Poisoning and Overdose have increased in recent times at exponential ratio, and most cases are with the initial attempt to harm oneself. this is very unfortunate. This presentation will help doctors and other health workers to be able to determine how to assist a patients who had overdosed on dangerous substances.

1. POISONING
AND
OVERDOSE
PRESENTED BY DR KD DELE
DEPT OF FAMILY MEDICINE

2. INTRODUCTION
Poisoning refers to the development of dose-related adverse effects
following exposure to chemicals, drugs.
Poisonings can be classified as:
◦ Self-harm or suicide
◦ Assault or homicide
◦ Unintentional or accidental, when no harm was intended – e.g. drug
misuse, drug abuse, taking too much of a drug for medical reasons

3. INTRODUCTION
A poisoning occurs when a person’s exposure to a natural or manmade
substance has an undesirable effect - CDC
The most common method of deliberate self-harm is by acute poisoning.
Most cases of acute poisoning are acts of deliberate self-harm in the adult.
They are usually accidental in children.

4. INTRODUCTION
All cases are initially managed as medical emergencies.
They require substance identification, risk assessment, resuscitation,
specific and non-specific treatment, and a period of observation.
Thereafter cases will require psychiatric assessment.
Remember that an apparently trivial act of self-harm may still indicate
serious suicidal intent

5. POISONING /OVERDOSETRENDS

6. POISONING /OVERDOSETRENDS
Among children under age 6, pharmaceuticals account for about 40% of
all exposures reported to poison centres
Men were 59% more likely than women to die
Whites had the highest death rate, followed by American Indians/Alaska
natives and then blacks
Highest death rate was among people 45-49 years of age
Lowest death rates were among children less than 15 years old

7. POISONING /OVERDOSETRENDS
Of the 22,767 deaths relating to pharmaceutical overdose in 2013,
◦ 16,235 (71.3%) involved opioid analgesics
(also called opioid pain relievers or prescription painkillers), and
◦ 6,973 (30.6%) involved benzodiazepines
Benzodiazepines are frequently found among people treated in EDs for
misusing or abusing Drugs
People who died of drug overdoses often had a combination of
benzodiazepines and opioid analgesics in their bodies

9. INITIALAPPROACH
Acute management in casualties include the following:
◦ Primary survey
◦ Toxicology history
◦ Adjuncts to primary survey
◦ Secondary survey
◦ Adjuncts to secondary survey
◦ Decontamination and elimination

10. RESUSCITATION
Presentation at casualties differ from person to person
Often non-specific
May range from perfectly stable patient to comatose patient. Sometimes DOA
You may get the history that the patient had overdosed on “something”
You may not get the exact drugs or the quantity overdosed
You may not get the history of having ingested toxin or overdosed on any drugs
High index of suspicion
“TOXIDROMES” are helpful

11. PRIMARY SURVEY:AIRWAY
LOOK LISTEN FEEL MANAGE
Airway protection:
◦ Intubation if necessary
◦ Anticipate vomiting
◦ Have effective suctioning

12. PRIMARY SURVEY: BREATHING
LOOK LISTEN FEEL MANAGE
Don’t forget universal antidotes
◦ (e.g. naloxone in benzos)
Patient not maintaining saturation:
◦ will need ventilatory support; start facemask; intubate
ARDS:
◦ high-flow oxygen, positive pressure ventilation, PEEP
Manage Hypoxia
◦ Ventilatory failure
◦ Bronchospasm
◦ Pulmonary oedema

13. PRIMARY SURVEY: CIRCULATION
LOOK LISTEN FEEL MANAGE
Secure venous access 2xLarge bore IV (18G)
While getting access draw blood for tests and HGT
Monitor BP, HR
ECG
Urinary catheter to monitor urine output
hypotension: fluids only, (vasopressors rarely)
hypertension: vasodilators, CCBs, BZDs

14. TACHYCARDIA
TCA
Phenothiazine
Theophylline
Chloral Hydrate
Any stimulant
SSRIs
SNRIs
BRADYCARDIA
Cholinergics
Beta Blockers
CCBs
Digoxin
Opiates
Sedative/hypnotics
Alpha agonists
GHB

15. PRIMARY SURVEY: DISABILITY
Seizure control
◦ benzodiazepine, phenytoin, phenobarbital, thiopentone
◦ INH induced seizures- pyridoxine
◦ paralyzing agents/muscle relaxants may be needed initially to control
prolonged seizures (e.g. pancuronium)
GCS
Focal neurology
PUPILS – size and reaction to light

16. PRIMARY SURVEY: EXPOSURE
Take off all clothes part of decontamination
Warm/cool, patient
Look for signs of trauma: head trauma important
Look for signs of medical illness
Look for body packing/stuffing
Look for toxidromes = constellations of signs and symptoms associated
with a class of toxin

17. ADJUNCTSTO PRIMARY SURVEY
ECG
Saturation monitor and cyclic BP measurements
ABG
Bloods: FBC, UEC, LFT,Toxicology screen, BhCG in females
Urine toxicology screen
Universal antidotes (if indicated)
◦ Oxygen
◦ Thiamine: 100mg IV/IM
◦ Dextrose: 1g/Kg (D50W in adults, D25W in paeds.)
◦ Naloxone: 2mg bolus IV/IM/SL/SC/ETT then 10mg repeat if no effect (paeds:
0.01mg/kg bolus then 0.1mg/Kg repeat)

18. SECONDARY SURVEY
Full head-to-toe examination:
look for
◦ Accurate vital signs (essential)
◦ Level of consciousness
◦ HR, BP, temp
◦ Pupils
◦ Skin
◦ Bowel sounds
◦ Reflexes, rigidity
Look for toxidromes
Look for trauma
Look for signs of medical illness
drug or toxin

19. TOXICOLOGICAL HISTORY
Obtain specific information from the patient, witnesses, and ambulance
personnel regarding:
Overdose details:
What, when, route, dose, co-ingested drugs, why?
Identify pills
◦ OldTTO charts; Ask family/friends; Drugs in the house; Containers;
Search patient – packing/stuffing
Consider body packing/stuffing if drug unknown
Specifically ask about SLOW - RELEASE preparations

20. TOXICOLOGICAL HISTORY
Obtain specific information from the patient, witnesses, and ambulance
personnel regarding:
Pharmaceutical agent or toxin ingested
(Remember that two or more drugs are taken in 30% of cases, and alcohol is a
common adjunct.)
Quantity of agent ingested (look for empty blister packets or bottles).
Time since ingestion.
Corroborate the history in the cooperative patient, but do not be misled, as
information supplied may be incomplete or deliberately false.

21. TOXICOLOGICAL HISTORY
Other relevant specific information from the patient, witnesses, and ambulance
personnel :
History of any toxic effects experienced from the poisoning.
Specific events prior to arrival in the emergency department (ED), such as:
◦ rapid deterioration in conscious level
◦ seizures.
Clinical features on presentation.

22. TOXICOLOGICAL HISTORY
Ambulance should bring all prescription bottles
Look through medications on old chart
Ask family/friend about possible medication/drugs
Ask what else is available in the house (INH example)
Bring in containers
Search the patient
Have family or police search the patient’s house

23. DIAGNOSTIC STUDIES
FBC, U&E, LFT, ABG, BHCG in females
S-Glucose, S-Tox screen
U-Tox Screen
ECG with cardiac monitoring

24. ADJUNCTSTO SECONDARY SURVEY
DECONTAMINATION
Gastric lavage
Induced vomiting
Activated charcoal
Shower
Irrigation
Whole bowel irrigation
ELIMINATION
Alkalinisation
Dialysis

25. DECONTAMINATION
What is decontamination?
Decontamination is the prevention of absorption into the bloodstream
Factors to consider:
◦ Is this a dangerous toxin?
◦ Is there likely to be further absorption?
◦ How long from the time of ingestion?
◦ Is there an effective antidote?
◦ Has the clinical course excluded the possibility of toxicity?

26. DECONTAMINATION
Drugs that SLOW gastric emptying and increase the possible time for gastric
emptying to be effective
◦ Anticholinergics
◦ Opiates
◦ Sedative/hypnotics

27. DECONTAMINATION
Methods of decontamination include:
InducedVomiting
Gastric Lavage
Shower
Cathartics
Whole bowel irrigation

28. DECONTAMINATION:
InducedVomiting
Never indicated
High risk of aspiration
Risk of oesophageal rupture
Unlikely to remove significant amount of toxin

29. DECONTAMINATION:
Gastric Lavage
The amount of toxin removed by gastric lavage is unreliable and often
negligible.
Risks often outweigh the benefit of this procedure.
Likely to have equal or greater efficacy when used with activated charcoal
American College of Emergency Physicians policy statement: little to indicate
value; selective use only.

30. DECONTAMINATION:
Gastric Lavage
Indications:
◦ No universal indications can be given
◦ Case-by-case consideration is appropriate
◦ Useful for drugs that slow gastric emptying e.g. opiates, anticholinergics,
sedatives
◦ Time since ingestions < 1-2 hours

31. DECONTAMINATION:
Gastric Lavage
CONTRAINDICATIONS:
Initial resuscitation not yet complete
Corrosive ingestion
Hydrocarbon ingestion
Unprotected airway: decreased LOC
POTENTIALCOMPLICATIONS
Injury to pharynx
Esophageal tears
Gastric perforation
Aspiration
Potentially lethal overdose, NO
effective antidote

32. DECONTAMINATION:
Gastric Lavage
Technique ofGastric Lavage
◦ Large gastric tube (36 French gauge)
◦ Left lateral position
◦ Tap water or saline
◦ 300 cc in, clamp, drain by gravity
◦ Continue until clear; follow lavage with activated charcoal

33. DECONTAMINATION:
Activated Charcoal
Decrease absorption
Lower peak serum levels
Beneficial only if substance still in GI tract

34. DECONTAMINATION:
Activated Charcoal
Indications:
All cases of potentially toxic overdoses
More effective earlier but history is so inaccurate, reasonable to give even with
later presentations
Consider using for overdose of toxin that doesn’t bind charcoal b/c of possibility
of co-ingestant.
Given even if late presentation

35. DECONTAMINATION:
Activated Charcoal
Dose
◦ No universal correct dose; no maximum dose known
◦ Ideal charcoal : drug ratio is 10 : 1
◦ Most common initial doses: 0.5 - 1.0 g/kg (Adults = 50 gm)
◦ Use larger doses (1.5 - 2.0 g/kg) for dangerous large ingestions of agents well
absorbed by charcoal:ASA, theophylline, verapamil.

36. DECONTAMINATION:
Activated Charcoal
DRUGSABSORBED BY AC:
◦ Aspirin
◦ Paracetamol
◦ TCA
◦ Digoxin
DRUGS NOTABSORBED BY AC :
◦ C Caustics
◦ H Hydrocarbons
◦ I Iron
◦ L Lithium, Lead
◦ E Ethanol

37. DECONTAMINATION:
Activated Charcoal
CONTRAINDICATIONS
Caustic ingestions: doesn’t bind,
obscures endoscopy
Unprotected airway
Hydrocarbons: increased risk of
aspiration andARDS
COMPLICATIONS
Very safe
GI upset
Bowel obstruction: case reports with
MDAC(multiple dosages)
Aspiration is biggest risk
◦ Trivial aspiration very common
◦ Significant aspiration rare

38. DECONTAMINATION:
Cathartics
Purgative agent
Increase GI transit speed, decrease transit time
No proven benefit
Effect on activated charcoal: occasionally beneficial, usually no effect.

39. DECONTAMINATION:
Cathartics
Three commonly used cathartics:
Sorbital: 1 gm/kg; repeat dose X 1 only at 0.5 mg/kg with MDAC if no
ileus/obstruction
Magnesium sulfate,
Magnesium citrate
No evidence of harm for single use if no contraindications

40. DECONTAMINATION:
Cathartics
COMPLICATIONS:
◦ Dehydration
◦ Electrolyte changes
◦ Abdominal distension
◦ GIT upset
◦ Children have more problems with
fluid and electrolyte shifts
CONTRAINDICATIONS:
◦ Bowel obstruction
◦ Ileus

41. DECONTAMINATION:
Whole Bowel Irrigation
Polyethylene glycol electrolyte lavage solution (PEG-ELS)
This is both electrolyte and osmolality balanced (isotonic components)
Thus no fluid/electrolyte shifts
Not dangerous even at huge volumes
Huge volumes are not dangerous
Components are not absorbed
Mechanical washout of bowel (doesn’t draw in fluid or stimulate motility)

42. DECONTAMINATION:
Whole Bowel Irrigation
INDICATIONS:
Serious overdose
Poor binding to activated charcoal
Sustained release
INDICATED FOR FOLLOWING DRUGS:
Iron
Lithium
Body packers
Body stuffers
Slow release preparations
ASA
CCBs
Valproic acid

43. DECONTAMINATION
Shower
For Dermatological exposure

44. ELIMINATION
Haemodialysis
Alkalinisation of serum
Ion trapping (alkalinisation of urine)

45. ELIMINATION:
Haemodialysis
Advantages:
◦ Corrects acid-base abnormalities
◦ Corrects electrolyte abnormalities
◦ Potential to clear large amount of drug

46. ELIMINATION:
Haemodialysis
TOXINSWELL REMOVED:
◦ Methanol
◦ Ethylene glycol
◦ ASA
◦ Lithium
◦ Valproic acid
◦ Theophylline
DIALYZABLE DRUGS:
◦ Low volume of distribution
◦ Low protein binding
◦ Small molecular weights
◦ Water soluble
◦ Single compartment kinetics
◦ Low endogenous clearance

47. ELIMINATION:
Alkalinisation of Serum
Changing serum pH in some cases increase binding of drug to albumin.
◦ Example:TCA
◦ pH from 7.45 to 7.5
◦ albumin binding from 95% to 96%
◦ free drug from 5% to 4%
◦ 20% reduction
Use IV Sodium bicarbonate

48. ELIMINATION:
Alkalinisation of Urine
IV Sodium bicarbonate
Urine pH>7.5
ASA in alkalinised form is not reabsorbed well
Ionisation constant pKa is a logarithmic function – small change in urine pH will
have a disproportionately larger effect on clearance of ASA

49. TOXIDROMES

50. CLINICAL MANIFESTATION:
TOXIDROMES
Toxidromes constellations of signs and symptoms commonly associated
with certain classes of drug/toxins.
These classes of drugs include: anticholinergics, cholinergics, opioids, and
sympathomimetics
Often identified with a basic history and physical examination
Rapid identification of the toxidrome saves time in evaluating and
managing a poisoned patient

51. TOXIDROMES
Toxidrome Clinical Manifestation Agents commonly involved
1. Anticholinergic • Hyperthermia, tachycardia,
hypertension
• Agitation, delirium, seizures
• Mydriasis
• Decreased bowel sounds
• Nonselective antihistamines
•Tricyclic antidepressants
• Antipsychotic drugs
• Benztropine
• Scopolamine, atropine
• Jimsonweed, deadly
nightshade, amanita muscaria
2. Cholinergic –
Nicotinic / Muscarinic
• Bradycardia(M),Tachycardia(N)
• Hypertension (N)
• Miosis
• Bronchorrhea
• Salivation, Lacrimation,
Urination, Diarrhoea, GI upset,
Emesis – “SLUDGE”
• Organophosphates
• carbamates
• Physostigmine
• Pilocarpine
• Betel nut
• Mushrooms: clitocybe dealbata,
C. illudens, Inocybe lacera
• Black widow spider venom (N)

52. TOXIDROMES
Toxidrome Clinical Manifestation Agents commonly involved
3. Sympathomimetic • Hyperthermia, tachycardia,
hypertension
• Agitation, delirium, seizures
• Mydriasis
• Increased bowel sounds
• Dry, flushed skin
• Cocaine, amphetamines
•Theophylline, caffeine
• Salicylates
• Monoamine oxidase (MAO)
inhibitors
• Sedative/hypnotic withdrawal
4. Opioid • Hypopnea/bradypnea
• Lethargy, obtundation
• Miosis
• All opiates and phenothiazines
• Hypoglycaemic agents
• Clonidine
5. Sedative-hypnotic • Hypothermia, bradypnea/
hypopnea
• Lethargy, stupor, obtundation
• Ethanol
• Benzodiazepines, barbiturates
• Meprobamate, methaqualone,
chloral hydrate

53. 1.AnticholinergicToxidrome

54. AnticholinergicToxidrome
Examples:
◦ Atropine
◦ antiepileptics
◦ anti psychotics: haloperidol , olanzapine,
◦ TCA’s amitriptyline
◦ eyedrops cyclopentolate
Mechanism of action:
◦ drugs have a affinity receptors blocking muscarinic receptors
Antidote:
◦ reversal ach inhibitor – physostigmine

55. 2.OpiateToxidrome

56. OpiateToxidrome
Examples:
◦ Pethidine Codeine Morphine
◦ Heroin tramadol
Mechanism of action: mu kappa and delta receptors
Antidote:
Naloxone
◦ Initial bolus of 100mq IVI or 400mg IMI
◦ Repeat boluses until adequate respiration
◦ Infusion 2/3 initial dose required to wake up patient per hour

57. 3. Sedative-HypnoticToxidrome

58. HypnosedativeToxidrome
Examples:
Ethanol, barbiturates, benzodiazepine, zolpidem, insomnia drugs.
Mechanism of action:
works on the GABA receptors
Antidote:
flumazenil not to be used.
Supportive. Fluids.
Monitoring. Intubate if necessary

59. Ethanol Intoxication: Management
Airway assessment and observation of the development of respiratory function
should be done.
Prevention of aspiration is also mandatory; therefore, placement of the patient
in a lateral position may be helpful/Antiemetic – Maxolon
IV- fluids, electrolyte and dextrose correction

60. Ethanol Intoxication: Management
In current clinical practice:
a protocol intravenous solution containing dextrose, magnesium, folate,
thiamine, and multivitamins is used
(e.g., a premixed intravenous solution of 1 l of 5% dextrose and 0.45% sodium
chloride, 2 g of magnesium sulphate, 1 mg of folate, and 100 mg of thiamine)
Metadoxine appears to be able to accelerate ethanol due to several
mechanisms including an increase in acetaldehyde dehydrogenase activity ,
ethanol and acetaldehyde plasma clearance, and urinary elimination of
ketones.

61. Ethanol Intoxication:Withdrawal
Article in clinical pharmacology and therapeutics In a double blind trial:
Diazepam and supportive care vs placebo and supportive care
Greater and more rapid improvement in diazepam group.
20mg every 2hours
All who was treated with diazepam were cured
72% treated in 6 doses median dosage to asymptomatic 3 doses no
complications
56% only supportive and placebo treatment were cured

62. Ethanol Intoxication: Suggested
regimen
Diazepam, 5 mg intravenously (2.5 mg/min).
If the initial dose is not effective, repeat the dose in 5 to 10 minutes.
If the second dose of 5 mg is not satisfactory,
10 mg for the third and fourth doses every 5 to 10 minutes.
If not effective, use 20 mg for the fifth and subsequent doses until sedation is
achieved.
Use 5 to 20 mg every hour as needed to maintain light somnolence.

63. 4.CholinergicToxidrome

64. CholinergicToxidrome
Examples:
organophosphate poisoning
insecticides
Mechanism of action:
increase acetylcholine activity centrally and peripherally.
Acetylcholine esterase inhibitors :
Acetylcholine agonists
Accumulation of acetylcholine at M-receptors

65. Cholinergic:
Organophosphate Management
Management e.g. ORGANOPHOAPHATE
Decontaminate
Resuscitate
Treat seizures

66. Cholinergic:
Organophosphate Management
•Atropine
◦ Antimuscarinic
◦ 0.5-2mg IVI initially the double dose every 5 minutes
◦ Until signs of atropinisation (decrease secretions, wheezing and increased
PR)
•Pralidoxime
◦ Regenerate enzyme activity
◦ Give immediately
◦ 1-2g initial bolus over 5-10 minutes then continuous infusion (20-40mg/kg)
over 24hrs.

67. Organophosphate Management
Special investigations
• Plasma-Pseudocholinesterase
• RBC-Acetylcholinesterase
• FBC, UCE, Glucose, LFT, ECG, CXR etc.

68. Organophosphate Management
Special Consideration In Management
◦ AVOID DIRECT CONTACT WITH PATIENTS
◦ Special attention to Respiratory muscle weakness and early intubation
◦ Do Not use Scoline
◦ Ventilation
◦ If Asymptomatic, monitor for at least 8-12 hours - especially after skin exposure
◦ Rebound Phenomena :T1/2 of Organophosphates longer than Atropine
◦ Give infusion of 20mg in 200ml Saline 8hrly

69. 5. SympathomimeticToxidrome

70. SympathomimeticToxidrome
Examples:
Cocaine, Amphetamines, Ritalin,
LSD, MDMA, MOA,
Caffeine, Theophylline, Salicylates
Mechanism of action:
sympathetic nervous system- directly or indirectly affecting catecholamines

71. SympathomimeticToxidrome
Management:
hypertension and tachycardia – benzodiazepines, not b blockers;
Rx seizures and agitation:
Rx hyperthermia,
fluids over 39.5
intubate
external cooling
ECG

72. SympathomimeticToxidrome:
Theophylline (COPD drug)
Competitive inhibitor of Phosphodiesterase isoenzymes
Actions in the body
◦ Relaxation of bronchial smooth muscle
◦ Positive Inotrope
◦ Increase Blood Pressure
◦ Increase Renal Blood flow
◦ Stimulation of respiratory centre
◦ Anti-inflammatory

73. SympathomimeticToxidrome:
Theophylline (COPD drug)
Narrow therapeutic index
Toxic dose:
◦ >50mg/kg
◦ Level >100mg/L
Serum levels serial samples very important every 2 – 4hrs
Sustained release formulations (delayed damage)
Monitor trend
ALWAYS ask for absolute value if positive on toxic screen

74. Theophylline: Clinical presentation
Acute
Gastrointestinal:Abdominal Pain;Vomiting (Haematemesis)
Musculoskeletal:Tremor, Anxiety
Cardiovascular:Arrhythmias; Tachycardia
Metabolic: Hypokalaemia, Hypophosphatemia, Hyperglycaemia, Metabolic
acidosis
High doses: Hypotension, ventricular arrhythmias, seizures (Resistant to anti-
epileptics)

75. Theophylline: Clinical presentation
Acute
Gastrointestinal:Abdominal Pain;Vomiting (Haematemesis)
Musculoskeletal:Tremor, Anxiety
Cardiovascular:Arrhythmias; Tachycardia
Metabolic: Hypokalaemia, Hypophosphatemia, Hyperglycaemia, Metabolic
acidosis
High doses: Hypotension, ventricular arrhythmias, seizures (Resistant to anti-
epileptics)

76. Theophylline: Clinical presentation
Chronic
Vomiting
Tachycardia
Hypotension (rare)
Seizures at lower levels
NO metabolic derangements

77. Theophylline: Management
Initial resuscitation (ABCs)
Activated Charcoal
◦ Gastric lavage not necessary after AC administered.
◦ Can give repeated doses after sustained release ingestion.
Treat presenting symptoms as they occur
Hypokalaemia
◦ It is due to intracellular movement of potassium.
◦ Not due to deficit.
◦ Spontaneous resolution usually.
◦ KCL 20mmol in 1000ml over 8hrs (Arrhythmias)
Monitor levels and vitals closely for at least 16-18hours

78. Theophylline: ICU Management
ICU referral and Dialysis
◦ Status Epilepticus (Poor overall prognosis)
◦ S-level more than 400μmol/L (LVH ICU)
Intermediate syndrome:
◦ proximal neuropathy , atropine x, 4d-3weeks brainstem lesion , ventilatory
support
Delayed:
◦ 4days later- demyelinated fibres- spastic( ^ tone reflex clonus) upper limb
recovery

79. Seretonin SyndromeToxidrome
Dif dx:
◦ NMS (slower onset no neuromuscular excitation, lead pipe rigidity)
◦ Anticholinergic syndrome
Examples: SSRI’s SNRI’s TCA’s ecstasy and nmda, herbal meds like (st johns
wort), lithium
Mechanism of action: excessive stimulation of serotonin receptors
Management: supportive and might need intubation…iCU.; resolve within 24-
48hours

80. Neuroleptic malignant toxidrome
Mechanism of action
◦ Blocking of dopaminergic neurotransmission in mesolimbic, hypothalamic
pituitary pathways
First impressions: dystonic with abnormal posturing, mute and staring to the
wall, incontinent and doing abnormal involuntary movements.
Vitals: hyperthermic, tachycardic, hypertensive, breathing dysregular manner
Rest of O/E: Leadpipe rigidity, generalised bradykinesia
Lab results: elevated CK, leucoukocytosis

81. Neuroleptic malignant toxidrome
Management:
◦ Supportive
◦ May need intubation and paralysis if over 39.2degree
◦ Dantrolene-muscle relaxant in severe rigidity
◦ ECT if refractory
◦ Role of benzo’s controversial.

82. Paracetamol (selective cox 3 inhibitor)
Pharmacokinetics
◦ Rapid absorption
◦ Peak plasma concentrations reached 30-60min
◦ T1/2 : Therapeutic 2-4hrsToxic 4-8hrs.

83. Paracetamol (selective cox 3 inhibitor)
Acute
◦ >200mg/kg in children
◦ 6-7g in adults
◦ CYP450 induction lower doses
◦ INH, ETOH, Fasting, Malabsorption
Chronic toxicity
◦ Daily supratherapeutic dose for 2-8 days.
◦ Especially with CYP450 induction
◦ Renal injury

84. Paracetamol (selective cox 3 inhibitor)
Clinical presentation:
NB!!Time post ingestion
Early
Asymptomatic
Anorexia, N&V
RARE
Metabolic Acidosis an altered mental
status
24 – 48hrs
Depending on dose and patient
factors
Altered LFT (AST, ALT) {Hepatic
necrosis}
Acute Fulminant Liver failure

85. Paracetamol (selective cox 3 inhibitor)
Poor Prognostic clinical findings
Encephalopathy
Metabolic Acidosis
Increased PT

86. Diagnostics
Paracetamol levels;
Ideally 1st sample = 4hrs post
ingestion
Plot on nomogram :
When to start treatment
Baseline investigations :
Most important (U&E, AST, ALT,
PT, INR)

87. Management
Initial resuscitation
N&V (Nausea &Vomiting)
◦ use Maxolon IVI or
◦ 5HT3 blockersOndansetron
Gastric lavage and Activated Charcoal (1st hour)
N-Acetylcysteine (See box)
Repeat AST,ALT, UCE following day to monitor
progress.
Dialysis
◦ if Paracetamol is very high complicated with
Coma/Hypotension
N-Acetylcysteine
Within 8hrs almost 100%
hepatoprotective
Administer in 3 doses:
150mg/kg in 200ml 5% Dextrose over 1
hour
50mg/kg in 500ml 5% Dextrose over 4
hours
100mg/kg in 1000ml 5% Dextrose over
16 hours
Maintenance dose:
100mg/kg in 1000ml 5% Dextrose every
16hours