Principles and Practice of Toxicology – PHA442

Quiz 2 Alternative
Name:
ID:
Dr: Yassin Alhariri
Give the correct answers for the questions related to each of the cases below. PLEASE CITE
THE REFERENCE for your answer whenever it is not derived from the correspondent case.

Case 1: Carbon monoxide toxicity

MA is a 71 years old man with a history of coronary artery disease, who after waking one cold
winter morning went to examine his furnace in basement. While downstairs, he acutely
developed headache, nausea, dizziness and near syncope with non radiating substernal chest
pain. He called to his wife who promptly contacted 911.

On arrival in the ED, the patient was noted to be tachycardiac, and tachypneic with a 100% face
mask in place. Physical examination revealed the pt’s skin to be pink, though his distal
extremities were cool to touch and an arterial bld gas demonstrated PH 7.35, COHb of 32%.

Upon further inquiry, the pt reported that he had cleaned his gas furnace with a wire brush the
preceding week. The patient’s wife who had no significant past medical history confided that she
too has experienced headache and nausea while in the house, but she had attributed these
symptoms to recent painting and other home renovation. The wife was immediately tested and
found to have a COHb conc of 28% even though her only symptoms were intermittent headache
and nausea.

Both individuals were initiated with 100% O2 until their COHb conc normalized. The husband
however developed an ataxic gait 2 days after therapy prompting his transfer to an out of state
hospital foe hyperbaric oxygen therapy. Despite of administration of hyperbaric O2 the husband
symptoms did not improve at 2 months follow up.
Questions:

1. In the case above, the fact that CO is a silent killer became evident, what precautions
should have been taken to prevent exposure to CO? (1)

- Install battery-operated or battery back-up CO detectors near every sleeping area in

your home.

- Check CO detectors regularly to be sure they are functioning properly.

2. What are the causes for CO toxicity in the case above? What are other sources for CO
poisoning?

- He had cleaned his gas furnace with a wire brush the preceding week.

- Fumes produced any time you burn fuel in cars or trucks, small engines, stoves,
lanterns, grills, fireplaces, gas ranges, or furnaces.

3. What are the signs and symptoms for CO toxicity? (1)

- Headache, Dizziness, Weakness, Upset Stomach, Vomiting, Chest Pain, Confusion.

4. What are the indications for hyperbaric oxygen therapy? (2)

• You have to do hyperbaric oxygen therapy if you have:

- Severe anemia.

- Brain abscess.

- Bubbles of air in your blood vessels

- Deafness, sudden.

5. Explain the role of heart disease as a probable factor in susceptibility to CO poisoning.

(3)

- One study found a relationship between CO poisoning and a higher incidence of IHD.

- Other study found that individuals with CO poisoning had a non-significantly greater
danger of CAD & CHF and a 1.83-fold higher risk of arrhythmia when compared to the
comparator cohort. Individuals exposed to CO who either had comorbid conditions or
whose severity was severe had a considerably and materially higher risk of developing all
three CVDs.
Case 2: Nicotine toxicity
A 17-year-old boy who had been under "house arrest” at his parent’s home for drug-
related offenses was threatened with being taken to the juvenile detention center because
of a domestic dispute with his family. He told his family that "they'll never take me alive"
and promptly swallowed a brownish liquid from an unlabeled test tube. He had obtained
this solution from a friend, expressly to take his own life in such a circumstance.

Approximately 1 to 2 min later, the patient vomited and collapsed, pulseless, to the
ground. Responding medics performed immediate cardiopulmonary resuscitation (CPR)
and advanced cardiac life support in less than 7 min. His initial rhythm of asystole
converted to ventricular fibrillation with 1 mg of intravenous epinephrine 1:10,000. He was
defibrillated, placed on lidocaine for premature ventricular contractions, given 50 %
dextrose in water (D50W), 2 mg naloxone, and transported to a hospital.

On arrival, the patient was in coma. His pulse was 100 beats/min; blood pressure was
70 mm Hg systolic. Vomitus was present at the nares. Breath sounds were remarkable for
the presence of extensive rhonchi. Bowel sounds were absent. Extremities were flaccid,
with response to deep pain. No corneal or deep tendon reflexes were present. A urine
toxicology screen was positive for nicotine; a serum toxicologic screen was negative.

Mechanical ventilation was maintained. The patient received gastric lavage with 2
L normal saline followed by instillation of 50 g activated charcoal. With the preliminary
diagnoses of overdose of an unknown agent, cardiopulmonary arrest, and probable aspiration
pneumonitis, the patient was managed supportively and admitted to the intensive care
unit. Some time later, detectives arrived with an old bottle of pesticide labeled nicotine
alkaloid, which they had obtained from a friend of the patient. The solution contained 870
mg of nicotine per mL. The patient's serum nicotine concentration, subsequently, was
shown to be 13,600 ng/mL. Over the next couple of hours, the patient had multiple
seizures, which were controlled with diazepam, phenytoin (Dilantin), mannitol, and
dexamethasone (Decadron). A CT scan showed cerebral edema, and EEG and evoked
potential testing showed no cortical function. The patient was assumed to have suffered
anoxic brain death. Intractable hypotension occurred on the 2nd hospital day, and the
patient died 64 hours post-ingestion.
 Questions:

1. What is the pathophysiology of nicotine toxicity? (4)

The symptoms of nicotine toxicity are caused by effects at nicotinic cholinergic receptors.

2. What are the general clinical manifestations for nicotine toxicity? (5)

Headache, coma. seizures, rapid breathing, abdominal cramps.

3. What were the clinical manifestations of nicotine toxicity in the victim?

Coma, seizure, difficult breathing, Vomiting and Hypotension.

4. What was the major cause of death in this victim?

Consuming large amount of concentrated nicotine.

5. Explain the management of nicotine toxicity. (6)

Atropine to slow heart rate.

Benzodiazepine to control seizure.
Ventilator to help breathing.
Case 3: Serotonin toxicity

A 55-year-old man was transferred from a community hospital emergency department to a major
teaching hospital emergency department with chief complaints of altered mental status and fever.
Immediately before transfer, the patient was treated with intravenous vancomycin and
ceftriaxone for possible meningitis. On arrival at the emergency department, the patient was
noted to be confused, restless, and diaphoretic, with a body temperature of 102.7° F and a heart
rate of 130 beats per minute. Further examination revealed tremors at rest, inducible and
spontaneous bilateral myoclonus of the feet, and hyperreflexia, specifically in both lower
extremities. The patient's past medical history included depression and anxiety, for which he had
been taking phenelzine sulfate and clonazepam for the last few years. His spouse reported that he
had been taking tramadol for the last 2 months, as needed, for headaches. A head CT scan
revealed no acute process. A urine drug screen was negative, and a complete blood count was
unremarkable. An arterial blood gas revealed metabolic acidosis with pH 7.32; pC0 2 and p02
were otherwise unremarkable. Due to severe restlessness that did not improve with lorazepam,
the patient was intubated and chemically paralyzed with rocuronium. Diagnostic lumbar
puncture was then done with an opening pressure of 8 mm Hg. Cerebrospinal fluid chemistries,
bacterial antigen, and gram stain were negative. A serum creatine kinase of 24,421 IU/L with
serum myoglobin of 4,944 mg/ml was noted. Aggressive fluid resuscitation using intravenous
saline at 250 cc/hr was initiated. The patient was then admitted to the neurotrauma intensive care
unit (NTICU) with a diagnosis of serotonin syndrome and rhabdomyolysis.

Supportive measures including sedation, mechanical ventilation, and fluid resuscitation were
provided at the NTICU. Phenelzine sulfate and tramadol were withheld. On his second day on
the NTICU, the patient's confusion and agitation improved, no further tachycardia and fever
were noted, and a reduction in tremors and hyperreflexia was observed. Serum creatinine and
CK were within normal limits. The patient was extubated and transferred out of the NTICU after
24 hours.
Questions:

1. What is the pathophysiology for serotonin toxicity? (7)

Either from increased concentrations of 5-HT or medications that act directly as

receptor agonists.

2. What are the signs and symptoms of the disease?

Confused, restless, and diaphoretic, inducible and spontaneous bilateral

myoclonus of the feet, and hyperreflexia.

3. What are the differential diagnoses for serotonin toxicity? (7)

Get a thorough history of the symptoms' onset, medication use, test results, and
clinical course to help distinguish between the various illnesses. The primary
distinction between the other states is neuromuscular activation.

4. Explain the management of the disease.

Identification and discontinuation of the offending serotonergic medication is

necessary for management, followed by supportive therapy such as sedation,
mechanical breathing, and fluid resuscitation.

5. Explain the preventive measures to avoid serotonin toxicity. (7)

Prevention of serotonin syndrome by education of both physicians and patients

regarding potent serotonergic drug interactions, and the clinical signs and
symptoms of serotonin syndrome to look out for.

With all the best and success

References
1. National Center for Environmental Health. Frequently asked questions [Internet]. Cdc.gov.
2022 [cited 2022 Nov 27]. Available from: https://www.cdc.gov/co/faqs.htm

2. Hyperbaric oxygen therapy [Internet]. Mayoclinic.org. 2022 [cited 2022 Nov 27].
Available from: https://www.mayoclinic.org/tests-procedures/hyperbaric-oxygen-therapy/
about/pac-20394380

3. Garg J, Krishnamoorthy P, Palaniswamy C, Khera S, Ahmad H, Jain D, et al.

Cardiovascular abnormalities in carbon monoxide poisoning. Am J Ther [Internet]. 2018
[cited 2022 Nov 27];25(3):e339–48. Available from:
https://pubmed.ncbi.nlm.nih.gov/24518173/

4. Schep LJ, Slaughter RJ, Beasley DMG. Nicotinic plant poisoning. Clin Toxicol (Phila)
[Internet]. 2009;47(8):771–81. Available from:
http://dx.doi.org/10.1080/15563650903252186

5. Nicotine poisoning [Internet]. Mount Sinai Health System. [cited 2022 Nov 27]. Available
from: https://www.mountsinai.org/health-library/poison/nicotine-poisoning

6. Nicotine poisoning [Internet]. Cleveland Clinic. [cited 2022 Nov 27]. Available from:
https://my.clevelandclinic.org/health/diseases/21582-nicotine-poisoning

7. Scotton WJ, Hill LJ, Williams AC, Barnes NM. Serotonin syndrome: Pathophysiology,
clinical features, management, and potential future directions. Int J Tryptophan Res
[Internet]. 2019 [cited 2022 Nov 27];12:1178646919873925. Available from:
http://dx.doi.org/10.1177/1178646919873925