Toxicology & Drug Management

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Incoming: Crush Injury

A construction worker has been pinned under rubble for 2 hours. Rescue is about to lift the debris.

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Clinical Scenario

27-year-old male, alert, right leg pinned under concrete slab. Vitals stable. Fire department is ready to lift. What do you do BEFORE they lift?

What's your first order?

The Golden Rules of Drug Absorption

Acids (pKa < 7)

Want to absorb MORE of an acid? → Add more acid (keeps it neutral/fat-soluble)

Want to block absorption of an acid? → Add a base (charges it up/water-soluble, pee it out)

Bases (pKa > 7)

Want to absorb MORE of a base? → Add more base (keeps it neutral/fat-soluble)

Want to block absorption of a base? → Add an acid (charges it up/water-soluble, pee it out)

💡 Board Translation

Neutral = fat-soluble = crosses membranes = bioavailable
Charged = water-soluble = stays in lumen/blood = excreted

Same pH → keeps it neutral → more absorption
Opposite pH → charges it → blocks absorption / promotes excretion

Acidic Drugs You Need to Know

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Aspirin

Acid

Mechanism Noncompetitive COX-1 and COX-2 inhibitor — irreversibly acetylates cyclooxygenase

Absorbed In the stomach — low pH keeps aspirin neutral and fat-soluble

Overdose? Give a base → charges it up → can't cross membranes → excreted

Board trap Reye Syndrome — aspirin + viral illness in kids → hepatic/cerebral damage. Never give aspirin to children with flu/chickenpox.

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Barbiturates

Acid

Mechanism Increase DURATION of chloride channel opening → enhances GABA effects → CNS depression

vs Benzos Benzos increase frequency. Barbiturates increase duration. 🔑Bar-DURATION — bars last all night (duration). Ben-FREQUENTly — you see Ben frequently.

Overdose? Give a base → charges it → excrete it

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Myoglobin

Very Acidic Protein

Why it kills Rhabdomyolysis releases myoglobin from crushed muscle → it has strong affinity for the kidney → acute kidney injury is the first organ hit

Causes Statins, crush injury, staph scalded skin syndrome, prolonged immobilization, seizures

Treatment IV fluids + bicarbonate — bicarb gives myoglobin a negative charge → decreases bioavailability → kidney excretes it instead of absorbing it

🚨 Crush Injury Protocol

Step 1: Get IV access immediately

Step 2: Start bicarb drip BEFORE lifting the object — this is critical

Step 3: Why before? All myoglobin is tamponaded (trapped) under the object. The second you lift it, the myoglobin floods the circulation

Step 4: Lift the object — bicarb is already protecting the kidneys

Step 5: Monitor renal function — myoglobin → dark brown urine, elevated CK

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TCAs (Tricyclic Antidepressants)

Acid

Key Drug Amitriptyline — drug of choice for chronic neuropathy

The Problem TCAs do 6 different things — they're dirty drugs. This makes overdose incredibly dangerous and unpredictable.

☝ Tap each action to expand:

Blocks Reuptake

Blocks reuptake of dopamine, norepinephrine, serotonin — all three go up. Increases sympathetic tone. This is why BP can go UP on one day...

Anticholinergic

Strongly anticholinergic → hot, dry skin, hyperthermia. Classic clue: no sweating (sweat glands are the only sympathetic tissue that's cholinergic). This is how you tell anticholinergic apart from pure sympathetic.

Blocks α1 Receptors

Alpha-1 normally causes vasoconstriction. Block it → vasodilation → blood pressure drops. So the same drug can raise OR lower BP depending on which action dominates that day.

Blocks Na+ Channels

Blocks sodium channels in the ventricle → widened QRS → risk of fatal arrhythmia. This is the lethal mechanism in TCA overdose.

Blocks AV Conduction

Slows conduction through the AV node → heart blocks, bradycardia.

Antihistaminic

H1 blockade → sedation, weight gain. This is why TCAs make you sleepy and hungry.

Basic Drugs You Need to Know

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Amphetamines

Base

Overdose Tx Give an acid → charges the amphetamine → water-soluble → excreted

Alert pt? If the patient is alert, give an acid orally (ex: Cola, orange juice) while waiting for EMS

Board Tip Remember: amphetamines are bases because they have an amine group (NH2) — amines are basic

The Medical Arsenal

Role	Agent	Formula	Use When...
Main Medical Acid	Ammonium Chloride	NH4Cl	Base overdose — need to acidify
Main Medical Base	Sodium Bicarbonate	NaHCO3	Acid overdose — need to alkalinize

☣️ Toxicology Management Protocols

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Weak Acid Ingestion

Patient swallowed aspirin/barbiturates/acetaminophen

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Treatment: Give a base → charges the acid → water-soluble → excreted

Options: Sodium bicarbonate (NaHCO3) or milk (basic)

90% of drugs are weak acids — this is the most common scenario

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Weak Base Ingestion

Patient swallowed amphetamines or other basic drugs

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Treatment: Give an acid → charges the base → water-soluble → excreted

Options: Ammonium chloride (NH4Cl) or acidic juice (Cola, OJ)

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Unknown Substance

Patient ingested something but you don't know what

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Assume it's a weak acid (90% of drugs are weak acids)

Treatment: Activated charcoal — binds the substance in the GI tract before absorption

Charcoal works best within 1-2 hours of ingestion

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Caustic / Corrosive Ingestion

Patient swallowed drain cleaner, bleach, or battery acid

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⚠️ DANGER ZONE — Different Rules Apply

DO NOT give the opposite pH! Acid + base → exothermic reaction → thermal burn ON TOP of the chemical burn

DO NOT induce vomiting! The caustic substance already burned the esophagus going down. Vomiting burns it AGAIN coming up.

DO: Give water — dilutes the substance, no chemical reaction

DO: Supportive care — protect the airway, assess for perforation

Chronic Complications

Stricture — scarring narrows the esophagus

Squamous cell carcinoma — chronic irritation/repair → metaplasia → dysplasia → cancer. Board loves this long-term complication.

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Incoming: TCA Overdose

A 45-year-old with depression found unresponsive with empty amitriptyline bottle.

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Clinical Scenario

EKG shows widened QRS. BP is 80/50. Skin is hot and dry. Pupils dilated. What is the MOST concerning cardiac finding, and what is your treatment?

What's the most dangerous thing happening to this heart?

🎯 Board Blitz

10 random questions from a pool of 16 — reload for a new set

☣️ Toxicology & Drug Management