Drug overdose
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Transcript of Drug overdose
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Case Study:Case Study:
A 17 year old young man took “pills” and some A 17 year old young man took “pills” and some alcohol after failing his exams. He is drunk and alcohol after failing his exams. He is drunk and depressed.depressed.
BP 120/80BP 120/80 HR 105 HR 105 Resp 14/minResp 14/min Temp 37 C Temp 37 C His airway is patent, he is breathing normallyHis airway is patent, he is breathing normally
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Case, continued:Case, continued:
He is treated with intravenous fluids, watched He is treated with intravenous fluids, watched until sober, given a psychiatric referral, and until sober, given a psychiatric referral, and sent home with his family.sent home with his family.
3 days later he returns with jaundice.3 days later he returns with jaundice.
WHAT IS YOUR DIAGNOSIS?WHAT IS YOUR DIAGNOSIS?
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Paracetamol PoisoningParacetamol Poisoning
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Paracetamol poisoningParacetamol poisoning
Diagnosis easily missedDiagnosis easily missed– often overlooked in historyoften overlooked in history– no characteristic early symptoms or signsno characteristic early symptoms or signs
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AcetaminophenAcetaminophenMetabolism Metabolism
Glucuronidation(non toxic)
Sulfation(non toxic)
NAPQI
P450
~ 5%
Glutathione + NAPQI= nontoxic product Liver cell damage
N-acetylcysteine (NAC)
~ 45% ~ 50%
NAPQI= N-acetyl-p-benzoquinone imine
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Paracetamol Toxicity:Paracetamol Toxicity:
Overdose:Overdose:– sulfation and glucuronidation saturatedsulfation and glucuronidation saturated
– increased production of p-450 metaboliteincreased production of p-450 metabolite• glutathione eventually depleted glutathione eventually depleted • reactive intermediate NAPQI injures cellsreactive intermediate NAPQI injures cells
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PCM toxicity, cont.PCM toxicity, cont.
High-risk groups: High-risk groups: enhanced p-450 activityenhanced p-450 activity – chronic alcoholicschronic alcoholics– chronic use of isoniazid (INH)chronic use of isoniazid (INH)
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PharmacokineticsPharmacokinetics
Tablets dissolve rapidlyTablets dissolve rapidly Peak level 3-4 hours after ingestionPeak level 3-4 hours after ingestion
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Clinical Manifestations of Toxicity:Clinical Manifestations of Toxicity:
Early: Early: non-specificnon-specific– anorexia, vomitinganorexia, vomiting
24-48 hrs:24-48 hrs:– onset of liver injuryonset of liver injury
• AST, ALT may exceed 10,000 IUAST, ALT may exceed 10,000 IU– renal injury may also occurrenal injury may also occur
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Paracetamol Toxicity, continued:Paracetamol Toxicity, continued:
2-5 days:2-5 days:– liver & kidney injury resolve in most patientsliver & kidney injury resolve in most patients– some patients may develop some patients may develop fulminant liver failurefulminant liver failure
• progressive rise in PT/INR, bilirubinprogressive rise in PT/INR, bilirubin• metabolic acidosis, hypoglycemiametabolic acidosis, hypoglycemia• encephalopathy encephalopathy • DEATHDEATH
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Prediction of Paracetamol Toxicity:Prediction of Paracetamol Toxicity:
History:History:– acuteacute ingestion of >200 mg/kg or >10 gm ingestion of >200 mg/kg or >10 gm
• 20 tablets in average-sized person20 tablets in average-sized person
– chronicchronic use of >4-6 gm/day in a high-risk group use of >4-6 gm/day in a high-risk group• Chronic alcohol abuse, isoniazid useChronic alcohol abuse, isoniazid use
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Prediction of PCM toxicity, cont.Prediction of PCM toxicity, cont.
Clinical evaluation:Clinical evaluation:– serum PCM level is best predictor, if availableserum PCM level is best predictor, if available– levels associated with “probable toxicity”:levels associated with “probable toxicity”:
• 200 mg/L at 4 hrs after acute ingestion200 mg/L at 4 hrs after acute ingestion• 100 at 8 hrs100 at 8 hrs• 50 at 12 hrs50 at 12 hrs
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Very early and transient increase in the PT/INR Very early and transient increase in the PT/INR may predict later LFT risemay predict later LFT rise– Normal PT/INR at 24 hrs may have good negative Normal PT/INR at 24 hrs may have good negative
predictive valuepredictive value
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Gut decontamination for PCMGut decontamination for PCM
Activated charcoal Activated charcoal Gastric lavageGastric lavage
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Treatment, continuedTreatment, continued
Antidote: Antidote: N-acetylcysteine (NAC)N-acetylcysteine (NAC)– provides SH group - binds to NAPQIprovides SH group - binds to NAPQI
• most effective if started within 8-10 hrs after ingestionmost effective if started within 8-10 hrs after ingestion– can be given PO or IVcan be given PO or IV– if vomiting, use IV routeif vomiting, use IV route
Alternate medication: oral Alternate medication: oral methioninemethionine
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Antidote: Antidote: N-acetylcysteine (NAC)N-acetylcysteine (NAC) N-acetylcysteine (NAC): effective if started within 8-10 N-acetylcysteine (NAC): effective if started within 8-10
hrs after ingestionhrs after ingestionFDA recommendation: FDA recommendation: Loading dose: 150mg/kg IV over 60 mins 4 hr Loading dose: 150mg/kg IV over 60 mins 4 hr
infusion of 50 mg/kg 16 hr infusion of 100 infusion of 50 mg/kg 16 hr infusion of 100 mg/kg.mg/kg.
Check renal/liver fnc testCheck renal/liver fnc test PT/INRPT/INRIf fulminant hepatic failure,final trt: If fulminant hepatic failure,final trt: liver transplantliver transplant
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SummarySummary
Ingestion < 200 mg/kg probably not toxicIngestion < 200 mg/kg probably not toxic If no serum level available treat based on doseIf no serum level available treat based on dose IV acetylcysteine or oral methionineIV acetylcysteine or oral methionine Start antidote within 8 hoursStart antidote within 8 hours
Liver or kidney damage is usually delayed to 24-Liver or kidney damage is usually delayed to 24-48 hrs after ingestion of paracetamol48 hrs after ingestion of paracetamol
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Case HistoryCase History A 17yr old nursing student was brought to A 17yr old nursing student was brought to
hospital deeply unconscious.hospital deeply unconscious. On probing it was discovered she took a heavy On probing it was discovered she took a heavy
dose of sleeping pills.dose of sleeping pills. Patient was hemodynamically stable but her Patient was hemodynamically stable but her
respiration was slightly shallow.respiration was slightly shallow. Her pupils were slightly constricted.Her pupils were slightly constricted. Patient was put on forced alkaline diuresis.Patient was put on forced alkaline diuresis. However, patient refused to improve even after 4 However, patient refused to improve even after 4
days of treatment. days of treatment.
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Patient developed some bullae over the legs.Patient developed some bullae over the legs. Patient remained in deep coma, but otherwise was Patient remained in deep coma, but otherwise was
stable.stable.Day 5:Day 5: Some response to deep stimuli was observedSome response to deep stimuli was observedDay 6:Day 6: Patient significantly regained consciousness but was Patient significantly regained consciousness but was
delirious. However, it lasted for short period.delirious. However, it lasted for short period.Day 10: DischargedDay 10: Discharged
Diagnosis?Diagnosis?
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Acute Barbiturate PoisoningAcute Barbiturate Poisoning
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BARBITURATESBARBITURATES Non-selective Non-selective CNS depressants.CNS depressants. Derivatives of barbituric acid (2,4,6- trioxo hexa hydro Derivatives of barbituric acid (2,4,6- trioxo hexa hydro
pyrimidine).pyrimidine). Popular sedative & hypnotics up to 1960’s.Popular sedative & hypnotics up to 1960’s. Can produce effects ranging from Can produce effects ranging from sedationsedation & & reduction reduction
of anxietyof anxiety to to unconsciousnessunconsciousness & & death death from respiratory from respiratory & cardio vascular failure.& cardio vascular failure.
USES:USES: Sedative & hypnotic.Sedative & hypnotic. Pre operative sedation.Pre operative sedation.
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Prolong the opening of chloride channel
Inhibiting excitable cells of the CNS
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1.1.LONG ACTING: (6-12 LONG ACTING: (6-12 hrs)hrs)
PhenobarbitonePhenobarbitone
2.2.SHORT ACTING: (<3 SHORT ACTING: (<3 hrs)hrs)
PentobarbitonePentobarbitone
3. 3. ULTRA-SOUND ULTRA-SOUND ACTING: (<15-20 mins)ACTING: (<15-20 mins)
ThiopentoneThiopentone
CLASSIFICATIONCLASSIFICATION::
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ACUTE BARBITURATE POISONINGACUTE BARBITURATE POISONING Leading cause of poisoning due to their ready Leading cause of poisoning due to their ready
availability.availability.
Most of the cases are suicidal but some are due to Most of the cases are suicidal but some are due to
error or ungraded exploration in children.error or ungraded exploration in children.
Short acting barbiturates are more dangerous than Short acting barbiturates are more dangerous than
long acting.long acting.
Shock & anorexia occur quickly.Shock & anorexia occur quickly.
Coma is more severe with short acting Coma is more severe with short acting
barbiturates.barbiturates.
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SYMPTOMS:SYMPTOMS: Stupor or coma, areflexiaStupor or coma, areflexia Peripheral circulatory collapse.Peripheral circulatory collapse. Weak & rapid pulse.Weak & rapid pulse. Cold clammy skin.Cold clammy skin. Slow & shallow breathing.Slow & shallow breathing. HypothermiaHypothermia Cutaneous bullae (blisters)Cutaneous bullae (blisters) Pupils – usually constrictedPupils – usually constricted Mild renal failure may occurMild renal failure may occur Death due to respiratory arrest or cardio vascular Death due to respiratory arrest or cardio vascular
collapsecollapse
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MANAGEMENT:MANAGEMENT:SCANDINAVIAN METHOD:
Hospitalisation
Support vital functions Prevent further absorption Increase elimination of drug
Conservative management with good nursing care
Appropriate detoxification or psychiatric after care
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HOSPITALIZATION:HOSPITALIZATION: Admitted to the hospital.Admitted to the hospital.
SUPPORT VITAL FUNCTIONS:SUPPORT VITAL FUNCTIONS: Consciousness.Consciousness. Airway , breathing , circulation.Airway , breathing , circulation. Blood pressure. Blood pressure. PREVENT FURTHER ABSORPTION:PREVENT FURTHER ABSORPTION: Emesis.Emesis. Gastric lavage.Gastric lavage. Activated charcoal & catharsis.Activated charcoal & catharsis.
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INCREASE ELIMINATION OF DRUG:INCREASE ELIMINATION OF DRUG: Forced alkaline diuresisForced alkaline diuresis Peritoneal dialysis.Peritoneal dialysis. Hemodialysis.Hemodialysis. HemoperfusionHemoperfusion
OTHER MEASURES:OTHER MEASURES: Psychiatric after care.Psychiatric after care.
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Forced Alkaline Diuresis (FAD)Forced Alkaline Diuresis (FAD)
Principles:Principles:Glucose/normal saline infusion Glucose/normal saline infusion Sodium bicarbonate added to make blood and, Sodium bicarbonate added to make blood and, in turn, urine alkaline. in turn, urine alkaline. A diuretic like furosemide intravenously givenA diuretic like furosemide intravenously givenPotassium replacement because potassium is Potassium replacement because potassium is usually lost in urine with diuretic therapyusually lost in urine with diuretic therapy
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In the first hour infuse:In the first hour infuse:500 ml 5% dextrose500 ml 5% dextrose
500 ml bicarbonate 1.4%500 ml bicarbonate 1.4%
500 ml dextrose 5%500 ml dextrose 5%
Potassium chloride should be added to keep serum potassium above 3.5 mmol/l.Potassium chloride should be added to keep serum potassium above 3.5 mmol/l.
a diuretic like furosemide is given 20 mg intravenouslya diuretic like furosemide is given 20 mg intravenously
Administer 1.5-2.0 litres of i.v. fluids per hour to maintain urine volume greater Administer 1.5-2.0 litres of i.v. fluids per hour to maintain urine volume greater
than 500 ml per hour. than 500 ml per hour.
Urine pH sould be maintained between 7.5 and 8.5.Urine pH sould be maintained between 7.5 and 8.5.
Several such cycles may be repeated till patient becomes conscious.Several such cycles may be repeated till patient becomes conscious.
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BENZODIAZEPINESBENZODIAZEPINES
Anxiolytic & hypnotic agents.Anxiolytic & hypnotic agents. Safest of all sedative drugs.Safest of all sedative drugs.
USES:USES:Management ofManagement of Anxiety disordersAnxiety disorders Seizure disordersSeizure disorders InsomniaInsomnia
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ANTIANXIETY:
Diazepam
Chlordiazepoxide
Lorazepam
Alprazolam
clonazepam
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Toxic symptoms-sedative action on the CNS.
Large doses-neuromuscular blockade .
Intravenous injection-peripheral vasodilation -fall in BP, shock.
↓se alveolar ventilation (↓se PO2 , ↑se PCO2 ).
Induce CO2 narcosis in persons with COPD.
Respiratory depressant effect with sedative drugs-concomitantly taken.
Death occurred in persons who concurrently injected ethanol / CNS depressant.
IV dosing-hypotension & respiratory depression-death.
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Overdose:Overdose: Toxic symptoms-sedative action on the CNS.Toxic symptoms-sedative action on the CNS. Intravenous injection-peripheral vasodilation -fall Intravenous injection-peripheral vasodilation -fall
in BP, shock.in BP, shock. ↓↓se alveolar ventilation (↓se PO2 , ↑se PCO2 ).se alveolar ventilation (↓se PO2 , ↑se PCO2 ). Induce CO2 narcosis in persons with COPD.Induce CO2 narcosis in persons with COPD. Respiratory depressant effectRespiratory depressant effect ComaComa
o COMA 1 (Stage 1): Responsive to painful stimuli but not to verbal or tactile COMA 1 (Stage 1): Responsive to painful stimuli but not to verbal or tactile stimuli, no disturbance in respiration or BP.stimuli, no disturbance in respiration or BP.
o COMA 2 (Stage 2):Unconscious, not responsive to painful stimuli, no COMA 2 (Stage 2):Unconscious, not responsive to painful stimuli, no disturbance in respiration or BP.disturbance in respiration or BP.
o IV dosing-hypotension & respiratory depression-death.IV dosing-hypotension & respiratory depression-death.
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MANAGEMENT:MANAGEMENT: DECONTAMINATION:DECONTAMINATION: Stomach wash within 6-12 hrsStomach wash within 6-12 hrs Activated charcoalActivated charcoal LIFE SUPPORTIVE PROCEDURES & LIFE SUPPORTIVE PROCEDURES &
SYMPTOMATIC TREATMENT:SYMPTOMATIC TREATMENT: Airway , breathing & circulationAirway , breathing & circulation Intravenous fluid administrationIntravenous fluid administration Endotracheal intubationEndotracheal intubation Assisted ventilationAssisted ventilation Supplemental oxygenSupplemental oxygen CORRECTION OF HYPOTENSION WITH CORRECTION OF HYPOTENSION WITH
DOPAMINE DOPAMINE
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ANTIDOTE TREATMENT: FLUMAZENILANTIDOTE TREATMENT: FLUMAZENILFlumazenil –reversing the coma induced by Flumazenil –reversing the coma induced by benzodiazepines.benzodiazepines.Mode of action – competitive antagonism specifically at Mode of action – competitive antagonism specifically at bezodizepine receptor sitebezodizepine receptor siteHas no effect on barbiturate, ethanol or other sedative toxicityHas no effect on barbiturate, ethanol or other sedative toxicityComplete reversal of benzodiazepine effect usually with a Complete reversal of benzodiazepine effect usually with a total slow iv dose of 1mg.total slow iv dose of 1mg.Administered in a series of smaller doses beginning with 0.2 Administered in a series of smaller doses beginning with 0.2 mg & progressively increasing by 0.1- 0.2 mg every minute mg & progressively increasing by 0.1- 0.2 mg every minute until a cumulative total dose of 3.5 mg is reached.until a cumulative total dose of 3.5 mg is reached.Duration of action only 2-3 hrs, thus resedation occurs within Duration of action only 2-3 hrs, thus resedation occurs within ½ hr – 2 hrs. ½ hr – 2 hrs. Thus repeat doses are required.Thus repeat doses are required.
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