Naloxone is an opiate antagonist that is used to treat intoxication or overdose from opiates (mainly heroin). It also has among its indications to treat respiratory depressions or CNS (Central Nervous System) depressions.

In this article we will know its characteristics, routes of administration, mechanism of action, adverse reactions, indications and precautions to be taken regarding its use.

Naloxone: characteristics

Naloxone is an opioid antagonist drug, which is indicated to treat opioid poisoning and respiratory depression . The fact that it is an opiate antagonist means that it “slows down” or blocks the effect of the substance. It is usually given as an injectable solution.

The main contraindication of naloxone is to present a hypersensitivity to it , or hypersensitivity to its main compound, naloxone hydrochloride (or any of its excipients).

Opiates

To understand how naloxone works, it is also important to know what an opiate is.

Opioids are substances that reduce pain, i.e. pain-relieving substances. They are natural substances (from seeds called “opium poppies”), but they can also be synthesized; moreover, can be used as drugs or as medication (depending on their use, characteristics,…). Opiates are morphine, heroin, hydrocodone, codeine, etc. These molecules act by binding to opioid receptors (a type of protein), minimising the person’s perception of pain .

Routes of administration

Naloxone is usually given intravenously (IV) through a solution for injection . It may also be given intramuscularly (IM), or it may be given through an intravenous infusion. The latter route of administration, which is less well known, consists of continuously introducing an intravenous solution into the bloodstream; it is performed by means of a catheter inserted into a peripheral or central vein.

However, it is important to note that in acute cases (especially for overdose of opiates such as heroin), the most recommended route of administration will be the intravenous (IV) route, since the effect occurs more quickly; specifically, the effect becomes evident after approximately 2 minutes. The duration of the effects will always depend on the dose ; in any case, it is generally between 1 and 4 hours.

If a second or third dose is needed, this will always depend on the opiate to be antagonized (or the type of respiratory depression or CNS that the patient has); specifically, the type, amount and route of administration used, among others.

Mechanism of action

Naloxone is actually composed of naloxone hydrochloride, which is a semi-synthetic derivative of morphine (a natural opiate). Its mechanism of action involves specifically antagonizing opioids; specifically, it acts by competing with opioid receptors.

This drug has a very high affinity with this type of receptor (i.e. it fits very well with them). What it does is displace opioid antagonists and agonists.

Composition and doses

On a chemical level, is derived from oxymorphone, a very powerful semi-synthetic opioid analgesic . The drug is composed of naloxone hydrochloride. Specifically, each 1-ml vial of naloxone contains 0.4 mg of naloxone hydrochloride.

The recommended doses in adults are usually 0.4 to 20 mg through the intravenous line. If there is no improvement in respiratory depression after administration by this route, it can be re-administered at 2-3 minute intervals (always by a medical professional). Of course, its use must be indicated and prescribed by doctors .

Indications

Naloxone is often known for its use during acute opiate intoxication or overdose . The main natural opiate is morphine. Another opiate drug is heroin, a drug synthesized from morphine.

Other indications for naloxone are: to treat respiratory depression or CNS (Central Nervous System) depression. The respiratory depression we mentioned is usually caused by the consumption of opiates, either natural or synthetic. It is also indicated for babies who have just been born, with mothers who have been taking opiates.

Another interesting fact is that when naloxone is administered in cases of opioid dependence, what happens is that the symptoms of physical dependence on it increase .

Pharmacokinetic properties

Pharmacokinetics has to do with the time of absorption of the drugs, the duration of their effect, etc. In other words, it encompasses the processes through which the drug passes once it is administered in the body. Naloxone (naloxone hydrochloride) is rapidly absorbed by the gastrointestinal tract .

But why is naloxone not usually given orally? It is also effective, but in order to produce the same effect as from the other routes, much higher doses would be needed to allow an antagonism of the opiates (in case of overdose). This is why it is administered intravenously and intramuscularly.

Precautions

Special caution should be taken with patients who are physically dependent on narcotics (narcotics are analgesic and/or anaesthetic drugs), or who have been intoxicated by such substances; this is because the use of naloxone can induce acute withdrawal . On the other hand, naloxone is not effective when respiratory depression is due to factors other than opiates.

Naloxone should also be used with caution in elderly patients, especially those with previous cardiovascular disease . This is because there are known cases where naloxone has caused serious cardiovascular adverse effects in the elderly.

Also, it is not recommended to take naloxone at high doses during surgery after consuming opioids. Special care or caution should be taken in cases of patients with cardiovascular disease, or patients taking cardiotoxic drugs that may cause heart problems.

Pregnancy and lactation

If you are pregnant, the relationship between the risks and benefits of taking naloxone should be assessed by consulting your family doctor or psychiatrist. Not much is known about taking naloxone during pregnancy, but it is known that it can cause withdrawal symptoms in the baby.

As for breastfeeding, it is not known whether or not naloxone can be passed into breast milk. It has also not been established whether children who are breastfed have any effects of naloxone.

Side effects

Like any drug, naloxone can also cause a number of adverse reactions in the patient, such as nausea, vomiting, tachycardia, hypo/hypertension, headache, postoperative pain and fainting , among others.

Other adverse reactions that may be caused by naloxone, and which have been reported especially in the postoperative period, are hypotension, hypertension, pulmonary edema, fibrillation and ventricular tachycardia. In addition, these adverse reactions have been seen mostly in people with cardiovascular disease or who have been taking similar drugs.

Bibliographic references:

  • Ferrandis, V. (2013). Professional Association of Physiotherapists of Castilla y León. Pharmacokinetics and pharmacodynamics. Course of Pharmacology for Physiotherapists.
  • Gregorio Marañon University Hospital. (2014). Continuous intravenous perfusion. Nursing documentation: 2 – 10.
  • Ministry of Health, Social Policy and Equality. (2018) Technical details: naloxone. 1 – 8.
  • Stahl, S.M. (2002). Essential Psychopharmacology. Neuroscientific bases and clinical applications. Barcelona: Ariel.
  • Vademecum. (2016). Naloxone.