• Thiopentone

     
       

    Daniel Jolley.

    3 articles.

    Created February 7, 2021, last updated almost 4 years ago.


    Collection: 134, Score: 1209, Trend score: 0, Read count: 1695, Articles count: 3, Created: 2021-02-07 23:05:19 UTC. Updated: 2021-02-07 23:26:11 UTC.

    Notes

    reference
    1

    Sedative-hypnotic drug with anaesthetic and anticonvulsant effects.

    A. Physiochemistry

    • Thiobarbiturate
    • Highly lipophilic
    • Presented in glass ampoule containing 2.5% powdered form: a. 500 mg thiopentone (anhydrous yellow powder) b. 30 mg sodium carbonate (buffer) c. 0.8 atm of N2 (reduces oxidation)
    • made up with H2O to 20 mL
    • pH 10.8, pKa 7.6 (ie. ~ pH 11 pKa 7)
    • Weak acid
    • 60% non-ionised @ pH 7.4 (vs. methohexitone 75%)
    • Racemic mixture (l potency > d)
    • Demonstrates tautomerism, with water soluble enol form (double bond) in solution → lipid sol keto form at pH 7.4.
    • First administered 1934

    B. Pharmacokinetics

    1. Dose - 5 mg/kg (methohexitone 2-3x more potent)
    2. Absorption - IV, oral, rectal (at higher doses)
    3. Distribution - Vdcc 0.4 L/kg, Vdss 2.5 L/kg
      • fat:blood coeff 11:1 (ie. thio will move into fat until [fat] 11x [blood])
    4. Protein binding - 75% (prop 98%, methohex 65%)
    5. Onset within 1 brain-arm circ time (< 60s), Offset 5-15 min
    6. Metabolism - alpha1 ½ 5 min, alpha2 ½ 1 h, ß ½ 8-11 h, CSHT-8h: 3 h; phase I p450 side-arm oxidation, desulfuration to pentobarbitone (t½ 40h) and ring cleavage to urea and 3-carbon fragments.
      • some extrahepatic (renal) metab.
      • NB: alpha1 ½ (fast-alpha) is equilibration with/from effect site - alpha2 ½ (slow-alpha) with slow compartments.
    7. Clearance - 4 mL/kg/min (methohexitone: 3x greater 12 mL/k/m)

    C. Pharmacodynamics

    1. Mech - potentiates GABA inhibition, dec rate of GABA dissociation (like propofol) and at high doses directly activ GABA rec.
    2. CNS - anaesthetic, anticonvulsant, sedative, ant-analgesic.
      • Dec CBF, CMRO2 (max 55%), ICP, IOP.
      • EEG (alpha → theta → delta) ⇣ freq, ⇡ ampl → burst suppression → isoelectric.
      • Some focal cerebral protection (requires 40 mg/kg !!)
    3. CVS - Negative inotrope (direct effect and indirect dec SNS outflow), dec CO 20%, vasodilation, dec venous return → ⇣ MAP 20-30%. Compensatory ⇡ HR.
      • Histamine release & dysarrythmias rarely occur.
    4. Resp
      • Respiratory depression (initial ⇡ TV, ⇣ RR)
      • Bronchoconstriction & laryngospasm risk (due to ⇣ SNS outflow).
    5. Renal - ⇣ RBF & GFR 2° ⇣ BP.
    6. GIT - ⇣ GIT motility, ⇣ HBF, enzyme induction.
    7. SEs - inhibits neutrophil function; anaphylaxis 1:20,000; porphyria (stims d-ALA synth); inta-arterial injection; thrombophlebitis (> methohexitone 3-4%).
    8. Crosses placenta; foetal tß½ 11-44h.
    Daniel Jolley  Daniel Jolley
     
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    Collected Articles

    • Anaesthesia · Aug 1988

      Randomized Controlled Trial Comparative Study Clinical Trial

      Comparison between propofol and thiopentone for induction of anaesthesia in children.

      Propofol 2.5 mg/kg was compared with thiopentone 5 mg/kg in a randomised open study, as an induction agent in paediatric anaesthesia. One hundred and twenty children who were to undergo elective surgery were included in the study. Both propofol and thiopentone produced a rapid and smooth induction with a low incidence of side effects. ⋯ Respiratory upsets occurred less frequently with propofol than with thiopentone, but propofol frequently induced discomfort on injection. Both agents provided satisfactory and controllable induction of anesthesia and no major adverse reactions occurred during or after anaesthesia. We conclude that propofol is a useful alternative as an induction agent in children.

      keep going… or not…

    • Br J Anaesth · Dec 1996

      Randomized Controlled Trial Comparative Study Clinical Trial

      Comparative effects of thiopentone and propofol on respiratory resistance after tracheal intubation.

      To compare the effects of propofol and thiopentone on tracheal intubation-induced bronchoconstriction, 37 patients were allocated randomly to anaesthesia with either thiopentone 4 mg kg-1 followed by a 15-mg kg-1 h-1 continuous infusion or propofol 3 mg kg-1 followed by a 9-mg kg-1 h-1 continuous infusion. Intubation was facilitated by vecuronium 0.1-0.2 mg kg-1. ⋯ Thirty minutes after commencing isoflurane-nitrous oxide anaesthesia, Rrs declined by 17.5 (SEM 3.6)% from baseline in the thiopentone group, but by only 1.6 (2.6)% in the propofol group. We conclude that the dose of propofol administered provided more protection against tracheal intubation-induced bronchoconstriction than an induction dose of thiopentone.

      expand abstract… or not…

    • Brit J Hosp Med · Oct 2006

      Comparative Study

      Etomidate vs thiopentone for rapid sequence induction in critically ill patients.

      no abstract available

      explore further… or not…

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