Toxicology

Question 1

Toxins causing Bradycardia

Answer 1

PACED: Propranolol (BetaBs), Poppies (Opioids), Physostigmine, Propoxyphene, Anticholinesterase drugs, Antiarrhythmics, Clonidine, CCBs, Ethanol/Alcohols, Digoxin, Digitalis

Question 2

Toxins causing Tachycardia

Answer 2

FAST: Free base cocaine, Freon, Anticholinergics, Antihistamines, Antipsychotic amphetamines, Alcohol WITHDRAWAL, Sympathomimetics, Solvents, Strychnine, Theophylline, TCAs, Thyroid hormones

Question 3

Toxins causing Hypothermia

Answer 3

COOLS: Carbon monoxide, Opioids, Oral hypoglycemics, Insulin, Liquor, Sedative-hypnotics

Question 4

Toxins causing Hyperthermia

Answer 4

NASA: Neuroleptic malignant syndrome, Nicotine, Antihistamines, Alcohol withdrawal, Salicylates, Sympathomimetics, Serotonin Syndrome, Anticholinergics, Antidepressants, Antipsychotics

Question 5

Toxins causing Hypotension

Answer 5

CRASH: Clonidine, CCBs, Rodenticides (Arsenic, Cyanide), Antidepressants, Amiophylline, Antihypertensives, Sedative-hypnotics, Heroin (Opioids)

Question 6

Toxins causing Hypertension

Answer 6

CT SCAN: Cocaine, Thyroid supplements, Sympathomimetics, Caffeine, Anticholinergics, Amphetamines, Nicotine

Question 7

Toxins causing Tachypnea

Answer 7

PANT: Phencyclidine (PCP), Pneumonitis, Phosgene, Paraquat, ASA, Nerve Agents, Noncardiogenic pulmonary edema, Toxin-induced metabolic acidosis

Question 8

Toxins causing Bradypnea

Answer 8

SLOW: Sedative-hypnotics, Liquor, Opioids, Weed

Question 9

In salicylate overdose, what does acidemia signify?

Answer 9

Loss of respiratory compensation (first sign is tachypnea), and acceleration of the toxicity (acid to the CNS)

Question 10

Sources of salicylate

Answer 10

Aspirin (acetylsalicylic acid), Topical salicylates, Analgesic balms, Oil of wintergreen, Willow bark, Alka Seltzer, Bismuth subsalicylate

Question 11

Progression of Acid-Base Disturbance and Toxicity in Acute ASA OD.

Answer 11

Early (0-4 hours): 20-60mg/dL, Respiratory alkalosis with alkalemia, GI distress, Mild-mod hyperpnea, Tinnitus, Lethargy.

Moderate (2-12 hours): 50-90mg/dL, Respiratory alkalosis + Metabolic acidosis with alkalemia or neutral pH, Severe hyperpnea, Lethargy or Agitation, Hyperthermia.

Severe (6-24 hours): >80mg/dL, Respiratory alkalosis or acidosis + Metabolic acidosis with acidemia, Severe hyperpnea, Coma or Acute Delirium, Hyperthermia, Pulmonary or Cerebral edema, Seizure, Cardiovascular collapse.

Question 12

Salicylate toxicity causes what metabolic issues?

Answer 12

Interferes with aerobic metabolism, Uncoupling of mitochondrial oxidative phosphorylation, Inhibition of Krebs cycle = increased pyruvic acid -> lactic acid, Increased lipid metabolism -> ketone bodies, Increased metabolic rate, temperature, tissue CO2 and O2 consumption, Tissue glycolysis = hypoglycemia, Ineffective anaerobic metabolism = decreased ATP production, Energy lost as heat = hyperthermia.

Question 13

How does ASA toxicity lead to hypokalemia?

Answer 13

1. Vomiting 2/2 stimulation of medullary chemoreceptor trigger zone.
2. Increased renal excretion of K, Na, HCO3 2/2 compensation to resp alkalosis + ASA-induced increased permeability of renal tubules losing more K.
3. Inhibition of active transport system 2/2 uncoupling of oxidation phosphorylation.

Question 14

Risk factors for salicylate-induced pulmonary edema

Answer 14

Age > 30, Chronic smoking, Chronic ASA ingestion, Metabolic acidosis, Neurologic symptoms, ASA > 80mg/dL, Large AGMA, Hypokalemia, Low pCO2.

Question 15

Two salicylate effects on CNS

Answer 15

1. Cerebral Edema = increased energy requirements, acidemia, direct cellular toxicity.
2. Neuroglycopenia = consumption of glucose in brain may be faster than supply (even with normal serum glucose). One or both of above can cause AMS, seizure, coma.

Question 16

How does ASA toxicity affect bleeding?

Answer 16

Therapeutic dose = increased bleed risk via irreversible inhibition of PLT COX. Overdose = vitamin K epoxide reductase is inhibited (similar to warfarin). Acquired coagulopathy prolongs prothrombin time, associated with increased risk of clinically significant bleeding.

Question 17

How are the elderly predisposed to salicylate toxicity from chronic therapeutic ingestions?

Answer 17

Decreased liver blood flow limits biotransformation of salicylate, Decreased renal function reduces salicylate clearance, Decreased albumin binding = increased free salicylate entering cells and passing through blood-brain barrier.

Question 18

Clinical features of salicylate toxicity?

Answer 18

GI upset, Tachypnea and respiratory alkalosis, Tinnitus & hearing disturbances (concentration-dependent reversible ototoxicity), Diaphoresis, AGMA, Hyperthermia, Coagulopathy, Cerebral edema, Pulmonary edema, Cardiovascular collapse, Death.

Question 19

DDx for Salicylism

Answer 19

Salicylism, Sepsis, CNS infection, Withdrawal syndromes, Alcoholic ketoacidosis, Diabetic ketoacidosis.

Question 20

Toxins causing AGMA

Answer 20

ASA, Colchicine, Iron, Isoniazid, Methanol, Ethylene glycol, Metformin, Cyanide.

Question 21

Toxins causing tinnitus

Answer 21

ASA, Aminoglycosides, Loop diuretics, Opioids, Methotrexate, Cisplatin, Quinine.

Question 22

Is activated charcoal useful for ASA overdose?

Answer 22

Yes. Can use MDAC as well. 25-50g NG q2-4h x 2-4 doses. For acute ingestions. NOT chronic.

Question 23

Main treatment objectives in ASA toxicity?

Answer 23

1. Correct fluid deficits and acid-base abnormalities.
2. Increase excretion.

Question 24

Treatment of Acute Salicylate Toxicity

Answer 24

Consider MD activated charcoal, 25g q2-4h x2-4 doses, Treat dehydration, urine output 2-3ml/kg/hr, Correct K depletion with goal serum 4.5-5.0, Alkalinize urine, goal pH 7.5-8.0, serum goal pH 7.55, NaHCO3 150mEq = 3amps, in D5W 1L, with KCl 40mEq @ 2-3ml/kg/hr, Dextrose 0.5-1.0g/kg IV for any CNS abnormalities, Hemodialysis if criteria met = AMS, coma, seizure, respiratory failure, pulmonary edema, serum pH <7.2, renal failure, hepatic failure, rapidly rising salicylate level, failure of urine alkalinization, ASA >100mg/dL in acute OD, ASA >40mg/dL in chronic OD.

Question 25

Indications to dialyze in ASA toxicity?

Answer 25

Deterioration in condition, Altered mental status, seizure, coma, Respiratory failure, pulmonary edema, need to intubate, Serum pH <7.2, Rapid rise in ASA level, ASA > 100mg/dL after acute OD, ASA > 40mg/dL after chronic OD, Renal failure, failure to alkalinize urine, Hepatic failure.

Question 26

Considerations in maternal ASA poisoning?

Answer 26

Greater [ASA] on fetal side of placenta, Relative fetal acidemia contributes to fetal distress, Associated with fetal demise, Treat expeditiously, Consult OB for delivery of distressed fetus in 3rd trimester if fetus viable.

Question 27

Differential for bilateral putamen hypodensity changes?

Answer 27

Methanol toxicity, CO toxic encephalopathy, Cyanide toxic encephalopathy, Hydrogen sulfide toxic encephalopathy, Hemolytic-uremic syndrome, Hypoxic-ischemic injury, Wilson disease, Leigh disease, Kearns-Sayre syndrome.

Question 28

What are causes of a double OG and AG?

Answer 28

Methanol, Ethylene glycol, Alcoholic ketoacidosis, Diabetic ketoacidosis, Uremia, Septic Shock, Multiorgan failure