Toxicology Board Review

Bing MD, PCP, MDMA, ASA, APAP, CO, MetHb, Weed

• Only 15 questions in all of peer vii??

• Lot of material, but few questions • Key words and descriptives

• Persistant hypoglycemia • Puffer fish, paralysis • Rust remover, pain • Canned food, wound, descending paralysis • Benzocaine, 85% SpO2 • Apnea, brady, hypotension • Blindness acidosis • Bradycardia,hypotension • Seizure, dysrhythmias • Love, toad, bradycardic • Tinnitus • Sulfonylurea, octretide • Tetrodotoxin, supportive • HF, Ca Gluconate • Botulism, antitoxin, supportive • Methemoglobinemia • Clonidine, naloxone • Methanol, fomepizole • BB, CCB • Tricyclic Antidepressants • Digoxin, digifab • Aspirin, bicarb/HD

• Ipecac – Vomit up 6-90% of drug – Toxic substance still in stomach (<1 hr) – Too big for lavage or too deadly – Contraindications: sig prior vomit, ams, asp risk, hypertensive crisis, sharp objects, caustics

Gastric Lavage

• Protect airway, left lat decub, suction • 36-40 French. Children 22-24 French • Acute poisoning (usually <1 hr) • Highly deadly (TCA, colchicine, lithium, BB, CCB) • Contraindication: – Caustic ingestion, large F.B., drug no longer in stomach, clear antidote

Activated Charcoal

• 60-90 Grams. Optimal 10:1 dose ratio • Not good for: lithium, iron, alcohol, sodium, strong acid/alkali • Multi-Dose: good for: phenobarbital, theophylline, digitoxin, phenytoin, carbamazepine. • Contraindication: no gut motility, loss of airway protection • Complication: SBO, ARDS from aspiration • Superior to ipecac

• Whole Bowel Irrigation – May be useful for agents not absorbed by AC, and body packers. – Golytely 1.5-2 L per hour, until effluent is clear – May occupy AC binding sites!

• Cathartic – Increases transit time to prevent desorption phenomenon (unbinding of AC/Drug). – ? Benefit – Sorbitol, Mag sulfate – Potential hypernatremia, hypermag

Question 1

#16: A 15 yo boy is found unresponsive at a party. There is no history of trauma. Vital signs are BP 100/60, HR 40, RR 12, T 36 o C. Physical exam is remarkable for absence of gag reflex with some vomit present in his mouth, PERRL and normal-sized, bradycardia, GCS 3. Cardiac monitor reveals narrow-complex sinus brady; FS is normal; there is no response to naloxone. The patient is intubated for airway protection; CT head is normal. Serum EtOH is 20 on arrival. The patient remains comatose for 5 hours but then suddenly awakens, pulls his ETT out, and attempts to leave.

Which of the following agents induces toxicity that is most consistent with this presentation?

A. Carisoprodol muscle relaxant, sedative, coma B. Flunitrazepam Roofie!, benzodiazepine C. GHB D. MDMA Ecstasy, sympathomimetic, agitation, tachy, hyperthermia E. Oxycodone, sustained release opioid, naloxone responsive

GHB

• g-Hydroxybutyric acid, GABA analog, inhibitory • Narcolepsy, cataplexy, Europe • Anabolic, body builders • Euphoria-inducing/sedating, recreational abuse and date rape • Rapid awakening (unlike Rohypnol) • CNS depression: nystagmus, ataxia, coma, respiratory depression, seizure-like activity, bradycardia, agitation on stimulation, amnesia

MDMA

• ‘ecstasy’, enactogen, enhances love, emotions. Used widely in 70’s. • Serotonergic agonism • Arousal, alertness, tooth grinding, insomnia • Chronic use -> deterioration of serotonergic neurons. • Hyponatremia (adh, oral hydration), sometimes severe!

• Hyperthermia, risk of serotonin syndrome • PMA - more potent, halluc, hypoglycemic, hyperkalemic, seizure, coma, QRS prolong, MAOI.

Amphetamine

• Rx’d for add, weight loss, narcolepsy • Agitation, htn, tachy, MI, hyperthermia • Rhabdo, dehydration • Releases NE/DA, mao inhibits, prevents uptake • Derivative, meth, crystal, ice, crank • Supportive care

Meth mouth

Inhalants

• Hydrocarbons (paint, air fresheners) – Huffing, bagging, sniffing – Euphoria, CNS depression, anoxia – Sudden Sniffing Death, beta-sensitize heart vtach, vfib. B-block, cardiovert. • Organic Nitrites (amyl, isobutyl) – Vasodilation, ‘rush’, relaxation sphincter, ha, nausea, syncope

Question 2

#50 A 40 yo man passed out while using a gas-powered cement cutter in his garage with the doors closed. His wife called 911; paramedics placed him on oxygen with a NRB mask. On arrival he c/o nausea and mild HA only. A venous blood COHb level of 20% confirms CO poisoning; neuro exam is normal. The hospital’s hyperbaric oxygen chamber is available.

What is the rationale for using it to treat this patient?

A. To correct the presumed associated metabolic alkalosis more rapidly causes metabolic acidosis B.

To decrease the COHb level more rapidly no level correlation C.

To decrease the likelihood of death no clear correlation with mortality D. To decrease the likelihood of delayed neurologic sequelae E.

To prevent the development of cardiac dysrhythmias not true

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Carbon Monoxide

• Odorless, colorless gas • Binds hemoglobin. Binds oxygenation disassociation curve to the left ->tissues less O2 • COHb levels (venous as good as arterial) • Smokers 5-10% • Binds to Heme proteins? Lipid peroxidation?

• Hyperbaric O2 to prevent Delayed Neurologic Sequelae (also decreases COHb, corrects acidosis) • DNS (memory changes, cortical blindness, parkinsonism) manifests 2-40 days after exposure.

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Cyanide

• Wool, silk, rubber burning, gold extraction, photography • Nitroprusside, apricots • Cytochrome a3 inhibitor -> cellulor hypoxia • HA, anxiety, hypotension, tachypnea, abd pain • Severe lactic acidosis > 10 • Elevated V O2 saturation • Hydroxycobalamin, sodium thiosulfate, sodium nitrite

Question 3

#86 In which of the following situations of known methanol ingestion are both administration of fomepizole (4 methylpyrazole) and performance of hemodialysis most indicated?

A.

B.

pH/Pco 2 7.10/10; methanol 0 mg/dL; EtOH 0 mg/dL pH/Pco 2 7.10/10; methanol 10 mg/dL; EtOH 300 mg/dL C.

pH/Pco 2 7.10/10; methanol 30 mg/dL; EtOH 30 mg/dL D.

pH/Pco 2 7.40/40; methanol 50 mg/dL; EtOH 10 mg/dL E.

pH/Pco 2 7.40/40; methanol 200 mg/dL; EtOH 300 mg/dL

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Methanol

(solvent in paints, wiper fluid, antifreeze) alcohol dehydrogenase (AD)

Formaldehyde

formaldehyde dehydrogenase

Formic acid

delayed: acidosis abd pain CNS depression snowstorm vision

• Fomepizole – Works as inhibitor of Alcohol dehydrogenase – High cost – Alternative is Ethanol >100 mg/dL • Hemodialysis – To remove methanol and formic acid – Also for high methanol levels (danger level 25) without acidosis (due to 54 hour half-life) – Also give folate in methanol.

Toxic Alcohol

• Isopropanol: rubbing alcohol – CNS depression – Ketosis without acidosis – Hypotension – Supportive mgmt • Ethylene Glycol: antifreeze – Sweet tasting, Urine fluoreses, High AG – Oxalate formation -> ARF. – Oxaluria causes hypocalcemia – Thiamine, pyridoxine

Osmolal gap if >10: 2 Na + Gluc/18 + BUN/2.8 + ETOH/x

M

ethanol 3.2

E

thylene glycol 6.2

D

iuretics (osmotic diuretics like mannitol)

I

sopropyl alcohol 6.4

E

thanol 4.6

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Question 4

#107 A 65 yo man with a severely depressed level of consciousness is brought to the ED by his grandson, who admits that his grandfather has been making moonshine. Labs reveal glucose of 80, EtOH of 40, and hgb of 8. Wrist drop is found on exam.

Which of the following statements regarding the cause of his AMS is correct?

A. Adults are generally thought to be at higher risk of CNS toxicity than children B.

C.

Has a known physiological role at low levels Is associated with a motor neuropathy more commonly than a sensory one D. Most important route of exposure in occupational setting is typically ingestion E.

Withdrawal from the agent can be life threatening

Lead Poisoning “Moonshine” often made in lead radiators Mostly inhaled. Disrupts heme synthesis(anemia), causes lead encephalopathy, Motor neuropathy with classic wrist drop Children more susceptible due to immature BB barrier. Rx: chelation therapy

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Question 5

#121 Which of the following statements regarding warfarin is correct?

A. Cimetidine antagonizes the effect of warfarin B. Clarithromycin antagonizes the effect of warfarin C. Concerns about the risks of increased thrombogenesis soon after initiation of warfarin therapy are largely theoretical D. Warfarin-induced skin necrosis is the most common complication of warfarin treatment E. Warfarin-induced skin necrosis typically occurs soon after warfarin therapy is started

• Blocks activation of Vit K - interferes with II, VII, IX, X, C and S • Initial increase in risk of thrombogenesis • Related to Skin Necrosis, 3-8 days after starting. Thrombosis of small vessels • Most common complication is bleeding • Cimetidine and Clarithroymycin inhibit metabolism of Warfarin -> potentiates effects.

Question 6

#136 A 47 yo man with bipolar disorder presents with confusion, tremulousness, and hyperreflexia. Regarding the agent that the patient is most likely poisoned from, which of the following is correct?

A. Activated charcoal is effective at decreasing the serum half life B.

Chronic toxicity is usually the result of renal failure or intravascular volume depletion C.

CNS symptoms correlate well with serum levels D. Diabetes mellitus is a complication of long-term therapy E.

It is associated with neuroleptic malignant syndrome

LITHIUM

• Confusion, tremor, hyperreflexia • Hypothyroidism, diabetes Insipidus • Can cause serotonin syndrome • Eliminated renally • Chronic toxicity, renal failure, volume depletion • Activated charcoal, not effective • Kayexalate, absorbs lithium and aids in elimination. Though not proven.

• Serum levels do not correlate with CNS sx’s.

Lithium

OG lavage, WBI if sustained release NS 2x maintenance HD: – level >4.0 mEq/L, elevated level and AMS, renal failure, or CHF. Repeat level after HD and 6 hours later.

Question 7

#153 With regard to salicylate poisoning, which of the following is correct?

A. A negative plain radiograph excludes the presence of enteric-coated or sustained-release aspirin in the GI tract B.

Ensuring hypoventilation after intubation is critical in management C.

Reversible sensorineuronal hearing loss correlates with serum salicylate levels D. The Done nomogram is essential in guiding therapy E.

Urinary pH is a determinant of mortality

Salicylates

• Acetyl Salicylate (aspirin) • Methyl Salicylate (deadly) Oil of wintergreen, ben gay, tiger balm • Clinical – N/V, hyperpnea, tachypnea, tachycardia – Tinnitus, confusion, lethargy – Diaphoresis, hyperthermia – Hepatitis, dehydration, rhabdomyolysis, hypokalemia

• Resp Alkalosis first: increase rate and depth • Then AG metabolic acidosis – Sulfuric, phosphoric acids from ARF – Lactic acid – Increase temp from uncoupling of Ox/Pho • Mixed Acid/Base but Alkalemic >7.4

• Then Acidotic from resp acidosis – Tiring out, pulm edema – Weak acid, in ionized form in blood. When acidotic, more is in non-ionized form => more tissue distribution!

• Treatment – Ferric Chloride 10% = purple urine!

– AC – Fluids – Hyperventilation – Urine Alkalinization: Sodium bicarb 3 amps in 1 L D5W with KCl. – Levels not helpful. Can be toxic at low levels. If clinically ASA, treat it – If not getting better, if Pulm edema, AMS, coagulopathy, absolute level >100, get HD

Question 8

#177 A 33 yo woman presents 7 hours after ingesting “about 30” Extra-Strength Tylenol tablets. She is asymptomatic. Acetaminophen level testing is ordered, but results will not be available for 2 hours. Which of the following treatment strategies is most appropriate?

A. Administer activated charcoal B.

Administer the initial dose of N-AC C.

Cancel the test, and request psychiatry consultation D. Perform gastric lavage, and administer activated charcoal E.

Take no action pending test results

Acetaminophen

• Tylenol, percocet, nyquil • Cytochrome p450 pathway leads to NAPQI --> cell dysfxn. • 0.5-24 hr: N/V, anorex, nl phy exam • 24-48 hr: RUQ pain, elev LFT/INR • 48-96 hr: hep dysfxn, acidosis, bleeding, coma • 150 mg / kg guideline toxic dose • pH <7.3, lactate >3.0, high phosphorus level, Cr >3.3 = markers of bad

NAC

• 100% effective if given within 8 hours • Oral: N/V/D • IV: rash, urticaria, angioedema, hypotension - mostly rate related • IV has benefit in hepatic failure • 150 mg / kg over 1 hour • 50 mg / kg over next 4 hours • 100 mg / kg over next 16 hours

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Question 9

#192 30 yo man presents after accidentally spilling household rust remover on his leg. He had no pain initially but has since developed persistent pain. Signs of skin damage are minimal. If the patient is suffering systemic toxicity, which of the following lab abnormalities is expected?

A. Alkalemia B.

Hypercalcemia C.

Hyperkalemia D. Hypermagnesemia E.

Hyponatremia

Hydrofluoric Acid

• Rust removers, etching and frosting glass, tanning, cleaning brick/stone.

• Varying types of exposure • Persistant pain OOPTE. • Life-threatening with dysrhythmias/electrolyte abnormalities • Oral/inhalational potentially fatal (>20% always serious) • Acidosis, hypocalcemia, hypomagnesemia, hyperkalemia. (H+ ions F- ions) • Calcium gluconate: topical, subcutaneous, intradermal injection, intraarterial, IV

Caustics

• Endoscopy for: – intentional ingestions. – Stridor, pain, vomiting, drooling.

• Early - within 24 hours - safer • IV Dex for airway edema • Bleach / Ammonia: household strength 3%, cleared clinically. Industrial - aggressive work-up. • Dishwasher detergent - severe burn

Question 10

#204 Which of the following metabolic complications is most likely to occur in the setting of both therapeutic use and overdose of valproic acid?

A. Elevated ammonia B.

Elevated calcium C.

Elevated carnitine D. Low sodium E.

Metabolic alkalosis

Valproic Acid

• Disruption of urea cycle • Metabolic acidosis, hypernatremia, hypocalcemia, low carnitine, elevated ammonia (complication of therapeutic use) • Hyperammonia: MS changes • Sometimes hepatitis with bumps in AST/ALT. • Carnitine may be beneficial.

• Very rarely renal failure, urea elevation

Question 11

#217 A 28 yo man presents complaining of withdrawal symptoms. He is yawning and sneezing; physical examination reveals mydriasis and piloerection. Which of the following statements regarding this withdrawal syndrome is correct?

A. Altered level of consciousness is typical B.

Buprenorphine administration is contraindicated C.

Clonidine is an effective treatment D. Convulsions occasionally occur E.

Inpateint therapy is required

Opioid Withdrawal

• Mydriasis, diarrhea, N/V, sneezing, piloerection.

• Clonidine helpful at decreasing overactivity. • Methadone and buprenorphine helpful • Outpatient management

Organophosphates

• Pesticides, Herbicides • Muscaric – S L U D G E – Miosis, bradycardia, bronchorrhea, bronchoconstriction • Treatment – Atropine - dose to dry secretions – Pralidoxime - synergistic, more effective earlier used.

Question 12

#225

Both neuroleptic malignant syndrome and serotonin syndrome:

A. Are characterized by autonomic instability and neuromuscular abnormalities B. Are characterized by hyperreflexia and clonus C. Have specific tests to confrm the diagnosis D. Occur soon after initiating drug administration E. Typically occur after overdose

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NMS Dopamine antagonist, occurs anytime after use, lead pipe Rigidity, bromocriptine(DA), amantadine, supportive, cooling. SSS Serotonergic agents, soon after initiating drug, Increased tone in lower ext, clonus, hypereflexia, cyproheptadine (antihistamine)

Malignant Hyperthermia

• Causes: succinylcholine, inhalational anesth • Minutes after use. Uncontrolled release of Ca from Sarcoplasmic reticulum • AMS, rigor mortis muscle tone, hyperthermia, autonomic instability, rising etCO2. • Benzos!

• Cooling • Dantrolene - decreases Ca release

Psych Meds

• SSRI – citalopram (Celexa), Escitalopram (Lexapro), fluoxetine, paroxetine, sertraline – Overdose: N/V, lethargy, sedation – Serotonin syndrome (watch for concomitant cocaine, meperidine, dextromethorphan, ecstasy, lithium) – Celexa and lexapro - watch for delayed QT prolong – Observation in ED for 6 hours.

Psych Meds

• Bupropion (Wellbutrin) - complex mech. Inhibit reuptake of NE, DA, 5HT. Seizure inducing. • Trazodone - CNS depression, hypotension • MAOI: Phenelzine (Nardil), tranylcypromine – Stop meds – Supportive: cooling, nitro for HTN, fluids/NE for hypotension. Benzos for serotonin/anxiolysis. Phentolamine for alpha blockade.

Question 13

#245 A 10-month boy is brought in by his parents after he turned blue at home. The mother says he has been fussy recently, which she presumed to be caused by teething; she has been treating him with a topical teething gel. On exam, the boy has marked cyanosis, including the perioral area and nail beds, mild tachypnea and tachycardia, room air O are normal.

2 sat 88% does not improve with oxygen. Lungs are clear; work of breathing and heart sounds

Which treatment is most likely to be successful in treating the cyanosis?

A. Botulinum antitoxin B. Deferoxamine C. Methylene blue D. Prostaglandin E 1 E. Sodium bicarbonate

MetHb

• Cyanosis: increased deoxygenated Hb or abnormal pigments, e.g. silver (argyria) • Oxidation of Fe in Hb from ferrous 2+ to ferric 3+: cannot bind O 2 , impairs 02 release from remaining normal Hb, shifting curve left • Overdose: benzocaine (teething gels), amyl nitrate, pyridium, sulfonamides • Chocolate-brown blood • Methylene blue accelerates NADPH methemoglobin reductase, contraindicated in G6PD, need exchange transfusion

Question 14

#274 A 15 yo boy BIBEMS after being found unresponsive in his bedroom. Near him was the empty bottle of his mother’s chronic pain pills, amitriptyline. QRS>0.1

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Which effect of the medication is most responsible for his EKG changes?

• • • • • a-Adrenergic receptor inhibition Antihistaminic effects GABA-A receptor antagonism Potassium channel blockade Sodium channel blockade

TCA

• Block reuptake of NE/DA/5HT • Anticholinergic (antimuscarinic) • Na channel blocker, QRS widens, neg inotropy • Alpha blockade: vasodilation • Antihistamine: sedation • Gaba blockade?

• QRS>100, 1/3 with seizure. QRS>160 1/2 Vdysrhythmia. QRS < 100 no tox.

• Right axis with QRS prolong, QT prolong, Sinus Tachy in setting of OD had 100% NPV.

TCA

• Multi dose AC, no ipecac. • Benzo for seizure. Phenytoin contraindicated. • Sodium Bicarb for dysrhythmia • NO physostigmine --> ?asystole, inconsequential effects.

Tox Brady

BB and CCB

• Hypotension, bradycardia • AC, WBI • Atropine, caution if WBI • CaCl2 up to 5 grams. Make sure no Digoxin.

• Glucagon - activates adenyl cyclase. 2-5 mg IVP. • Catecholamine - NE • Insulin / Glucose - cardiac inotropy, chronotropy • Amrinone • IA balloon pump

Digoxin

• Foxglove, Oleander, Bufo Toads, Love Stone • Increase vagal tone. Sinus brady.

• Inhibits Na-K pump • Most common EKG abnormality: PVC. Also see DAD, hyperk, bidirectional QRS, and plenty of blocks • If hyperkalemic = bad • N/V, lethargy, confusion, drowsiness

Digoxin

• MDAC • Treatment: Digibind/Digifab – K > 5, Serum Dig >10, undiagnosed brady, Vent or brady dysrhythmias. • Treatment Dysrhythmias: – Atropine for Brady, – K or Mg replacement, Amiodarone, Lidocaine, Phenytoin, low shocks

Question 15

#379 Which of the following statements regarding the use of ketamine for procedural sedation is correct?

A. Advantages include maintenance of protective airway reflexes and absence of cardiovascular effects B.

Concurrent use of benzos to prevent emergence reactions does not significantly prolong clinical recovery time C.

Development of intense myoclonic jerking indicates a latent seizure disorder and should be treated with a benzo D. Induces dissociation between the cortical and limbic systems, resulting in amnesia, sedation, and analgesia E. Laryngospasm is rare, but when it occurs an emergent surgical rescue airway is often needed

Ketamine

• Peds procedural sedation leading agent • Dissociative anesthetic, PCP derivative (Special K, Fort Dodge, Vitamin K), benzathonium chloride • Analgesia, amnesia, sedation, catecholamine release • Rapid onset: <1 min IV, 5 min IM, Duration: 15 min IV, 30-120 min IM • Atropine/glycopyrrolate decreases salivation/secretions, benzos prolongs recovery by 30% • Side effects: emergence reactions (peds <10yo; hallucinations >10 yo), laryngospasm

PCP (Phencyclidine)

• Nystagmus, mid position, blank stare • AMS, halluc, coma, seizure • Bizarre, labile, agitation • Hyperthermia, rhabdomyolysis • Tachycardic,hypertension, mild • Rx: low dose haldol, benzo, supportive

Mushrooms

• Amanita - death cap, destroying angels, GI sx’s, hepatorenal tox, 5-24 hours after ingestion, multi AC, PCN, Hemoperfusion, 20% mortality, Liver Tx.

• Gyromitrin - GI, coma, seizure, hepatorenal tox, 5 10 hours, mortality rare. Vit B6 antidote for neuro symptoms with benzos. • Coprine - disulfiram like. HA, flush, palp, hypotension. 20-120 min. supportive • Psilocybin - LSD like 30-60 min. Benzos, quiet environment

Snakes

• Crotalid (mobile fangs) – Pit vipers (rattlesnake, cottonmouth, copperhead) – N/V, diaph, paresthesias, weak, resp failure, bleeding, ATN, anaphylaxis, myonecrosis, ARDS – Tetanus, irrigate, mark border, fasciotomy if indicated – Antivenin: proph with diphenhydramine, epi drip ready • Halts swelling, reverses coagulopathy, decreases morbidity – Crofab

Snakes

• Elapid (front fixed fangs) – Coral, cobra, mamba – Local tissue, systemic signs up to 13 hours – Potent neurotoxin: resp failure, paralysis, fasciculations, weakness – Give Eastern coral snake Antivenin right away. 5 10 vials.

Spiders

• Latrodectus (Black Widow) – N/V, diaph, pavor mortis, salivation, htn, tachycardic, ams, seizure, muscle rigidity – Sx’s in a few hours, peak at 1-2 days – Benzo/opioids. – Antivenin for infants, elderly, extreme pain, seizures, CV instability

Spiders

• Loxosceles – Necrotic arachnidism • Erythema, central visible that becomes necrotic within a day. • N/F/C/S, rash, hemolysis, DIC, coagulopathy • Tetanus, dapsone, abx, HBO?, no antivenin.

Fishes

• Scrombroid – Mahi mahi, yellow tail – Bacteria form histamine on surface of fish. – Flushing, n/v/d/abd pain. Palpitations – Rx: h1 block, h2 block, ivf

Ciguatera

• From large reef dwelling fish: sea bass, barracuda, red snapper, yellow-tail • Dinoflagellates produce ciguatoxin • Binds sodium channels and stimulates cholinergics • 2-6 hours after ingestion abdominal pain, n/v/diarrhea.

• Dysesthesia, reversal of temp. Loose/painful teeth. Perioral tingling. Metallic taste. • Hypotension, bradycardia, pruritis, painful ejaculation • AC, IVF, mannitol?, amitryptline for pain.