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 BARBITURATESMECHANISM OF ACTION AND TOXICITYGENERAL USES OF BARBITURATES TOXICOKINETICS ADVERSE EFFECTS OF BARBITURATES TOXIC EFFECTS OF BARBITURATESUSUAL FATAL DOSESPOSTMORTEM APPEARANCESTREATMENT OF BARBITURATE POISONING
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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. THIOPENTALb. 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. AMOBARBITALb. APROBARBITALc. BUTABARBITALd. BUTALBITAL
4. LONG-ACTING BARBITURATES:- Duration of action: >6-12 hours- Examples include:a. MEPHOBARBITALb. 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-HYPNOTIC2. PRE-OPERATIVE SEDATION3. GTCS4. FEBRILE CONVULSIONS5. STATUS EPILEPTICUS
TOXICOKINETICS :1. ORAL ROUTE Preferred for SEDATIVE-HYPNOTIC action2. I.V ROUTE Preferred for :a. STATUS EPILEPTICUS managementb. Induction/ maintenance of GENERAL ANAESTHESIA3. Distributed widely4. Undergoes HEPATIC OXIDATION to form metabolites , like:A. ALCOHOLSB. KETONESC. PHENOLSD. CARBOXYLIC ACIDS5. 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 cheeksB. Erythematous or exfoliative dermatitis
TOXIC EFFECTS OF BARBITURATES :1. Slurred speech2. Ataxia3. Lethargy4. Confusion5. Headache6. Nystagmus7. CNS depression8. ComA9. Shock10.Constricted pupils
11. Hypothermia12. 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 GRAMS2. FOR AM0BARBITAL, SECOBARBITAL, PENTOBARBITAL:2-3 GRAMS………………..
POSTMORTEM APPEARANCES :1. PERIPHERAL CYANOSIS2. FROTH AT MOUTH AND NOSE3. BARBITURATE BLISTERS , PRESENT ON:- Buttocks- Calves- Forearms4. HIGHLY CONGESTED LUNGS5. STOMACH EROSION………………..
TREATMENT OF BARBITURATE POISONING :- There is no specific ANTIDOTE for BARBITURATE POISONING
- EMERGENCY & SUPPORTIVE MEASURES:Include:a. AIRWAY PROTECTIONb. ASSISTED VENTILATION(IF NECESSARY)c. Treat COMA, HYPOTHERMIA and HYPOTENSION if they occurd. 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 required2. CARDIAC OUTPUT and SYSTEMIC VASCULR RESISTANCE, according to the formula:
SVR= [80(MAP-CVP)]/ CO,WhereMAP = MEAN ARTERIAL PRESSURECVP = 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. IntubationH. 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” ; 4TH EDITION; MCGRAW HILL PUBLICATIONS; PAGE: 124-126
2. “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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