Antidotes & reversal agents

Replenishes glutathione to neutralize toxic NAPQI; most effective within ~8 h of overdose.

For severe anticholinergic toxicity — "red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare, full as a flask." For glycopyrrolate, which crosses the blood–brain barrier poorly, its label suggests neostigmine (also quaternary, so it stays outside the brain) for the peripheral effects and physostigmine, which does cross the blood–brain barrier, if CNS symptoms occur.

Dabigatran → idarucizumab; apixaban/rivaroxaban → andexanet alfa (boxed warning: thromboembolic and ischemic events, cardiac arrest, and sudden death — monitor for thromboembolic events and for signs that precede cardiac arrest, and restart anticoagulation when medically appropriate). Protamine neutralizes heparin; how much is needed depends on the heparin given and falls quickly as time passes after an IV heparin dose, and it is infused slowly. Protamine’s boxed warning: it can cause severe hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, and pulmonary vasoconstriction/hypertension; risk rises with high doses, rapid administration, repeated doses, and prior protamine exposure (including NPH insulin), and fish allergy may add risk — keep vasopressors and resuscitation equipment immediately available, and do not give it for bleeding without prior heparin use. Phytonadione (vitamin K) has its own boxed warning: fatal hypersensitivity reactions, including anaphylaxis, have occurred during and right after IV and IM injection, even with dilution and on the first dose, so the label says to avoid the IV and IM routes unless the subcutaneous route is not feasible and the serious risk is justified.

Competitive benzodiazepine antagonist — reverses sedation/respiratory depression. Use cautiously: it can precipitate seizures or acute withdrawal in benzodiazepine-dependent or chronic-use patients. Its boxed warning says seizures are most frequent after long-term benzodiazepine sedation and in serious cyclic (tricyclic) antidepressant overdose, so be prepared to manage seizures; the label’s warnings add that it is not recommended in serious cyclic-antidepressant poisoning.

Binds and inactivates digoxin; reverses life-threatening toxicity — refractory dysrhythmias, severe bradycardia, or hyperkalemia from acute overdose.

Blocks muscarinic receptors — reverses cholinergic excess (SLUDGE) and the accompanying bradycardia in a cholinergic crisis. In organophosphate poisoning, atropine is given with pralidoxime, which reactivates cholinesterase and treats both muscarinic and nicotinic effects (it works only early, before the enzyme “ages”).

IV 20% lipid emulsion is the antidote for local anesthetic systemic toxicity (LAST) (first explained as a "lipid sink"); dantrolene stops the runaway calcium release of malignant hyperthermia. Each must be immediately available — lipid emulsion wherever potentially toxic local-anesthetic doses are given, dantrolene wherever MH-triggering agents are used.

"Rule of 15": treat, recheck glucose in 15 min, repeat. Not a drug antidote but the NCLEX-critical rescue.

Iron-chelating antidote for acute iron overdose — a leading cause of fatal poisoning in young children. Chelation is indicated for a serum iron above 500 mcg/dL, metabolic acidosis, shock, or signs of organ dysfunction, and is given as a continuous IV infusion (StatPearls).

Reverses magnesium toxicity (respiratory/cardiac depression). Keep at the bedside during the infusion, and give it with caution — calcium can itself precipitate heart block; in a patient taking digitalis the label warns that calcium given for magnesium toxicity can cause serious conduction changes, including heart block.

Toxicity → hold, hydrate, correct sodium; hemodialysis for severe toxicity.

Reverses nondepolarizing blockade only — neostigmine (an AChE inhibitor, give with an antimuscarinic) raises ACh to outcompete the blocker; sugammadex directly encapsulates rocuronium/vecuronium. Depolarizing succinylcholine is not reversible this way. For malignant hyperthermia, give dantrolene immediately.

Pure competitive µ-opioid antagonist; reverses respiratory depression. Short half-life — monitor for re-sedation and repeat as needed.

For overdose cardiotoxicity — TCAs are lethal in overdose (narrow therapeutic index): cardiac sodium-channel blockade widens the QRS (> 100 ms) and causes ventricular arrhythmia. IV sodium bicarbonate overcomes the block. Limit dispensed quantities in at-risk patients.