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

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 ,WATSAPP PHARM.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 :

“ 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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