thiopental (Pentothal)

Introduction

Tradename: Pentothal. DEA controlled substance: class 3.

Indications

• induction of anesthesia
• hypnosis as lone therapy for short procedures with minimal painful stimuli
• in combination with other anesthetics for surgery
• adjunct for endotracheal intubation in head injury patients
• control of convulsive states
  • epilepsy
• treatment of elevated intracranial pressure
• hypoxia, cerebral ischemia
• narcoanalysis

Contraindications

• variegate or acute intermittent porphyria

Caution:

• asthma
• unstable aneurysms
• pharyngeal infections (cough, laryngospasm & bronchospasm may occur)
• hypotension

pregnancy category = c

safety in lactation = ?

Dosage

• induction of anesthesia
  • neonates: 3-4 mg/kg
  • infants: 5-8 mg/kg
  • children 1-12 years: 5-6 mg/kg
  • adults: 3-5 mg/kg 50-75 mg every 20-40 seconds, repeated as necessary
• 1.5-5 mg/kg has been used to reduce intracranial pressure in neurosurgical patients repeated as needed
• seizures:
  • children: 2-3 mg/kg/dose, repeat as needed
  • adults: 25-100 mg PRN

Injection: 500 mg, 5 g (25%).

Dosage adjustment in renal failure

• creatinine clearance < 10 mL/min: 75% of normal dose

Pharmacokinetics

• rapid onset & duration of action (within 30-60 seconds)
• high lipid solubulity
• metabolized by the liver; pentobarbital is metabolite
• duration of anesthesia is approximately 5-30 minutes
• elimination 1/2life is 3-8 hours

elimination via liver

1/2life = 6-7 hours

protein binding = 75-90 %

elimination by hemodialysis = -

Adverse effects

• common (> 10%)
  • pain of IM injection
• less common (1-10%)
  • cramping, diarrhea, rectal bleeding
• uncommon (< 1%)
  • radial nerve palsy, hemolytic anemia, thrombophlebitis, hypotension, peripheral vascular collapse, seizures, tremor, headache, nausea/vomiting, involuntary muscle movement, twitching, rigidity, respiratory depression, hiccups, coughing, circulatory depression, myocardial depression, cardiac arrhythmias, rhinitis, emergence delirium, prolonged somnolence & recovery, anxiety, erythema, pruritus, urticaria, apnea, laryngospasm, bronchospasm, sneezing, dyspnea, anaphylaxis
• other
  • extravasation or intra-arterial injection causes necrosis due to pH of 10.6
  • accumulation may occur with chronic dosing due to lipid solubility
  • prolonged recovery may result from redistribution of thiopental from fat stores

• drug adverse effects of psychotropic agents
• drug adverse effects of sedatives

Drug interactions

• CNS depressants
• barbiturates induce cyt P450 1A2, 2C9 & 3A4
  • may diminish levels of drugs metabolized by cyt P450 1A2, 2C9 & 3A4

• drug interaction(s) of beta-adrenergic receptor antagonists with barbiturates

Laboratory

• specimen:
  • serum, plasma (heparin, EDTA)
  • stable for at least 24 hours at room temperature & 8 weeks at 20 degrees C
• methods: GLC, GC-MS, HPLC

Mechanism of action

• ultra-short-acting barbiturate
• depresses CNS to produce anesthesia & hypnosis without analgesia
• enhances chloride conduction in the presence of GABA
• depresses transmission at autonomic ganglia
• causes retrograde amnesia

More general terms

• barbiturate
• sedative/hypnotic (tranquilizer)

Additional terms

• cytochrome p450 1A2 (cytochrome P3-450, phenacetin deethylase, cytochrome p450-4, CYP1A2)
• cytochrome P450 2C9; cytochrome P450 BP-1; cytochrome P450 MP-4; S-mephenytoin-4-hydroxylase; limonene 6-monooxygenase; limonene 7-monooxygenase (CYP2C9, CYP2C10)
• cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3000715
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3000714
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=1244
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5449
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3033018
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3033016