Toxicology – Alcohol Withdrawal

Definition

Alcohol withdrawal is a hyperadrenergic syndrome that develops after abrupt reduction or cessation of alcohol in someone with chronic heavy use. Symptoms can begin within several hours and may progress over the next few days.

Typical Presentation

Early withdrawal commonly causes:

• Anxiety
• Tremor
• Sweating
• Tachycardia
• Hypertension
• Agitation

Some patients may develop symptoms overnight and notice tremor or autonomic symptoms on waking.

Neurologic Features

As withdrawal progresses, patients may develop:

• Hallucinations – visual, auditory, or tactile
• Seizures
• Delirium tremens (DTs)

Alcohol-withdrawal hallucinations can occur while cognition is still relatively preserved.

Delirium Tremens

DTs represent severe withdrawal and are characterized by:

• Marked autonomic hyperactivity
• Confusion or delirium
• Agitation
• Hallucinations
• Severe tremor
• Tachycardia and hypertension

This is a medical emergency and requires close monitoring.

Mechanism of Action

Chronic alcohol exposure increases inhibitory GABAergic tone and suppresses excitatory NMDA/glutamate signaling.

Over time, the brain compensates by:

• Downregulating GABA activity
• Upregulating NMDA activity

When alcohol is suddenly removed, the balance shifts toward excessive CNS excitation, producing autonomic overactivity, hallucinations, and seizures.

Management

Treatment is aimed at controlling CNS hyperactivity and preventing complications.

Main therapies include:

• Benzodiazepines as first-line treatment
• Fluids and correction of electrolyte abnormalities when needed
• Thiamine supplementation in patients at risk of deficiency
• Close monitoring for seizures or delirium

Severe or refractory withdrawal may require:

• Phenobarbital
• ICU-level care
• Airway support if needed
• Additional sedative agents under specialist supervision

Key Points

• Alcohol withdrawal reflects excessive CNS excitation after removal of chronic alcohol exposure.
• Early symptoms are mainly autonomic: tremor, sweating, tachycardia, and hypertension.
• Hallucinations can occur before delirium.
• Seizures and DTs indicate more severe withdrawal.
• Benzodiazepines are the mainstay of treatment.

Toxicology – When Activated Charcoal Is Helpful

Overview

Activated charcoal can reduce gastrointestinal absorption of many ingested toxins when given early, particularly when the substance is known to bind well to charcoal.

Its usefulness depends on:

• The toxin involved
• Time since ingestion
• Amount ingested
• Airway protection
• Gastrointestinal function

Substances Commonly Adsorbed by Activated Charcoal

Examples include:

• Acetaminophen
• Aspirin and other salicylates
• Amphetamines
• Atropine
• Barbiturates
• Carbamazepine
• Colchicine
• Digoxin
• Phenytoin
• Quinine
• Theophylline
• Tricyclic antidepressants
• Valproic acid
• Many other medications and organic toxins

Single-Dose Activated Charcoal

A single dose may be considered when:

• A potentially toxic substance has been ingested
• The substance is known to bind charcoal
• Presentation is early enough that meaningful drug remains in the GI tract
• The patient has a protected airway and no major contraindication

Multidose Activated Charcoal (MDAC)

MDAC involves repeated doses of activated charcoal and can enhance toxin elimination in selected poisonings.

It works by:

• Reducing continued gastrointestinal absorption
• Interrupting enterohepatic or enteroenteric recirculation
• Creating a concentration gradient that promotes movement of some drugs from blood back into the gut

Classic Drugs for MDAC

A common group to remember includes:

• Carbamazepine
• Dapsone
• Phenobarbital
• Quinine
• Theophylline

Aminophylline is also relevant because it is metabolized to theophylline.

Key Points

• Activated charcoal is most useful for toxins that are well adsorbed and still present in the GI tract.
• MDAC is reserved for a relatively small group of drugs, especially carbamazepine, dapsone, phenobarbital, quinine, and theophylline.
• Airway safety remains essential before charcoal administration.
• Charcoal should not be used automatically for every overdose; toxin-specific benefit and contraindications should always be considered.

Toxicology – Mnemonic: When Activated Charcoal Is Not Helpful

Overview

Activated charcoal can reduce gastrointestinal absorption of many toxins when given early after ingestion, but it is not effective for every substance and may be unsafe in certain situations.

Charcoal generally provides little or no benefit for substances that do not bind well to it, including:

• Caustic acids or alkalis
• Heavy metals
• Alcohols
• Hydrocarbons
• Iron
• Lithium
• Some rapidly absorbed or poorly adsorbed toxins

It should also be avoided when there is a major aspiration risk or intestinal obstruction.

Mnemonic – “CHARCOAL”

• C – Caustics / Corrosives

    Charcoal does not meaningfully adsorb strong acids or alkalis and may complicate evaluation of caustic injury.

• H – Heavy Metals

    Metals such as iron and lead are poorly bound by activated charcoal.

• A – Alcohols

    Toxic alcohols and ethanol are not effectively adsorbed.

• R – Rapidly Absorbed Toxins

    Charcoal is less useful once a toxin has already been absorbed.

• C – Cyanide

    Charcoal has limited practical usefulness in severe cyanide poisoning, where rapid antidotal and supportive treatment is the priority.

• O – Other Insoluble / Poorly Adsorbed Substances

    Some compounds simply do not bind charcoal effectively.

• A – Aliphatic Hydrocarbons

    Examples include fuels and similar hydrocarbons; aspiration risk is often more concerning than gastrointestinal absorption.

• L – Laxatives

    Additional cathartic therapy is generally not beneficial and can increase complications.

Contraindications / Situations to Avoid Charcoal

Activated charcoal should generally not be given when:

• The airway is unprotected and aspiration risk is high
• There is bowel obstruction or severe ileus
• Caustic ingestion is suspected
• Hydrocarbon aspiration risk outweighs potential benefit

Key Points

• Activated charcoal is selective, not universal.
• The mnemonic CHARCOAL helps recall substances for which it is usually ineffective or inappropriate.
• Timing matters because charcoal works best before significant absorption has occurred.
• Airway safety is more important than giving charcoal.

Toxicology – Toxins and Conditions Treatable With Dialysis

Overview

Hemodialysis can enhance elimination of certain toxins, especially substances that are relatively small, water-soluble, have a low volume of distribution, and are not highly protein bound. It is also useful when poisoning causes severe acid-base abnormalities, kidney failure, or life-threatening clinical deterioration.

A classic memory aid for major dialysis indications is “AEIOU”, while several toxicologic agents are especially important to recognize.

Isopropanol

Hemodialysis can remove isopropanol, but it is rarely required.

It may be considered in exceptionally severe poisoning with:

• Profound hypotension
• Severe CNS depression
• Markedly elevated concentrations with clinical instability

Salicylates

Hemodialysis is an important treatment for severe salicylate poisoning.

It should be considered when there is:

• Severe neurologic toxicity
• Pulmonary edema
• Significant acid-base disturbance
• Kidney dysfunction
• Progressive clinical deterioration
• Very high serum salicylate concentrations

Clinical status is generally more important than relying on a single concentration cutoff.

Theophylline / Methylxanthines

Extracorporeal removal can be useful in severe theophylline toxicity, particularly when there is:

• Refractory hypotension
• Serious ventricular dysrhythmias
• Persistent or recurrent seizures
• Severe toxicity with markedly elevated serum levels

Uremia

Uremia results from accumulation of nitrogenous waste products in advanced kidney dysfunction.

Possible manifestations include:

• Nausea and vomiting
• Weakness
• Confusion or altered mental status
• Neuropathy
• Muscle cramps
• Seizures
• Pericarditis or pericardial effusion

Dialysis removes accumulated toxins and helps correct associated fluid, electrolyte, and acid-base abnormalities.

Methanol

Hemodialysis removes both methanol and formate, its major toxic metabolite.

It is especially important when methanol poisoning causes:

• Significant metabolic acidosis
• Visual abnormalities
• Kidney dysfunction
• Severe clinical deterioration
• High methanol concentrations

Dialysis is usually combined with inhibition of alcohol dehydrogenase using fomepizole.

Barbiturates

Dialysis may be considered in selected cases of severe barbiturate poisoning, particularly with long-acting agents such as phenobarbital and severe persistent toxicity.

Hemodialysis is generally more effective than peritoneal dialysis for toxin removal.

Lithium

Lithium is highly dialyzable and hemodialysis may be required in severe poisoning.

Important indications include:

• Significant neurologic toxicity
• Seizures or coma
• Kidney failure
• Serious cardiovascular instability
• Persistently high or rising lithium concentrations

Repeat dialysis may sometimes be necessary because lithium can redistribute from tissues back into the bloodstream after treatment.

Ethylene Glycol

Hemodialysis removes ethylene glycol and its toxic metabolites.

It may be needed when there is:

• Severe metabolic acidosis
• Acute kidney injury
• Major electrolyte abnormalities
• Severe clinical toxicity
• High ethylene glycol concentrations

Treatment is usually combined with fomepizole to prevent continued formation of toxic metabolites.

Key Points

• Dialysis decisions should be based on the patient’s clinical condition, laboratory abnormalities, toxin characteristics, and serum concentration, rather than a single number alone.
• Important dialyzable toxins include salicylates, lithium, methanol, ethylene glycol, and theophylline.
• Hemodialysis is usually preferred over peritoneal dialysis when rapid toxin removal is required.
• Severe neurologic toxicity, refractory shock, major acidosis, or kidney failure are common reasons to consider extracorporeal treatment.

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125. Toxicology – Antidote: Hyperbaric Oxygen Therapy (HBOT)

Indications

Hyperbaric oxygen therapy may be considered for selected severe poisonings involving asphyxiant toxins, particularly carbon monoxide poisoning. It has also been discussed as an adjunct in severe hydrogen sulfide or cyanide toxicity, although evidence is much less established for these exposures.

Asphyxiant Toxins

Asphyxiants interfere with normal aerobic metabolism and oxygen utilization.

They can be divided broadly into:

• Simple asphyxiants: Reduce the amount of available oxygen in the surrounding environment.
• Systemic asphyxiants: Interfere with oxygen transport or prevent cells from using oxygen normally.

Examples include:

• Carbon monoxide: Forms carboxyhemoglobin and interferes with oxygen delivery
• Cyanide: Inhibits mitochondrial cytochrome oxidase
• Methemoglobin-forming agents: Oxidize hemoglobin so it cannot effectively carry oxygen
• Hydrogen sulfide: Can inhibit mitochondrial respiration in a manner similar to cyanide

Mechanism of Action

HBOT exposes the patient to 100% oxygen at pressures greater than normal atmospheric pressure, usually in a specialized hyperbaric chamber.

This greatly increases the amount of oxygen dissolved directly in the plasma, allowing oxygen delivery to tissues even when hemoglobin-dependent transport is impaired.

In carbon monoxide poisoning, HBOT also:

• Accelerates removal of carbon monoxide from hemoglobin
• Improves tissue oxygenation
• May reduce ongoing neurologic injury in selected severe cases

Clinical Use

For carbon monoxide poisoning, HBOT may be considered when significant features are present, such as:

• Loss of consciousness
• Persistent neurologic abnormalities
• Myocardial ischemia or serious cardiac involvement
• Severe metabolic acidosis
• Pregnancy with significant exposure
• Other evidence of severe poisoning

Exact indications vary, so consultation with a hyperbaric medicine specialist, poison center, or medical toxicologist is recommended.

Risks and Contraindications

Potential complications include:

• Ear or sinus barotrauma
• Oxygen toxicity
• Pulmonary barotrauma
• Claustrophobia

An untreated pneumothorax is the major absolute contraindication because increased chamber pressure can worsen trapped pleural air.

Key Points

• HBOT increases the amount of dissolved oxygen in plasma.
• Its best-established toxicologic role is in selected cases of severe carbon monoxide poisoning.
• Its role in cyanide and hydrogen sulfide poisoning is much less certain and should not delay established antidotal and supportive treatment.
• Hyperbaric treatment requires specialist consultation and access to an appropriate facility.

Toxicology – Antidotes: Atropine & Pralidoxime (2-PAM)

Indications

Atropine and pralidoxime are used for cholinergic poisoning, especially from:

• Organophosphate insecticides
• Nerve agents
• Selected carbamate insecticides

These poisonings result from excessive acetylcholine activity caused by inhibition of acetylcholinesterase.

Mechanism of Action – Atropine

Atropine is a competitive muscarinic acetylcholine receptor antagonist.

It blocks the effects of excess acetylcholine at muscarinic receptors and is especially important for treating:

• Excess bronchial secretions
• Bronchospasm
• Bradycardia
• Other muscarinic manifestations

Atropine does not reverse the underlying acetylcholinesterase inhibition and has limited effect on skeletal muscle weakness.

Mechanism of Action – Pralidoxime (2-PAM)

Organophosphates bind to and inhibit acetylcholinesterase, causing acetylcholine to accumulate.

Pralidoxime can reactivate the inhibited enzyme by removing the organophosphate from acetylcholinesterase, provided this is given before the enzyme-toxin complex undergoes “aging.”

Aging refers to a chemical change that makes the organophosphate–acetylcholinesterase bond effectively irreversible.

Pralidoxime is particularly helpful for nicotinic and neuromuscular effects, including:

• Muscle weakness
• Fasciculations
• Respiratory muscle paralysis

Management

Treatment priorities include:

• Airway and respiratory support
• Rapid atropine administration for significant secretions and respiratory compromise
• Pralidoxime for suspected organophosphate toxicity
• Benzodiazepines for seizures, marked agitation, or severe muscle activity
• Appropriate decontamination while protecting healthcare personnel from secondary exposure

Atropine may need to be repeatedly administered and titrated to improvement in airway secretions and ventilation, rather than to a fixed total dose.

Carbamate Poisoning

Carbamates generally inhibit acetylcholinesterase reversibly and for a shorter duration than organophosphates.

• Atropine remains important
• The benefit of pralidoxime is less certain, but it may be considered in severe or unclear cholinergic poisoning when organophosphate exposure cannot be excluded

Key Points

• Atropine treats muscarinic symptoms, especially excessive secretions and bronchospasm.
• Pralidoxime reactivates acetylcholinesterase before aging occurs.
• Early pralidoxime is most important in significant organophosphate poisoning.
• Severe cases may require unusually large cumulative amounts of atropine.
• Benzodiazepines are used when seizures or severe CNS manifestations occur.

Toxicology – Ipecac

Indication

No routine indication. Syrup of ipecac was historically kept in homes to induce vomiting after accidental poison ingestion, especially in children. It is no longer recommended for routine prehospital management of poisoning.

Mechanism of Action

Ipecac is derived from the roots and rhizomes of the Cephaelis ipecacuanha plant.

It causes vomiting through two main effects:

• Direct irritation of the stomach and intestinal lining
• Stimulation of the central chemoreceptor trigger zone

Why It Is No Longer Recommended

Inducing vomiting has not been shown to reliably improve outcomes after poisoning and can create additional problems, including:

• Aspiration
• Delayed administration of more effective treatments
• Prolonged vomiting
• Difficulty giving activated charcoal or other therapies

Adverse Effects

Repeated or chronic use can cause significant toxicity, including:

• Persistent vomiting
• Electrolyte disturbances
• Muscle weakness
• Cardiomyopathy

Key Points

• Ipecac should not be used routinely after toxic ingestion.
• It has largely been replaced by supportive care and more selective decontamination strategies.
• Chronic misuse can cause serious cardiac toxicity.
• Poisoning exposures should be discussed with a poison control center or medical professional rather than treated by inducing vomiting at home.

Toxicology – GI Decontamination: Whole Bowel Irrigation

Indications

Whole bowel irrigation (WBI) may be considered for selected poisonings in which a substance is expected to remain in the gastrointestinal tract for a prolonged period.

Examples include:

• Large ingestions of sustained-release or enteric-coated medications
• Certain slowly absorbed toxic substances
• Some iron or lead ingestions
• Ingestion of multiple transdermal patches
• Selected sustained-release drugs such as calcium channel blockers, theophylline, venlafaxine, or bupropion

Because evidence and indications vary, WBI should generally be discussed with a medical toxicologist or poison control center.

Mechanism of Action

WBI uses a polyethylene glycol–electrolyte lavage solution (PEG-ELS) to rapidly move gastrointestinal contents through the bowel.

PEG-ELS is designed to be essentially iso-osmotic, allowing large volumes to pass through the intestine with relatively little net fluid or electrolyte absorption.

The goal is to:

• Shorten gastrointestinal transit time
• Reduce continued absorption of substances still present in the bowel
• Promote elimination of intact tablets, drug packets, or poorly absorbed toxic material

Administration

PEG-ELS is given orally or through a nasogastric tube in a monitored setting and continued until bowel output is adequately cleared.

The exact rate and duration depend on factors such as:

• Patient size and age
• Substance involved
• Clinical condition
• Tolerance of the lavage

Important Limitations

WBI is not appropriate for every overdose and may be unsafe in patients with:

• Bowel obstruction or ileus
• Gastrointestinal perforation
• Significant GI bleeding
• Hemodynamic instability
• An unprotected airway or high aspiration risk

Key Points

• WBI is most useful when the toxic substance may remain in the gut for a long time.
• It is conceptually similar to bowel preparation used before colonoscopy, but in toxicology it is used for decontamination.
• Polyethylene glycol (PEG) is completely different from ethylene glycol, the toxic alcohol found in antifreeze.
• WBI should be used selectively and usually with toxicology guidance.

Toxicology – Antidote: Octreotide for Sulfonylurea Poisoning

Indication

Octreotide is used for sulfonylurea or meglitinide overdose, especially when recurrent or persistent hypoglycemia is occurring.

Mechanism of Action

Octreotide is a long-acting somatostatin analog that suppresses insulin release from the pancreas.

In sulfonylurea poisoning, giving dextrose raises the blood glucose but can also stimulate additional insulin secretion, causing another episode of hypoglycemia. Octreotide helps break this cycle by reducing pancreatic insulin release.

It is usually used together with dextrose to:

• Correct low blood glucose
• Reduce recurrent hypoglycemia
• Decrease the need for repeated dextrose administration

Administration

Octreotide is typically given by subcutaneous or IV dosing at repeated intervals, with the exact regimen adjusted for age, severity, and clinical response.

Treatment should be accompanied by close glucose monitoring, particularly because recurrent hypoglycemia can occur after the initial correction.

Monitoring

Important monitoring includes:

• Frequent bedside blood glucose checks
• Mental status
• Oral intake when appropriate
• Recurrence of hypoglycemia after dextrose is reduced or stopped

Key Points

• Octreotide helps prevent the cycle of repeatedly “chasing the glucose” with dextrose.
• It works by inhibiting insulin secretion, rather than simply raising blood glucose.
• Children with suspected sulfonylurea ingestion require particularly cautious observation because even small exposures can cause prolonged hypoglycemia.
• Recurrent hypoglycemia may occur for many hours, so observation is often necessary even after the glucose initially normalizes.

Toxicology – Antidote: Digoxin Immune Fab

Indications

Digoxin immune Fab is the specific antidote for severe or life-threatening cardiac glycoside toxicity. It may be considered when poisoning produces findings such as:

• Hemodynamic instability or significant hypotension
• Severe symptomatic bradycardia or advanced conduction abnormalities
• Dangerous ventricular dysrhythmias
• Significant hyperkalemia in acute poisoning
• Rapidly worsening toxicity after a major exposure

It can also bind several naturally occurring cardiac glycosides found in plants such as foxglove, oleander, dogbane, milkweed, and lily of the valley.

Mechanism of Action

Digoxin immune Fab consists of antibody fragments that bind circulating digoxin and related cardiac glycosides.

Once bound:

• Free digoxin concentrations fall
• Digoxin dissociates from its tissue receptors
• Inhibition of the Na⁺/K⁺-ATPase decreases
• The digoxin–Fab complexes are subsequently cleared from the body

This can rapidly reverse serious cardiac and systemic toxicity.

Digoxin Toxicity Mechanism

Normally, digoxin inhibits the Na⁺/K⁺-ATPase pump, increasing intracellular sodium.

This reduces the activity of the Na⁺/Ca²⁺ exchanger, causing intracellular calcium to rise. More calcium becomes available for release from the sarcoplasmic reticulum, producing digoxin’s positive inotropic effect.

At toxic concentrations, however, excessive intracellular calcium promotes abnormal automaticity and dysrhythmias. Digoxin also increases vagal activity, which slows the sinus rate and conduction through the AV node.

Administration

The amount of digoxin immune Fab required depends on factors such as:

• Whether toxicity is acute or chronic
• The estimated amount of digoxin involved
• Serum digoxin concentration when appropriately timed
• Severity of the patient’s clinical findings

In severe emergencies, empiric treatment may be given without waiting for laboratory confirmation. Dosing should follow current toxicology or poison-center guidance.

Monitoring After Fab

Monitor:

• ECG and cardiac rhythm
• Potassium
• Renal function
• Blood pressure and clinical response

Potassium may decrease rapidly as toxicity reverses, so hypokalemia can develop after treatment.

Important Laboratory Point

After an acute ingestion, a digoxin concentration obtained too early—before tissue distribution is complete—can be difficult to interpret; levels are generally most useful several hours after ingestion.

After digoxin immune Fab is administered, routine digoxin assays can measure both bound and unbound drug and may therefore show a markedly elevated total digoxin concentration that does not represent ongoing toxicity.

Key Points

• Digoxin immune Fab directly binds and neutralizes circulating cardiac glycosides.
• Severe dysrhythmias, cardiovascular instability, and significant hyperkalemia are important warning signs of serious toxicity.
• Digoxin’s increased contractility comes from increased intracellular Ca²⁺, while its slowing of heart rate and AV conduction is largely related to enhanced vagal effects.
• Do not interpret routine serum digoxin levels normally after Fab has been administered.