ANTIDOTE:Activated Charcoal Dr Rokhsareh Meamar MD, Ph.D Associate Professor of Medical Sciences Department of Medical Toxicology

Mechanism The entire effect of activated charcoal takes place in the GI tract. Oral activated charcoal is not absorbed through the GI wall but passes straight through the gut unchanged. The surface (internal and external) of activated charcoal is manufactured to possess a chemical nature that attracts certain molecules (xenobiotics). Activated charcoal forms an equilibrium between free xenobiotic and xenobiotic that is adsorbed to it through relatively weak intermolecular forces

Mechanism Activated charcoal can also bind substances excreted in the bile, interrupting enterohepatic circulation. The benefits of this technique include its ability to decontaminate the gut without requiring invasive procedures, the rapidity of its administration, and its overall safety in both adults and children. The actual adsorption of a xenobiotic by AC is believed to rely on hydrogen bonding, ion–ion,dipole, and van der Waals forces, suggesting that most xenobiotics are best adsorbed by AC in their dissolved, nonionized form.

Time frame for when decontamination Reviews and recommendations note that clinical benefit is more likely if activated charcoal is administered within I hour of toxin ingestion, but that potential benefit of administration after more than I hour cannot be excluded The absolute time frame for when decontamination is indicated depends on many factors, such as the rate of gastric emptying, the rate of xenobiotic absorption, and the possibility of enterohepatic and enteroenteric recirculation.

Pharmacokinetics Activated charcoal is pharmacologically inert and unabsorbed. Its GI transit time is influenced by the type and quantity of an ingested xenobiotic, fasting and hydration status, muscarinic and opioid receptor xenobiotic properties, perfusion, and the use of associated cathartics or evacuants, among other factors.

Pharmacokinetic In vitro studies demonstrate that adsorption begins within about 1 minute of AC administration but may not achieve equilibrium for 10 to 25 minutes. AC’s clinical efficacy is inversely related to the time elapsed after ingestion and depends largely on the rate of absorption of the xenobiotic. Early AC administration is more important with rapidly absorbed xenobiotics, in which AC functions to prevent xenobiotic absorption by achieving rapid adsorption in the GI tract. After a xenobiotic is systemically absorbed or parenterally administered, AC may still enhance elimination through a mechanism referred to as GI dialysis.

Which one?? Activated charcoal decreases the systemic absorption of most xenobiotics, including APAP, aspirin, barbiturates, cyclic antidepressants, phenytoin, theophylline, and most inorganic and organic materials AC is capable of rapidly removing volatile anesthetic gases such as isoflurane, sevoflurane, and desflurane from anesthetic breathing circuits, which is potentially important in patients who are susceptible to or develop malignant hyperthermia.

Which one?? Notable xenobiotics not amenable to AC are the alcohols, acids and alkalis, heavy metal(iron, arsenic, lead, mercury) lithium, laxatives (magnesium, potassium, and sodium salts).

ROLE OF ACTIVATED CHARCOAL IN GASTROINTESTINAL DECONTAMINATION Single-Dose Activated Charcoal Multiple-Dose Activated Charcoal

Contraindications (SDAC)  Depressed mental status without airway protection (risk of aspiration) The decision to intubate a poisoned patient is often complicated, but it should be made independently of the decision to give AC. In particular, tracheal intubation should not be performed for the sole purpose of giving AC. Late presentation (ie, no toxin is likely to remain in the stomach) Increased risk and severity of aspiration associated with AC use (eg, hydrocarbon ingestion) Need for endoscopy (eg, significant caustic ingestion) – AC is likely to impair visibility during endoscopy Toxins poorly adsorbed by AC (eg, metals including iron and lithium, alkali, mineral acids, alcohols) Presence of intestinal obstruction (absolute contraindication) or concern for decreased peristalsis (relative contraindication)

Concomitant Administration of Activated Charcoal with Cathartics Cathartics are often used with AC; however, evidence suggests that AC alone is comparably effective to AC plus a single dose of cathartic (sorbitol or magnesium citrate) a cathartic is used, it should be used only once. Cathartics decrease the transit time for the passage of the activated charcoal (and presumably the adsorbed toxin) through the GI tract. Repeated doses of magnesium-containing cathartics are associated with hypermagnesemia, and repeated doses of any cathartic are associated with dehydration, hypotension, and severe or fatal fluid and electrolyte derangements. AC with sorbitol is not recommended for children younger than one year of age.

Concomitant Administration of Activated Charcoal with Cathartics Experimental studies have found conflicting evidence regarding reduction in drug absorption when activated charcoal is administered with a cathartic compared with administration of activated charcoal alone. There is no experimental evidence that giving cathartics alone reduces drug absorption, and there are no clinical studies of poisoned patients to indicate that the addition of a cathartic to activated charcoal either limits the toxin's bioavailability or changes the patient's clinical outcome.

Contraindications for cathartic Contraindications for cathartic use are ingestion of a substance that will result in diarrhea, age of <5 years, renal failure (magnesium-containing cathartics are contraindicated), intestinal obstruction, and ingestion of any caustic material

Because sorbitol with AC may cause electrolyte imbalances, it is not recommended in children. However, if sorbitol-containing AC is the only formulation available, it may be given but only for one dose.

ROLE OF ACTIVATED CHARCOAL IN GASTROINTESTINAL DECONTAMINATION Single-Dose Activated Charcoal Multiple-Dose Activated Charcoal

Multiple-Dose Activated Charcoal when large amounts of xenobiotics are ingested and dissolution is delayed when xenobiotic formulations exhibit a delayed or prolonged release phase (eg, enteric coated, extended release), when GI motility is impaired because of co-ingestants, or when reabsorption can be prevented In the postabsorptive phase, MDAC may decrease the elimination half-lives of certain xenobiotics

Multiple-Dose Activated Charcoal Used with dapson, carbamazepine, digitoxin and digoxin, phenobarbitol, theophyline, meprobamate and quinine

MDAC in neonatal MDAC added as an adjunct to phototherapy in neonatal hyperbilirubinemia produced a significantly greater decline in bilirubin concentrations than in those receiving phototherapy alone.

Adverse effects Although the use of AC is relatively safe, emesis, which typically occurs after rapid administration; constipation; and diarrhea frequently occur after AC administration However, black stools that are negative for occult blood, black tongues, and darkened mucous membranes are frequently observed. Serious adverse effects of AC include pulmonary aspiration of AC with or without gastric contents, leading to airway obstruction, acute respiratory distress syndrome, bronchiolitis obliterans, and death; peritonitis from spillage of enteric contents, including AC, into the peritoneum after GI perforation; and intestinal obstruction and pseudo-obstruction, especially after repeated AC doses in the presence of either dehydration or prior bowel adhesions.

PREGNANCY AND LACTATION AC has been safely administered to pregnant patients as part of poisoning management. Murine and lapine studies have not demonstrated any teratogenic risk. Activated charcoal’s lack of absorption would not predispose it to breast milk excretion, although definitive safety in lactation has not been established.

DOSING AND ADMINISTRATION The optimal SDAC dose is unknown. However, most authorities recommend a minimum AC dose of 1 g/kg of body weight or a 10:1 ratio of AC to xenobiotic, up to an amount that can be tolerated by the patient or 25-100g PO Minimum dose :25 g (Maximum dose 100 g)

Children up to one year of age: 10 to 25 g, or 0.5 to 1.0 g/kg   Children 1 to 12 years of age: 25 to 50 g, or 0.5 to 1.0 g/kg (maximum dose 50 g) Mix 1:3 soda for pediatrics Adolescents and adults: 25 to 100 g (with 50 g representing the usual adult dose)

Dose OF MDAC  In general, after the initial dose, AC should be administered by subsequent doses of 0.25 to 0.50 gram/kg (12.5 grams/h) repeated one to three times at intervals ranging from I to 4 hours. Examples of acceptable regimens include 50 g administered every four hours, or 25 g every two hours Multidose: Initial dose: 25 to 50 g; followed by multiple doses of 10 to 25 g every 4 hours

Administration Administration is similar to that of AC, but the concurrent use of a cathartic, such as sorbitol is not recommended. This is of particular importance with young children, in whom the development of diarrhea may lead to dangerous fluid shifts and electrolyte imbalance

Dosage form BICARBON tablet 250 mg Carbogol Capsule NORIT tablet 250 mg