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Collections with the topic tag Thiopentone
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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
- Dose - 5 mg/kg (methohexitone 2-3x more potent)
- Absorption - IV, oral, rectal (at higher doses)
- 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])
- Protein binding - 75% (prop 98%, methohex 65%)
- Onset within 1 brain-arm circ time (< 60s), Offset 5-15 min
- 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.
- Clearance - 4 mL/kg/min (methohexitone: 3x greater 12 mL/k/m)
C. Pharmacodynamics
- Mech - potentiates GABA inhibition, dec rate of GABA dissociation (like propofol) and at high doses directly activ GABA rec.
- 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 !!)
- 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.
- Resp
- Respiratory depression (initial ⇡ TV, ⇣ RR)
- Bronchoconstriction & laryngospasm risk (due to ⇣ SNS outflow).
- Renal - ⇣ RBF & GFR 2° ⇣ BP.
- GIT - ⇣ GIT motility, ⇣ HBF, enzyme induction.
- SEs - inhibits neutrophil function; anaphylaxis 1:20,000; porphyria (stims d-ALA synth); inta-arterial injection; thrombophlebitis (> methohexitone 3-4%).
- Crosses placenta; foetal tß½ 11-44h.