Common Toxicities Flashcards
Ethylene glycol poisoning
Ingestion of ethylene glycol (antifreeze, deriving solutions, engine coolant, etc.) causes metabolism into toxic metabolites
- ethylene glycol -> glycoaldehyde -> glycolic acid -> oxalic acid (toxic)
- this is done in the liver by alcohol dehydrogenase enzymes after GI absorption.
Multiple stages of poisoning based on time:
1st stage: (30 min-12 hrs)
- * high osmolal gap (serum osmolarity will be high)
- mimics being drunk (headache, dizziness, slurred spoked, euphoria, vomiting
- tachypnea/tachycardia
- nystagmus and seizures
2nd stage: (12-24 hrs)
- *metabolic acidosis and oxalate crystals in tissues, vasculature, blood.
- *pulmonary edema with kussmaul respiration’s
- signs of CHF
- increased BUN and creatinine
- ** if not caught in this stage, patient will likely die
3rd stage: (24-72 hrs)
- oxalate crystals in urine and kidneys
- kidney failure
- hypocalcemia
- hypomagnesemia
- coma
Treatment:
- *fomepizole (inhibits alcohol dehydrogenase) and ethanol injection (competitively inhibits alcohol dehydrogenase)
- the danger isnt actual ingesting ethylene glycol, its metabolizing it to oxalic acid*
- give IV fluids/medications to counter current metabolic issues and to flush ethylene out of system
- hemodialysis ( if severe acidosis
Fetal hydantoin syndrome
Caused by prenatal exposure to phenytoin due to maternal use.
Symptoms/signs:
- microcephaly
- congenital heart defects
- growth retardation
- carniofacial anomalies
- stiffness/tapered fingers with nail hypoplasia
- umbilical/inguinal hernia
- low set hairline with pilonidal sinuses
Treatment:
- supportive only
Mercury poisoning
Excessive exposure to mercury, causes toxic and teratogenic effects.
- disrupts functional groups by irreversibly binding to them and stopping important cell processes (DNA/RNA synthesis, Nucleic acid synthesis, protein synthesis)
- also crosses BBB and binds to functional groups
- heavily concentrates in kidneys, GI and pulmonary system
Exposures: * = most common
- thiomersal
- *tuna fish
- fluorescence blurbs
- fungicides/pesticides
- batteries
- *paint
- various homeopathic remedies
- being a miner/vermeil worker/taxidermist
Acute signs/symptoms:
- coughing
- dyspnea
- bloody stool/urine
- vomiting
- hypoperfusion shock
- hypo/hypertension
- cytopenia
- conjunctivitis
- GI ulcers
Chronic signs/symptoms:
- classic triad*
1) tremors
2) memory loss/fatigue/mental instability
3) gingivostomatitis (swelling of gums and mouth w/ canker sore-like lesions)
Diagnosis:
- mercury in urine/blood with compounded anemia present
- NAG, albumin in urine
Treatment:
- chelation therapy via IV dimercaprol
- supportive care
Paracetamol (acetaminophen) poisoning
Excessive ingestion of acetaminophen resulting in build up toxic NAPQI metabolite in the hepatic system via cytochrome P450 metabolism
- depletes the natural glutathione levels and causes accumulation of NAPQI
4 stages: (based on time after ingestion)
1st: (0-24 hrs)
- nonspecific signs of toxicity ( feeling sick, diarrhea, fever, he ache, stupor, stomach pain, etc.)
2nd: (24-72 hrs)
- signs of hepatotoxicity (jaundice, ALT/AST levels increase, upper right quadrant pain)
- signs of renal failure (creatinine and BUN increased, hemouria, frequent urination)
3rd: (72-96 hrs)
- full liver failure
- this is where patients die usually
4th: recovery stage only
- Risk factors:
- too much acetaminophen
- concomitant use with isoniazid, rifampin, phenobarbital (drugs that inhibit CYP450 system)
- concomitant use of zidovudine, TMX (drugs that deplete glutathione levels)
- chronic alcohol use
- hepatic diseases (cirrhosis, hepatitis, etc.)
- Gilbert syndrome (inherited deficiency in glucuronidation which causes increases in bilirubin concentration and inability to process acetaminophen fully)
Signs/symptoms:
- right upper quadrant pain
- jaundice
- hypoglycemia
- coagulopathy
- hepatic encephalopathy
- impaired renal function
- metabolic acidosis
- increased BUN and creatinine in urine and blood
- increased AST/ALT levels
- decreased PTT/INR and overall pH
Treatment:
- acetylcysteine (replenishes glutathione levels and detoxifies NAPQI metabolites)
- liver transplant
- symptomatic treatments as needed
Serotonin syndrome
Excessive presence of serotonin (5-HT) levels. Results in over-activation of central serotonin receptors and neuromuscular/autonomic excitation.
- can be caused by too much synthesis or too little reputable of serotonin
Increased 5HT synthesis causes:
- OD of serotonergic drugs which produces high levels of phentermine and L-tryptophan.
- use of amphetamines/dopamine agonists
- use of triptans/antidepressants and ergots
- use of MAOis or dextromethorphan.
Decreased serotonin reuptake:
- OD on SSRIs
- OD on SNRIs
- OD on tricyclic antidepressants
- concomitant use of a serotonerigic drug with St. John’s wort
- abuse of ecstasy
Signs/symptoms:
- neuromuscular excitiation (hyperreflexia, tremors, clonus, (+) babinski skin bilaterally)
- autonomic nervous system hyperactivity (vomiting, diarrhea, HTN, tachycardia, hyperthermia, increased diaphoresis)
- AMS is present (especially agitation)
- WBC count and creatine phosphokinase are high in blood
- serum bicarbonate is lower in blood
- *special hunter serotonin toxicity criteria is met
Treatment:
- cyproheptadine (antidote and Antagonizes 5-HT2 receptors
- benzodiazepines and antihypertensives for supportive therapy only
- discontinue serotonergic drug use
What is the hunter serotonin toxicity criteria?
Helps to narrow down serotonin toxicity crisis
Requires both:
1) history of taking a serotonergic drug
2) any of the following:
- spontaneous clonus
- inducible clonus + agitation/diaphoresis
- Ocular clonus + agitation/diaphoresis
- tremor + hyperreflexia
- hypertonic + fever greater than 38C/100F + ocular/inducible clonus
Acute radiation syndrome (ARS)
Excessive exposure to ionizing radiation. Affects the follow 4 organ systems the most
1) neurology (CNS symptoms mostly)
2) GI
3) Hematopoietic system
4) cutaneous/integumentary
Usually takes 21 days prior to overexposure to fully set in the illness and end-organ damage
- symptoms can appear anywhere from 12 hrs (stage 21) to 30 minutes (stage 3) from exposure
- if the dose is higher than 10-12 Gy, death is pretty much guaranteed
Risk factors:
- occupational exposures
- over treatment in medical therapy
- being less than 12 yrs or greater than 60 yrs
Signs/symptoms:
- meningeal inflammation, cerebral edema, increased ICP, cerebral hemorrhages
- abdominal cramping/pain
- chronic loose stools
- vomiting
- GI ulcers
- *pancytopenia and anemia in blood tests
- bone marrow hypoplasia
- *desquamation and ulceration of skin.
- *permanent hair loss
- *GI segmental inflammation and fibrosis
- excruciating headache
- hypotension
- (+/-) loss of consciousness
- grades on the metropolitan scoring scale
Treatment:
- *give IV potassium iodide (minimizes radioactive isotope damage)
- external decontamination of wounds
- *chelating agent diethylene-trilaminar-pentaacetic acid (DTPA)
- *oral ferric hexacyanoferrate (prevents resorption of radtiation in GI tract)
- *sodium bicarbonate (to protect kidneys
- bone marrow/stem cell transplant
Arsenic poisoning
Excessive exposure to arsenic
- disrupts metabolic processes in cellular respiration and enzyme reactions
*Arsenic concentrates in keratin-rich tissues (nails/skin/hair)
Risk factors:
- contaminated ground water and excess industrial pollution
- foods grown in contained ground water (especially rice)
- coal power plants
- glass manufactures
- OD on therapeutic arsenic contain compounds used against cancer (arsenic trioxide)
Signs/symptoms:
- *hyper/hypo pigmentation
- *hepatotoxicity
- peripheral neuropathy
- diarrhea/vomiting
- *Mee’s lines on nails (multiple white lines on dark finger nail
- *garlic breath
- arrhythmias
- pancytopenia
- peripheral gangrene (“black foot”)
- increases malignancies (especially squamous cell carcinoma and basal cell carcinoma
- renal failure
- encephalopathy
- fluid and electrolyte imbalances
- *prolonged QT syndrome
- hyporeflexia a
- seizures/delirium
- elevated bilirubin, ALT/AST/ BUN/ creatinine levels
Treatment:
- chelating therapies: Dimercaprol*
- fluid and electrolyte administration
Cyanide poisoning
Excessive exposure to cyanide compounds
- arrests cellular respiration mechanisms (TCA/ETC)
- irreversibly binds to cytochrome C oxidase in the ETC making ATP production impossible through aerobic mechanisms
- only can use anaerobic mechanisms
Risk factors:
- *industrial exposure (especially plastic/textiles/metal)
- *inhalation of smoke from burning synthetic materials
- consumption of false fingernail remover acetonitrile
- *high doses of sodium nitroprusside
- *high consumption of peach/apricot/chokecherry pits
Signs/symptoms:
- *lactic acidosis
- signs of CHF
- hyperpnea
- pulmonary edema
- musty almond scented breath
- HTN and tachycardia
- dysrhythmias
- presence of cyanide/thiocyanate in urine
- very low oxygen sat (<80%)
- very bright red blood (similar to monoxide poisoning
- flushing “cherry-red” cyanosis (similar to monoxide poisoning)
- seizures and AMS
Treatment:
- hydroxocobalamin (vitamin B12a) (binds to cyanide ions and acts chelating agent)
- amyl nitrate/sodium nitrate (forms methemoglobin and allows oxygen to still bind to RBCs, however low affinity still)
- sodium thiosulfate (converts cyanide -> thiocyanate which can be excreted easily through urine)
