SBM GI > 03-23 Toxicology PHARM > Flashcards
03-23 Toxicology PHARM Flashcards
In the exam the 3 questions will be clinical vignettes concerning cases of poisoning by and treatment for three of the following: —Carbon monoxide —Organophosphate (carbamyl/malathion/parathion) —Iron —Lead —Arsenic —Acetaminophen —Aspirin —Benzodiazepines —Methanol —Ethylene glycol
Dimercaprol
Chelator (arsenic, mercury, lead when give with EDTA)
EDTA calcium or disodium
Chelator (lead)
- used before succimer for acute lead poisoning
- Given w/ Ca2+ b/c it chelates Ca2+ and could cause hypocalcemia
Unithiol
Chelator (acute arsenic, mercury or lead)
Succimer
Chelator (lead in children and adults; acute mercury and arsenic)
Deferoxamine and Deferasirox
Chelator (Iron)
- acute iron poisoning
- iron overload
- blood transfusions
- thalassemia
- myelodysplastic syn
Penicillamine
Chelator (copper/Wilson’s; adjunct for arsenic, gold and lead chelation)
N-acetylcysteine NAC
Antidote for acetaminophen
Activated charcoal
Antidote gastric absorption
Flumazenil
Antidote benzodiazepines
Fomepizole
Antidote methanol and ethylene glycol
Define bioaccumulation
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
Define biomagnification
the fold increase in concentration of a substance that occurs in a food chain as a consequence of bioaccumulation
Define endocrine disruptors
Chemicals in the environment that have endocrine effects (estrogen/anti-androgen/thyroid). Potential cause of infertility, reproductive cancers or birth defects.
Define ADI
Acceptable daily intake (ADI) Daily - intake of chemical which during lifetime appears to be without appreciable risk.
Define Threshold Limit Value (TLV)
Exposure limit to a specific agent for a stated period of time-(shorter time = higher level). Used for occupational control.
CO Poisoning
- Nature of the gas
- Common Sources of CO
- Testing
- Tx
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
?Solvent poisoning
- Example poisons
- Acute vs. chronic presentation
- Tx
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
Pesticide Poisoning: Two types
- Relative Toxicity of each?
- S/Sx/Effects?
- Tx?
TWO TYPES
- Chlorinated hydrocarbons (DTT, DDD, dioxin etc)
- Moderately toxic, bioaccumulates
- concerns about endocrine disruption
- no specific treatment
- 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)
Lead poisoning
- Acute vs. Chronic Presentation
- Pedi complications
- Tx
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
Arsenic Poisoning
- Sources
- Acute Presentation
- Chronic Presentation
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
Mercury Poisoning
- Sources
- Acute Presentation
- Chronic Presentation
- Treatment
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
Iron Overdose
- Sources
- Acute Presentation
- Treatment
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
ABCDs of Poison Management
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
Chelator Basic Facts
- 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)
DDx for posioned patient presenting w/ HTN and tachy
Amphetamines, cocaine and anticholinergics
DDx for posioned patient presenting w/ hypotension and brady
Calcium channel blockers, beta-blockers, clonidine and sedative hypnotics
DDx for poisoned pt presetning w/ Hypotension and tachycardia
Tricyclic antidepressants, vasodilators and beta-agonists
DDx for poisoned pt w/ rapid RR
Salicylates, carbon monoxide, other toxins that cause metabolic acidosis or cellular asphyxia.
DDx for poisoned pt w/ hyperthermia
sympathomimetics, anticholinergics, salicylates, and drugs producing seizures or muscular rigidity
DDx for poisoned pt presenting w/ hypothermia
any CNS-depressant drug, especially when accompanied by exposure to a cold environment
What should you screen for w/ Tox screen in suspected poisoning?
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
Decontamination Techniques
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).
Acetaminophen Poisoning
- Mechanism
- Treatment
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.
ASA Poisoning
- Mechanism
- S/Sx
- Tx
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.
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
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.
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
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!
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
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: Deferoxamine
- 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
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
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.
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
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.