1. GENERAL ANAESTHETICS

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.

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.

4. TYPES OF GENERAL
ANAESTHETICS
• Inhalational agents.
• Intravenous agents.

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.

6. 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 anaesthetics and
are unusual with intravenous agents.
• Anaesthesia effects are divided into 4 stages of
increasing depth of CNS depression.

7. STAGE OF ANALGESIA:
• Patient experiences Analgesia without
amnesia but later Amnesia ensues.
STAGE OF SURGICAL ANAETHESIA:
• 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.

8. 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
anaethesia.
STAGE OF MEDULLARY DEPRESSION:
• Begins with cessation of spotantenous
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.

9. • 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.

10. 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.

11. 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 in the
inspired air.

12. • Pulmonary ventilation rate.
• Pulmonary blood flow…and
• The concentration gradient of
anaesthetic between arterial and mixed
venous blood.

13. 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 equibrium
concentration.

14. ANAESTHETIC
CONCENTRATION IN INSPIRED
AIR
• Increases in the inspired anaesthetic
concentration will increase the rate of
induction of anaethesia by increasing the
rate of transfer into blood.

15. 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.

16. 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.

17. 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.

18. • 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.

19. • Methoxyflurane is metabolized rapidly to
release Fluoride ions at levels that can be
nephrotoxic.
• Nitrous oxide is metabolized to a very
small extent.

20. 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.

21. 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.

22. • 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.

23. 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 depresss mucocilliary
function with the resultant pooling of mucus;
atelectasis ( no air in alveoli ) and respiratory
infections.
• Inhaled agents are bronchodilators, Halothane
being most potent

24. 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.

25. 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.

26. 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.

27. 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 Curretage.

28. TOXICITY
• Hepatotoxicity common following the use
of Halothane and Chloroform.
• Nephrotoxicity common with
Methoxyflurane.

29. 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.

30. EFFECT ON REPRODUCTION
• Miscarriages are common in operating
room female staff than expected in
general population but the evidence is not
strong.

31. INTRAVENOUS ANAESTHETICS
• Thiobarbiturate ( Thiopentone and
Methohexital ).
• Opioid analgesics and neuroleptics.
• Arylcyclohexylamines ( Ketamine ) which
produces a state called dissociative
anaesthesia.
• Miscellaneous ( Etomidate, Steroids
anesthetics, Propanidid )

32. ULTRA SHORT ACTING
BARBITIRATES
• THIOPENTONE:…Metabolised 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.

33. OPIOID ANALGESICS
ANAESTHETICS AND
NEUROLEPTANAESTHESIA
• Intravenous Morphine 1 Mg/Kg and
subsequently Fentanyl 50µg/ Kg is useful
in patients with minimal circulatory
reserve.
• Problems….Awareness during
anaesthesia or post-operative recall and
respiratory depression requiring assisted
ventilation.

34. • Dose of Opioid may be reduced with
simultaneous administration of short
acting Barbiturate or Benzodiazepine with
Nitrous oxide to acieve balanced
anaesthesia.

35. NEUROLEPTANAESTHESIA
• Patient becomes completely disinterested and
detached from environment..loss consciousness
or ability to obey commands or communicate
with others. The desire to move or change
position is lost.
• Droperidol ( a butyrophenone ) and Fentanyl (an
opioid analgesic ). This drug combination is
usually used with Nitrous oxide to produce
general anaesthesia.

36. 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
sympthatetic stimulation and is a powerful
analgesic.

37. • Increases cerebral blood flow ( increase
intracranial pressure ).
• Emergence phenomenon ( disorientetion,
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.

38. ETOMIDATE
• 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.

39. BENZODIAZEPINES
• Diazepam, Lorazepam and Midazole.
• Diazepam and Lorazepam are not water
soluble and their I.V. use necessitates a
nnon-aqueous vehicle whuch may be
irritating.
• Benzodiazepines are most useful in
anaesthesia as premedication and can be
used for intraoperative sedation.

40. 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 problemis epilepticform convulsios occur
occasionally in patients without epilepsy.

41. DIISOPROPYLPHENOL
• Produces anaesthesia at rate similar to
that of I.V. barbiturates.
• Investigational drug.
• Plasma half-life 2 to 3 minutes.