The document provides a history of anaesthesia, beginning with its term being coined in 1846 and derived from Greek words meaning "without" and "sensation". Natural substances like alcohol, opium and cannabis were previously used for anaesthesia but resulted in high mortality. Milestones in the development of anaesthesia are noted, including the first use of ether in 1842 and chloroform in 1847. Various inhalation anaesthetics developed throughout the 20th century including halothane, enflurane and intravenous agents like thiopentone and propofol. The document discusses the mechanisms, pharmacology, uses and administration of various anaesthetic agents like halothane, enflurane, ether, nitrous oxide, ketamine

1. History Of Anaesthesia

2. ANAESTHESIA
Term coined by American physician Oliver Wendell Holmes in 1846
Derived from Greek words: an-without and anaesthesia-sensation
Natural substances like alcohol, opium, cannabis were used previously that
resulted into high mortality due to shock, pain and blood loss

3. As per records,
 1540- Paracelsus administered ether to chicken
 1800- Nitrous oxide was recognized but wasn’t successfully used
 Henry Hill Hickman administered CO2 to experimental animal
 1842- Ether was used in human

4.  1845- Horace Wells used Nitrous oxide to relive dental pain but
had failure
 1846-William Morton gave demonstration of use of diethyl ether
as surgical anaesthesia
 1847-James Simpson introduced chloroform

5.  1875-First IV technique by using chloral hydrate
 1884- Cocaine was used as local anaesthesia
 1898- First spinal anaesthesia was described
 1929-Cyclopropane was used as general anaesthetic

6.  1930s – Development of barbiturate (pentobarbitone) by J.W
Wright
 1934- Thiopentone developed
 1956- Introduction of halothane

7. THANK YOU

8. INHALATION ANAESTHETICS
INTRODUCTION
 CNS ACTING DRUGS ADMINISTERED BY BREATHING TO PRODUCE GENERAL ANAESTHESIA.
 MOST COMMONLY ADMINISTERED THROUGH AN ANAESTHESIA MASK OR ENDOTRACHEAL TUBE
CONNECTED TO AN ANAESTHETIC MACHNINE.
 RECOVERY DOESN’T DEPEND UPON DRUG METABOLISM AND THEREFORE THEIR ACTION IS
EXPECTED TO BE SIMILAR IN ALL MAMMALS.
ADVANTAGES OVER INJECTABLE ANAESTHETICS :
 THE DEPTH OF ANAESTHESIA DURING MAINTENANCE CAN BE EASILY CONTROLLED BY ADJUSTING
THE TOTAL FLOW RATE OF ANAESTHETIC DRUG.

9.  PERMIT PROTECTION OF AIRWAYS DUE TO INTUBATION.
 DURATION OF CLINICAL EFFECT AND ELIMINATION IS NOT DEPENDENT ON THE BODY
DETOXIFICATION MECHANISMS.
 USEFUL IN SPECIES FOR WHICH THERE IS LITTLE INFORMATION ON USE OF GENERAL
ANAESTHETICS.
 INCIDENCE OF ANAESTHETIC RELATED TOXICITY IS RARE.
 SHORT ANAESTHETIC HANGOVER.
CLASSIFICATION
1. VOLATILE LIQUID/ NON GASEOUS INHALATION ANAESTHETIC
i. MAJOR VOLATILE ANAESTHETICS
EG: HALOTHANE, ENFLURANE, ISOFLURANE, DESFLURANE AND SEVOFLURANE.
II. MINOR VOLATILE ANAESTHETICS
EG: DIETHYL ETHER, METHOXYFLURANE, CHLOROFORM AND TRICHLOROETHYLENE.

10. 2. GASEOUS INHALATION ANAESTHETICS
i. MAJOR GASEOUS ANAESTHETICS
EG: NITROUS OXIDE
II. MINOR GASEOUS ANAESTHETICS
EG: XENON AND CYCLOPROPANE
HALOTHANE
 MULTIHALOGENATED NON IRRITATING
VOLATILE LIQUID.
 RAPID INDUCTION AND RECOVERY, POTENCY,
NON FLAMMABILITY AND MINIMAL SIDE
EFFECTS.

11. PHARMACOLOGICAL EFFECTS
 DOSE RELATED DEPRESSION OF CNS CAPABLE OF DEPRESSING ALL FUNCTIONS OF CNS AT ALL
LEVEL UNTIL COMA OR DEATH.
 INDUCTION: SMALL ANIMALS(3 TO 5 MINUTES), RECOVERY(5 TO 15 MINUTES).
 STAGE II IS BYPASSED AND EXCITEMENT, NAUSEA AND VOMITING ARE UNCOMMON.
 PUPILS MAY BE CONSTRICTED, RESPIRATION MAY BE SHALLOW BUT RAPID AND ABDOMINAL
MUSCLES ARE RELAXED ONLY AT DEEPER PLANES.
 CAUSES DEPRESSION OF MYOCARDIAL CONTRACTILITY BY REDUCING INTRACELLULAR CA++
CONCENTRATION.
 DECREASES SYMPATHETIC NERVOUS SYSTEM ACTIVITY AND ANTAGONISES SYMPATHETIC
RESPONSE.
 HYPOVENTILATION, ACCUMULATION OF CO2 IN BLOOD IF THE RESPIRATION IS NOT ASSISTED.

12.  BOTH AMPLITUDE AND FREQUENCY OF RESPIRATORY MOVEMENTS ARE DECREASED.
 DECREASES MOTILITY, TONE AND PERISTALTIC ACTIVITY OF THE INTESTINAL TRACT.
 DEPRESSES THERMOREGULATORY CENTRES IN THE HYPOTHALAMUS.
 NOT A NEPHROTOXIC AGENT, BUT IT PRODUCES OLIGURIA DUE TO DECREASED RENAL BLOOD
FLOW AND GLOMERULAR FILTRATION RATE.
 MODERATE TO GOOD RELAXATION OF SKELETAL MUSCLES IN LIGHT ANAESTHETIC PLANES.
 DECREASES TONE AND MOTILITY OF UTERUS.
 MODERATE TO GOOD ANALGESIA.

13. PHARMACOKINETICS
 RAPIDLY ABSORBED AND RAPIDLY EXCRETED THROUGH LUNGS.
 UPTO 20% OF INSPIRED HALOTHANE IS BIOTRANSFORMED IN THE LIVER.
SIDE EFFECTS/ ADVERSE EFFECTS
VASODILATION, HYPOTENSION, CARDIAC ARRYTHMIAS AND SHIVERING AND TREMORS ON
RECOVERY. MALIGNANT HYPERTHERMIA HAS BEEN REPORTED IN PIGS, HORSES, DOGS AND CATS.

14. CONTRAINDICATIONS
CONGESTIVE HEART FAILURE, CARDIAC DISEASE, LIVER DISEASE AND MALIGNANT HYPERTHERMIA
OR SIGNIFICANT HEPATOTOXICITY.
DRUG INTERACTIONS
 POTENTIATES ACTION OF NON-DEPOLARISING NEUROMUSCULAR BLOCKERS AND ALSO
GANGLIONIC BLOCKERS.
 AS HALOTHANE SENSITIZES MYOCARDIUM TO CATECHOLAMINES, CONCOMITANT USE OF
DRUGS LIKE EPINEPHRINE AND DOPAMINE MAY PRODUCE SEVERE ARRYTHMIAS.

15. CLINICAL USES AND ADMINISTRATION
 ANAESTHESIA OFTEN INDUCED BY ULTRA SHORT ACTING BARBITURATE TO PERMIT
ENDOTRACHEAL INTUBATION MAINTAINED WITH HALOTHANE MIXTURE.
 BEST USED IN CLOSED REBREATHING SYSTEM WITH PRECISION THERMOSTABLE OR
THERMOCOMPENSATED, CALIBRATED VAPOURISERS.
DOSE
INDUCTION: (ALL SPP.2 TO 4% OF INSPIRED CONCENTRATION)
MAINTENANCE: SMALL ANIMAL(0.5 TO 1.5)%
LA( 1- 2%).

16. ENFLURANE
HALOGENATED ETHER THAT RESEMBLES HALOTHANE IN MOST OF ITS PHYSICOCHEMICAL,
PHARMACOLOGICAL AND ANAESTHETIC PROPERTIES.
PHARMACOLOGICAL EFFECTS
 POTENT DEPRESSANT OF CNS WITH RAPID AND SMOOTH INDUCTION AND RECOVERY.
 ASSOCIATED WITH DOSE DEPENDENT MYOCARDIAL DEPRESSION AND HYPOTENSION.
 LOWER INCIDENCE OF ARRYTHMIAS AND LESSER SENSITISATION OF MYOCARDIUM TO
CATECHOLAMINES THAN DOES HALOTHANE.

17.  CAUSES BRONCHODILATION AND INHIBITS BRONCHOCONSTRICTION.
 REDUCES TONE AND MOTILITY OF GI SMOOTH MUSCLES.
 PRODUCES ADEQUATE MUSCLE RELAXATION FOR MOST SURGICAL PROCEDURES.
PHARMACOKINETICS
RAPIDLY ABSORBED, ONLY 2 TO 3 % IS METABOLISED IN LIVER AND REST IS EXCRETED UNCHANGED
VIA THE LUNGS.

18. SIDE EFFECTS / ADVERSE EFFECTS
 DURING DEEP ANAESTHESIA, JERKING OR TWITCHING OF MUSCLES OF FACE, NECK OR LIMBS MAY
BE SEEN.
 CARDIOVASCULAR DEPRESSION, IN HORSES PARTICULARLY, IS GREATER THAN THAT PRODUCED BY
HALOTHANE.
CONTRAINDICATION
SHOULD BE AVOIDED IN EPILEPTIC IN PATIENTS IN HAVING PREEXISTING ABNORMALITIES IN THE EEG
OR A HISTORY OF A SEIZURE DISORDER.
DRUG INTERACTIONS
LESS AMOUNT OF NON DEPOLARIZING RELAXANTS CAN BE USEFUL WITH ENFLURANE FOR ACUTE
NEUROMUSCULAR BLOCKING.

19. CLINICAL USES AND ADMINISTRATION
 INDUCTION WITH BARBITURATES IS PREFERRED.
 ADMINISTRATION SIMILAR TO HALOTHANE WITH CALIBRATED VAPORIZER CAPABLE OF
DELIVERING ACCURATELY LOW INSPIRED CONCENTRATIONS.
DOSE
INDUCTION : ALL SPP. 4-6 %
MAINTENANCE : ALL SPP. 1 -3%

20. DIETHYL ETHER
 THE USE OF ETHER AS GENERAL ANAESTHETIC HAS DECLINED IN LAST 10 TO 15 YEARS DUE TO
AVAILABILITY OF BETTER ANAESTHETICS.
PHARMACOLOGICAL EFFECT
 IT IS HIGHLY SOLUBLE IN BLOOD WHICH PRODUCES SLOW(3 – 10 MIN) AND UNPLEASANT
INDUCTION WITH STRUGGLING, DELIRIUM AND EXCITEMENT. RECOVERY IS SLOW WITH MARKED
VOMITING AND NAUSEA.
 UNLIKE HALOGENATED ANAESTHETICS, ETHER STIMULATES RESPIRATION IN THE EARLY STAGES
OF ANAESTHESIA AND IT IS MOST EFFECTIVE MUSCLE RELAXANT AMONG INHALANT
ANAESTHETICS.

21. PHARMACOKINETICS
PRIMARILY EXCRETED UNCHANGED UPTO 80% VIA THE LUNGS. IT’S COMPLETE ELIMINATION
REQUIRES OVER 24 HOURS.
SIDE EFFECTS/ADVERSE EFFECTS
PRODUCES ONLY EXCITEMENT, INCREASE RESPIRATION, DELIRIUM AND ENHANCED RESPIRATORY
AND SALIVARY SECRETION. OVERDOSAGE MAY PRODUCE CARDIAC PULMONARY DEPRESSION WITH
FALL IN B.P HYPOVENTILATION AND RESPIRATORY PARALYSIS.
CONTRAINDICATION
ACUTE AND CHRONIC RESPIRATORY DISEASES, ACIDOSIS, SHOCK AND SURGERY REQUIRING USE OF
ELECTROCAUTERY.

22. CLINICAL USES AND ADMINISTRATION
ADMINISTERED BY CLOSED SYSTEM WHICH MINIMIZES DISPERSAL OF AN EXPLOSIVE MIXTURE
INTO THE OPERATING ROOM. ALSO BY OPEN DROP METHOD WHICH LEADS TO INHALATION OF HIGH
CONCENTRATIONS WITH PARALYSIS OF RESPIRATORY CENTER, HENCE SHOULDN’T BE ROUTINELY
PRACTICED.
DRUG INTERACTIONS:
IN LAB ANIMALS, THERE IS DEPRESSION OF AMINOPROPYRINE ELIMINATION WHEN USE WITH
ETHER.
DOSE
INDUCTION: ALL SPP. 10 – 40 %
MAINTENANCE : ALL SPP. 3 – 12%

23. NITROUS OXIDE
LOW SOLUBILITY, LIMITED CARDIOVASCULAR AND RESPIRATORY DEPRESSION AND MINIMAL
TOXICITY.
MECHANISM OF ACTION
 NOT CLEAR EXACT MECHANISM OF ACTION.
 THROUGH RECENT STUDIES IT SEEMED TO MODERATELY BLOCK NMDA RECEPTORS WHICH
PROVIDE ANAESTHETIC, HALLUCINOGENIC AND EUPHORIANT EFFECTS.
 WEAKENLY INHIBITS AMPA KAINATE, GABAC RECEPTOR AND 5-HT3 RECEPTORS.
 SLIGHTLY POTENTIATES GABAA AND GLYCINE RECEPTORS.

24. PHARMACOLOGICAL EFFECTS
 RELATIVELY INSOLUBLE IN BLOOD HAVING RAPID ONSET AND OFFSET OF ACTION AND LOW
POTENCY.
 GENERALLY USED AS A CARRIER AND ADJUVENT TO OTHER ANAESTHETICS.
 INDUCES ANAESTHESIA FOLLOWED BY CONVULSIVE SEIZURES.
 HEART RATE, CARDIAC OUTPUT, ARTERIAL B.P AND RESPIRATORY RATE REMAIN RELATIVELY
UNCHANGED.
 ONLY A GOOD ANALGESIC NOT A MUSCLE RELAXANT.

25. PHARMACOKINETICS
RAPIDLY ABSORBED THROUGH LUNGS AND METABOLISM DOESN’T OCCUR IN BODY.
SIDE EFFECTS/ ADVERSE EFFECTS
 RAPIDLY DIFFUSES BACK FROM TISSUES AND BLOOD INTO ALVEOLI WHEN THE SOURCE OF
GAS IS INTERRUPTED WHICH COULD DILUTE OXYGEN CAUSING DIFFUSION HYPOXIA.
 INACTIVATION OF COBALAMINE FORM OF VIT.B12 BY OXIDATION WITH POST OPERATIVE NAUSEA
AND VOMITING.

26. CONTRAINDICATIONS
IN PATIENTS HAVING TRAPPED AIR POCKETS (I.E. PNEUMOTHORAX, AIR EMBOLISM), IF N2O IS USED
GREATER THAN 50%, IT WILL DIFFUSE INTO THE AIR CONTAINING CAVITY FASTER THEN N WILL
DIFFUSE OUT RESULTING IN AN EXPANSION OF THE POCKET.
DRUG INTERACTIONS
COMPATIBLE WITH MOST PRE ANAESTHETICS AND OTHER INHALANT ANAESTHETICS.
CLINICAL USES AND ADMINISTRATION
 USED AS ADJUVENT TO POTENT VOLATILE ANAESTHETICS WHERE IT SPEEDS THE UPTAKE OF
SECOND AGENT INTO THE BLOOD DUE TO SECOND GAS EFFECT.

27.  NORMALLY 60-70% N2O + 25 – 40% O2+ 0.2-2% ANOTHER POTENT INHALANT ANAESTHETICS IS
USED.
 ADMINISTERED WITH A SEMI CLOSED OR CLOSED SYSTEM WITH OXYGEN.
DOSE
INDUCTION : ALL SPP. 50 – 70 %
MAINTENANCE: ALL SPP. 66%

28. XENON
 IT CAN’T BE MANUFACTURED AND MUST BE EXTRACTED FROM AIR, SO IS VERY EXPENSIVE.
 EXTREMELY BLOOD SOLUBLE, MINIMUM SIDE EFFECT AND ENVIRONMENTALLY FRIENDLY.

29. CYCLOPROPANE
 MORE DEPRESSANT AND MOST POTENT ANAESTHETIC.
 SENSITIZES THE HEART TO ARRYTHMOGENIC ACTION OF CATECHOLAMINES AND
STIMULATES SYMPATHOADRENAL ACTIVITY.
 USE RESTRICTED TODAYS BECAUSE OF ITS HAZARD OF EXPLOSION.

30. Intravenous anesthesia
PREPARED BY – PUJA BARAL AND PREM GM

31. Mechanism of action
 Potentiating GABAa receptor activity
 Increases chloride conductance

32. Commonly used intravenous anesthesia
 Ketamine
 Thiopental sodium
 Propofol

33. Classification of intravenous anesthesia
 Inducing agents
e.g. thiopentone , propofol , etomidate
 Dissociative agents
e.g. ketamine
 Neurolept analgesia
e.g. fentanyl-droperidol

34. KETAMINE
Ketamine is dissociative anesthetics are agents which induce a state of altered CNS
activity anaesthetized patients feels totally dissociated from its s environment.

35. Ketamine
 It is extremely versatile agent because it can be
administrated as the both IV and IM route without
appreciable tissue irritation

36. M.O.A OF KETAMINE
Ketamine bind to NDMA receptor
prevents the binding of excitatory neurotransmitter glutamate at the NDMA receptor.
antagonism of NDMA receptors produces a cerebral dissociation
Between the thalamocortical

37. produces an alter consciousness or catalepsy.
In addition to anesthetic , its bind with other pain receptor produces
analgesic.

38. Pharmacologic effects
1. Nervous system:- it produces fairly rapid anesthesia(45-60
seconds) which last about 10-60 minutes.
 IM injection takes few minutes which last for an hours.
 It induces stage-1 and stage -2nd anesthesia.
 Paralysis of movement
 Dissociative anesthesia.
2. Cardiovascular effects:- it increases heart rate and cardiac
output and blood pressure.
3. Respiratory Effects:- does not cause significant respiratory depression
at normal dose.

39. 4. Other effects:- it has not significant effects on liver and kidney in normal doses.
Ketamine stimulates salivation and lachrymation which may becomes copious.
SIDE-EFFECTS
 increased salivation , muscle twitching, mild tonic convulsions, emesis, vocalization etc.
 High doses develop apnoea.
 Its has hallucinations characters in human.

40. Pharmacokinetics
 Route of administration:- IV,IM:- it is absorbed and distributed all over the body tissues
with highest level found in the brain, liver and lungs. It binds to plasma proteins.
 Distribution: highly lipido-philic drugs
 Onset action: rapid
 Metabolism: Liver
 Excretion:- urinary and biliary excretion.

41. Contraindications and precautions.
It is contradicted inpatients prone to seizure activity( e.g. Epilepsy).
it should not recommended to renal or hepatic disease and head injury
Patients.
It is not used as sole agent in dog and horse. if used it should be used with
xylazine.

42. clinical use and administration
It is use in cats and sub-human primates, human and many other
species for restraint, for general anesthesia and to provide analgesia.
DOSE
Cats:- 11-33 mg/kg IM(preferred), SC or IV
Dogs:- 2mg/kg, IV
Primates:- 2-4 mg/ kg, IV.

43. Thiopental sodium
 Ultra short acting barbiturate
 Most commonly used in veterinary practice
 Standard drugs for induction of general anesthesia
 Occasionally used for purpose of euthenesia

44. Pharmacological effects
 Depresses CNS and produces hypnosis and anesthesia without much analgesia
 Myocardial depressant , decreases cardiac output and lower blood pressure
 Respiratory depressant
 Depresses GI tract motility initially and then increases both tonus and motility
 Weak muscle relaxant

45. Pharmacokinetics
 Rapid onset of action ( with in one second )
 Metabolised by hepatic microsomal system
 Depends upon the redistribution of drug out of the CNS and not on metabolism
 Half life 7 hours

46. Side effect
 Myocardial and circulatory depression, thrombophlebitis, bronchospasm, nausea
and vomiting, allergic reaction , shivering and muscle twisting.

47. Treatment
 Cardio-pulmonary support, respiratory stimulants, alkalinising the patient and
diuresis.

48. Contraindication and precaution
 Contraindicated to asthma and hypersensitivity reaction

49. Clinical use
 Used for the induction of general anesthesia

50. Clinical use
 Used for the induction of general anesthesia

51. Dose
 Dogs and cats : 20-30 mg/kg, IV
 Cattle and horses : 8-15 mg/kg, IV
 Pigs : 10-20 mg/kg, IV
 Sheep and goats : 20-25 mg/kg, IV

52. Propofol
 Short acting
 For induction and maintenance of general anesthesia
 Widely used in both human and veterinary medicine
 Largely replacing sodium thiopental

53. Pharmacological effect
 Rapid onset of action
 Rapid recovery due to both rapid distribution and metabolism
 Direct myocardial depression and peripheral vasodilation due to arterial
hypotension

54. Pharmacokinetics
 High metabolic clearance in liver
 Rapidly enters CNS, placenta and show large volume of distribution
 Half life about 1.4 hours
 Cats doesn’t metabolite as dogs.

55. Side effects
 No significant adverse effect at normal dose
 Produce pain on injection
 Vomiting and excitation during recovery

56. Treatment
 Cardiopulmonary support and discontinuation of propofol

57. Contraindication
 Contraindicated to the patient hypersensitive to it and having hepatic and renal
diseases

58. Clinical use
 Rapid , smooth and complete recovery
 Inducing and maintenance of general anesthesia

59. Dose
 Dogs and cats : 6mg/kg IV slowly over 30-60 seconds
 Small ruminants : 4 mg/kg slow IV
 Pigs : 2-5 mg/kg IV

60. DISSOCIATIVE ANAESTHESIA
PRESENTATION BY:
ROLL.NO. 32,33

61. Anaesthesia:
An- without, aesthesis- sensation
Dissociative anaesthesis:
Detachment or dissociation from the environment
and self.
Cyclohexamines (Ketamine, Phencyclidine,
Tiletamine)

62. KETAMINE:
Prototype drug
[2-(O-chlorophenyl)-2-
(methylamino)-cyclo-hexanone]
White crystalline powder with
characteristic odour.

63. Plasma protein binding 50-55% in dogs and horses
35-50% in cats
Metabolism Hepatic
Exceretion Mostly in urine
Half life 1 hr
Route of administartion IV or IM #
Onset of action 45-60 sec when given by IV
10 minutes when given IM
Duration of action 10-60 minutes when administered by IV
2 hours when given by IM
Distribution Highly distributed in all parts
(highest level found in brain, liver and lungs)

64. DOSE RATE
(For anaesthesia)
• 10-15 mg/kg b.wt , IMDogs
• 2mg/kg b.wt, IV
• 10mg/kg b.wt, IM
Cattle, Horse,
Sheep, Swine
• 2-4 mg/kg b.wt, IV
• 10-15 mg/kg b.wt, IMPrimates
Cats • 11-33 mg /kg b.wt, IM(without premedication)
• 22mg/kg , IM

65. Mechanism of Action:
 Works by the inhibition of N- methyl- D- asparate (NMDA) receptor operated channels.

66. General mechanism of NMDA receptor
 They are Glutamate receptor
found in nerve cells
 When neurotransmitter
glutamate binds to NMDA
receptor, it causes inflow of
intracellular calcium to post-
synaptic neuron
 Ca2+ flux through NMDARs is
thought to be critical in synaptic
plasticity
 Synaptic plasticity associated
with learning, memory and pain

67. Mechanism of action of ketamine
 Binds to NMDA receptor
 Prevents the binding of excitatory neurotransmitter glutamate at the NDMA
receptor.
 Produces a cerebral dissociation between the thalamocortical and limbic
systems.
 Altered consciousness and catalepsy
 In addition to anesthetic, it binds with other pain receptor to produce analgesic
effect.

68. Pharmacological effects:
-Induces stage I and stage II anaesthesisa,
but not stage III
-Increase in sympathetic tone
-Increases heart rate, cardiac output and
blood pressure
-At higher doses, respiratory rate decrease
-Causes increase in laryngospasm,
bronchospasm abd coughing.

69. Side Effects
Excessive salivation
Muscle twiching
Convulsions
Hallucinations

70. Contraindications and precautions
Contraindicated in patients Prone to seizure
activity
Contraindicated in patients with hepatic or renal
disease, hypertension, heart failure, hypothermia,
depression and hypovolemia
Not to be used as sole agent in caesarean,
abdominal and orthopaedic surgery

71. Thank you!