Exam 1

8 questions per week (lecture)

Recall toxicologic disasters in history and review U.S. regulatory initiatives instated in an attempt to prevent future disasters.

Toxins — naturally occurring harmful chemicals

Xenobiotics — foreign substances/chemicals

Describe how toxicokinetic and toxicodynamic interact to determine the consequences, severity, and duration of toxic effects.

Toxicokinetic — ADME or a toxin/xenobiotic under circumstances that produce toxicity

Toxicodynamic — relationship of toxic xenobiotic concentrations to their clinical effects

Absorption

Site — GI, lungs, skin
principles — solubility, hydrophilicity, simple diffusion, facilitated transport)
Important — Cmax and Tmax

Distribution

Initially — determined by blood flow and rate of diffusion out of the capillary bed → organ or tissue
Final — depends on affinity of substance for various tissues
Concepts to consider — Vd, plasma protein binding, storage, BBB permeability

Metabolism: biotransformation — chemical modification to promote excretion

Phase 1 — oxidation, reduction, and hydrolysis
Phase 2 — conjugation with an ionized group
- Phase 1 and 2 accomplished by small number of enzymes with broad substrate specificities
Site: main site liver, can occur in blood, skin, GI tract, kidneys
Supratherapeutic Doses — enzymes can become saturated → slow metabolism (5 half life rule no longer applies)

Excretion

Site: kidneys, lungs, GI tract, body secretions
- Hydrophilic (charged) — kidney excretion
- Lipophilic (uncharged) — liver metabolism → kidney excretion

Enterohepatic Circulation = Enterohepatic Recycling

compound → excrete into bile → enter intestine → modified → intestinal re-absorption (instead of fecal elimination)
- Examples of drugs: indomethacin, digoxin, methotrexate

Discuss the common tools, procedures, and lab values utilized in assessment and management of toxicology and emergency medicine patients.

Define three characteristics of a drug that make it a good candidate for therapeutic drug monitoring (TDM).

Differentiate trough, peak, and random blood draw types for TDM.

Compare and contrast automated (spectrophotometry immunoassay) and specialized (chromatography, mass spectrometry) methods for drug measurement.

List two benefits and two challenges of urine drug screening.

What kills the patient when they are poisoned?

How can you tell a patient is poisioned? What methods do you use?

Know the toxidromes (Opioids, sedatives/hypnotics, anti-muscarinic, cholinergic, serotonin neurotoxicity, sympathomimetics)

Describe the pathophysiology of acetaminophen toxicity and the role of its toxic metabolite.

Recognize the signs and symptoms of acetaminophen toxicity and interpret laboratory tests, including serum acetaminophen levels.

Outline the indications for acetaminophen toxicity treatment, both acute and chronic.

Review the clinical manifestations and management of acute NSAID toxicity.

Review glucose homeostasis, hypoglycemia presentation and management, and the pathophysiology of T1 and T2 diabetes.

Describe the toxicokinetic and toxicodynamic of common diabetes medication overdoses, including metformin, insulin, and sulfonylureas.

Develop treatment plans for diabetes medication overdoses, including the use of dextrose, octreotide, hemodialysis, and supportive care.

Define how Betablockers, Calcium channel blockers, and digoxin cause bradycardia.

Understand common sources of exposure to toxic doses of caffeine and nicotine.
Understand underlying pathophysiology that leads to toxicity.

Understand the reasoning for the use and avoidance of certain medications in the treatment of toxicity.