03-23 Toxicology PHARM

Question 1

Dimercaprol

Answer 1

Chelator (arsenic, mercury, lead when give with EDTA)

Question 2

EDTA calcium or disodium

Answer 2

Chelator (lead)

• used before succimer for acute lead poisoning
• Given w/ Ca2+ b/c it chelates Ca2+ and could cause hypocalcemia

Question 3

Unithiol

Answer 3

Chelator (acute arsenic, mercury or lead)

Question 4

Succimer

Answer 4

Chelator (lead in children and adults; acute mercury and arsenic)

Question 5

Deferoxamine and Deferasirox

Answer 5

Chelator (Iron)

• acute iron poisoning
• iron overload
  
  • blood transfusions
  • thalassemia
  • myelodysplastic syn

Question 6

Penicillamine

Answer 6

Chelator (copper/Wilson’s; adjunct for arsenic, gold and lead chelation)

Question 7

N-acetylcysteine NAC

Answer 7

Antidote for acetaminophen

Question 8

Activated charcoal

Answer 8

Antidote gastric absorption

Question 9

Flumazenil

Answer 9

Antidote benzodiazepines

Question 10

Fomepizole

Answer 10

Antidote methanol and ethylene glycol

Question 11

Define bioaccumulation

Answer 11

Increasing conc of a substance in the environment resulting from environmental persistence and physical properties (chemically stable, resistant to metabolism and lipid soluble) leading to accumulation in biological tissues

Question 12

Define biomagnification

Answer 12

the fold increase in concentration of a substance that occurs in a food chain as a consequence of bioaccumulation

Question 13

Define endocrine disruptors

Answer 13

Chemicals in the environment that have endocrine effects (estrogen/anti-androgen/thyroid). Potential cause of infertility, reproductive cancers or birth defects.

Question 14

Define ADI

Answer 14

Acceptable daily intake (ADI) Daily - intake of chemical which during lifetime appears to be without appreciable risk.

Question 15

Define Threshold Limit Value (TLV)

Answer 15

Exposure limit to a specific agent for a stated period of time-(shorter time = higher level). Used for occupational control.

Question 16

CO Poisoning

• Nature of the gas
• Common Sources of CO
• Testing
• Tx

Answer 16

Nature of Gas

• binds to hbg w/ 200X affinity of O2; colorless, odorless, tasteless, etc.

Source

• vehicle exhaust, Spillage from appliances, Building fires, Forklifts, snow blowers, Generators, heaters
• Zamboni (ice skaters/hockey players)

Testing for CO

• measure carboxyhemoglobin w/ blood test
• Re-call that carboxyhemoglobin will read as oxyhemoglobin when you measure Pulse Ox

Treatment

• 100% O2 +/- hyperbaric chamber

Question 17

?Solvent poisoning

• Example poisons
• Acute vs. chronic presentation
• Tx

Answer 17

Examples

• gasoline
• toluene
• benzene

Presentation

Acute: CNS depression w/ ataxia → coma

Chronic: Neuro- and bone marrow toxicity, leukemia; pneumoinits if inhaled

Treatment

• depends on route of expsoure…?
• If ingested: do NOT induce vomiting → aspiration → pnuemonitis

Question 18

Pesticide Poisoning: Two types

• Relative Toxicity of each?
• S/Sx/Effects?
• Tx?

Answer 18

TWO TYPES

1. Chlorinated hydrocarbons (DTT, DDD, dioxin etc)
   
   • Moderately toxic, bioaccumulates
   • concerns about endocrine disruption
   • no specific treatment
2. Organophosphates

• Can be lethal
• Binds and inhibits Acetyl-cholinestarase → ↑[ACh] → Muscarinic & nicotinic activation → SLUDGE (Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis)
• Tx w/Atropine (block receptor activation) + Pralidoxime (regenerate poisoned cholinesterase)

Question 19

Lead poisoning

• Acute vs. Chronic Presentation
• Pedi complications
• Tx

Answer 19

Acute: abdominal colic and CNS ∆s

Chronic: peripheral neuropathy (wrist-drop), anorexia, anemia, tremor, GI symptoms, RBC Basophilic stippling, lead gum lines (seen here)

• Kids also get: growth delay, neurocog deficits, and developmental delay

Tx: PO Succimer

Question 20

Arsenic Poisoning

• Sources
• Acute Presentation
• Chronic Presentation

Answer 20

Sources

• Acute: intentional poisoning/suicide attempt
• Chronic: usu. enviro (ground water, soil)
• NH: 20% wells water has >10 ppb arsenic
• Bangladesh: wells have >50 ppb

Acute S/Sx

• severe GI discomfort, rice water stools, vomiting
• capillary damage with dehydration and shock (similar to typhoid and cholera)

Chronic

• skin changes, hair loss
  
  • Mee’s lines [seen here] Transverse white lines across nail, in shape of lunula (“nail moon”)
• bone marrow depression, anemia
• nausea and GI disturbances

Question 21

Mercury Poisoning

• Sources
• Acute Presentation
• Chronic Presentation
• Treatment

Answer 21

Sources

• Acute poisoning from inorganic Hg (salts and metallic) usually occupational, dental labs, wood preservatives, insecticides and batteries.
• Organic Hg used was used as anti-fungal agent (seeds, paints, wall paper)
  
  • high potential to bioaccumulate
  • more toxic than ionic or metallic mercury compounds
  • Highly fetal toxic

Acute Presentation

• chest pain shortness of breath
• nausea, vomiting, gastroenteritis
• kidney damage
• CNS damage

Chronic Presentation

• sore gums and teeth
• GI disturbance
• neurological and behavioral changes
  
  • Mad Hatters (felt processing of hats)

Treatment

Chelation should be started asap with:

• PO succimer or
• IM dimercaprol

Question 22

Iron Overdose

• Sources
• Acute Presentation
• Treatment

Answer 22

Sources

• often the result of ingesting too many iron supplement pills, prenatal vitamins/accidental overdose by child

Acute Presentation

• vomiting, GI bleeding
• lethargy
• grey cyanosis
• Subsequent signs of severe GI necrosis can occur, pneumonitis, jaundice, seizures and coma

Treatment

• Can’t use charcoal (does not bind iron)
• use gastric lavage if within 60 minutes
• if longer than an hour use whole bowel irrigation (Polyethylene glycol bowel prep (GoLYTELY, Colyte))
• Deferoxamine is the chelating agent of choice

Question 23

ABCDs of Poison Management

Answer 23

All Poisonings: ABCDs

Airway: cleared of vomitus/obstruction; oral airway or intubate PRN

Breathing: breathing rate, pulse ox, ABGs if doubt. Vent PRN

Circulation: continuous monitoring pulse, BP, urine output, and eval periph perfusion. Place IV line to monitor serum glucose etc.

Dextrose: patients w/ AMS should receive dextrose challenge unless bedside glucose test indicates hypoglycemia not an issue

Question 24

Chelator Basic Facts

Answer 24

• Have 2 (bidentate) or more (polydentate) electronegative groups to complex with cationic metal atoms
• Organometals not chelated
  
  • _​_e.g. Pb in gas, organic Hg thru bioaccum. (e.g. fish)

Question 25

DDx for posioned patient presenting w/ HTN and tachy

Answer 25

Amphetamines, cocaine and anticholinergics

Question 26

DDx for posioned patient presenting w/ hypotension and brady

Answer 26

Calcium channel blockers, beta-blockers, clonidine and sedative hypnotics

Question 27

DDx for poisoned pt presetning w/ Hypotension and tachycardia

Answer 27

Tricyclic antidepressants, vasodilators and beta-agonists

Question 28

DDx for poisoned pt w/ rapid RR

Answer 28

Salicylates, carbon monoxide, other toxins that cause metabolic acidosis or cellular asphyxia.

Question 29

DDx for poisoned pt w/ hyperthermia

Answer 29

sympathomimetics, anticholinergics, salicylates, and drugs producing seizures or muscular rigidity

Question 30

DDx for poisoned pt presenting w/ hypothermia

Answer 30

any CNS-depressant drug, especially when accompanied by exposure to a cold environment

Question 31

What should you screen for w/ Tox screen in suspected poisoning?

Answer 31

*For most cases this takes too long and is not specific to all potential toxins.* Acetaminophen level * assesses need for antidote N-acetylcysteine Serum levels of salicylate (aspirin), ethylene glycol, methanol, theophylline, carbamazepine, lithium, valproic acid, and others * assesses need for hemodialysis

Question 32

Decontamination Techniques

Answer 32

_Charcoal_: * for most ingestions charcoal is favored. (no more ipecac, rare gastric lavage) * large surface area of charcoal absorbs the toxin and unlike emesis and lavage this process can continue as drug passes through intestines, also works for enteric coated pills which are absorbed from intestine and less in stomach * will NOT bind iron, lithium, or potassium and it binds alcohols and cyanide poorly. _Cathartics_: * laxatives may hasten exit of toxin from body but no hard evidence that it helps * Whole bowel irrigation with a balanced polyethylene glycol-electrolyte solution (GoLYTELY, CoLyte) can enhance gut decontamination after ingestion of iron tablets, enteric-coated medicines, slow release formulations, illicit drug-filled packets, and foreign bodies. _Hemodialysis_: especially useful in cases where drug can be removed and fluid and electrolyte imbalances can be corrected (eg, salicylate, lithium), also where toxic metabolites are formed (formic acid in methanol poisoning; oxalic and glycolic acids in ethylene glycol poisoning). _Urinary pH Manipulation_: urinary alkalinization is useful in cases of salicylate overdose (e.g. furosemide plus sodium bicarbonate infusion with potassium to counteract hypokalemia).

Question 33

Acetaminophen Poisoning * Mechanism * Treatment

Answer 33

One of the most common pharmaceuticals seen in both intentional and accidental poisoning. **Mechanism** * normal metabolism is saturated and it is metabolized in the liver via the P450 system to a toxic metabolite * This covalently binds to vital proteins and the lipid bilayer of hepatocytes * this results in hepatic injury and subsequent centrilobular liver necrosis **Treatment** * N-acetylcysteine * ↑ glutathione stores, combines directly with acetaminophen's reactive metabolite as a glutathione substitute, and enhances sulfate conjugation * If within 1-2 hours after ingestion of acetaminophen, use activated charcoal. * Supportive therapy: IV fluids, oxygen, and cardiac monitor.

Question 34

ASA Poisoning * Mechanism * S/Sx * Tx

Answer 34

Mechanism * uncouples oxidative phosphorylation → ↑ O2 consumption, ↑ CO2 production, accelerated activity of glycolytic and lipolytic pathways, depletion of hepatic glycogen, hyperpyrexia * Hyperventilation → resp alk → dehydration & a compensatory metab acidosis **S/Sx** * ↑ anion gap (lactate accum.) * ABG levels: **mixed resp alk and metab acidosis** * ↑ temperature * prolonged bleeding time, GI hemorrhage * nausea & vomiting (from GI irritation & stimulation of CTZ). Vomiting, hyperpnea (↑ depth & rate), and hyperth → dehydration * _Tinnitus_ & reversible _hearing loss_ **Treatment** * ABCs * w/in 60 minutes gastric lavage; longer: charcoal * Sodium bicarb to alkalinize urine → increase salicylate excretion and correct acidosis. * Administer w/ fluids and potentially a diuretic (furosemide) with additional potassium to correct for hypokalemia which will rapidly develop. * Hemodialysis: best method to quickly remove salicylate & restore acid-base balance & fluids in severe poisoning * Consider whole bowel irrigation if large mass of enteric coated pills ingested.

Question 35

5-year old girl is brought to ED in December by her mother, who complains that her daughter seems confused. The mother reports that her daughter has complained of intermittent headaches since the two of them moved into the first floor of an older apartment building 6 months ago. The mother has been at home with the daughter for the past 24 hours and the girl appears lethargic and is complaining of joint aches, nausea, and a headache. P 120, BP 130/85, RR 25, O2 sat 100% on room air. The girl’s mother also notes having a slight headache that started yesterday. Which of the following diagnostic tests should be most rapidly pursued? * A. Carboxyhemoglobin level * B. CT scan of the head * C. Direct laryngoscopy * D. ECG * E. Toxicology screen

Answer 35

A. Carboxyhemoglobin level * The older apartment building may indicate a lead paint risk, however, the time of year, and shared symptoms of mother and daughter suggest carbon monoxide.

Question 36

43 y/o ♂ crop duster is brought to ED w/ weakness and profuse sweating. He is wheezing and has abdominal cramps and diarrhea. PE: miosis, bradycardia, and muscle fasciculations. The patient says that he was spraying a local cornfield with malathion and accidentally flew through his back-draft. Treatment aimed at correcting the patient’s weakness and labored breathing would include: * A) benzodiazepines * B) ipecac * C) nicotine * D) physostigmine * E) pralidoxime

Answer 36

E) pralidoxime * Pt has SLUDGE symptoms (Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis) * Malathion is an **organophosphate** which inhibits acetylcholinesterase (AChE), leading to the accumulation of acetylcholine (Ach). Anti-cholinergic drugs work to counteract the effects of excess acetylcholine by blocking receptor binding (atropine) and reactivating AChE (pralidoxime). * Answer D) physostigmine acts like organophosphates!

Question 37

A mother brings her 3-year-old child to the ED. The child has been vomiting and complaining of abdominal pain all afternoon. He has vomited more than 10 times and the last 2 have contained small amounts of bright red blood. He has had a little nonbloody diarrhea. He has not been tolerating fluids and is beginning to look a little listless. * On exam you find the child to have normal color, but he seems less alert and interactive than you would expect. * T 36.5°C, P 170, RR 28, and BP 98/58. * His abdomen is slightly and diffusely tender. He has dry mucous membranes. * You obtain some lab work and notice that the child has normal renal function but low serum bicarbonate, indicating a possible metabolic acidosis. The mother now suspects he may have been playing with her prenatal vitamins. The child states that he ate a bunch of “candy” in the bathroom (about 3 hours ago). * Part A] What component of prenatal vitamins is most likely the cause of this childs symptoms? * A) Folic acid * B) Iron * C) Calcium * D) Vitamin D. * Part B] Assuming the child took the prenatal vitamins 3 hours ago. What is the best next step in treatment for this patient? * A) Whole bowel irrig w/ polyethylene glycol solution * B) Gastric lavage * C) Activated charcoal * D) Syrup of Ipecac * Part C] •Based on the number of pills the mother now suspects are missing and the severity of the symptoms you decide to use a chelating agent.•Which one would you choose? * A) Succimer * B) EDTA * C) Deferoxamine * D) Dimercaprol

Answer 37

PART A - Answer is B) Iron * Folic acid, calcium, and vitamin D require higher doses to become toxic. * With iron, toxicity in children is evident at doses from 10 mg/kg and up. * If each prenatal vitamin pill contains 30 mg iron (RDA for pregnant women) for a 10kg child 4 pills could be toxic. PART B - Answer is A: Whole bowel irrig w/ P.E.G. sol'n * Iron will have left the stomach by 3 hours and lavage will therefore not be that efficient. * Activated charcoal does not bind iron well * vomiting has already occurred so more vomiting with ipecac will not useful. PART C - Answer is C: De**_fer_**oxamine * Deferoxamine specifically chelates free iron but poorly binds other trace metals. * It does not bind iron that is biologically incorporated e.g. iron in microsomal and mitochondrial cytochromes and hemoproteins

Question 38

A 42 year old woman ingested 30 x 625 mg pills of a common analgesic. Her mother reported that the previous day the patient had shown signs of nausea, vomiting & generalized malaise. The patient confessed to what she had taken previously and the mother then brought her immediately to the Emergency Department. She currently has right upper quadrant abdominal pain with elevated plasma AST & ALT levels. * The specific antidote that should be used to treat this patient is: * A) acetaminophen * B) flumazenil * C) succimer * D) N-acetylcysteine * E) naloxone

Answer 38

Correct answer is D) N-acetylcysteine * In acetaminophen overdose a normally minor metabolite accumulates. * Normally the metabolite is conjugated by glutathione and excreted, but the glutathione reserves can be used up at which point the metabolite is available to damage hepatocytes and potentially cause severe or fatal liver damage. * NAC replenishes the glutathione reserves preventing this from happening.

Question 39

A 74-year old woman with severe osteoarthritis is brought in because of confusion, fever and possible hearing loss which has been observed over the last 2 days. She takes no prescription drugs but does take over-the-counter aspirin for her joint pain. Her family is concerned that she may have taken too many of these pills and the confusion may have exacerbated this. Which of the following would be the best means of treating this patient? * A) Gastric lavage, IV fluids and urine acidification * B) Gastric lavage, IV fluids and urine alkalization * C) Activated charcoal, IV fluids and urine acidification * D) Activated charcoal, IV fluids and urine alkalization

Answer 39

Correct answer is D) Activated charcoal, IV fluids and urine alkalization. * As ingestion was chronic over at least 2 days gastric lavage will not be useful as this would only remove stomach contents. * Activated charcoal will bind drug in the stomach and intestine and is especially indicated for enteric coated drugs. * Aspirin is a weak acid so raising the pH of the urine can increase aspirin excretion by up to 10-fold.