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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
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BARBITURATE POISONING: A PRECISE INSIGHT PRESENTED BY : VISHNU.R.NAIR, 4TH 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 17th ppt overall…and 2nd 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 ,watsapppharm.d group) , well-wishers and everyone worldwide for ur support and love • Do send me ur reviews based on this ppt • Thanks for reading……………happy reading!!!!
DEFINITION OF BARBITURATES : “ DERIVATIVESof BARBITURIC ACID, used as SEDATIVE-HYPNOTICS , and also for the treatment of EPILEPSY”………………
CLASSIFICATION OF BARBITURATES : • ULTRA-SHORT ACTING BARBITURATES : • Duration of action: >0.5 hours • Examples include: • THIOPENTAL • 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: • AMOBARBITAL • APROBARBITAL • BUTABARBITAL • BUTALBITAL 4. LONG-ACTING BARBITURATES: • Duration of action: >6-12 hours • Examples include: • MEPHOBARBITAL • 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 : • SEDATIVE-HYPNOTIC • PRE-OPERATIVE SEDATION • GTCs • FEBRILE CONVULSIONS • STATUS EPILEPTICUS
TOXICOKINETICS : • ORAL ROUTE Preferred for SEDATIVE-HYPNOTIC action • I.V ROUTE Preferred for : • STATUS EPILEPTICUS management • Induction/ maintenance of GENERAL ANAESTHESIA 3. Distributed widely 4. Undergoes HEPATIC OXIDATION to form metabolites , like: • ALCOHOLS • KETONES • PHENOLS • CARBOXYLIC ACIDS 5. Excreted as such in URINE/ as GLUCURONIC ACID conjugates…………………………
ADVERSE EFFECTS OF BARBITURATES : • RESIDUAL DEPRESSION (After the main effect of the drug ceases) • PARADOXICAL EXCITEMENT (especially in elderly) • HYPERSENSITIVITY REACTIONS : • include: • Localized swelling of eyelid, lips or cheeks • Erythematous or exfoliative dermatitis
TOXIC EFFECTS OF BARBITURATES : • Slurred speech • Ataxia • Lethargy • Confusion • Headache • Nystagmus • CNS depression • Coma • Shock • 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 - RESPIRATORY ARREST - COMA • HYPOTHERMIA
USUAL FATAL DOSES : 1.FOR PHENOBARBITONE : 6-10 grams 2. FOR AM0BARBITAL, SECOBARBITAL, PENTOBARBITAL: 2-3 GRAMS………………..
POSTMORTEM APPEARANCES : • PERIPHERAL CYANOSIS • FROTH AT MOUTH AND NOSE • 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: • AIRWAY PROTECTION • ASSISTED VENTILATION(IF NECESSARY) • 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 WARMFLUIDS , 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: • FOR PRE-HOSPITAL DECONTAMINATION : Give ACTIVATED CHARCOAL (If available) • FOR IN- HOSPITAL DECONTAMINATION : • Give ACTIVATED CHARCOAL • Focus on GASTRIC LAVAGE (In cases of MASSIVE INGESTION of BARBITURATES) • ENHANCED ELIMINATION: • URINE ALKALINIZATION (Only for PHENOBARBITAL) • REPEAT DOSE ACTIVATED CHARCOAL (Only for PHENOBARBITAL) • HAEMODIALYSIS & HAEMOPERFUSION (In patients, not responding to SUPPORTIVE CARE)…
BIBLIOGRAPHY/ REFERENCE : • ALBERTSON.E.T; “BARBITURATES”; “POISONING AND DRUG OVERDOSE by KENT.R.OLSON” ; 4TH EDITION; MCGRAW HILL PUBLICATIONS; PAGE: 124-126 • “ALCOHOLS & SEDATIVES: BARBITURATES”; “TEXTBOOK OF FORENSIC MEDICINE& TOXICOLOGY BY DR.V.V.PILLAY”; 17TH EDITION; PARAS MEDICAL PUBLISHERS; PAGE: 598-599………………………
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