Phenobarbital; Uses, Dosage, Side effects, Drug Interactions

A barbituric acid derivative that acts as a nonselective central nervous system depressant. It promotes binding to inhibitory gamma-aminobutyric acid subtype receptors and modulates chloride currents through receptor channels. It also inhibits glutamate-induced depolarizations. Phenobarbital is occasionally used to treat trouble sleeping, anxiety, and drug withdrawal and to help with surgery. It usually begins working within five minutes when used intravenously and half an hour when administered orally. Its effects last for between four hours and two days.

Mechanism of Action of Phenobarbital

Phenobarbital acts on GABAA receptors, increasing synaptic inhibition. This has the effect of elevating seizure? threshold and reducing the spread of seizure activity from a seizure focus. Phenobarbital may also inhibit calcium channels, resulting in a decrease in excitatory transmitter release. The sedative-hypnotic effects of phenobarbital are likely the result of its effect on the polysynaptic midbrain reticular formation, which controls CNS arousal.

or

Although the drugs act throughout the CNS, a site of particular sensitivity is the polysynaptic midbrain reticular formation which is concerned with the arousal mechanism. Barbiturates induce an imbalance in central inhibitory and facilitatory mechanisms influencing the cerebral cortex and the reticular formation. The significance of the effect of barbiturates on neurotransmitters is unclear. It appears that the drugs decrease the excitability of both presynaptic and postsynaptic membranes. It has not been determined which of the various actions of barbiturates at cellular and synaptic levels are responsible for their sedative and hypnotic effects.

Indications of Phenobarbital

• Hyperbilirubinemia
• Seizures
• Sedation
• Alcohol Withdrawal Syndrome
• Febrile Convulsions
• Feeling Anxious
• Hyperbilirubinemia
• Menopausal Symptoms
• Sleeplessness
• Withdrawal Symptoms
• Generalized seizure
• Partial onset seizure? Epilepsy

Contra-Indications of Phenobarbital

• the high amount of ammonium in the blood
• Porphyria
• Having thoughts of suicide
• Alcohol Intoxication
• drug abuse
• Depression
• Unconsciousness resulting from liver cell deterioration
• Severe liver disease
• Temporarily stops breathing while sleeping
• Pregnancy
• Poisoning by drug phenobarbital

Dosage? of Phenobarbital

Strengths: 15 mg; 30 mg; 60 mg;100 mg;

Sedation

Daytime Sedation

• 30 to 120 mg orally, IM, or IV in 2 or 3 divided doses
• Maximum dose: 400 mg during a 24-hour period

Preoperative Sedation

• 100 to 200 mg IM 60 to 90 minutes before surgery

Insomnia

• Recommended dose: 100 to 200 mg orally once a day
• Maximum dose: 400 mg during a 24-hour period

Parenteral

• Recommended dose: 100 to 320 mg IM or IV once a day
• Maximum dose: 400 mg during a 24-hour period

Seizures

Acute? Convulsions

• 20 to 320 mg IM or IV every 6 hours as necessary

Anticonvulsant

• Agitation.
• 60 to 200 mg orally per day

Pediatric Dose for Seizures

Anticonvulsant

• Agitation.
• Initial dose: 15 to 20 mg/kg orally
• Recommended dose: 3 to 6 mg/kg orally

Parenteral

• 4 to 6 mg/kg/day for 7 to 10 days or 5 to 15 mg/kg/day IM or IV

Status epilepticus

• Initial dose: 15 to 20 mg/kg IV over 10 to 15 minutes

Side Effects of Phenobarbital

The most common

• Memory or concentration problems
• Excitement, irritability, aggression, or confusion
• Dizziness
• constipation
• muscle aches
• Nausea and vomiting
• Severe stomach ache
• diarrhoea,
• anorexia,
• flatulence,
• headache,
• dizziness,
• heartburn
• joint pain

 Common

• Memory loss.
• Impaired attention span.
• Agitation.
• Depression.
• Nausea and vomiting
• Severe stomach ache
• Severe diarrhea
• Mouth sores
• Vaginal thrush
• Skin rash
• Headache

Rare/Less common

• Confusion
• Fever or sore throat
• Rash
• Slowed breathing or breathing difficulties
• Sores in the mouth
• Broken blood vessels under the skin
• Easy bruising or bleeding
• Swelling of the eyes, lips, or cheeks
• Blistering or peeling of the skin
• Restless muscle movements in the eyes, tongue, jaw, or neck

Drug Interactions of Phenobarbital

Phenobarbital may interact with following drugs, supplements & may change the efficacy of the drug

• albendazole
• alcohol
• allopurinol
• antihistamines (e.g,. cetirizine, doxylamine, diphenhydramine, hydroxyzine,loratadine)

• antiseizure medications e.g., clobazam, levetiracetam, phenobarbital, phenytoin, , valproic acid, zonisamide)
• aripiprazole
• “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
• benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
• beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
• calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
• captopril
• celecoxib
• chloroquine
• cholecalciferol
• cyclosporine
• dantrolene
• domperidone
• “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
• gabapentin
• H2 antagonists (e.g., famotidine, ranitidine)
• mirabegron
• montelukast
• non-steroidal anti-inflammatory medications (NSAIDs;e.g., diclofenac, ibuprofenserotonin antagonists (anti-emetic medications;, naproxen)
• phosphodiesterase 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
• quinolone antibiotics (e.g., levofloxacin, norfloxacin, moxifloxacin)
• selective serotonin reuptake inhibitors (SSRIs; e.g., paroxetine, fluoxetine,citalopram)
•  e.g., granisetron,ondansetron)
• “statin” anti-cholesterol medications (e.g., atorvastatin, lovastatin,simvastatin)
• theophylline
• thiazide diuretics (water pills; e.g., hydrochlorothiazide, indapamide, metolazone)
• tramadol
• tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine,

• selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine, paroxetine, sertraline)
• sildenafil
• tramadol
• tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)
• valproic acid
• warfarin
• zafirlukast

Pregnancy & Lactation of Phenobarbital

FDA Pregnancy Category D

Pregnancy

Medications used to prevent major seizures should not be stopped. The use of this medication is not recommended during pregnancy. However, the decision about whether or not to stop the medication must weigh the potential benefits against the potential risks. If you become pregnant while taking this medication, contact your doctor immediately.

Lactation

This medication passes into breast milk. If you breastfeeding-feeding mother and are taking phenobarbital, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

References