Thiopental is an ultra short-acting barbiturate that is commonly used for induction of anesthesia. It works by facilitating the inhibitory neurotransmitter GABA at GABAA receptors in the brain, causing sedation, hypnosis and general anesthesia. Thiopental has a rapid onset within 10-20 seconds after intravenous injection and its effects wear off within 5-15 minutes. It is highly soluble in water and stable in solution. Common uses include induction of anesthesia, treatment of increased intracranial pressure, and cerebral protection during certain surgeries. Side effects include respiratory depression, emergence delirium and prolonged recovery.

1. Presenter: Anish Mohan
Moderator: Dr. Pavan G
S

2. • These are drugs that when given intravenously in
an appropriate dose, cause a rapid loss of
consciousness

3. CLASSIFICATION BASED ON CHEMICAL
STRUCTURE
BARBITURATES PHENCYCLIDINES
• Thiopental • Ketamine
• Thiamylal
• Methohexital BENZODIAZEPINES
• Midazolam
PHENOLS
• Propofol
IMIDAZOLES
• Etomidate

4. MOST COMMONLY USED ONES
• Thiopental
• Propofol
• Etomidate
• Ketamine

5. IDEAL IV ANAESTHETIC AGENT
• SHOULD BE WATER SOLUBLE, STABLE IN SOLUTION AND LONG SHELF LIFE.
• LACK OF PAIN ON INJECTION, VENO IRRITATION OR TISSUE DAMAGE FROM
EXTRAVASATION.
• LOW POTENTIAL TO RELEASE HISTAMINE OR PRECIPITATE HYPERSENSITIVITY
REACTIONS.
• RAPID AND SMOOTH ONSET OF ACTION.
• RAPID METABOLISM TO PHARMACOLOGICALLY INACTIVE METABOLITES.
• SHOULD PRODUCE SLEEP IN ONE ARM BRAIN CIRCULATION TIME.
• LACK OF CVS & RS DEPRESSION.
• RAPID AND SMOOTH RETURN OF CONSCIOUSNESS AND COGNITIVE SKILLS.
• ABSENCE OF POST-OPERATIVE NAUSEA AND VOMITING OR PROLONGED
SEDATION.

7.  Sulphur derivative of Barbituric Acid.
i.e. Thio barbiturate.
 Ultra short acting barbiturate.

8. POOR ANALGESIC, WEAK MUSCLE RELAXANT.
Commonest inducing agent used.

9. Fig : Chemical Structure of Thiopentone
Sulphur make it more lipid soluble and more potent
 Sulphur at second carbon atom position.
5-ethyl-5-(1-methylbutyl)-2-thiobarbituric acid

10. PROPERTIES
Highly soluble in water / NS yielding highly
alkaline solution,stable for 48 hrs.
 Powder form stable at room temperature.
 Refrigerated solution stable up to 2 week.

11. • PH OF 2.5% SOLUTION IS 0.5.
• COMMERCIAL PREPARATION CONTAIN IT SODIUM SALT
WITH ANHYDROUS SODIUM CARBONATE TO PREVENT
PRECIPITATION OF ACID FORM.
• AVAILABLE AS 1 GM POWDER FOR RECONSTITUTION.

12. • 1 GM YELLOW POWDER
• RECONSTITUTED WITH 20 ML NORMAL SALINE
TO GET 50MG/ML SOLUTION
• FROM THAT 5 ML (250MG) IS TAKEN AND
DILUTED TO 10ML
• TO BECOME 250/10 => 25MG/ML

13. PHARMACOKINETICS
 Onset of action of i.v. injection - 10-20 sec.
peak 30-40 sec. duration for awakening 5-15
min.
Volume of distribution is 2.5 Lit. per Kg.

14.  Ultimate elimination due to hepatic
metabolism.
 Effect site equilibration time is rapid.
Brain – 30 Sec. Muscle – 15 Min. Fat > 30
Min.

15. TERMINATION OF ACTION
1) Redistribution
a) Lipid solubility (most important factor)
 High Lipid Solubility makes it to cross blood
brain
barrier & lean body tissue rapidly.
b) Protein Binding
 Highly bound to albumin & other plasma
protein.
 72 – 86% Binding.

16.  Affected by physiological PH. Disease state &
parallels lipid solubility
 Hepatic disease & chronic renal disease
decrease
protein Binding, increase free form.
c) Ionization
 Only non-ionized part crosses Blood-Brain-
Barrier.
 Thiopentone has PKA 7.6 so 61% of it is
non-ionized at physiologic PH
 As PH decreases (acidosis) non-ionized form

17. 2)Metabolism
 By liver microsomal enzymes mainly, Slightly in
CNS & kidney.
 By oxidation, dealkylation & conjugation to
hydroxy Thiopental & carboxylic acid
derivatives
more water soluble & excreted rapidly.

18.  Affect by hepatic enzyme activity more than blood
flow.
 Metabolism at 4-5 mg./Kg. dose exhibits first order
kinetics.
 At very high doses (300-600 mg/Kg.) exhibit zero
order kinetics.

19. 3) Renal Excretion
 Protein Binding limits filtration.
 High lipid solubility increase
reabsorption.
Elimination Half Life 11.6 Hours
Low elimination
clearance(3.4ml/kg/min)
Prolonged in obese patient & pregnancy.

20. MECHANISM OF ACTION
 Sedation & Hypnosis by interaction with
inhibitory neurotransmitters GABA on GABAA
receptor.
 GABA facilitatory & GABA mimetic action.
 Increases GABA mediated transmembrane
conductance of Cl– ion  Causes
hyperpolarization & inhibition of post synaptic
neuron.

21.  Decrease rate of dissociation of GABA from
receptor.
In high doses itself activate GABA receptor.
 Inhibit synaptic transmission of excitatory
neurotransmitter via glutamate & neuronal
nicotinic acetylcholine receptors.

22. PHARMACODYNAMICS
Central nervous system
 Dose dependent effect
sedation  sleep  anaesthesia  coma.
 Acts on Reticular Activating System & Thalamus.
 Induces General Anaesthesia  loss of consciousness,
amnesia &  response to pain R.S. & C.V.S. depression.
 Depresses transmission in sympathetic nervous system,
 BP.

23.  Dose related  cerebral metabolic rate of
oxygen (CMRO2), reduces metabolic activity,
neuronal signalling & impulse trafficking.
 cerebral metabolic rate of oxygen (CMRO2)

 cerebral vascular resistance

 cerebral blood flow

 Intracranial pressure

24. Somatosensory, Brainstem auditory & visual
evoked potential are depressed.
 infract size in cerebral emboli & temporary
focal ischemia
  burst suppression, protect in profound
hypotension..

25. • HIGH DOSES DESULFURATION
PENTOBARBITAL
(LONG LASTING CNS DEPRESSANT)

26. Respiratory system .
 Neurogenic, Hypercapnic & hypoxic drive depressed.
 Depression of medullary & pontine ventilatory
centres.
 Apnoea likely in presence of narcotics.
Cough & laryngeal reflexes not depressed until high
doses given.
 Bronchospasm & laryngospasm likely in light plane,
added by sympathetic depression

27. Cardiovascular system
 At 5 mg/Kg doses, 10-20 mmHg decrease in BP due to
blockade.
 Compensated by carotid sinus baroreceptor mediated
increase in peripheral sympathetic nervous system
activity.
Leads to unchanged myocardial contractility & 15 – 20
beats/min increase in Heart Rate.
 Direct myocardial depression occurs at doses used
to increase intracranial pressure.

28. DEPRESSION OF SYMPATHETIC NERVOUS
SYSTEM & MEDULLARY VASOMOTOR CENTER

DILATATION OF PERIPHERAL CAPACITANCE
VESSEL

POOLING OF BLOOD

 VENOUS RETURN

 CARDIAC OUTPUT

 BLOOD PRESSURE

29.  Changes exaggerated in hypovolemic
patient, patient on B-blocker drugs &
centrally acting anti hypertensive.

30. SKELETAL MUSCLE
•  NEURO MUSCULAR EXCITABILITY
• SUPPRESSION OF ADRENAL CORTEX & DECREASED CORTISOL LEVEL, BUT IT IS
REVERSIBLE.

31. 7) Liver
 Decreased hepatic blood flow
 Induction of microsomal enzyme & increase
metabolism of drugs,
For Ex. Oral-anticoagulant, Phenytoin, TCA,
Vit. K, Bile Salt, corticosteroid.
 Increased Glucouronyl transferase activity.
 Increased  aminolavilunate activity &
precipitate
porphyria’s.

32. • PLACENTAL TRANSFER OCCURS BUT DRUG
METABOLISED BY FOETAL LIVER & DILUTED
BY ITS BLOOD VOLUME SO LESS DEPRESSION.

33. CLINICAL USES
1) Induction
 3 – 5 mg/Kg. produces unconsciousness in 30
sec.
with smooth induction & rapid emergence.
 Loss of eyelid reflex & corneal reflex used for
testing induction.
 Consciousness regained 10-20 Min. but
residual
CNS depression persist for more than 12 Hours.
 Dose requirement decreased in early

34.  Patient with sever anaemia, burns,
malnutrition,
malignant disease, wide spread uraemia,
ulcerative colitis, intestinal obstruction
requires
lower doses.

35. adult child infant
Induction dose 3-5 mg/Kg. 5-6 mg/Kg 6-
8Mg/Kg.
Anaesthesia supplementation - i.v. 0.5 – 1
mg/Kg
Thiopental infusion seldom used
long context- sensitive half-time
prolong recovery period

36. CLINICAL USES
2) ANTICONVULSANT
• FOR RAPID CONTROL OF STATUS EPILEPTICUS
• DOSE 0.5 – 2 MG/KG. REPEATED AS NEEDED

37. 3) Treatment of increased intracranial
pressure
Cerebral vasoconstriction

 cerebral blood Flow

 cerebral blood volume

 intracranial pressure
  cerebral metabolic O2 demand by 55%
 dose 1 – 4 mg/kg i.v.

38. 4) Cerebral Protection
 In focal ischemia eg. Carotid
endarterectomy,
thoracic aneurysm resection, profound
controlled-hypotension, Incomplete cerebral
emboli.
 Barbiturate narcosis – i.v. bolus 8 mg/Kg.
 EEG burst suppression – mean total dose 40
mg/Kg.
 Infusion – 0.05 to 0.35 mg/Kg/min with
inotropic & ventilatory support.

39. SIDE EFFECTS
 Garlic onion taste.
 Allergic reaction.
 Local tissue reactions & necrosis.
 Urticarial rash, facial edema, hives,
bronchospasm
& anaphylaxis.
 Pain at injection site.

40. Respiratory System
 Dose related respiratory depression
 Transient apnea, patient with chronic lung
disease more susceptible.
 Laryngospasm, bronchospasm.
Central nervous system
 Emergence delirium, prolonged somnolence
&
recovery, Headache

41. Gastro-intestinal system
Nausea, Emesis, Salivation
Dermatologic
Phlebitis, necrosis, gangrene.
.

42. Contraindications
 Patient with respiratory obstruction &
inadequate airway.
 Cardiovascular instability & shock.
 Status asthmaticus.
 Porphyria’s eg. Acute intermittent,
variegate
porphyria, hereditary copro-porphyria
Known
hypersensitivity.

43. CAUTION
 Hypertension, hypovolemia, ischemic heart
disease,
 Acute adrenocortical insufficiency, Addison’s
disease, myxedema.
 Uraemia, septicaemia, hepatic dysfunction.
.

44. ACCIDENTAL INTRARTERIAL INJECTION
• INTENSE VASOCONSTRICTION
• THROMBOSIS
• TISSUE NECROSIS

45. TREATMENT
• INTRARTERIAL ADMININISTRATION OF
LIGNOCAINE(PROCAINE).
• HEPARINISATION
• SYMPATHECTOMY (STELLATE GANLION BLOCK,
BRACHIAL PLEXUS BLOCK).

46.  Thiopentone solution is highly alkaline incompatible
for mixture with drug such as opioid
catecholamines neuromuscular blocking drugs as
these are acidic in nature.
 Probenecid prolongs action, aminophylline
antagonize.
 CNS depressant eg. narcotics, sedative hypnotic,
alcohol, volatile anaesthetic agent prolongs &
potentiate its actions.
INTERACTIONS

47. Induces metabolism of oral anticoagulants,
digoxin, B-blocker, corticosteroids, quinidine,
theophylline.
 Action prolonged by MAO inhibitors,
chloramphenicol.

48. Dose should be reduced
 In geriatric- 30- 40% decrease central
compartment volume & slowed
redistribution
 Hypovolemic Patient,
High risk surgery patient with
concomitant use of narcotic & sedatives

50. •ITS A PHENCYCLIDINE DERIVATIVE
•WAS THE FIRST ANESTHETIC TO BE USED.
•SINCE 1970 ITS BEEN CLINICALLY USED.
•Comes in VIALS with 50mg/ml
•1mg diluted in 5ml Normal Saline to make it
10mg/ml

51. KETAMINE
• A PHENYLCYCLOHEXYLAMINE DERIVATIVE
• KETAMINE HYDROCHLORIDE (2-[O-CHLOROPHENYL]-2-
[METHYLAMINO] CYCLOHEXANONE HYDROCHLORIDE)
• AVAILABLE AS RACEMIC MIXTURE
• EXISTS AS 2 ISOMERS, R(-) AND S(+) FORMS
• S(+) MORE POTENT
• LIPOPHILIC
• RAPIDLY DISTRIBUTED INTO HIGHLY VASCULAR ORGANS, AND
BRAIN

52.  PRESERVATIVE USED IS BENZOTHORIUM CL.
 PRODUCES PROFOUND ANALGESIA,
 PRODUCES DISSOCIATIVE ANESTHESIA
CHARACTERISED BY DISSOCIATION BETWEEN
THALAMO CORTICAL AND LIMBIC SYSTEM .
 RESEMBLES A CATALEPTIC STATE WITH VARYING
DEGREES OF HYPERTONIC,PURPOSEFULL SKELETAL
MOVEMENTS.EYES OPEN , NYSTAGMUS GAZE,PT IS
NONCOMMUNICATIVE.
 PRODUCES EMERGENCE DELIRIUM.

53. PHARMACO KINETICS
 HIGH LIPID SOLUBILITY-LARGE VD
 ELIMINATION ½ LIFE - 2-3HRS.
• DISTRIBUTION
• INITIALLY DISTRIBUTED TO HIGHLY PERFUSED TISSUES AND IS THEN REDISTRIBUTED
TO LESS WELL PERFUSED TISSUES
• REDISTRIBUTION RESULTS IN TERMINATION OF ITS ACTION
• T½Α IS ABOUT 10-15 MINUTES

54. METABOLISM
 EXTENSIVELY IN LIVER.
 CYTO-P450 ----> DEMETHYLATION ----> NORKETAMINE(ACTIVE
METABOLITE) 1/3-1/5TH AS POTENT AS KETAMINE.
 IT IS RESPONSIBLE FOR PROLONGED EFFECTS OF ANALGESIA.ON RPTD
DOSE/INFUSION.
 EXCRETED THROUGH KIDNEY.

55. PHARMACODYNAMICS
 CENTRAL NERVOUS SYSTEM
 PRODUCES DISSOCIATIVE ANAESTHESIA.
 DISSOCIATES THALAMOCORTICAL SYSTEM FROM LIMBIC SYSTEM
 PATIENTS APPEAR TO BE DISSOCIATED FROM THE ENVIRONMENT.

56.  DEPRESSES CNS BY BLOCKING THE NMDA RECEPTORS.
 KETAMINE CAUSES PROFOUND ANALGESIA.
 ↑CEREBRAL BLOOD FLOW, CEREBRAL METABOLIC RATE OF OXYGEN, & INTRACRANIAL
PRESSURE – NOT IDEAL FOR NEUROSURGERY & PATIENTS WITH RAISED
INTRACRANIAL PRESSURE.
 PRODUCES EMERGENT PHENOMENON, CAN BE PREVENTED BY PRIOR
ADMINISTRATION OF BENZODIAZEPINES – NOT RECOMMENDED IN PATIENTS WITH H/O
PSYCHIATRIC DISEASE.
 CAN STIMULATE SEIZURE FOCUS – NOT INDICATED IN EPILEPTIC PATIENTS.

57. • CARDIOVASCULAR SYSTEM
• INDIRECT EFFECT OF INCREASED CENTRALLY MEDIATED
RELEASE OF CATECHOLAMINES FROM ADRENAL MEDULLA
INCREASED
• MYOCARDIAL CONTRACTILITY,
• HEART RATE,
• SYSTEMIC VASCULAR RESISTANCE,
• BLOOD PRESSURE &
• CARDIAC OUTPUT

58. • NOT INDICATED IN PATIENTS WITH
• CORONARYARTERY DISEASE AND
• HYPERTENSION.
• DRUG OF CHOICE IN PATIENTS WITH
• HYPOVOLEMIA
• LOW CARDIAC OUTPUT STATES
• RIGHT → LEFTT SHUNTS.

59.  RESPIRATORY SYSTEM
 LITTLE EFFECT ON VENTILATORY DRIVE IN NORMAL PERSONS.
 APNOEA IN INFANTS & NEONATES WHEN GIVEN INTRAVENOUSLY.
 PRODUCES BRONCHODILATATION – USEFUL IN PATIENTS WITH
BRONCHIAL ASTHMA.
 NEAR NORMAL AIRWAY REFLEXES ARE PRESERVED.
 INDUCES COPIUS SALIVATION - AN ANTI SIALOGOGUE DRUG HAS
TO BE ADMINISTERED.

60. OTHER EFFECTS:
 HIGH RISK OF PONV.
 PREVENTS POST OPERATIVE SHIVERING.
 PER OPERATIVE ANALGESIC DOSE DECREASES POST OPERATIVE MORPHINE
REQUIREMENT.

61. MECHANISM OF ACTION
•INTERACTS WITH
• NMDA (N-METHYL-D-ASPARTATE) GLUTAMIC
ACID CA++ CHANNEL RECEPTORS IN CORTEX AND
LIMBIC SYSTEM
• CENTRAL OPIOID RECEPTORS (Μ, Κ)
• MONOAMINERGIC RECEPTORS IN SPINAL CORD
• VOLTAGE-GATED CA++ CHANNELS
• VOLTAGE-GATED NA+ CHANNELS

62. ANALGESIC EFFECT VIA INHIBITION OF CA++
INFLUX
• AT PRESYNAPTIC NERVE TERMINALS (Κ OPIOID RECEPTOR,
MONOAMINERGIC RECEPTORS IN SPINAL CORD,
MONOAMINERGIC RECEPTORS IN SPINAL CORD)
• AT POSTSYNAPTIC NMDA RECEPTORS

63. • NON-COMPETITIVE ANTAGONISM OF NMDA RECEPTOR CA++
CHANNEL PORE
• INTERACTS WITH PHENCYCLIDINE BINDING SITE STEREO
SELECTIVELY, LEADING TO SIGNIFICANT INHIBITION OF RECEPTOR
ACTIVITY, THIS ONLY OCCURS WHEN THE CHANNEL IS OPENED

64. KETAMINE – MECHANISM OF ACTION
• EFFECT ON VOLTAGE-SENSITIVE CA++ CHANNELS
• PRODUCES NON-COMPETITIVE INHIBITION OF K+-STIMULATED
INCREASED INTRACELLULAR CA++
• EFFECT ON OPIOID RECEPTORS
• ANTAGONIST AT Μ, AGONIST AT Κ
• S(+) KETAMINE IS 2-3 TIMES MORE POTENT THAN R(-) KETAMINE AS
AN ANALGESIC
• AFFINITY FOR RECEPTOR IS 10000 FOLD WEAKER THAN THAT OF
MORPHINE

65. KETAMINE – MECHANISM OF ACTION
• EFFECT ON DESCENDING INHIBITORY MONOAMINERGIC
PAIN PATHWAYS
• ANALGESIC PROPERTY MAY INVOLVE THESE PATHWAYS, ALTHOUGH DIFFICULT TO
SEPARATE KETAMINE-SENSITIVE OPIOID RECEPTOR ACTION
• LOCAL ANAESTHETIC ACTION
• BLOCKADE OF NA+ CHANNEL
• EFFECT ON MUSCARINIC RECEPTORS
• ANTAGONISTIC ACTION AS KETAMINE PRODUCES ANTICHOLINERGIC SYMPTOMS
(POST ANAESTHETIC DELIRIUM, BRONCHO DILATATION, SYMPATHOMIMETIC
ACTION)

66. • DOSE:
• INDUCTION-GA: 0.5-2MG/KG IV
4-6MG/KG IM.
• MAINTAINANCE-GA : 0.5-1MG/KG IV
• SEDATION : 0.2-0.8MG/KG IV OVER 2-3 MIN .

67. CLINICAL USE OF KETAMINE
• PAIN CONTROL (LIMITED VALUE)
• KETAMINE CAN ONLY INHIBIT NMDA ACTIVITY WHEN THE RECEPTOR-
OPERATED ION CHANNEL HAD BEEN OPENED BY NOCICEPTIVE
STIMULATION, HENCE PRE-EMPTIVE ANALGESIA WITH KETAMINE IS
INEFFECTIVE
• NEUROPROTECTION
• ACTIVATION OF NMDA RECEPTOR IS IMPLICATED IN CEREBRAL
ISCHAEMIC DAMAGE, HENCE BY BLOCKING THE RECEPTOR, KETAMINE
HAS NEUROPROTECTIVE POTENTIAL
• SEPTIC SHOCK
• REDUCE THE NEED FOR INOTROPES VIA INHIBITION OF
CATECHOLAMINE UPTAKE
• REDUCE PULMONARY INJURY VIA REDUCTION IN ENDOTOXIN-
INDUCED PULMONARY HYPERTENSION AND EXTRAVASATION

68. CLINICAL USE OF KETAMINE
• ASTHMA THERAPY
• ANTI-INFLAMMATORY
• SPASMOLYTIC
• INCREASED CATECHOLAMINE CONCENTRATIONS,
INHIBITION OF CATECHOLAMINE UPTAKE,
• VOLTAGE-SENSITIVE CA++ CHANNEL BLOCKADE,
• INHIBITION OF POSTSYNAPTIC NICOTINIC OR
MUSCARINIC RECEPTORS

69.  Anaesthesia for haemorrhagic shock patients
 sympathomimetic effects
•Analgesia - greater for somatic than visceral pain
•induction of anesthesia-
•most candidates belong to asa-grade 4.and cvs
disorders(ihd), reactive airway disease, septic shock ,
hypovolemia.
•in malignant hyperthermia,
•congenital heart disease with risk of rt – lt shunts.
•pain management-cancer pain,neuropathic pain,
ischemic/phantum limb.
•sedation-pediatric group they have fewer adverse emergence
reaction .
•reversal of opiod toleranse.

70. • SIDE EFFECTS-
• EMERGENCE REACTION.
• CONTRAIDICATED- PATIENTS WITH HIGH ICP, ICSOL,
OPEN EYE INJURY, VASCULAR ANNEURYSMS,PTS
WITH PSYCHIATRIC DISORDERS(SCHIZOPHRENIA).

71. THANK YOU