
enhancing inhibitory
neurotransmission.
Ketamine predominantly inhibits
excitatory neurotransmission at
glutamatergic synapses.
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18. Molecular actions of GAs:
Chloride channels gated by the
inhibitory neurotransmitter GABA
They are sensitive to clinical
concentrations of a wide variety of
anaesthetics including
halogenated inhalational agents and
many iv agents (Propofol,
barbiturates, Etomidate and
neurosteroids).
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19. Clinical concentrations of inhalational
anaesthetics enhance the ability of
Glycine to activate Glycine gated chloride
channels (Glycine receptors).
Glycine receptors have an important
inhibitory neurotransmission in the spinal
cord and brain stem.
Propofol, neurosteroids and barbiturates
potentiate Glycine – activated currents
whereas Ketamine and Etomidate do not.
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20. Subanaesthetic concentrations of inhalational
anaesthetics inhibit some classes of neuronal
nicotinic acetylcholine.
This effect may play a role in mediating the
analgesic effects of inhalational anaesthetic
agents.
General anaesthetics that do not have
significant effects on GABAA or Glycine
receptors are
Ketamine, nitrous oxide and xenon these
agents inhibit the NMDA receptors.
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21. GAs bind on specific sites
on GABAA – receptor
protein.
Since GABA mimetics can
produce unconsciousness
GABAA receptors may have
a role in mediating the
hypnotic effects of GAs.
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22. PHARMACOKINETICS OF
INHALED ANAESTHETICS
UPTAKE AND DISTRIBUTION:
 The rate at which a given
concentration of anaesthetic in the
brain is reached depends on -;
 The solubility properties of the
anaesthetic.
 Its concentration in the inspired air.
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23.  Pulmonary ventilation rate.
 Pulmonary blood flow…and
 The concentration gradient
of anaesthetic between
arterial and mixed venous
blood.
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24. SOLUBILITY
Nitrous oxide with low solubility in
blood reaches high arterial tensions
rapidly
which in turn results in more rapid
equilibrium with the brain and faster
induction of anaesthesia.
In contrast even after 40 minutes
Methoxyflurane has reached only 20 %
of the equilibrium concentration.
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25. ANAESTHETIC CONCENTRATION IN
INSPIRED AIR
Increases in the inspired
anaesthetic concentration
will
increase the rate of
induction of anaesthesia by
increasing the rate of
transfer into blood.
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26. PULMONARY VENTILATION
An increase in pulmonary
ventilation is accompanied by only
slight increase in arterial tension of
anaesthetic with low solubility but
can significantly increase tension
of agents with moderate or high
blood solubility.
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27. PULMONARY BLOOD FLOW
An increase in pulmonary
blood flow slows the rate
of rise in arterial tension
particularly for those
anaesthetics with
moderate to high blood
solubility.
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28. ARTERIAL-VENOUS CONCENTRATION
GRADIENT
Venous blood returning to the lungs
may contain significantly less
anaesthetic than that present in
arterial blood
the greater this difference in tensions
the more time it takes to achieve
equilibrium.
15 to 20 % of inspired Halothane is
metabolized during an average
anaesthetic procedure.
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29. 2 to 3 % of Enflurane is
metabolized over the same period.
Halothane is normally oxidized to
Trifluoroacetic acid and release
bromide and chloride ions.
Under condition of low oxygen
tension Halothane is metabolized
to the Chlorotrifluo-ethyl free
radical which
is capable of reacting with hepatic
membrane components.
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30. Methoxyflurane is
metabolized rapidly to
release Fluoride ions at
levels that can be
nephrotoxic.
Nitrous oxide is
metabolized to a very small
extent.
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31. MINIMUM ALVEOLAR ANAESTHETIC
CONCENTRATION
(MAC)….Of an anaesthetic is that
concentration which results in immobility in
50 % of patients when exposed to a
noxious stimulus such as surgical incision.
MAC values decrease in elderly patients
but are not affected greatly by
 sex; height and weight.
Drugs like the opioid analgesics or
sedative- hypnotics decrease MAC
value.
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32. CLINICAL PHARMACOLOGY OF
INHALED ANAESTHETICS EFFECTS ON
CARDIOVASCULAR SYSTEM:
BLOOD PRESSURE….Decrease by
Halothane and Enflurane due to a
reduction in cardiac output; Isoflurane
due a decrease in systemic vascular
resistance ( not cardiac output ).
Diethyl ether and Cyclopropane raise
the BP by their ability to liberate
catecholamines.
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33. HEART RATE:….. Halothane causes
bradycardia by direct depression of atrial
rate.
Methoxyflurane ; Enflurane and Isoflurane
increase heart rate.
All inhaled anaesthetics tend to increase right
atrial pressure which reflects depression of
myocardium.
 Enflurane and Halothane are very
depressant. Nitrous oxide is also
depressant. Cyclopropane; Diethyl ether
and Fluroxene are not.
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34. EFFECTS ON RESPIRATORY
SYSTEM:
With the exception of Nitrous oxide and
Diethyl ether which liberate catecholamines
all inhaled anaesthetics are respiratory
depressants and they cause an increase in
resting PaCO2 with Isoflurane an Enflurane
being most depressants.
Inhaled anesthetics depress mucocilliary
function with the resultant pooling of mucus;
atelectasis ( no air in alveoli ) and respiratory
infections.
Inhaled agents are bronchodilators,
Halothane being most potent
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35. EFFECT ON BRAIN
Inhaled anaesthetics decrease
metabolism in the brain.
They increase cerebral blood flow by
decreasing cerebral vascular
resistance.
 Hyperventilation of the patient before
the anesthetic is given avoids increase
in intracranial pressure from inhaled
anaesthetics.
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36. EFFECT ON THE KIDNEY
All decrease GFR, increase renal
vascular resistance and cause a
decrease in renal blood flow which
may be due to an impairment of
auto-regulation of renal flow.
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37. EFFECT ON LIVER
All cause a decrease in hepatic
blood flow which range from 15 to
45 %.
Transient changes in liver function
tests have been observed.
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38. EFFECTS ON UTERINE SMOOTH
MUSCLE
Isoflurane; Halothane and
Enflurane are potent uterine
muscle relaxants-
Useful in intrauterine foetal
manipulation but will cause
increased bleeding during
Dilatation and Curettage.
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39. TOXICITY
Hepatotoxicity common
following the use of
Halothane and
Chloroform.
Nephrotoxicity common
with Methoxyflurane.
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40. CHRONIC TOXICITY
MUTAGENICITY:…Anaesthetic that
contain Vinyl moiety ( fluroxene and
Divinyl-ether ) may be mutagens.
CARCINOGENS:
No study has demonstrated the
existence of cause and effect
relationship between anaesthetic
and cancer.
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41. EFFECT ON REPRODUCTION
Miscarriages are common
in operating room female
staff than expected in
general population
but the evidence is not
strong.
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42. INTRAVENOUS ANAESTHETICS
Thiobarbiturate ( Thiopentone and
Methohexital ).
Opioid analgesics and
neuroleptics.
Arylcyclohexylamines ( Ketamine )
which produces a state called
dissociative anaesthesia.
Miscellaneous ( Etomidate,
Steroids anesthetics, Propanidid ).
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43. ULTRA SHORT ACTING BARBITIRATES
THIOPENTONE:…Metabolized at a rate
of 12 to 16 % per hour.
Large doses cause a fall in BP; stroke
volume and cardiac output…due to
depression of myocardium.
It is a potent respiratory depressant.
Cerebral metabolism and oxygen
utilization are decreased also cerebral
blood flow is decreased.
It also decrease blood flow and GFR.
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44. OPIOID ANALGESICS ANAESTHETICS AND
NEUROLEPTANAESTHESIA
Intravenous Morphine 1 Mg/Kg and
subsequently Fentanyl 50g/ Kg is
useful in patients with minimal
circulatory reserve.
Problems….Awareness during
anaesthesia or post-operative
recall and respiratory depression
requiring assisted ventilation.
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45. Dose of Opioid may be
reduced with
simultaneous
administration of short
acting Barbiturate
or Benzodiazepine with
Nitrous oxide to achieve
balanced anaesthesia.
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46.  NEUROLEPTANAESTHESIA
 Droperidol ( a Butyrophenone ) and
Fentanyl (an Opioid analgesic ).
This drug combination is usually used
with Nitrous oxide to produce general
anaesthesia.
Patient becomes completely
disinterested and detached from
environment.
Loss consciousness or ability to obey
commands or communicate with
others retained. The desire to move or
change position is lost.
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47. KETAMINE
Produce dissociative anaesthesia
characterized by catonia, amnesia, and
analgesia.
It is lipophilic and rapidly distributed to
highly vascular brain and then
redistributed to other tissues.
Undergoes hepatic metabolism and
renal and biliary excretion.
Produces cardiovascular stimulation
via central sympathatetic stimulation
and is a powerful analgesic.
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48. Increases cerebral blood flow
(increase intracranial pressure ).
Emergence phenomenon
(disorientation, sensory and
perceptual illusion and vivid
dreams following anaesthesia ) is a
problem.
This can be avoided by giving
Diazepam 0.2 to 0.3 Mg/Kg I.V. 5
minutes before administration of
Ketamine.
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49. Causes rapid induction of anaesthesia with
minimal CVS and respiratory changes.
It is lipid soluble with Vd of 4.5L/Kg.
Excreted mainly as metabolites in the
urine.
Produces hypnosis within 2 Seconds.
Hypotension and a low frequency of
apnoea.
Causes high incidence of myoclonia and
pain during injection.
It may cause adreno-cortical suppression
via inhibitory effects on steroidogenesis.
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50. BENZODIAZEPINES
Diazepam, Lorazepam and Midazolam.
Diazepam and Lorazepam are not
water soluble and their I.V. use
necessitates a non-aqueous vehicle
which may be irritating.
Benzodiazepines are most useful in
anaesthesia as premedication and can
be used for intraoperative sedation.
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51. PROPANIDID
Produce anaesthesia as rapid as
Thiopentone.
Recovery is more complete and
accumulation less likely with Propanidid
than with Thiopentone.
It is rapidly metabolized by cholinesterase.
Causes hypotension ( due to peripheral
dilatation ) and negative inotropic effect on
the heart.
Major problem is epileptic form convulsions
occur occasionally in patients without
epilepsy.
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52. DIISOPROPYLPHENOL
Produces anaesthesia at
rate similar to that of I.V.
barbiturates.
 Investigational drug.
 Plasma half-life 2 to 3
minutes.
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53. XENON
is an inert gas extracted from air.
It is insoluble in blood and produces very rapid
induction.
It produces surgical anaesthesia when
administered with 30% oxygen.
It is not metabolised at all and has no adverse
effects in major organ systems.
May be available in future if its high cost can be
overcome.
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