Naloxone

Pharmacological properties

Naloxone is a competitive opiate receptor antagonist and belongs to the group of so-called pure opiate receptor antagonists. it mainly blocks m-receptors and, thanks to a significant affinity for these receptors, naloxone displaces narcotic analgesics from binding sites, thus eliminating the symptoms of opioid overdose and eliminating the effects of both endogenous opiate peptides and exogenous opioid analgesics; to a lesser extent affects other opiate receptors.

The introduction of naloxone prevents, weakens or eliminates (depending on the dose and time of administration) the effects of opioid analgesics, restores breathing, reduces sedation and euphoria, weakens the hypotensive effect.

Naloxone eliminates the effects of a wide group of narcotic drugs of both agonists and antagonists of opiate receptor agonists: morphine, apomorphine, diamorphine (heroin), codeine, dihydrocodeine, trimeperidine, methadone, pentazocine, fentanyl, buprenorphine.

The drug eliminates central and peripheral toxic symptoms: respiratory depression, narrowing of the pupils, slowing down of the stomach, dysphoria, coma and cramps, as well as the analgesic effect of narcotic analgesics, in addition, it eliminates the toxic effect of high doses of alcohol.

Naloxone is also effective in combating respiratory dysfunctions in mixed poisoning caused by opioids in combination with barbiturates, benzodiazepines and alcohol.

Naloxone provokes withdrawal syndrome in patients with opioid dependence.

The drug does not have analgesic activity, does not cause dysphoria and psychomimetic symptoms, the development of addiction and the formation of drug dependence.

With the on / in the introduction of the drug begins in 0.5–2 minutes, the duration of action is 20–40 minutes. When i / m or s / c administration is effective after 2-3 minutes, the duration of action is 2.5-3 hours. The average half-life is 1-1.5 hours; in newborns, longer (3 hours). Naloxone is metabolized in the liver to form glucuronides. Metabolites are excreted in the urine.

The use of hepatic and renal failure has not been studied. Penetrates through the blood-brain and placental barriers.

Indications

Overdose of narcotic analgesics, benzodiazepines, barbiturates, coma in acute alcohol poisoning. in anesthesiology it is used to accelerate the recovery from anesthesia, neuroleptanalgesia, in case of respiratory center depression caused by halothane or ketamine, during operations for focal epilepsy, before completion of controlled breathing; to restore breathing in newborns after administering opioid analgesics to the mother; with shock in combination therapy; as a diagnostic tool in patients with suspected opioid dependence.

Application

The dose of the drug and the route of administration depend on the condition of the patient and the amount of opioid agent present in the body.

In case of an overdose of narcotic analgesics, Naloxone-M is administered intravenously (slowly dropwise, for 2-3 minutes), intravenously or s / c: for adults - at a dose of 0.4 mg. In life-threatening conditions, an iv route of administration is preferred. If the effect is insufficient, the drug is re-administered in the same dose every 3-5 minutes until consciousness and spontaneous breathing are restored. If, after the introduction of the total dose of 10 mg, the recovery of consciousness and breathing does not occur, then the diagnosis of poisoning with opioid analgesics is called into question.

The initial dose for children is 0.005-0.01 mg / kg body weight. If necessary, repeated administration of the drug is possible. To accelerate the exit from surgical anesthesia, Naloxone-M is prescribed iv in adults at a dose of 0.1-0.2 mg (0.0015-0.003 mg / kg body weight); children - 0.001-0.002 mg / kg body weight every 2-3 minutes until the appearance of spontaneous breathing and recovery of the patient’s consciousness, but without distinct pain and discomfort. If there is no desired effect, the drug is re-administered in doses up to 0.1 mg / kg body weight every 2-3 minutes. If it is impossible to carry out an intravenous injection, the drug is administered intramuscularly or subcutaneously in divided doses.

For newborns, the initial dose is 0.01 mg / kg body weight.The introduction can be repeated in accordance with the principles of use in adults with postoperative respiratory depression on the background of the use of opioid analgesics. In case of respiratory depression in newborns caused by the administration of opioid analgesics during childbirth, Naloxone-M is administered at a dose of 0.1 mg / kg body weight IM, SC or IV. Before administering the drug, you must make sure the airway in the newborn. Perhaps prophylactic IM administration of 0.2 mg (0.06 mg / kg body weight).

To diagnose opioid dependence, Naloxone-M is administered at a dose of 0.8 mg iv and the patients condition is monitored in order to identify signs of withdrawal.

Contraindications

Hypersensitivity to naloxone.

Side effects

With the rapid administration of naloxone-m, various reactions may occur.

From the digestive tract: nausea, vomiting.

From the cardiovascular system: tachycardia, hypertension, cardiac arrest.

From the side of the central nervous system: trembling, cramps.

Allergic reactions: skin rash, itching.

Other: increased sweating.

When using Naloxone-M in the postoperative period in doses exceeding the necessary, analgesia and agitation may disappear, arterial hypotension or hypertension, ventricular tachycardia, ventricular fibrillation, pulmonary edema.

When used in therapeutic doses in patients whose body does not contain opioids, Naloxone-M usually does not cause side effects.

special instructions

The duration of action of some opioid analgesics may exceed the duration of action of naloxone-m, therefore, patients should be under constant medical supervision and in conditions that make it possible to conduct mechanical ventilation and other resuscitation measures.

Patients with opioid dependence should be administered the drug very carefully, since withdrawal syndrome may occur.

Use with caution during pregnancy and lactation. It is not known whether naloxone with breast milk is excreted. The use of the drug during pregnancy and lactation is possible in assessing the risk / benefit ratio.

During the use of Naloxone-M it is forbidden to drive vehicles and service moving mechanisms.

Interactions

Naloxone-m eliminates the analgesic effect of opioid analgesics, reduces the effects of buprenorphine and tramadol, but its effect is short-lived.

With the simultaneous use of Naloxone-M may reduce the antihypertensive effect of clonidine.

Overdose

Symptoms: nausea, vomiting, ag, ventricular tachycardia, ventricular fibrillation, cardiac arrest, pulmonary edema.

Treatment: symptomatic. To prevent overdose, it is necessary to strictly adhere to the recommended doses of the drug.

Storage conditions

In the dark place at a temperature of 15-25 ° C.