Thiopentone is an ultra short-acting barbiturate used for induction of anesthesia. It works by enhancing the effect of the inhibitory neurotransmitter GABA at GABAA receptors in the brain, causing sedation, hypnosis and general anesthesia. It has a rapid onset of 10-20 seconds when given intravenously and is redistributed and metabolized quickly, typically causing awakening within 5-15 minutes. Common uses include induction of anesthesia and treatment of increased intracranial pressure. Side effects are generally mild and related to its cardiovascular and respiratory depressant effects.

1. THIOPENTONE
Guided by
Dr. Abhay Bodhey
Presented by
Dr. Upendra

2. INTRODUCTION
 Sulphur derivative of Barbituric Acid.
i.e. Thio barbiturate.
 Ultra short acting barbiturate.
 Synthesised by Tabern and Volwiler in 1935.
 Introduce clinically by Ralph waters and John Lundy
for induction of anaesthesia.

3. Poor analgesic, weak muscle relaxant.
Commonest inducing agent used.

4. 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

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

6. PROPERTIES
pH of 2.5% solution is 10.5.
 Commercial preparation contain it sodium
salt with anhydrous sodium carbonate to
prevent ppt.of acid form.
 Available as 0.5 gm and 1 gm powder for
reconstitution.
• Refrigerated solutions- stable upto 2
weeks

7. PHARMACOKINETICS
 Onset of action of i.v. injection - 10-20 sec.
peak 30-40 sec. duration for awakening 5-15
min.
Prompt awakening after single i.v. inj. is due to
rapid redistribution to lean body tissue (muscle)
Volume of distribution is 2.5 Lit. per Kg.

8.  Ultimate elimination due to hepatic metabolism.
 Effect site equilibration time is rapid.
Brain – 30 Sec. Muscle – 15 Min. Fat > 30 Min.
 Context sensitive half life is prolonged.

9. 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.
 Only unbound fraction crosses Blood-Brain-Barrier.

10.  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
increases.
 Metabolism induced changes in PH affect more.

11.  Rapid distribution half life – 8.5 Min.
 Slow distribution half life – 62.7 Min

12. 2)Metabolism
 By liver microsomal
enzymes mainly, Slightly
in CNS & kidney.
 10 – 24 % Metabolised
each hour.

13.  By oxidation, dealkylation & conjugation to
hydroxy Thiopental & carboxylic acid derivatives
more water soluble & excreted rapidly.
 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.

14. 3) Renal
Excretion
 Protein Binding
limits filtration.
 High lipid
solubility increase
reabsorption.

15. Elimination Half Life 11.6 Hours
Low elimination clearance(3.4ml/kg/min)
Prolonged in obese patient & pregnancy.
Short in paediatric patient.

16. MECHANISM OF
ACTION Sedation & Hypnosis by interaction with
inhibitory neurotransmitters GABA on GABAA
receptor.
 GABA facilitatory & GABA mimetic action.
 GABAA receptor has 5 glycoprotein sub unit.
 Increases GABA mediated
transmembrane conductance of Cl– ion,
Causes hyperpolarization & inhibition of post
synaptic neuron.

17.  ↓↓ rate of dissociation of GABA from receptor.
It high doses itself activate GABA receptor.
Fig. GABAA
Channel
Complex
 Inhibit synaptic transmission of excitatory
neurotransmitter via glutamate & neuronal nicotinic
acetylcholine receptors.

18. PHARMACODYNAMI
CS
Central nervous system
Dose dependent effect
sedation → sleep →
anaesthesia → coma.

19.  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.

20.  Dose related ↓↓ CMRO2, reduces metabolic
activity, neuronal signalling & impulse trafficking.
↓↓ CMRO2
↓
↑↑ cerebral vascular resistance
↓
↓↓ cerebral blood flow
↓
↓↓ Intracranial pressure
 Somatosensory, Brainstem auditory & visual
evoked potential are depressed.

21.  ↓↓ burst suppression, protect in profound
hypotension.
↓↓ infract size in cerebral emboli & temporary
focal ischemia.

22. High doses desulfurationHigh doses desulfuration
pentobarbitalpentobarbital
(long lasting CNS Depressant)(long lasting CNS Depressant)

23. Respiratory system .
 Neurogenic, Hypercapnic
& hypoxic drive
depressed.
 Depression of medullary &
pontine ventilatory
centres.
 Apnoea likely in presence
of narcotics.

24. Cough & laryngeal reflexes not depressed
until high doses given.
 Bronchospasm & laryngospasm likely in
light plane, added by sympathetic depression

25. Cardiovascular system
 At 5 mg/Kg doses, 10-20
mmHg ↓↓ in BP due to
sympathetic blockade.
 Compensated by carotid sinus
baroreceptor mediated ↑↑ in
peripheral sympathetic nervous
system activity.

26.  Leads to unchanged myocardial contractility &
15 – 20 beats/min ↑↑ in Heart Rate.
 Direct myocardial depression occurs at doses used
to ↓↓ intracranial pressure.

27. Depression of sympathetic nervous
system & medullary vasomotor center
↓
Dilatation of peripheral capacitance
vessel
↓
Pooling of blood
↓
↓↓ venous return
↓
↓↓ cardiac output
↓
↓↓ Blood Pressure

28.  Changes exaggerated in hypovolemic patient,
patient on B-blocker drugs & centrally acting anti
hypertensive.
Skeletal muscle
↓↓ Neuro muscular excitability.

29. 5) Kidney
↓↓ blood flow & GFR .
6) Suppression of adrenal cortex &
↓↓ cortisol level, but it is reversible.

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

31. Placental transfer occurs but drug
metabolised by foetal liver & diluted by its
blood volume so less depression.

32. 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 ↓↓ in early pregnancy, ↑↑ child
with thermal injury.

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

34. 2) Anticonvulsant
 for rapid control of status epilepticus
 dose 0.5 – 2 mg/kg. repeated as needed

35. 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.

36. 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.

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

38. Cardiovascular system
Cardiovascular depression
a) Peripheral vasodilation & pooling of blood - ↓↓ BP.
b) ↓↓ availability of Ca++ to myofibrils-↓↓ contractility.
c) Direct negative inotropic action, ↓↓ ventricular filling.
 These changes more when i.v. bolus given
 If given to hypovolemic patient, reduces cardiac output
(69%), in patient without compensatory mechanism
cardiovascular collapse.

39. 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

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

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

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

43. Accidental Intrarterial injectionAccidental Intrarterial injection
Intense vasoconstrictionIntense vasoconstriction
ThrombosisThrombosis
Tissue necrosisTissue necrosis

44. TreatmentTreatment
Intrarterial admininistration ofIntrarterial admininistration of
Lignocaine(procaine).Lignocaine(procaine).
HeparinisationHeparinisation
Sympathectomy(stellate ganlion block,Sympathectomy(stellate ganlion block,
brachial plexus block).brachial plexus block).

45.  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

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

47. 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