Pentobarbital; Uses, Dosage, Side Effects, Drug Interactions Pentobarbital Sodium is the sodium salt of pentobarbital, a short-acting barbituric acid derivative with central nervous system (CNS) depressant property. Pentobarbital sodium binds to the gamma-aminobutyric acid (GABA)-A subtype receptor, resulting in modulation of chloride transport through receptor channels and potentiation of GABA-induced increases in chloride conductance. This enhances postsynaptic responses to the inhibitory actions of GABA and causes CNS depression. In addition, this agent inhibits glutamate induced nerve depolarization and depresses voltage-activated calcium currents. or Pentobarbital or pentobarbitone is a short-acting barbiturate. Pentobarbital can occur as both a free acid and as salts of elements such as sodium and calcium. The free acid is only slightly soluble in water and ethanol. It is a short-acting barbiturate that is effective as a sedative and hypnotic (but not as an anti-anxiety) agent and is usually given orally. It is prescribed more frequently for sleep induction than for sedation but, like similar agents, may lose its effectiveness by the second week of continued administration. In high doses, pentobarbital causes death by respiratory arrest. In the United States, the drug has been used for executions of convicted criminals. Lundbeck (one of many manufacturers) does not permit its sale to prisons or corrections departments to carry out the death penalty Mechanism of Action of Pentobarbital Barbiturates are metabolized primarily by the hepatic microsomal enzyme system, and the metabolic products are excreted in the urine, and less commonly, in the feces. Pentobarbital binds at a distinct binding site associated with a Cl- ionopore at the GABAA receptor, increasing the duration of time for which the Cl- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged. All of these effects are associated with marked decreases in GABA-sensitive neuronal calcium conductance (gCa). The net result of barbiturate action is acute potentiation of inhibitory GABAergic tone. Barbiturates also act through potent (if less well characterized) and direct inhibition of excitatory AMPA-type glutamate receptors, resulting in a profound suppression of glutamatergic neurotransmission. Indications of Pentobarbital Typical applications for pentobarbital are sedative, hypnotic for short term, preanesthetic and control of convulsions in emergencies Status Epilepticus Sedation Insomnia Sleeplessness Severe Convulsion Withdrawal Symptoms Generalized seizure Partial onset seizure Epilepsy Pentobarbital also has an application in reducing intracranial pressure in Reye’s syndrome, traumatic brain injury and induction of coma in cerebral ischemia patients. For the short-term treatment of insomnia. Contra-Indications of Pentobarbital Porphyria High blood pressure Heart hisease Abnormally low blood pressure Pneumonia Lung failure causing loss of breath Decreased lung function Liver problems Periods of Not breathing Pregnancy Chronic obstructive lung disease Dosage of Pentobarbital Strengths: 30mg ;60 mg; 50 mg;100 mg; 120 mg; 200 mg; 50 mg/mL; 18.2 mg/5 mL Insomnia Oral capsules or elixir: 100 mg orally at bedtime. Rectal suppository: 120 to 200 mg rectally. Injection: 100 to 200 mg IM or IV. Sedation Oral capsules or elixir: 100 mg orally at bedtime. Rectal suppository: 120 to 200 mg rectally. Injection: 100 to 200 mg IM or IV. Side Effects of Pentobarbital 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 Pentobarbital Pentobarbital may interact with following drugs, supplements & may change the efficacy of the drug albendazole alcohol allopurinol alpha blockers (e.g., alfuzosin, doxazosin, silodosin, tamsulosin) amphetamines (e.g., dextroamphetamine, lisdexamphetamine) anti-cancer medications (e.g., cabazitaxel, docetaxel; doxorubicin; etoposide, ifosfamide, irinotecan, vincristine) antihistamines (e.g., cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine) antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone) “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole) baclofen barbiturates (e.g., butalbital, pentobarbital phenobarbital) benzodiazepines (e.g., chlordiazepoxide, clonazepam, diazepam, lorazepam) beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol) bupropion calcitriol calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil) carbamazepine carvedilol celecoxib ciprofloxacin clobazam oral corticosteroids (e.g., dexamethasone, hydrocortisone, prednisone) cyclosporine doxycycline folic acid gabapentin “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin) lansoprazole loperamide losartan macrolide antibiotics (e.g., clarithromycin, erythromycin) methylfolate methylphenidate multivitamins montelukast nitrates (e.g., isosorbide dinitrate, isosorbide mononitrate) ondansetron phenytoin progestins (e.g., dienogest, levonorgestrel, medroxyprogesterone, norethindrone) proton pump inhibitors (e.g., lansoprazole, omeprazole) ranitidine selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine,paroxetine, sertraline) sildenafil “statin” anti-cholesterol medications (e.g., atorvastatin, lovastatin, simvastatin) theophyllines (e.g., aminophylline, oxtriphylline, theophylline) thiazide diuretics (e.g., chlorothiazide, hydrochlorothiazide) tramadol tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine) valproic acid warfarin zafirlukast Pregnancy & Lactation 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 are a breastfeeding mother and are taking phenobarbital, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. References DrugBank http://www.drugbank.ca/drugs/DB00312 http://www.drugbank.ca/drugs/DB00312#enzymes http://www.drugbank.ca/drugs/DB00312#targets https://www.drugs.com/mtm/pentobarbital-injection.html https://www.drugs.com/ppa/pentobarbital.html EPA DSStox https://comptox.epa.gov/dashboard/dsstoxdb/results?search=DTXSID7023435 https://www.drugs.com/mtm/pentobarbital-injection.html European Chemicals Agency (ECHA) https://echa.europa.eu/substance-information/-/substanceinfo/100.000.895 https://echa.europa.eu/substance-information/-/substanceinfo/100.000.294 https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/61979 https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/63811 European Chemicals Agency – ECHA https://www.echa.europa.eu https://www.echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database/-/discli/details/61979 https://www.echa.europa.eu/web/guest/information-on-chemicals/cl-inventory-database/-/discli/details/63811 https://www.webmd.com/drugs/2/drug-5461/pentobarbital-sodium-injection/details/list-contraindications Human Metabolome Database (HMDB) http://www.hmdb.ca/metabolites/HMDB0014457 NCIT https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C47662 HSDB https://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+@rel+76-74-4 ClinicalTrials.gov https://clinicaltrials.gov/ DailyMed https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=PENTOBARBITAL https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=PENTOBARBITAL+SODIUM FDA Orange Book https://www.fda.gov/Drugs/InformationOnDrugs/ucm129662.htm MassBank of North America (MoNA) http://mona.fiehnlab.ucdavis.edu/spectra/browse?inchikey=WEXRUCMBJFQVBZ-UHFFFAOYSA-N SpectraBase https://spectrabase.com/compound/CMIDElRh6z0#K4WnZzUOxcw https://spectrabase.com/compound/CMIDElRh6z0#DQQE4cxEeFZ https://spectrabase.com/compound/CMIDElRh6z0#A1lqxA3m21l https://spectrabase.com/compound/CMIDElRh6z0#9uP31uVSUQQ https://spectrabase.com/compound/CMIDElRh6z0#MD4MfKl9UJ https://spectrabase.com/compound/CMIDElRh6z0#CXgfjSC4SI7 https://spectrabase.com/compound/CMIDElRh6z0#1wBbhz3Xw7s https://spectrabase.com/compound/CMIDElRh6z0#93WuhhqdmfY NIST http://www.nist.gov/srd/nist1a.cfm PubMed Health http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0001383/ http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011665/ http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011664/ http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011666/ Springer Nature Read more … WHO ATC https://www.whocc.no/atc/ https://www.whocc.no/atc_ddd_index/ Wikipedia https://en.wikipedia.org/wiki/Pentobarbital https://www.wikidata.org/wiki/Q27264032 https://www.wikidata.org/wiki/Q27107638 https://pubchem.ncbi.nlm.nih.gov MeSH https://www.ncbi.nlm.nih.gov/mesh/68010424 http://www.nlm.nih.gov/mesh/meshhome.html Show More