BARBITURATE POISONING A PRECISE INSIGHT PRESENTED BY VISHNU

BARBITURATE POISONING: A PRECISE INSIGHT PRESENTED BY : VISHNU. R. NAIR, 4 TH YEAR PHARM. D, NATIONAL COLLEGE OF PHARMACY (NCP), KERALA UNIVERSITY OF HEALTH SCIENCES (KUHS), KERALA STATE.

INDEX/ CONTENTS OF THIS PRESENTATION : GENERAL ACKNOWLEDGEMENT DEFINITION OF BARBITURATES CLASSIFICATION OF BARBITURATES MECHANISM OF ACTION AND TOXICITY GENERAL USES OF BARBITURATES TOXICOKINETICS ADVERSE EFFECTS OF BARBITURATES TOXIC EFFECTS OF BARBITURATES USUAL FATAL DOSES POSTMORTEM APPEARANCES TREATMENT OF BARBITURATE POISONING

GENERAL ACKNOWLEDGEMENT : • “NOTHING IS IMPOSSIBLE, UNLESS U RESOLVE TO GO FOR IT”ANONYMOUS • THIS IS MY 17 TH PPT OVERALL…AND 2 ND ON TOXICOLOGY • THANKING MY TOXICOLOGY TEACHER, AND MANY OTHER TEACHERS, FOR HER GUIDANCE ON MAKING NOTES AND REFERENCE , AND EMOTIONAL SUPPORT • THANKING THE ALMIGHTY FOR EVERLASTING BLISS AND LOVE • THANKING MY PARENTS, COUSINS, FRIENDS(MY CLASS , WATSAPP PHARM. D GROUP) , WELL-WISHERS AND EVERYONE WORLDWIDE FOR UR SUPPORT AND LOVE

DEFINITION OF BARBITURATES : “ DERIVATIVES of BARBITURIC ACID, used as SEDATIVE-HYPNOTICS , and also for the treatment of EPILEPSY”………………

CLASSIFICATION OF BARBITURATES : 1. ULTRA-SHORT ACTING BARBITURATES : - Duration of action: >0. 5 hours - Examples include: a. THIOPENTAL b. METHOHEXITAL 2. SHORT-ACTING BARBITURATES: - Duration of action : >3 -4 hours - Examples include: a. PENTOBARBITAL b. SECOBARBITAL

3. INTERMEDIATE-ACTING BARBITURATES: - Duration of action : >4 -6 hours - Examples include: a. AMOBARBITAL b. APROBARBITAL c. BUTABARBITAL d. BUTALBITAL 4. LONG-ACTING BARBITURATES: - Duration of action: >6 -12 hours - Examples include: a. MEPHOBARBITAL b. PHENOBARBITAL…………………

MECHANISM OF ACTION & TOXICITY : • BARBITURATES Causes GENERALIZED DEPRESSION of neuronal activity in brain • DRUG Interacts with BARBITURATE RECEPTOR Leads to increase in GABA -MEDIATED CHLORIDE CHANNEL CURRENTS Causes SYNAPTIC INHIBITION • DRUG also depresses CENTRAL SYMPATHETIC TONE & CARDIAC CONTRACTILITY Leads to HYPOTENSION…………….

GENERAL USES OF BARBITURATES : 1. SEDATIVE-HYPNOTIC 2. PRE-OPERATIVE SEDATION 3. GTCS 4. FEBRILE CONVULSIONS 5. STATUS EPILEPTICUS

TOXICOKINETICS : 1. ORAL ROUTE Preferred for SEDATIVE-HYPNOTIC action 2. I. V ROUTE Preferred for : a. STATUS EPILEPTICUS management b. Induction/ maintenance of GENERAL ANAESTHESIA 3. Distributed widely 4. Undergoes HEPATIC OXIDATION to form metabolites , like: A. ALCOHOLS B. KETONES C. PHENOLS D. CARBOXYLIC ACIDS 5. Excreted as such in URINE/ as GLUCURONIC ACID conjugates……………

ADVERSE EFFECTS OF BARBITURATES : 1. RESIDUAL DEPRESSION (After the main effect of the drug ceases) 2. PARADOXICAL EXCITEMENT (especially in elderly) 3. HYPERSENSITIVITY REACTIONS : - include: A. Localized swelling of eyelid, lips or cheeks B. Erythematous or exfoliative dermatitis

TOXIC EFFECTS OF BARBITURATES : 1. Slurred speech 2. Ataxia 3. Lethargy 4. Confusion 5. Headache 6. Nystagmus 7. CNS depression 8. Com. A 9. Shock 10. Constricted pupils

11. Hypothermia 12. Cutaneous bullae (blisters) 13. Respiratory arrest or CV collapse………………… FOR MILD-MODERATE INTOXICATION: - SLURRED SPEECH - ATAXIA - NYSTAGMUS FOR HIGHER DOSES: - HYPOTENSION - HYPOTHERMIA - RESPIRATORY ARREST - COMA

USUAL FATAL DOSES : 1. FOR PHENOBARBITONE : 6 -10 GRAMS 2. FOR AM 0 BARBITAL, SECOBARBITAL, PENTOBARBITAL: 2 -3 GRAMS………………. .

POSTMORTEM APPEARANCES : 1. PERIPHERAL CYANOSIS 2. FROTH AT MOUTH AND NOSE 3. BARBITURATE BLISTERS , PRESENT ON: - Buttocks - Calves - Forearms 4. HIGHLY CONGESTED LUNGS 5. STOMACH EROSION………………. .

TREATMENT OF BARBITURATE POISONING : - There is no specific ANTIDOTE for BARBITURATE POISONING - EMERGENCY & SUPPORTIVE MEASURES: Include: a. AIRWAY PROTECTION b. ASSISTED VENTILATION(IF NECESSARY) c. Treat COMA, HYPOTHERMIA and HYPOTENSION if they occur d. For COMA, focus on the following treatment principles: * DEXTROSE : For ADULTS (50% solution, 50 ml. I. V), for CHILDREN (25% solution, 2 ml/kg I. V) • THIAMINE : 100 mg (I. V) • NALOXONE : Initially 0. 4 mg I. V If no response to therapy give 2 mg I. V if no response to therapy give 10 -20 mg I. V

E. For HYPOTHERMIA, focus on the following treatment principles: • If patient is not in CARDIAC ARREST REWARM SLOWLY , using BLANKETS, WARM I. V FLUIDS • If patient is in CARDIAC ARREST Use GASTRIC/ PERITONEAL LAVAGE with WARM FLUIDS , and perform CPR • For VENTRICULAR FIBRILLATION Use BRETYLIUM (5 -10 mg I. V) • Perform OPEN CARDIAC MASSAGE/ PARTIAL CARDIOPULMONARY BYPASS under non-responsiveness of the above measures……………. . F. For HYPOTENSION, focus on the following treatment principles: • Use I. V FLUIDS/ LOW DOSE PRESSORS(DOPAMINE) • Focus on PATIENT REWARMING • FLUID CHALLENGE CONCEPT: Use NORMAL SALINE(10 -20 ml/kg) / any other CRYSTALLOID SOLUTION

• Give DOPAMINE (5 -15 mcg/kg/min) • If above measures are not effective insert CENTRAL VENOUS PRESSURE (CVP) MONITOR/ PULMONARY ARTERY CATHETER , to check : 1. If fluids are required 2. CARDIAC OUTPUT and SYSTEMIC VASCULR RESISTANCE, according to the formula: SVR= [80(MAP-CVP)]/ CO, Where MAP = MEAN ARTERIAL PRESSURE CVP = CENTRAL VENOUS PRESSURE • Normal value of SVR : 770 -1500 • If CVP is low give more IV FLUIDS • If CO is low give DOBUTAMINE/ DOPAMINE • If SVR is low give NOREPINEPHRINE (4 -8 mcg/min)

G. Intubation H. SUPPLEMENTAL OXYGEN - DECONTAMINATION PRINCIPLES: 1. FOR PRE-HOSPITAL DECONTAMINATION : Give ACTIVATED CHARCOAL (If available) 2. FOR IN- HOSPITAL DECONTAMINATION : - Give ACTIVATED CHARCOAL - Focus on GASTRIC LAVAGE (In cases of MASSIVE INGESTION of BARBITURATES) - ENHANCED ELIMINATION: 1. URINE ALKALINIZATION (Only for PHENOBARBITAL) 2. REPEAT DOSE ACTIVATED CHARCOAL (Only for PHENOBARBITAL) 3. HAEMODIALYSIS & HAEMOPERFUSION (In patients, not responding to SUPPORTIVE CARE)…

BIBLIOGRAPHY/ REFERENCE : 1. ALBERTSON. E. T; “BARBITURATES”; “POISONING AND DRUG OVERDOSE BY KENT. R. OLSON” ; 4 TH EDITION; MCGRAW HILL PUBLICATIONS; PAGE: 124 -126 2. “ALCOHOLS & SEDATIVES: BARBITURATES”; “TEXTBOOK OF FORENSIC MEDICINE& TOXICOLOGY BY DR. V. V. PILLAY”; 17 TH EDITION; PARAS MEDICAL PUBLISHERS; PAGE: 598 -599……………

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