Valentovic - Poisoning and Overdose Flashcards
For the initial exam, the following should be determined first:
- Identify toxins
- Estimate dose
- Determine status of respiration and circulation
(worsened with a previous disease state!)
Deaths from acute poisoning are usually due to ___________ and ____________
Cardiovascular complications (cocaine, methamphetamine) and depressed respiration (barbiturates, opiates, alcohol)
Most common poisonings in children < 5 years of age:
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- Fe containing vitamins
- Pesticides
- OTC cold remedies
- Cleaning supplies
Most common poisonings in people >18 years of age:
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- Analgesics
- Sedatives/hypnotics
- Substance abuse
- Antidepressants
- Alcohol
* or combination of the above
Supportive care:
- Essential to maintain ______ and _____
- People die from respiratory depression (HYPOXIA!) - respiration further decreased by mixing: _____, _____, ____ or _____ (respiratory depressants)
- Circulation can be modified by: ____, ____, ____
- Circulation and respiration
- Barbiturates (relax vascular smooth muscle so dec BP), Opiates, Benzodiazepines, or Alcohol
- Cocaine, Carbon Monoxide, Opiates (dec HR)
Need to remove toxin to prevent further absorption into the body - e.g. most common exposures:
- carbon monoxide - ________
- drugs - ________
- Solvents, pesticides - ________
Enhance elimination - alkalinize urine for acidic drugs
Use antidote or antagonist
- Inhalation
- Ingestion
- Dermal (industrial accidents)
What method for terminating exposure to a toxin:
- Mechanical (finger, spoon) is not effective for removing stomach contents –> only gives you a gag reflex
- Use syrup of Ipecac**
- For ingestion of acetaminophen, ASA, antihistamines, vitamins, cold remedies, benzodiazepines, pesticides [Paraquat]
Emesis
What is the mechanism of action of Syrup of Ipecac?
- Irritates the stomach
- Rapidly absorbed, stimulates the CTZ (chemoreceptor trigger zone) in the Brain
- results in nausea and vomiting
* Occurs within ~30 minutes
What are some contraindications for emesis?
****Don’t use emesis when toxin is more dangerous when aspirated!
- Corrosive agents (Drain cleaner, ammonia or electric dishwasher cleaner)
- Loss of gag reflex (can aspirate)
- Comatose (can aspirate)
- Sharp objects - e.g. glass (do surgery!)
- Agents associated with seizures
- TCAs, GHB, Strychnine [all lower the seizure threshold]
- Ingestion of hydrocarbons (furniture polish)
What method for terminating exposure to a toxin:
- Agent is activated and added to lavage fluid to enhance removal of toxins
- Adsorbs drugs, then the mixture is removed by lavage or through feces
- Uses: acetaminophen, aspirin, amphetamines, benzodiazepines, digoxin, opiates, malathion, nicotine, syrup of ipecac
***Use syrup of ipecac first, then add this method on.
Lavage and Activated Charcoal
Lavage and activated charcoal are not used for what toxins?
- Corrosives (draino, ammonia)
- Caustic agents
- Acids, Alkali, Most metals or Petroleum distillates
- Alcohols
What antagonist?
- For opiate overdose (codeine, heroin, morphine)
- Competitive, reversible antagonist at mu receptor
- short half-life, so sometimes have to give multiple times
- To reverse respiratory depression of opiates****
Naloxone
What antagonist?
- Benzodiazepine overdose (diazepam, oxazepam, etc)
- Competitive, reversible antagonist at benzo receptor
- Reverse respiratory depression so individual won’t die from hypoxia
Flumazenil
________: used to alkalinize urine, to enhance the excretion of acidic drugs
- e.g. Barbiturates, ASA (salicyclic acid)
**** Acidification of urine for alkali drugs is not effective bc body compensates to easily.
Sodium Bicarbonate
What toxin?
- Major target is aspiration into lungs –> chemical-induced pneumonitis
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Poisonings mostly in children < 3 years old
- Most common: household solvents - gasoline, mineral spirits (paint thinner), furniture polish, kerosene
Petroleum distillates
Risk of aspiration is dependent upon what 3 factors?
******Which one is the best determinant of aspiration potential of petroleum distillates?
- Viscosity - best determinant******, expressed in SUS units
- Volatility
- Surface tension
******Viscosity and aspiration risk are inversely related
(low viscosity or SUS unit = high aspiration risk)
What determinant of aspiration potential?
A. Low levels allows for spread from mouth to trachea and lungs (e.g. siphoning gasoline)
B. Displaces oxygen from alveoli, leads to hypoxia
movement from liquid to gas
A. Surface Tension
B. Volatility
What type of abuse?
- Inhalation of paint, glue, spray cooking oil, lighter fluid, gasoline, toluene
- Death due to cardiac arrest or hypoxia –> Permanent brain damage [affects membrane fluidity]
- Solvents are absorbed through your lungs –> get in to blood stream to your heart –> effect membrane fluidity –> effecting muscle contractility of the heart –> speeds up heart –> arrhythmia and cardiac arrest
- May cause rash!***** (from solvents around the face)
Huffing - abuse of aerosol propellants
What aerosol propellant?
________ causes blindness and hearing loss
_________ causes gasoline leukemia (damage to bone marrow)
—> Huffing while pregnant can lead to ____, ____, ____.
Toluene
Benzene
–> Decreased birth weight, increased fetal death, nerve damage
What toxicity?
- Primarily occurs in young children*
- Route: ingestion of multivitamins or supplements
- Leading cause of fatal overdose in this age group (<6 yo)
Iron Toxicity
The toxic dose of iron is calculated on ________ content.
******What is the toxic dose??
- Ferrous sulfate (anhydrous): 36.8% Fe
- Ferrous Gluconate: 11.6% Fe
ELEMENTAL Fe
> 20 Mg/Kg********
What is the toxic dose for iron if 10 tablets each containing 100 mg were ingested by a 10 kg child?
Ferrous gluconate was ingested (11.6% Fe)
Is this dose a toxic amount?
**************
11 mg elemental iron x 10 tablets = 110 mg
The kid weighs 10 kg. So 110 mg/10 kg = 11 Mg/Kg –> NOT TOXIC
What is the toxic dose for iron if 10 tablets each containing 100 mg were ingested by a 10 kg child?
Ferrous sulfate was ingested (anydrous 36.8% Fe)
Is this dose a toxic amount?
**************
36.8 mg elemental Fe x 10 tablets = 368 mg
The kid weighs 10 kg. So 338 mg/10 kg = 38 Mg/Kg –> TOXIC!!!
Describe each stage of Iron Toxicity:
First stage:
Second phase:
Third Phase:
Fourth Phase:
First: 1-4 hours, vomiting, stomach pain, diarrhea (irritation)
Second: 6-24 hours, apparent recovery phase, lethargy but no vomiting
Third: 12-24 hours, organ failure of heart, liver, kidney, nervous system
Fourth: 4-6 weeks, scarring causes pyloric obstruction
What can be used to treat iron toxicity?
- mechanisms?
- Drug?
- Emesis
- Lavage in combo with bicarbonate to decrease Fe absorption (raising stomach pH lowers amount of iron that can be absorbed)
- Chelation - Deferoxamine (given IV to remove Fe systemically)
What toxin?
- Active ingredient in many cough and cold preparations, OTC analgesics
- Targets: Liver and Kidney
- Over 60,000 children <6 years old treated between 2000-2003 for this toxicity
- #1 cause of liver failure in the US!***
Acetaminophen
Target sites of Acetaminophen toxicity:
1st area of Failure: Liver - leads to ________ necrosis
2nd area of Failure: Kidney - leads to ________ necrosis
* Different mechanisms of damage (different metabolites)
Liver - Centrilobular
Kidney - Proximal Tubular
Acetaminophen metabolized by _____ to it’s toxic metabolite: ___________
- Detoxification occurs by binding to _______
- Liver damage occurs when hepatic depletion of this occurs (only have a finite amount!)
- P450******
- N-acetyl-benzoquinoneimine (NAPQI)******
Liver damage when NAPQI no longer has Glutathione to bind to and starts to bind other proteins.
- Glutathione******
Acetaminophen toxicity -
- First 24 hours have minor GI upset, nausea
- After 24-48 hours, hepatic damage appears
- Excellent correlation of acetaminophen blood levels with ___________
Time expired since ingestion and prediction of toxicity
Treatment of Acetaminophen toxicity:
- Emesis
- Lavage with activated charcoal
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**********Antidote: __________ (give orally! 100% absorbed in the liver, also approved for IV) –> ideally given within 6-8 hours
- taken up by cell and provides CYS**** for glutathione synthesis
- Glutathione is ineffective (<1% enters cell)
****** n-ACETYLCYSTEINE******
THE #1 CLINICAL ANTIDOTE IN THE US
Facts: Combination of Acetaminophen (Tylenol) and Alcohol
- Hepatic toxicity with Therapeutic doses
- Alcohol lowers hepatic glutathione levels
- Alcohol induces CYP450 (2E1), increases NAPQI formation
- Alcohol diminishes NADPH (cofactor to maintain GSH in reduced state, reduced state is what binds NAPQI)
- Excess NADH/lower NAD, less APAP glucuronidation (conjugation reaction that detoxifies acetaminophen before metabolized by P450)
Alcohol ——> ____________ —> _____________
*What enzymes, what products?
Alcohol——> Acetaldehyde (via Alcohol dehydrogenase)
Acetaldehyde —> Acetate (via Aldehyde dehydrogenase)
** Acetate to Krebs Cycle
What toxicity?
- ASA, MethylSalicylate (sports cremes - Icy Hot, Bengay)
- Follows first and zeroth order kinetics
- First order - headache dose (~2 aspirin tablets), t1/2 = 2-4 hr
- Zeroth order - arthritis doses (~16 tablets/day), t1/2 = 18-20 hr
In toxicity it follows Zeroth order, the half life change goes from 2-4 hours to 18-20 hours. Can take 4 days to get rid of.
Aspirin/Salicylate Toxicity
Remember:
Zero Order (constant amount)
First Order (constant fraction)
Aspirin is converted to the toxic agent, __________
- Can then be converted to:
- Acyl glucuronides, Phenyolic glucuronides
- Salicyluric acid (glycine conjugate)
- Gentisic acid –> Gentisuric acid
Bonus: What order kinetics does toxicity follow?
Salicylic Acid
Bonus: Zero order!
bc no P450 metabolism, the conjugation reactions become saturated
and that’s why you go to zero order in overdose.
What are the mechanisms for Salicylate Toxicity?
- ________ - stimulates respiratory centers in the medulla
- _________ - stimulates CO2 production
- Hyperventilation
- Uncouples oxidative phosphorylation (dec ATP)
Symptoms of what toxicity?
- Headache, tinnitus, sweating, hyperventillation, fever, drowsiness
- Fever more common in children
- Acid-base (affects glucose metabolism resulting in formation of ketones which are potent acids causing aciosis)
- Electrolyte imbalance (loosing sodium and water from sweating)
Salicylate toxicity
What are the stages of Salicylate toxicity?
- _______ - stimulation of respiratory centers in the medulla, lowers PCO2 (30-60 mins)
- ______ - increased bicarb excretion
—— adults stop here, kids continue on…
- ______ - high salicylates over time inhibit respiration, increase PCO2
- ______ - uncoupled OxPhos causes increase in ketones, lactic acid, pyruvic acid (organic acids in blood lowering blood pH)
- Respiratory alkalosis aka hyperventilation
- Renal compensation
_____ADULTS STOP HERE, KIDS CONTINUE________
- Respiratory acidosis
- Metabolic acidosis
Electrolyte and Fluid Imbalance with Salicylates:
- Increased bicarb excretion –> carrying Na+ and this ion
- Dehydration - hyperventilation and sweating, fever
- Low Serum ______ levels - renal excretion of bicarb & organic acids –> carrying Na+ and this ion.
Potassium! (aka hypokalemic)
*****What do you measure for determining salicylate toxicity on a nomogram?
* Good correlation with time of ingestion and prediction of severity of toxicity
PLASMA SALICYLATE CONCENTRATION! ******
Treatment of Salicylate toxicity?
- Emesis, lavage +/- activated charcoal
- Alkalinize urine –> GIVE IV BICARBONATE to ionize the salicylate acidic drug so more ionized and less gets in to the brain (Inc. Salicylic acid 4x)
- effective for ASA, methyl salicylate
- Correct electrolytes and fluid
- Correct body temperature to normal
What toxin?
- Greater CNS depression than ethanol, less of a dose than ethanol for inebriation
- Converted to acetone in body, less affinity for enzymes than ethanol
- Toxicity is gastric pain (drying to membranes), ketones, ketoacidosis
Isopropyl Alcohol
What toxin?
- Toxicity is to the eye!
- Photophobia, blindness
- ______ to formaldehyde to formic acid (mitochondrial inhibitor)
What causes the Blindness?***********
Methanol!
******* FORMIC ACID is what causes BLINDNESS (mitochondrial inhibitor)
What toxin?
- In radiator fluid
- Induces inebriation, nausea at a lower dose than ethanol
- ***irreversible anuric Renal failure
- ______ to glycoaldehyde to Glycolic acid to oxalic acid
- Oxalic acid crystals deposit in lumen of kidney!
Ethylene Glycol
Treatment for alcohols:
- Emesis or lavage < 3 hours due to rapid absorption
- Treatment with IV ________: greater affinity for alcohol dehydrogenase than others
- _________ - inhibitor of alcohol dehydrogenase
- IV Ethanol
- Fomepizol
A 2 yo has symptoms of stomach pain, nausea, chills, and vomiting. An x-ray shows 10 opaque oval looking shapes (pills/vitamins). The child says he ate some candy he found in his parent’s bathroom.
- What tests should be run on the child?
- The child has an ALT of 10 U/l (normal), a BUN of 15 mg% (normal) and a plasma iron of 350 ug/dl (normal: 50- 150 ug/dl).
- What treatment do you suggest?
- Check liver!
- Emesis, Lavage
- Chelator - Deferoxamine to reduce systemic level of iron
Mr Hour is brought to ER by his wife. He has a cough, HA, congestion, stomach pain, sees halos around lights. He admitted to drinking corn liquor.
- What potentially toxic substances could be contained in the corn liquor?
- What do his symptoms suggest is the toxic agent?
- Methanol, Lead
- Methanol causing the blindiness/vision issues.
- bc Lead has more causes towards cognitive funciton and hemotopoetic system.
