Naloxone

NALOXONE

Mechanism of Action

Naloxone (Narcan) is a competitive opioid receptor antagonist. Its affinity for opioid µ receptors appears to be much greater than for opioid κ or δ receptors Naloxone has no significant agonist activity.

Clinical Uses

Naloxone reverses the agonist activity asso-ciated with endogenous (enkephalins,endorphins) or exogenous opioid compounds. A dramatic example is the reversal of unconsciousness that occurs in a patient with opioid overdose who has received naloxone. Perioperative respiratory depression caused by excessive opioid administra-tion is rapidly antagonized (1–2 min). Some degree of opioid analgesia can often be spared if the dose of naloxone is limited to the minimum required to maintain adequate ventilation. Low doses of intra-venous naloxone reverse the side effects of epidural opioids without necessarily reversing the analgesia.

Side Effects

Abrupt reversal of opioid analgesia can result in sympathetic stimulation (tachycardia, ventricular irritability, hypertension, pulmonary edema) caused by severe, acute pain, and an acute withdrawal syn-drome in patients who are opioid-dependent. The extent of these side effects is proportional to the amount of opioid being reversed and the speed of the reversal.

Dosage

In postoperative patients experiencing respira-tory depression from excessive opioid administra-tion, intravenous naloxone (0.4 mg/mL vial diluted in 9 mL saline to 0.04 mg/mL) can be titrated in increments of 0.5–1 mcg/kg every 3–5 min until adequate ventilation and alertness are achieved. Doses in excess of 0.2 mg are rarely indicated. The brief duration of action of intravenous naloxone (30–45 min) is due to rapid redistribution from the central nervous system. A more prolonged effect is almost always necessary to prevent the recurrence of respiratory depression from longer-acting opi-oids. Therefore, intramuscular naloxone (twice the required intravenous dose) or a continuous infu-sion (4–5 mcg/kg/h) is recommended. Neonatal respiratory depression resulting from maternal opioid administration is treated with 10 mcg/kg, repeated in 2 min if necessary. Neonates of opioid-dependent mothers will exhibit withdrawal symp-toms if given naloxone. The primary treatment of respiratory depression is always establishment of an adequate airway to permit spontaneous, assisted, or controlled ventilation.

Drug Interactions

The effect of naloxone on nonopioid anesthetic agents such as nitrous oxide is insignificant. Naloxone may antagonize the antihypertensive effect of clonidine.