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Flashcards in topic 27 Deck (13):

What is the most common toxin ingested? What toxin leads to the most deaths?

Analgesics most ingested

Sedative/hypnotics/antipsychotics lead to most deaths


What is the MW of salicylic acid? Why is that significant? What is its pKa? What happens to its Vd in overdose? What is its protein binding level? What is it therapeutic level? Toxic level? What is its halflife at therapeutic dose? At toxic dose? What is the elimination? What is the mechanism of toxicity? What are some symptoms as a result?

• MW of salicylic acid is 138 Daltons (easily

• pKa is 3.5 (weak acid)

• Vd is 0.2 to 0.3 L/kg in therapeutic dosing but
increases to 0.3 to 0.5 L/kg in overdose

• Extensive protein binding (90% at 10 mg/dL)

• Therapeutic levels are generally 15-30 mg/dL
and toxic levels exceed that.

• ASA t½ is 2-4 hrs normal dosing

• ASA t½ may be as long as 20 hrs with
toxic levels (18-36 hrs in untreated cases)

• Elimination is normally first order, but switches to
Michaelis-Menten in overdose

• Salicylates interfere with Krebs cycle limiting ATP
production and inhibit carbohydrate metabolism. Uncouple oxidative phosphorylation

Anion Gap metabolic acidosis, Fever, increased O2 use, increased CO2 production, tissue glycolysis, Hyperglycemia (may see hypoglycemia in children), lack of production of coagulation factors, delay clotting in a number of ways, metabolic acidosis in newborns (contraindicated in 3rd trimester)


How is salicylate overdose managed? What is the key to treatment? What is the antidote? What is given to help with lack of clotting? What is the antidote? What else is it used for?

• Key to treatment is to prevent salicylate from entering the cells and causing toxicity.

Vitamin K is administered to help with clotting

sodium bicarbonate is the antidote-makes the urine pH higher--->increased clearance

Also used for sodium channel blockers and metabolic acidosis


What is the normal dose of acetaminophen (APAP) in children and in adults? What levels are potentially toxic in children and in adults? How is APAP metabolized? What can cause a delay of peak plasma levels? How are toxic metabolites of APAP processed by the body? What is the antidote? What does it do? When is it most effective? How does it work?

• In normal doses of 10 to 15 mg/kg in children
or 625 mg to 1000 mg in adults, APAP is a
relatively safe drug.

• Acute overdose of 7.5 grams in adults or >150
to 200 mg/kg in children is potentially toxic

• Peak plasma levels of APAP may be delayed if
co-ingested with a narcotic or other drug that
may slow GI motility

• Overall, APAP metabolized by glucuronidation
(60%), sulfation (30%), CYP450 2E1  NAPQI

• NAPQI detoxified by glutathione

• Prevents acetaminophen-induced hepatotoxicity, especially when administered within 12 hours after an overdose. Promotes formation of Glutathione and binds to NAPQI.


What are two important categories of NSAIDS? some examples? What are common symptoms of NSAID overdose? How fatal are they compared to tylenol/aspirin? What level of overdose isn't serious? What level will start to be treated? What level could cause serious damage?


Propionic acids: Ibuprofen, naproxen (Aleve), oxaprozin

Common ingestants
– Fatalities are 6 to 7 times higher for ASA and APAP

• Common symptoms of overdose
– CNS depression
– Respiratory depression
– Metabolic acidosis
– Renal insufficiency may occur

• Overdoses up to 200 mg/kg are usually
well tolerated.
• Gastric emptying and administration of activated charcoal should be performed in an ER if 200 to 400 mg/kg ingested.
• Ingestion of > 400 mg/kg may be associated with a significant risk for serious toxicity.


What do CADs in OD lead to? What happens after awhile of excess NE effects? What does treatment focus on?

• CADs in OD lead to:
– excessive NE reuptake blockade
– direct quinidine-like effect
– central plus peripheral anticholinergic effects.

• NE excess effects give way to NE depletion after metabolism by COMT
• May see arrhythmias (VT, VFib) which give
way to bradycardia, hypotension, collapse

• Treatment focus on:
– Alkalinization with NaHCO3 & +/- hyperventilation
– Na+ bolus to overcome sodium channel blockade
– GI decontamination (with caution)
– Arrhythmia and seizure control plus ICU care.


What are the symptoms of iron overdose? What is the antidote? How does it work? What are the adverse effects of the antidote?

• Hypotension, hypovolemia, blood loss may
occur leading to metabolic acidosis,
• Cellular damage from free radicals

Deferoxamine (DFO)

• Chelates iron, either in chronic iron overload conditions such as hemachromatosis , or in

• Adverse effects include hypotension, acute lung injury (hypoxemia, fever, infiltrates, eosinophilia) in high dose therapy for longer than 24 hours, visual loss, and anaphylaxis.


What are some common anticonvulsants? What affects do they have? How are they treated in OD?

• CBZ is a Na+ channel blocker
– supportive care in OD, multi-dose AC (MDAC)

• Valproic acid (VPA) enhances GABA
– in overdose may consume carnitine and affect
mitochondrial fatty acid oxidation

• Phenytoin blocks Na+ channels
– supportive care in oral overdose, IV overdose may
result in arrhythmias

• Phenobarbital mechanism GABAergic
– supportive care in overdose, MDAC


What are some symptoms of opiate overdose? What is the antidote?

• Overdoses result in CNS depression or coma

• Seizures especially with meperidine (normeperidine metabolite)

• Miosis is characteristic (mydriasis with some)

• Respiratory depression, arrest and pulmonary
edema may occur

• Heroin classically causes pulmonary edemaabruptly; may be delayed if intranasal use

• Hypotension, bradycardia, circulatory collapse
and cardiac arrest have occurred.

Naloxone is the antidote


What is the pattern of cocaine use? What is a common symptom in children? What are other symptoms? What is the toxic dose? Lethal?

• Pattern: early, then advanced stimulation, and then depression

• Seizures may occur, especially in children

• Cocaine may cause CNS hemorrhage, myocardial infarction, pulmonary edema, pneumothorax and pneumomediastinum after smoking crack, seizures, and rhabdomyolysis

• Cocaine toxic dose usually 500-1,200 mg po

• Cocaine lethal dose is individual dependent but
can be as low as 20 to 30 mg IV


In general, what do amphetamines do? What symptoms do they cause? What do they do compared to cocaine?

Stimulate central and peripheral adrenergic receptors

• Abusers often go on “binges” for 2 to 3 days

• Can cause: – tachycardia, hypertension, hyperthermia, agitation, seizures, CNS hemorrhage, rhabdomyolysis

• Compared to cocaine, amphetamines are less likely to cause seizures, arrhythmias, and myocardial ischemia


What are two sedative/hypnotics? How do they work? What are the symptoms of OD? How are they treated? Antidote?

• Barbiturates result in excess GABA and
CNS depression and respiratory
depression: supportive care, no antidote

• Benzodiazepines (BZD) increase GABAergic tone
– flumazenil is competitive antagonist at GABAA
chloride channel BZD subreceptor (Should not be used if there's any possibility of a mixed drug overdose, so mainly supportive care is done)


What are some cardiac glycosides? What do they do in overdose? What are the clinical effects? How are they treated?

• Cardiac glycosides (digoxin, other plants) – Common plants include oleander

• Cardiac glycosides in overdose poison the Na+/K + ATPase pump.

• Leads to excessive calcium levels intracellularly
& potential for after-depolarizations

• Clinically may see bradycardia or arrhythmias

• Vomiting is common, altered color vision

• May see hyperkalemia

• Treatment is correction of electrolytes and Fab
antibodies (Digibind® or Digifab®)