Paracetamol and sedative overdosage

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PARACETAMOL & SEDATIVE OVERDOSAGE

OVERVIEW

• Considered to be a safe and cheap analgesic/anti-pyretic

• OTC• One of the most common overdosed drugs

worldwide• Most common cause of acute hepatic failure

in the UK & US

OVERVIEW

• Leading indication for hepatic transplantation in patients with drug induced liver disease

• Single dose of 10- 15 G can produce clinical evidence of liver injury

• Fatal fulminant liver failure is usually associated with a dosage of > 25 G

OVERVIEW

• Blood levels of > 30 micg/ml 4 hours after ingestion are predictive of severe hepatic disease

• Levels < 15 micg/ ml are predictive of low risk• More risk of damage if liver is already

damaged by infection (virus), alcohol or other illness

OVERVIEW

• Available as suppositories- 120,125,325 & 650 mg

• Chewtabs- 8 mg• Pedtabs - 16 mg• Regular tabs- 325 mg• Extra strong tabs- 500, 650, 1000 mg• Drops, suspension

OVERVIEW

• Maximum permissible daily dose : 4 g• Now has been reduced to 3 g

CLINICAL FEATURES

• Nausea, vomiting, diarrhoea, abdo minal pain, shock- first 24 to 48 hours

• Once these symptoms abate, features of hepatic injury appears.

• Maximum derangement & hepatic failure occurs around day 6

• SGOT/PT maybe raised around 10000

CLINICAL FEATURES

• Coma, convulsions, irritability, seizures• Renal failure • myocarditis

PROGNOSIS

• Depends on

• Quantity ingested• Timing of initiation of treatment• Pre-morbid health

TREATMENT

• Supportive measures• Airway• Breathing circulation• Gastric lavage- oral administration of activated

charcoal/ cholestyramine to prevent the absorbtion of the residual drug

• Not useful if given > 3 min after ingestion

TREATMENT

• Levels> 200 micg/ml after 4h• Or 100 micg/ml after 8 hours are indications• Administration of sulfhydril

compounds( cystamine, cysteine or NAC) reduces the severity of hepatic necrosis.

• They work by acting as a reservoir of – SH groups that bind to the toxic metabolytes or stimulate the synthesis/ repletion of hepatic glutathione

TREATMENT

• Must be given within 8 hours and maybe effective upto as late as 24 to 36 hours

• Dose of NAC- 140 mg/kg stat followed by 70 mg/kg Q4h for 15 to 20 doses

• If evidence of hepatic failure occurs while on treatment with NAC, consider LT

• Lactate levels > 3.5 mmol/L is a fair indicator of the need for LT

PREVENTION

• Keep all medications out of reach of children• Know the correct dosage• Never mix medicines containing acetaminophen

with other drugs• Remove all medications out of reach of adults if

there is a past/ family history of suicide/attempt• Avoid PCM in those who consume > 3 units of

alcohol/day

BARBITURATE OVERDOSAGE

• Earliest class of hypnotic-sedatives to be developed

• Marilyn Monroe & Judy Garland famous victims• Lethal dose varies according to individual

tolerance (2-10 G is potentially fatal)• With other CNS depressants like alcohol,opiates

or BZD, the severity of barbiturate overdosage is amplified.

• Depresses CNS & respiration

BARBITURATE OVERDOSAGE

• SIGNS & SYMPTOMS• Sluggishness, incoordination• Difficulty in thinking, slow speech• Faulty judgement, drowsiness• Shallow breathing, staggering• Apnea, hypoxia

BARBITURATE OVERDOSAGE

• ARDS• Paranoia• Combativeness• Tachycardia, bradycardia, hypotension, Shock• Coma, death

BARBITURATE OVERDOSAGE

• SIGNS• Hypothermia• Depressed pupillary reflex• Nystagmus• Squint• Supressed DTR

BARBITURATE OVERDOSAGE

TREATMENTSupportive care/ decontamination/Accelerate

eliminationSecure airwayEndotracheal intubation- if depressed sensorium,

respiratory failure, hypoxia, raised ICT O2 Venous access

BARBITURATE OVERDOSAGE

• Naloxone 2 mg. IV to all with depressed sensorium

• Measure rectal temperature- rewarming measures

• Pressors- noradrenaline, dopamine, fluids• Decontamination- activated charcoal 1G/kg

Q6H• Cathartics, gastric lavage

BARBITURATE OVERDOSAGE

Alkalinise urineSodabicarb 1 meq/kg folowed by continuous

infusonAdd 100- 150 meq of NaHco3 to 850 ml of D5 %Dialysis- hemofiltration preferred over HDIntravenous lipid emulsion (ILE) is emerging as

an antidote

TRICYCLIC ANTIDEPRESSANTS

• One of the most dangerous drugs• Anti-cholinergic and cardiac depressant

properties(Quinidine like NA+ channel blockade)

• Newer anti-depressants like sertraline, fluoxetine, fluvoxamine, citalopram, bupropion, trazodone, venlaflaxine etc. are structurally unrelated to TCAD and produce less cardiotoxicity

TRICYCLIC ANTIDEPRESSANTS

• They can produce seizures & serotonin syndrome

• S & S may occur abruptly in around 30-60 minutes

• Anti-cholinergic effects- dilated pupils, tachycardia, dry mouth, flushed skin, fasciculations & reduced peristalsis

TRICYCLIC ANTIDEPRESSANTS

• Cardiotoxicity- widens QRSc leading to ventricular arrhythmias, AV block, and hypotension

• Prolonged QT – Venlaflaxine, Citalopram• Severe intoxication- coma, seizures especially

Venlaflaxine & Bupropion• Hyperthermia- due to anticholinergic induced

reduced sweating

TRICYCLIC ANTIDEPRESSANTS

• Diagnosed by the combination of anticholinergic side effects & prolonged QRSc with seizures

• Degree of widening of the QRSc corelates directly with the severity of intoxication rather than the drug levels

• Serotonin syndrome- agitation, delirium, muscular hyperactivity, fever

TRICYCLIC ANTIDEPRESSANTS

• TREATMENT• Observe all cases for atleast 6 hours• Admit all patients with anti-cholinergic effects

or cardiotoxicity• Activated charcoal, gastric lavage• Cannot be removed by dialysis as they are

highly tissue bound

TRICYCLIC ANTIDEPRESSANTS

• SPECIFIC TREATMENT• NAHCO3 50 to 10 meq IV- alleviates the NA –

channel depressing effect• Maintain pH between 7.45- 7.50• IV MG or overdrive pacing for long QT sy

ndrome/Torsades de pointes• Serotonin syndrome- Benzodiazepines,

cyproheptadine 4 mg P/O 3 to 4 doses

TRICYCLIC ANTIDEPRESSANTS

• Severe hyperthermia

• neuromuscular paralysis• External cooling• intubation