This document provides guidance on the evaluation and management of poisoning and overdose. It discusses evaluating asymptomatic vs symptomatic patients, prioritizing treatment of life-threatening complications, and managing common complications including coma, hypothermia, hypotension, hypertension, arrhythmias, seizures, and hyperthermia. It also reviews decontamination methods, antidotes, and other treatments such as activated charcoal, whole bowel irrigation, and hemodialysis.

1. POISONING

2. INITIAL EVALUATION: POISONING OR
OVERDOSE
• Patients with drug overdoses or poisoning may be asymptomatic or symptomatic.
• It is important to quickly assess the potential danger , consider gut and skin decontamination to
prevent absorption, treat complications if they occur and observe the asymptomatic patient for
an appropriate interval.
• Asymptomatic vs symptomatic.

3. THE SYMPTOMATIC PATIENT
• In symptomatic patients, treatment of life threating complications rather than depth diagnostic
evaluation.
• Most common complications that occur: Coma, Hypothermia, Hyperthermia, Hypotension,
Hypertension, Arrhythmias and Seizures

4. Coma
Assessment and complications
• It is commonly associated with ingestion of large doses of antihistamines (eg,
diphenhydramine), benzodiazepines, and other sedative-hypnotic drugs, ethanol, opioids,
antipsychotic drugs, or antidepressants.
• It may cause complications include Respiratory failure, pulmonary aspiration of gastric contents,
hypoventilation and hypoxia .
• To prevent above complications, protection of airway and assisted ventilation

5. Coma
Treatment( Emergency management):
• Initial management of coma by remember word (ABCD). A: airway, B: breathing, C: circulation,
D: drugs(dextrose, thiamine, and naloxone or flumazenil).
• Airway by insertion of an artificial nasal or oropharyngeal airway and endotracheal intubation .
• Breathing: assess the quality and depth of respiration and provide assistance if necessary with a
bag-valve-mask device or mechanical ventilator. O2 may needed.

6. Coma
• Circulation: measure HR, BP, continuous ECG monitoring and estimate tissue perfusion. In addition, do
lab tests such as CBC, LFTs, Scr, electrolytes and drugs.
• Drugs
1. Dextrose and thiamine: give 50% dextrose(50-100ml) as IV bolus to all comatose patients unless blood
sugar test role out for hypoglycemia(BG< 70mg/dl). In alcoholic or very malnourished patients who may
have thiamine deficiency ,give thiamine 100 mg IV or IM.
2. Opioid antagonists: Naloxone, 0.4–2 mg IV, may reverse opioid-induced respiratory depression and coma.
May need additional dose (up to 5-10mg). Continuous monitoring for at least 3-4 hours after the last
dose.
3. Flumenazil: 0.2–0.5 mg intravenously, repeated as needed up to a maximum of 3 mg, may reverse
benzodiazepine-induced coma.

7. Hypothermia
Assessment and complications
• Typical Body temperature less than 35 ° C
• It is commonly accompanies coma due to opioids, ethanol, hypoglycemic agents,
phenothiazines, barbiturates, benzodiazepines, and other sedative-hypnotics and central
nervous system depressants
• It may cause or aggravate the HOTN that will not reverse until the temperature normalized.

8. Hypothermia
Treatment( Emergency management):
• Rewarming is initial treatment in all patient to prevent heat loss.
• Removing and replacing wet and cool clothes with dry and warm clothes ) or by active
external rewarming.
• active external rewarming involves applying external heat to the patient’s skin

9. Hypotension
Assessment and complications
• BP less than 90/60mmHg.
• It may be due to antihypertensive drugs such as B-blockers, CCBs, iron, trazodone, quetiapine,
disulfiram or poisoning form carbon monoxide, hydrogen sulfide, aluminum or zinc phosphide,
arsenic, and certain mushrooms.
• Hypotension can cause hypovolemia and depressed cardiac contractility
 Treatment
• Give isotonic crystalloid (NS or LR) up to (1-2) L as 200 ml IV bolus.
• If not response to fluid, administer NE or dopamine upon patient characteristic.

10. Treatment( cont. for HOTN)
• HOTN due to TCAs or other sodium channel blockers overdose can be treated with sodium
bicarbonate 50–100 mEq by IV bolus injection.
• NE 4–8 mcg/min is more effective than dopamine in some patients with TCAs overdose.
• For B-blocker overdose, glucagon (5–10 mg IV) may be of value.
• For calcium channel blocker overdose, administer calcium chloride, 1–2 g IV(repeated doses may
be necessary; doses of 5–10 g and more have been given in some cases.
• Intralipid 20% lipid emulsion in highly lipid-soluble drugs such as bupivacaine, bupropion,
clomipramine, and verapamil to improve hemodynamic status

11. Hypertension
Assessment and complications
• SBP > 130 or DBP > 80 mmHg
• It may be due to poisoning with amphetamines and synthetic stimulants, anticholinergics,
cocaine, products (containing caffeine, phenylephrine, ephedrine),monoamine oxidase (MAO)
inhibitors, and other drugs.
• sever HTN , DBP 105–110 mm Hg in a person who does not have chronic hypertension) can
result in acute intracranial hemorrhage, myocardial infarction, or aortic dissection.

12. Hypertension
Treatment
• Treat if the patient is symptomatic or if the DBP is higher than 105–110 mm Hg.
• Agitated or anxious patients may benefit from a sedative agent (lorazepam) or (haloperidol or
olanzapine).
• Persistent HTN administer phentolamine IV, or nitroprusside sodium IV. If excessive tachycardia is
present, add esmolol IV, or labetalol IV.
• B-blockers alone may worse HTN.

13. Arrhythmias
Assessment and complications
• They may occur with a variety of drugs or toxins.
• They may also occur as a result of hypoxia, metabolic acidosis, or electrolyte imbalance , or
following exposure to chlorinated solvents overdose. Atypical ventricular tachycardia (torsades de
pointes) is often associated with drugs that prolong the QT interval.

15. Arrhythmias
Treatment
• Correct hypoxia and electrolyte imbalance
• Ventricular arrhythmias persist, administer lidocaine or amiodarone.
• Wide QRS complex tachycardia due to TCAs overdose or diphenhydramine or class Ia
antiarrhythmic drugs give sodium bicarbonate, 50–100 mEq intravenously by bolus infusion.
• Torsades de pointes associated with prolonged QT interval may respond to intravenous
magnesium (2 g intravenously over 2 minutes)
• For tachyarrhythmias induced by chlorinated solvents or sympathomimetic agents, use
propranolol or esmolol.

16. Seizures
Assessment and complications
• It may be caused by many poisons and drugs, including amphetamines, antidepressants
(especially tricyclic antidepressants, bupropion, and venlafaxine), antihistamines (especially
diphenhydramine), antipsychotics, camphor, synthetic cannabinoids, cocaine, isoniazid (INH),
tramadol, and theophylline.
• It may be also, due to hypoxia, hypoglycemia, hypocalcemia, hyponatremia, withdrawal from
alcohol or sedative-hypnotics, head trauma, central nervous system infection, or idiopathic
epilepsy.
• Prolonged or repeated seizures may lead to hypoxia, metabolic acidosis, hyperthermia, and
rhabdomyolysis.

17. Seizures
Treatment
• Administer lorazepam, 2–3 mg, or diazepam, 5–10 mg IV, If no access for IV give midazolam, 5–
10 mg intramuscularly.
• If convulsions continue, administer phenobarbital, 15–20 mg/kg slowly IV over no less than 30
minutes.
• Propofol infusion effective for some resistant drug-induced seizures.
• Other antidotes and therapies can be recommended according to drug toxcicity.

19. Hyperthermia
Assessment and complications
• Typical Body temperature higher than 38 ° C
• It is a rapidly life-threatening complication, Severe hyperthermia >40°C can rapidly cause brain
damage and multiorgan failure, including rhabdomyolysis, AKI, and coagulopathy
• It may be due to amphetamines ,atropine and other anticholinergic drugs, cocaine, salicylates,
TCAs, and Antipsychotic agents . Overdoses or use of serotonin reuptake inhibitors

20. Hyperthermia
Treatment
• Removing the patient’s clothing, spraying the skin with tepid water.
• If the patient not response within 30-60 min or if there is significant muscle rigidity or hyperactivity
give nondepolarizing NMBAs such as( rocuronium, vecuronium). Once patient paralyzed must be
intubated and mechanically ventilated and sedated.
• Dantrolene (2–5 mg/kg IV) may be effective for hyperthermia associated with muscle rigidity that
does not respond to neuromuscular blockade. (malignant Hyperthermia).
• Bromocriptine, 2.5–7.5 mg orally daily for neuroleptic malignant syndrome.
• Cyproheptadine, 4 mg orally every hour for three or four doses, or chlorpromazine, 25 mg IV or
50 mg intramuscularly, has been used to treat serotonin syndrome.

21. ANTIDOTES & OTHER TREATMENT
• When there is an antidote available for specific drug give it right away but be aware of its side
effects.

22. Some toxic agents for which there are
specific antidotes.
Toxic Agent Specific Antidote
Acetaminophen N-Acetylcysteine
Anticholinergics (eg, atropine) Physostigmine
Anticholinesterases (eg, organophosphate pesticides) Atropine and pralidoxime (2-PAM)
Benzodiazepines Flumazenil (rarely used)
Snake venom Specific antivenin
Opioids Naloxone, nalmefene
Methanol, ethylene glycol Ethanol (ethyl alcohol) or fomepizole (4-methylpyrazole)
Isoniazid Pyridoxine (vitamin B6)
Heavy metals (eg, lead, mercury, iron) and arsenic Specific chelating agents
Digitalis glycosides Digoxin-specific Fab antibodies
Cyanide Sodium nitrite, sodium thiosulfate; hydroxocobalamin
Carbon monoxide Oxygen (hyperbaric oxygen of uncertain benefit)
Sulfonylurea oral hypoglycemic drugs Glucose, octreotide

23. DECONTAMINATION OF THE SKIN
• Corrosive agents can harm skin and eyes and should be rapidly removed.
• Wash the affected areas with water or saline.
• For oily substances (eg, pesticides), wash the skin at least twice with soap and shampoo the
hair.
• Specific decontaminating solutions or solvents (eg, alcohol) are not recommended b/c they
may enhance absorption.
• Dilute hypochlorite solution may be used in some cases, but not in the eyes.

24. DECONTAMINATION OF THE EYES
• Act quickly to prevent serious damage.
• Flush the eyes with saline or water.
• Remove contact lenses if present & put Local anesthetic drops if available
• Lift the tarsal conjunctiva to look for undissolved particles and to facilitate irrigation.
• Continue irrigation for 15 minutes or until each eye has been irrigated with at least 1 L of solution.
• In case of an acid or base toxin, continue irrigation until pH of the tears is 6-8.
• For alkali injuries an amphoteric decontamination solution (Diphoterine, Prevor) may be used.
• After irrigation is complete, perform a careful examination of the eye, refer to an ophthalmologist if

25. GASTROINTESTINAL DECONTAMINATION
• induced emesis or gastric lavage
• No improved outcomes after gastric emptying.
• For small or moderate ingestions of most substances, oral activated charcoal alone without
prior gastric emptying is recommended.
• In some cases, when the interval after ingestion has been more than 1–2 hours and the
ingestant is non–lifethreatening, even charcoal is withheld.
• Exceptions are large ingestions of anticholinergic compounds and salicylates, and ingestion of
sustained-release or enteric-coated tablets, which often delay gastric emptying and remain
intact for several hours.
• Gastric emptying is not generally used for ingestion of corrosive agents or petroleum distillates,
because further esophageal injury or pulmonary aspiration may result.

26. A. Activated Charcoal
• Effectively adsorbs almost all drugs and poisons.
• Poorly adsorbed substances include iron, lithium, potassium, sodium, mineral acids, and
alcohols.
• Indications can be used for prompt adsorption of drugs or toxins in the stomach and intestine.
• May provoke vomiting, which could lead to pulmonary aspiration in an unconscious patient.
• Contraindications should not be used 1) for convulsing patients unless its given in gastric tube
and the airway is protected by endotracheal tube. OR 2) for patients with ileus or intestinal
obstruction or 3) whom endoscopy is planned.
• Technique Administer activated charcoal, 60–100 g orally or via gastric tube, mixed in water.
Repeated doses may be given to ensure gastrointestinal adsorption or to enhance elimination of
some drugs.

27. B. Whole Bowel Irrigation
• large volumes of polyethylene glycol-electrolyte solution can mechanically cleanse the entire
intestinal tract.
• There is no significant gain or loss of systemic fluids or electrolytes.
• Indications used for massive iron ingestion in which intact tablets are visible on abdominal
radiographs. & ingestions of lithium, sustained-release and entericcoated tablets, and
swallowed drug-filled packets.
• Contraindications Do not use in patients with suspected intestinal obstruction. Use with
caution in patients who are unconscious or have depressed airway protective reflexes.
• Technique Administer a balanced polyethylene glycolelectrolyte solution into the stomach via
gastric tube at a rate of 1–2 L/h until the rectal effluent is clear.
• This may take several hours. It is most effective when patients are able to sit on a commode to
pass the intestinal contents.

28. C. Increased Drug Removal
• 1. Urinary manipulation
• Forced diuresis is dangerous; the risk of complications (fluid overload, electrolyte imbalance)
usually outweighs its benefits.
• Some drugs (eg, salicylates, phenobarbital) are more rapidly excreted with an alkaline urine.
• To alkalinize the urine, add 100 mEq (two ampules) of sodium bicarbonate to 1 L of 5% dextrose
in 0.2% saline, and infuse this solution intravenously at a rate of about 150–200 mL/h.
• Acidification (sometimes promoted for amphetamines, phencyclidine) is not very effective and is
contraindicated in the presence of rhabdomyolysis or myoglobinuria

29. • 2. Hemodialysis
• The indications for dialysis are as follows:
(1) known or suspected potentially lethal amounts of a dialyzable drug
(2) poisoning with deep coma, apnea, severe hypotension, fluid and electrolyte
or acid-base disturbance, or extreme body temperature changes that cannot be
corrected by conventional measures
(3) poisoning in patients with severe kidney, cardiac, pulmonary, or hepatic
disease who will not be able to eliminate toxin by the usual mechanisms.
• Continuous renal replacement therapy is of uncertain benefit for elimination
of most poisons but has the advantage of gradual removal of the toxin and
correction of any accompanying acidosis, and its use has been reported in the
management of lithium intoxication.

30. Recommended use of hemodialysis in poisoning
Poison Common Indications
Carbamazepine Seizures, severe cardiotoxicity; serum level > 60 mg/L
Ethylene glycol Acidosis, serum level > 50 mg/dL
Lithium Severe symptoms; level > 4–5 mEq/L, especially if kidney impairment
Note: dialysis of uncertain value; consult with medical toxicologist
Methanol Acidosis, serum level > 50 mg/dL
Phenobarbital Intractable hypotension, acidosis despite maximal supportive care
Salicylate Severe acidosis, CNS symptoms, serum level > 100 mg/dL (acute
overdose) or > 60 mg/dL (chronic intoxication)
Theophylline Serum level > 90–100 mg/L (acute) or seizures and serum level
Valproic acid Serum level > 900–1000 mg/L or deep coma, severe acidosis

31. • 3. Repeat-dose charcoal
• Studies have failed to prove better outcome using repeat dose charcoal.

32. DIAGNOSIS OF POISONING
• Physical examination & lab tests help in identifying the ingested toxin and treatment.

33. Syndromes present with
poisoning
Syndrome Clinical presentation Drugs
A.
Sympathomimetic
Syndrome
BP & HR & temperature are elevated
Reflex bradycardia
pupils are dilated, and the skin is sweaty, though mucous membranes are dry.
Patients are usually agitated, anxious, or frankly psychotic.
Examples: Amphetamines, cocaine, ephedrine,
pseudoephedrine, synthetic cathinones and
cannabinoids.
B. Sympatholytic
Syndrome
BP & HR & Temperature are decreased.
The pupils are small or even pinpoint
Patients are usually unconscious
Examples: Barbiturates, benzodiazepines and
other sedative hypnotics, gamma-
hydroxybutyrate (GHB), clonidine and related
antihypertensives, ethanol, opioids.
C. Cholinergic
Syndrome
Stimulation of muscarinic receptors causes bradycardia, miosis, sweating, and
hyperperistalsis as well as bronchorrhea, wheezing, excessive salivation, and
urinary incontinence.
Nicotinic receptor stimulation may produce HTN & tachycardia as well as
muscle weakness.
Agitated and anxious.
Examples: Carbamates, nicotine,
organophosphates , physostigmine.
D. Anticholinergic
Syndrome
Tachycardia & mild HTN, body temperature is often elevated. Dilated pupils.
The skin is hot, and dry. Peristalsis is decreased, and urinary retention is
common. Patients may have myoclonic jerking movements. Agitated delirium is
frequently seen.
Examples: Atropine, scopolamine, other naturally
occurring and pharmaceutical anticholinergics,
antihistamines, tricyclic antidepressants.

34. Laboratory Tests
• Measured serum osmolality and calculated osmol gap, electrolytes and anion gap, glucose,
creatinine, blood urea nitrogen (BUN), creatine kinase, urinalysis and electrocardiography.
• Quantitative serum acetaminophen and ethanol levels should be determined in all patients with
drug overdoses.

35. A. Osmol Gap
• Increases in the presence of large quantities of low-molecular-weight substances, most
commonly ethanol. Others are acetone, ethylene glycol, isopropyl alcohol, methanol, and
propylene glycol.

36. Use of the osmol gap in toxicology.
• Calculated osmolality =2[Na (mEq/L)] +
Glucose (mg/dL)
18
+
BUN (mg/dL)
2.8
• Delta osm = Measured osmolality – Calculated osmolality = 0 ± 10
• Serum osmolality may be increased by contributions of exogenous substances such as alcohols
and other low-molecular-weight substances.
• Since these substances are not included in the calculated osmolality, there will be a gap
proportionate to their serum concentration.

37. B. Anion Gap
• Metabolic acidosis associated with an elevated anion gap is usually due to an
accumulation of lactic acid or other acids.
• Common causes of elevated anion gap in poisoning include carbon
monoxide, cyanide, ethylene glycol, propylene glycol, medicinal iron, INH,
methanol, metformin, ibuprofen, and salicylates.
• Massive acetaminophen overdose can cause early-onset anion gap metabolic
acidosis.

38. C. Toxicology Laboratory Testing
• A comprehensive toxicology screen is of little value in the initial care of the
poisoned patient because results usually do not return in time to influence
clinical management.

39. Drug or Toxin Treatment
Acetaminophen Specific antidote (N-acetylcysteine) based on serum level
Carbon monoxide High carboxyhemoglobin level indicates need for 100% oxygen, consideration of hyperbaric oxygen
Carbamazepine High level may indicate need for hemodialysis
Digoxin On basis of serum digoxin level and severity of clinical presentation, treatment with Fab antibody
fragments (eg, DigiFab) may be indicated
Ethanol Low serum level may suggest nonalcoholic cause of coma (eg, trauma, other drugs, other alcohols);
serum ethanol may also be useful in monitoring ethanol therapy for methanol or ethylene glycol
poisoning
Iron Level may indicate need for chelation with deferoxamine
Lithium Serum levels can guide decision to institute hemodialysis
Methanol, ethylene glycol Acidosis, high levels indicate need for hemodialysis, therapy with ethanol or fomepizole
Methemoglobin Methemoglobinemia can be treated with methylene blue intravenously
Salicylates High level may indicate need for hemodialysis, alkaline diuresis
Theophylline Immediate hemodialysis or hemoperfusion may be indicated based on serum level
Valproic acid Elevated levels may indicate need to consider hemodialysis or L-carnitine therapy, or both

40. Abdominal Imaging
• A plain film (or CT scan) of the abdomen may reveal radiopaque iron tablets, or other toxic
material.
• Studies suggest that few tablets are predictably visible (eg, ferrous sulfate, sodium chloride,
calcium carbonate, and potassium chloride).

41. When to Admit
• •The patient has symptoms and signs of intoxication that are not expected to clear within a 6- to
8-hour observation period.
• Delayed absorption of the drug might be predicted to cause a later onset of serious symptoms
(eg, after ingestion of a sustained-release product)
• Continued administration of an antidote is required (eg, N-acetylcysteine for acetaminophen
overdose).
• Psychiatric or social services evaluation is needed for suicide attempt or suspected drug abuse.

42. Selected poisoning

43. Amphetamines and cocaine
• They are widely abused for their euphorigenic and stimulant properties.
• Both drugs may be smoked, snorted, ingested, or injected.
• Toxic dose of each drug is highly variable and depends on the route of administration and
individual tolerance.
• Clinical finding(symptoms) : anxiety, tachycardia, hypertension, diaphoresis, dilated pupils,
agitation, muscular hyperactivity, and psychosis. In severe intoxication, seizures and
hyperthermia may occur.
• chronic use may cause cardiomyopathy
• The diagnosis is supported by finding amphetamines or the cocaine metabolite
benzoylecgonine in the urine.

44. Amphetamines and cocaine
Treatment(Emergency and Supportive Measures):
• Maintain a patent airway and assist ventilation, if necessary.
• Treat seizures
• Treat hypertension.
• Treat tachycardia or tachyarrhythmias with a short-acting beta-blocker such as esmolol (25–100
mcg/kg/min by intravenous infusion).
• Treat hyperthermia
• Rapidly lower the body temperature in patients who are hyperthermic (temperature higher than
39–40°C).
• Give IV fluids to prevent AKI.

45. Anticoagulants
• Anticoagulants include vitamin k antagonist (warfarin), direct thrombin inhibitor (dabigatran,
argatroban, bivalirudin) and the factor Xa inhibitors (rivaroxaban, apixiban, and edoxaban).
• Toxicity may be due to overdose or accumulation of drugs in patient with renal impairment.
• Clinical finding: hemoptysis, gross hematuria, bloody stools, hemorrhages into organs and bleeding
into joint space

46. Anticoagulants
Treatment(Emergency and Supportive Measures):
• D/C drug that cause bleeding
• If warfarin obtain INR and PPT( increased within 12–24 hours after overdose of warfarin)
• No need for INR and PPT with DOAs
• If the patient has ingested an acute overdose, administer activated charcoal.
• Warfarin over dose: treat according to INR value.
• DOAs(dabigatran, rivaroxaban, apixiban, and edoxaban). Idarucizumab has been approved by
the FDA for reversal of the thrombin inhibitor dabigatran.
• andexanet remains under investigation for reversal of the factor Xa inhibitors (apixaban,
edoxaban and rivaroxaban). The efficacy of FFP and PCC Iis uncertain.

48. Carbon monoxide
• It is colorless, odorless gas produced by the combustion of carbon-containing materials.
• Poisoning may occur as a result of suicidal or accidental exposure to automobile exhaust, smoke
inhalation in a fire, or accidental exposure to an improperly vented gas heater.
• MOA carbon monoxide binds to hemoglobin result in reduced oxygen-carrying capacity and
altered delivery of oxygen to cells

49. Carbon monoxide
• Clinical finding(symptoms):
o With low level(10-20%): headache, dizziness, abdominal pain, and nausea.
o With higher levels(50-60%): confusion, Hypotension, coma, and seizures dyspnea, and
syncope may occur.
o Carbon monoxide poisoning should be suspected in any person with severe headache or
acutely altered mental status, especially during cold weather, when improperly vented
heating systems may have been used.
• Diagnosis depends on specific measurement of the arterial or venous carboxyhemoglobin
saturation. Levels of CO does not correlates with symptoms.

50. Carbon monoxide
Treatment(Emergency and Supportive Measures):
• Maintain a patent airway and assist ventilation, if necessary. Remove the victim from exposure.
Treat patients with coma, hypotension, or seizures.
• Administer 100% O2 by face-mask or endotracheal tube.
• Hyperbaric oxygen therapy (HBO) can provide 100% oxygen under higher than atmospheric
pressures .
• Indications for HBO in patients with carbon monoxide poisoning include a history of loss of
consciousness, CoHb greater than 25%, metabolic acidosis and age over 50 years.

51. ACETAMINOPHEN- Paracetamol
• Analgesic, found in prescription and non-prescription products.
• Metabolized by glucuronidation & sulfation & via the P450 mixed-function oxidase system
(2E1) to a highly toxic reactive intermediate.
• This toxic intermediate is normally detoxified by cellular glutathione.
• With acute acetaminophen overdose (greater than 150–200 mg/kg, or 8–10 g in an average
adult), hepatocellular glutathione is depleted and the reactive intermediate attacks other cell
proteins, causing necrosis.
• Patients with enhanced P450 2E1 activity, such as those who chronically abuse alcohol and
patients taking INH, are at increased risk for developing hepatotoxicity.
• Hepatic toxicity may also occur after overuse of acetaminophen—eg, as a result of taking
two or three acetaminophen-containing products concurrently or exceeding the
recommended maximum dose of 4 g/day for several days.
• The amount of acetaminophen in US oral prescription combination products is limited by
the FDA to no more than 325 mg per tablet.

52. Clinical findings
• Shortly after ingestion, patients may have nausea or vomiting, but there are usually no other
signs of toxicity until 24–48 hours after ingestion, when hepatic aminotransferase levels begin to
increase.
• With severe poisoning, fulminant hepatic necrosis may occur, resulting in jaundice, hepatic
encephalopathy, acute kidney injury, and death.
• Rarely, massive ingestion (eg, serum levels greater than 500–1000 mg/L [33–66 mmol/L]) can
cause early onset of acute coma, seizures, hypotension, and metabolic acidosis unrelated to
hepatic injury.
• The diagnosis after acute overdose is based on measurement of the serum acetaminophen level.

54. Treatment:
• A. Emergency and Supportive Measures Administer activated charcoal if it can be given within 1–2
hours of the ingestion. Although charcoal may interfere with absorption of the oral antidote
acetylcysteine, this is not considered clinically significant.
• B. Specific Treatment with N-acetylcysteine is indicated; it can be given orally or intravenously.
Oral treatment begins with a loading dose of N-acetylcysteine, 140 mg/kg, followed by 70 mg/kg
every 4 hours. Dilute the solution to about 5% with water, juice, or soda.
• If vomiting interferes with oral N-acetylcysteine administration, consider giving the antidote
intravenously.
• The conventional oral N-acetylcysteine protocol in the United States calls for 72 hours of
treatment.
• The FDA-approved 21-hour intravenous regimen of acetylcysteine (Acetadote) calls for a loading
dose of 150 mg/kg given intravenously over 60 minutes, followed by a 4-hour infusion of 50
mg/kg, and a 16-hour infusion of 100 mg/kg.
• Treatment with N-acetylcysteine is most effective if it is started within 8–10 hours after ingestion.
• Hemodialysis is indicated with massive overdose.

55. Methemoglobinemia inducing agents
• Agents are capable of oxidizing ferrous hemoglobin to its ferric state (methemoglobin), a form
that cannot carry oxygen.
• Agents include: benzocaine, aniline, propanil (an herbicide), nitrites, nitrogen oxide gases,
nitrobenzene, dapsone, phenazopyridine and others.
• Clinical finding(symptoms): dizziness, nausea, headache, dyspnea, confusion, seizures, and coma.
• Severity of symptoms depends on the percentage of hemoglobin oxidized to methemoglobin.
Severe poisoning occur when fraction higher than 40-50%.
• Sever metabolic acidosis may be present and hemolysis in patient with G6PDD .

56. Methemoglobinemia inducing agents
Treatment(Emergency and Supportive Measures):
• Administer O2 therapy
• If the causative agent was recently ingested, administer activated charcoal.
• Methylene blue, for symptomatic patients, administer 1–2 mg/kg (0.1–0.2 mL/kg of 1%
solution) intravenously. The dose may be repeated once in 15–20 minutes if necessary.
• Methylene blue not recommended in patient with hereditary methemoglobin reductase
deficiency or G6PDD.
• In sever cases , blood transfusion may be necessary.

57. Salicylates
• Salicylates (aspirin, methyl salicylate, bismuth subsalicylate)
• They uncouple cellular oxidative phosphorylation, resulting in anaerobic metabolism and excessive
production of lactic acid and heat, and they also interfere with several Krebs cycle enzymes.
• Single ingestion of more than 200 mg/kg of salicylate is likely to produce significant acute
intoxication. Poisoning may also occur as a result of chronic excessive dosing over several days

58. Salicylates
• Clinical finding(symptoms):
• Acute ingestion: nausea and vomiting, occasionally with gastritis.
• Moderate intoxication is characterized by hyperpnea (deep and rapid breathing), tachycardia, tinnitus, and elevated
anion gap metabolic acidosis
• Serious intoxication may result in agitation, confusion, coma, seizures, cardiovascular collapse, pulmonary edema,
hyperthermia, and death.
• Central nervous system intracellular glucose depletion can occur despite normal measured serum glucose levels
• Diagnosis poisoning is suspected in any patient with metabolic acidosis and is confirmed by measuring the
serum salicylate level.
• severe poisoning after an acute overdose , levels greater than 100 mg/dL
• subacute or chronic ntoxication may suffer severe symptoms with levels of 60–70 mg/dL
• respiratory alkalosis with an underlying metabolic acidosis.

59. Salicylates
Treatment(Emergency and Supportive Measures):
• Administer activated charcoal orally, for optimal efficacy ratio should be (10:1)(charcoal: poison),
administer over 24 hours every 2-4 hours. (by lexi 50-100g followed by 25-50 g every 4 hours) along with
whole bowel irrigation.
• If the patient ingest >10g aspirin should do gastric lavage followed by administration of extra doses of
activated charcoal.
• Give glucose-containing fluids(dextrose 5%+0.9%NS) to reduce the risk of cerebral hypoglycemia.
• Treat metabolic acidosis with intravenous sodium bicarbonate
• Alkalinization of the urine: Add 100 mEq (two ampules) of sodium bicarbonate to 1 L of 5% dextrose in
0.2% saline, and infuse this solution intravenously at a rate of about 150–200 mL/h. Unless the patient is
oliguric or hyperkalemic, add 20–30 mEq of potassium chloride.

60. Salicylates
Treatment (Cont.):
• Hemodialysis is indicated for patients with severe metabolic acidosis, markedly altered mental
status, or significantly elevated salicylate levels, greater than 100–120 mg/dL after acute
overdose or greater than 60–70 with subacute or chronic intoxication).

61. Theophylline and caffeine
• Theophylline toxicity may occur after an acute single overdose or intoxication may occur as a result
of chronic repeated overmedication or reduced elimination resulting from hepatic dysfunction or
interacting drug (eg, cimetidine, erythromycin).
• Half life 4-6 hours , but this may increase to more than 20 hours after overdose.
• Toxic Level >20 mg/ml.
• Clinical finding(symptoms):
o Mild intoxication causes nausea, vomiting, tachycardia and tremulousness
o Severe intoxication is characterized by ventricular and supraventricular tachyarrhythmias, hypotension, and
seizures. Status epilepticus
o After acute overdose (but not chronic intoxication), hypokalemia, hyperglycemia, and metabolic acidosis are
common.

62. Theophylline and caffeine
• Diagnosis is based on measurement of the serum theophylline concentration.
• Seizures and hypotension are likely to develop in acute overdose patients with serum levels
greater than 100 mg/L . Serious toxicity may develop at lower levels (ie, 40–60 mg/L in patients
with chronic intoxication
• Serum caffeine levels are not routinely available in clinical practice, but in a study of 51 fatal
cases the median level was 180 mg/L (range 33–567 mg/L).

63. Theophylline and caffeine
Treatment(Emergency and Supportive Measures):
• Administer activated charcoal orally as described previously.
• Hemodialysis is effective in removing theophylline and is indicated for patients with status epilepticus
or markedly elevated serum theophylline levels (eg, greater than 100 mg/L after acute overdose or
greater than 60 mg/L with chronic intoxication
• Treat seizures with benzodiazepines. Phenytoin not effective.
• Treat tachycardia with B-blockers (esmolol or propranolol)

64. HYPOGLYCEMIC DRUGS
• Insulin and the insulin secretagogues are the most likely to cause hypoglycemia.
• Metformin can cause lactic acidosis, especially in patients with impaired kidney function or after
intentional drug overdose

65. Clinical Findings
• Hypoglycemia may occur quickly after injection of short-acting insulins or may be delayed and
prolonged, especially if a large amount has been injected into a single area, creating a “depot”
effect.
• Hypoglycemia after sulfonylurea ingestion is usually apparent within a few hours but may be
delayed several hours, especially if food or glucose-containing fluids have been given

66. Treatment
• Give sugar and carbohydrate-containing food or liquids by mouth, or intravenous
dextrose if the patient is unable to swallow safely.
• For severe hypoglycemia, start with D50W, 50 mL intravenously, repeat, if needed.
• Follow up with dextrose-containing intravenous fluids (D5W or D10W) to maintain a
blood glucose greater than 70–80 mg/dL.
• For hypoglycemia caused by sulfonylureas and related insulin secretagogues, consider
use of octreotide, a synthetic somatostatin analog that blocks pancreatic insulin
release. A dose of 50–100 mcg octreotide subcutaneously every 6–12 hours can reduce
the need for exogenous dextrose and prevent rebound hypoglycemia
• Admit all patients with symptomatic hypoglycemia after sulfonylurea overdose.
Observe asymptomatic overdose patients for at least 12 hours.
• Consider hemodialysis for patients with metformin overdose accompanied by severe
lactic acidosis (lactate greater than 20 mmol/L or pH < 7.0).

67. OPIATES & OPIOIDS
• Prescription and illicit opiates and opioids (morphine, heroin, codeine, etc)
• Popular drugs of misuse and abuse and the cause of frequent hospitalizations for
overdose.
• These drugs have widely varying potencies and durations of action; for example, some
of the illicit fentanyl derivatives are up to 2000 times more potent than morphine
• All of these agents decrease CNS activity and sympathetic outflow by acting on opiate
receptors in the brain.

68. Clinical Findings
• Mild intoxication is characterized by euphoria, drowsiness, and constricted pupils.
• More severe intoxication may cause hypotension, bradycardia, hypothermia, coma, and
respiratory arrest.
• Pulmonary edema may occur.
• Death is usually due to apnea or pulmonary aspiration of gastric contents.
• Methadone may cause QT interval prolongation and torsades de pointes.
• While the duration of effect for heroin is usually 3–5 hours, methadone intoxication
may last for 48–72 hours or longer.
• Tramadol, dextromethorphan, and meperidine also cause seizures.
• With meperidine, the metabolite normeperidine is probably the cause of seizures and
is most likely to accumulate in patients with CKD
• Many opioids, including fentanyl, tramadol, oxycodone, and methadone, are not
detected on routine urine toxicology “opiate” screening.

69. Treatment
• A. Emergency and Supportive Measures Protect the airway and assist ventilation. Administer
activated charcoal for recent large ingestions.
• B. Specific Treatment Naloxone is a specific opioid antagonist that can rapidly reverse signs of
narcotic intoxication.
• Although it is structurally related to the opioids, it has no agonist effects of its own.
• Administer 0.2–2 mg intravenously and repeat as needed to awaken the patient and maintain
airway protective reflexes and spontaneous breathing.
• Very large doses (10–20 mg) may be required for patients intoxicated by some opioids (eg,
codeine, fentanyl derivatives).
• Caution: The duration of effect of naloxone is only about 2–3 hours; repeated doses may be
necessary for patients intoxicated by long-acting drugs such as methadone.
• Continuous observation for at least 3 hours after the last naloxone dose is a must.