specific toxins part i. acids examples –toilet bowl cleaner –rust remover –phenol (carbolic...
Post on 11-Jan-2016
214 Views
Preview:
TRANSCRIPT
Specific Toxins
Part I
Acids
• Examples– Toilet bowl cleaner– Rust remover– Phenol (carbolic acid)– Hydrochloric acid
• Severe burning of stomach
• Absorption, systemic acidemia
Acids
• Loss of airway = most immediate threat
• Secure airway against edema
• IV with LR, NS for volume loss
• Emesis, gastric lavage contraindicated
• Dilution with water, milk NOT recommended
Alkalis
• Examples– Drain cleaner– Washing soda– Ammonia– Lye (sodium hydroxide)– Bleach (sodium hypochlorite)
• Severe burning of esophagus, stricture formation
Alkalis
• Loss of airway = most immediate threat
• Secure airway against edema
• IV with LR, NS for volume loss
• Emesis, gastric lavage contraindicated
• Dilution with water, milk NOT recommended
Hydrocarbons
• Examples– Kerosene– Gasoline– Lighter fluid– Turpentine– Furniture polish
Hydrocarbons
• Signs/Symptoms– Choking, coughing, gagging– Vomiting, diarrhea, severe abdominal pain– Chemical pneumonitis, pulmonary edema
If the patient is coughing, aspiration has occurred
Hydrocarbons
• Signs/Symptoms– Euphoria, confusion/anxiety, seizures– Increased myocardial irritability, arrhythmias
(adrenergic agents may cause V-fib)
– Liver damage, hypoglycemia
Hydrocarbons
• Management– 100% oxygen with good humidification– IV tko– Monitor ECG– Drug therapy
• D50W for hypoglycemia
• Diazepam for seizures• Antiarrhythmics
Hydrocarbons
• Inducing emesis controversial– Should NOT be induced with low viscosity
hydrocarbons
Hydrocarbons
• If ingestion has occurred recently, emesis probably should be induced with:– Halogenated hydrocarbons (carbon tetrachloride)– Aromatic hydrocarbons (toluene, xylene, benzene)– >1cc/kg gasoline, kerosene, naptha– Petroleum products with toxic additives (lead
tetraethyl, pesticides)
Hydrocarbons
Seek advice of medical control and poison control center
Methanol
methyl alcohol
wood alcohol
wood naphtha
Methanol
• Sources– Industry– Household solvents– Paint remover– Fuel, gasoline additives– Canned heat– Windshield washer antifreeze
Methanol
• Toxic dose– Fatal oral: 30-240ml– Minimum: 100 mg/kg– Example
• Windshield washer fluid 10% Methanol• 10 kg child needs only 10 cc to be toxic
Methanol
• Mechanism of toxicity– Methanol slowly metabolized to formaldehyde– Formaldheyde rapidly metabolized to formic
acid• Acidosis• Ocular toxicity
Methanol Metabolism
OC
OH
H+_
HOC
OH
Formic Acid
CH
OH
Formaldehyde
HOHH
HC
Methanol
Alcohol dehydrogenase
Aldehyde dehydrogenase
Methanol
• Overdose Presentation– Inebriation– Gastritis– Osmolar gap
(osmolar gap as little as 10mOsm/L is consistent with methanol poisoning)
Methanol
• Overdose Presentation– Latent period of up to 30 hours – Severe anion gap metabolic acidosis– Visual disturbances, blindness
(“standing in a snowstorm”)– Seizures– Coma– DEATH
Methanol
• Management– High concentration oxygen– IV tko– ECG monitor– if < 30 minutes lavage or induce emesis
(if not done then it is probably useless)
Methanol
• Management– Sodium Bicarbonate– Folic acid
• 50mg IV every 4 hours
• Helps convert formic acid to CO2, H2O
– Give specific antidote
Methanol
• The specific antidote for methanol toxicity
10% EtOH solution in D5W
7.5 ml/kg loading dose and 1.5 ml/kg/hr maintenance
100 proof (50%) EtOH
1.5 ml/kg loading dose and 0.3 ml/kg/hr maintenance
Ethanol Metabolism
H
H
H
C HO
H
H
C
CH
OH
H
H
C
HOC
OH
H
H
C
Krebs Cycle
Ethanol
Acetic Acid
Acetaldehyde
Alcohol dehydrogenase
Aldehyde dehydrogenase
Methanol
Alcohol dehydrogenase
Ethanol Methanol
Acetic Acid
CO2 + H2O + Energy
Urine
Methanol
• Specific antidote– Fomepizole (4-methylpyrazole)– Inhibits alcohol dehydrogenase– Produces same end result as ethanol
without causing intoxication
Ethylene Glycol
• Antifreeze (95% ethylene glycol)
• Tastes sweet
• Kids, animals like taste/drink large quantities
Ethylene Glycol
• Mechanism of toxicity– Metabolized via alcohol dehydrogenase to
glycoaldehyde then to glycolic , glyoxylic, and oxalic acids
– Acids lead to anion gap metabolic acidosis– Oxalate binds with calcium
• Forms crystals causing tissue injury• Produces hypocalcemia
Ethylene Glycol
• Toxic dose– Approximate lethal oral dose: 1.5ml/kg– Example
• 10 kg child needs 15ml for lethal dose
Ethylene Glycol
• Overdose Presentation (first 3-4 hours)– Patient may appear intoxicated– Gastritis, vomiting– Increase in osmolar gap– No initial acidosis
Ethylene Glycol
• Overdose Presentation (after 4-12 hours)– Anion gap acidosis– Hyperventilation– Seizures, coma– Cardiac conduction disturbances, arrhythmias– Renal failure– Pulmonary, cerebral edema
Ethylene Glycol
• Management– Lavage if within 2 hours– Sodium bicarbonate– Fomepizole or ethanol– Folic acid, pyridoxine, thiamine
(enhance metabolism of glyoxylic acid to nontoxic metabolites)
Cyanide
But first…• A little review of
biochemistry and biophysics
Staying alive requires energy...
• The natural tendency of the universe is for things to become more disorderly.
• This trend toward disorder is called entropy.
• Complex systems (including us) don’t tend to last long, unless…
• They have a constant supply of energy to combat entropy.
Organisms capture and store the energy they need in the form of...
• The “currency” cells use to pay off the energy debt built up fighting entropy.
• Formed by capturing energy released as the cell breaks down large molecules through glycolysis and the Krebs Cycle.
Adenosine Triphosphate (ATP)
Glycolysis• In cytoplasm• Does not require oxygen• Breaks glucose molecule into
two pyruvic acid molecules• Net gain of 2 ATP• If oxygen absent, pyruvate
converted to lactate• If oxygen present, pyruvate
changed to acetate (acetyl-CoA) and sent to Krebs Cycle
The Krebs Cycle• In mitochondria• Requires oxygen• Strips H+ and electrons
off of acetate, leaving CO2
• Sends the H+ and electrons to the electron transport chain
Electron Transport/Oxidative Phosphorylation
• In mitochondria• Electrons pass down a
series of carriers--losing energy as they go
• It’s like a series of waterfalls• Energy is released and
stored as ATP
• Electrons and H+ bind to O2, making H2O
• 36 ATP produces per glucose molecule
Oxidative Phosphorylation
NAD NADH2
2H
FAD FADH2
Ox. Cyt. b Red. Cyt. b
Ox. Cyt. c Red. Cyt. c
Ox. Cyt. a Red. Cyt. a
Red. Cyt. a3Ox. Cyt. a3
1/2O2
2H+
H2O
ADP + Pi
ADP + Pi
ADP + Pi
ATP
ATP
ATP
Putting It All Together• Cells have to have energy to stay alive.• Cells get energy by breaking down glucose in two phases: glycolysis
and the Krebs Cycle.• Glycolysis yields 2 ATP and pyruvate.• Pyruvate is changed to acetate (acetyl-CoA) and sent to the Krebs
Cycle.• The Krebs Cycle strips hydrogen and electrons off acetate and feeds
them into the electron transport chain.• Movement of electrons down the transport chain releases energy which
is trapped as ATP.
• At the end of the chain, the electrons combine with hydrogen and
oxygen to form water.
Cyanide
• Chemical, plastic industries
• Metallurgy, jewelry making
• Blast furnace gases
• Fumigants, pesticides
• Present in various plants– apples, pears, apricots, peaches, bitter
almonds
Cyanide
• Acrylonitrile is metabolized to cyanide
• Nitroprusside (Nipride) if given too long is metabolized to cyanide
• Acetonitrile in some fingernail glues has caused pediatric deaths
Cyanide is so common that all mammals have an enzyme called rhodonase that detoxifies cyanide by
converting it to thiocyanate
Cyanide
• Mechanism of Toxicity– Chemical asphyxiant– Inhibits functioning of cytochrome a3– Stops electron transport, oxidative
phosphorylation– Blocks aerobic utilization of oxygen
Cytochrome A3
Fe2+Fe3+ 2H+
2e-
2e-
1/2 O2
H2O
Cytochrome a
Cyanide Toxicity
Fe2+Fe3+ 2H+
2e-
2e-
1/2 O2
H2O
Cytochrome a
CN-
Cyanide
• Clinical Presentation– Variable onset speed with different forms– Headache, nausea, dyspnea, confusion– Rapid, weak pulse– Bright-red venous blood– Syncope, seizures, coma– Agonal respirations, bradycardia,
cardiovascular collapse
Cyanide
• Management– Treat all cases as potentially lethal– Support oxygenation, ventilation– ECG– IV tko– Cyanide Antidote Kit
Cyanide Antidote Kit
• Amyl nitrite, Sodium nitrite– Oxidize iron in hemoglobin from Fe2+ to Fe3+
(methemoglobinemia)– Methemoglobin binds cyanide, removing it
from cells
• Sodium thiosulfate– Provides rhodonase with sulfide anion– Speeds conversion of cyanide to thiocyanate
CN-
Cyanide Antidote Kit
Fe3+ Fe2+ 2H+
2e-
2e-
1/2 O2
H2O
Cytochrome a Fe2+ Fe3+CN-NO2 -
SCN-
Cyanide Antidote Kit
• Amyl nitrite, sodium nitrite – Only be used in serious cyanide poisonings– Can induce life-threatening tissue hypoxia
secondary to methemoglobinemia
• Sodium thiosulfate – Can be used by itself– Is relatively benign
Salicylates
Salicylates
• Examples– Aspirin– Oil of wintergreen
• Uses– Analgesics– Antipyretics– Anti-inflammatories– Platelet function inhibitors
Salicylates
• Mechanism of Toxicity– Direct stimulation of respiratory center, causing
respiratory alkalosis– Irritation of gastrointestinal tract, causing decreased
motility, pylorospasm, nausea, vomiting, hemorrhagic gastritis
– Decreased prothrombin levels/platelet dysfunction, causing prolonged clotting times
– Uncoupling of oxidative phosphorylation
Aspirin Toxicity
NAD NADH2
2H
FAD FADH2
Ox. Cyt. b Red. Cyt. b
Ox. Cyt. c Red. Cyt. c
Ox. Cyt. a Red. Cyt. a
Red. Cyt. a3Ox. Cyt. a3
1/2O2
2H+
H2O
ADP + Pi
ADP + Pi
ADP + Pi
Heat
Heat
Heat
Results of Oxidative Phosphorylation Uncoupling
• ATP production decreases, resulting in CNS and cardiovascular failure.
• Cells attempt to compensate by increasing the rate they process glucose anaerobically through glycolysis.
• Lactic and pyruvic acids accumulate, leading to metabolic acidosis.
• Hypoglycemia results as liver sugar stores are depleted.• In absence of sugar cells begin to metabolize lipids, ketone
bodies are produced, acidosis worsens.• Energy normally trapped as ATP is wasted as heat, causing
a rise in body temperature.• The rise in body temperature accelerates metabolism,
increasing tissue oxygen demand and worsening acidosis.
Salicylates
– Vomiting– Lethargy– Hyperpnea– Respiratory alkalosis– Metabolic acidosis
– Coma– Seizures– Hypoglycemia– Hyperthermia– Pulmonary edema
Clinical Presentation: Acute Toxicity
Salicylates
• Clinical Presentation: Chronic Toxicity– Usually young children, confused elderly– Confusion, dehydration, metabolic acidosis– Higher morbidity, mortality than acute
overdose– Cerebral, pulmonary edema more common
Salicylates
• Acute Toxicity Management– Oxygen, monitor, IV– GI tract decontamination– Activated charcoal– Replace fluid losses, but do NOT overload– Control hyperthermia
Salicylates
• Acute Toxicity Management– Bicarbonate for metabolic acidosis– D50W for hypoglycemia– Diazepam for seizures
Acetaminophen
Acetamophen
• Examples– Tylenol– Tempra– Datril
• Uses– Analgesic– Antipyretic
Acetaminophen
• Mechanism of toxicity– N-acetyl p-benzoquinonimine, normal
product of acetaminophen metabolism, is hepatotoxic
– Normally is detoxified by glutathione in liver– In overdose, toxic metabolite exceeds
glutathione capacity, causes liver damage
Acetaminophen Metabolism
APAP APAP-glucuronide
APAP-sulfate
Urine Urine Urine
N-acetyl-p-benzo-quinonimine
Cysteine Congugates
UrineGlutathione
28- 52% 45-55%
2- 4%
2- 4%
2- 4%P-450 MFO
Acetaminophen Toxicity
APAP APAP-glucuronide
APAP-sulfate
Urine Urine Urine
Cysteine Congugates
Urine
Hepatocyte Protein
Congugates
Cell DeathGlutathione
N-acetyl-p-benzo-quinonimine
Acetaminophen• Minimum toxic dose
– Adult: 7 grams– Child: 140 mg/kg
• Onset of symptoms is slow, initially non-specific
Stage Time Symptoms
I 1/2 to 24h Anorexia, NV, malaise, diaphoresis
II 24 to 48h Abdominal pain, liver tenderness, increased liver enzymes, oliguria
III 72 to 96h Peak enzyme abnormality, Increased bilirubin and PT
IV 4d to 2wk Resolution or progressive hepatic failure
Acetaminophen
• Management– Induce emesis– Do NOT give activated charcoal– Give specific acetaminophen antidote
Acetaminophen
• The specific antidote for acetaminophen toxicity.
Mucomyst
• N-acetylcysteine Another sulfur-containing amino acid Substitutes for glutathione. Allows continued detoxification of NAPBQI. 140mg/kg initially followed by 70mg/kg every 4 hours
17 times. Tastes, smells like rotten eggs Mix with chilled fruit juice to decrease odor, taste
Can Mucomyst (NAC) Be Given If The Patient’s Gotten Activated
Charcoal?• AC and NAC are not given simultaneously• AC is given in the first 4 hours. NAC is given after 4 hours.• The effective dose of NAC is equal to the amount of APAP
ingested.• Patients receive a total dose of 1330 mg/kg, so most are
over-treated.• The reduction in NAC absorption caused by AC (8 to 39%)
applies only to the first dose.• So the potential total decrease in absorption is 4.5%• A patient would have to ingest 1275 mg/kg for this to
become a problem.
top related