Phenobarbital

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Contents 1 Introduction 2 Indications 3 Dosage 4 Pharmacokinetics 5 Adverse-effects 6 Drug-interactions 7 Laboratory 8 Mechanism-of-action 9 More General Terms 10 Additional Terms 11 Internet Database 12 References

Introduction

• Tradenames: Luminal, Barbita, Solfoton. DEA-controlled substance: class 4.

Indications

• seizures:

• partial seizures
• generalized tonic-clonic seizures
• focal seizures
• prevention of febrile seizures in infants & young children

• 3rd line agent for management of status epilepticus
• prevention & treatment of neonatal hyperbilirubinemia
• lowering bilirubin in chronic cholestasis

Dosage

• load 15-20 mg/kg up to 300-800 mg IV @ 25-50 mg/min
• maintenance: 60 mg PO BID/ TID
• Children: 3-6 mg/kg/day

• Tabs: 15, 16, 30, 60 100 mg.
• Elixir: 15 & 20 mg/5 mL (120 mL).
• Injection: 65 mg/mL (1 mL), 130 mg/mL (1 mL) injectable form also works given rectally [6]

Pharmacokinetics

• well absorbed after oral administration
• onset of action:

• within 5 minutes of IV administration
• 20-60 minutes after oral dosage

• duration of action 4-10 hours
• 1/2life is 53-140 hours, increased with cirrhosis
• steady state in 21 days
• metabolized by the liver
• eliminated as active & inactive drug in the urine
• alkalinization of the urine increases excretion
• therapeutic level for seizures is 15-35 mg/L
  

• elimination via liver
• elimination via kidney
• 1/2life = 50-140 hours adult
• 1/2life = 40-70 hours child
• protein binding = 45-50 %
• elimination by hemodialysis = +
• elimination by hemoperfusion = +
• elimination by peritoneal dialysis = +/-

Adverse-effects

• common (> 10%)

• dizziness, lightheadedness, drowsiness, hangover effect, pain at site of injection

• less common (1-10%)

• confusion, depression, unusual excitement, nervousness, constipation, faintness, headache, nausea/vomiting, insomnia, nightmares

• uncommon (< 1%)

• agranulocytosis, rash, exfoliative dermatitis, hallucinations, hypotension, megaloblastic anemia, Stevens-Johnson syndrome, thrombocytopenia, thrombophlebitis, respiratory depression

• other [3,7]

• neurologic:

• sedation
• ataxia
• confusion
• dizziness
• impotence
• depression
• impaired reaction time
• hyperkinetic activity

• arrhythmias
• connective tissue disorders
• hepatic dysfunction
• osteoporosis
• hypothermia

• overdose [8]

• nystagmus
• ataxia
• hypotension
• stupor, coma
• respiratory depression
  
• drug adverse effects of anticonvulsants

Drug-interactions

• phenobarbital metabolism decreased & serum levels increased by: valproic acid, phenytoin, methylphenidate, chloramphenicol, propoxyphene
• enhances metabolism of other drugs via induction of cyt P450 1A2, cyt P450 2B6, cyt P450 2C9 & cyt P450 3A4
• increases effects of alcohol, benzodiazepines, CNS depressants, valproic acid
• decreases effects of digoxin, doxycycline, anti-fungal agents, tricyclic antidepressants, theophylline, warfarin, oral contraceptives, beta blockers, phenothiazines, cyclosporine, corticosteroids, ethosuxumide, quinidine, haloperidol, chloramphenicol
• disulfiram inhibits metabolism of phenobarbital
  
• drug interaction(s) of beta-adrenergic receptor antagonists with barbiturates

Laboratory

• specimen:

• serum, plasma ( heparin, EDTA)
• stable at room temperature for several hours
• stable for 1 year at -20 degrees C

• methods: GLC, HPLC, EIA, FPIA, FIA

Mechanism-of-action

• interferes with impulse transmission from the thalamus to the cerebral cortex
• thought to increase inhibitory effects of GABA by increasing permeability of chloride

More General Terms

• barbiturate
• anticonvulsant

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)
• phenobarbital in serum/plasma

Internet Database

PubChem: 4763
PubChem: 5981
PubChem: 3042923

References

1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
2. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 700
3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
5. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
6. Prescriber's Letter 13(10): 2006 Alternative or 'Off-label' Routes of Drug Administration Detail-Document#: [1] (subscription needed) [2]
7. Medical Knowledge Self Assessment Program (MKSAP) 15, American College of Physicians, Philadelphia 2009
8. Henry's Clinical Diagnosis & Management by Laboratory Methods, 21st edition, McPherson RA & Pincus MR (es), W.B. Saunders Co., Philadelphia, PA. 2007, pg 311

phenobarbital; PB; PHB (Luminal, Barbita, Solfoton)