Naloxone acts as a potent μ-opioid receptor inverse agonist. Because of its high affinity for the μ-opioid receptor, it knocks other ligands out of the receptor. If naloxone is administered without previous administration of opioids, it has few biological effects, notably a lower pain threshold.
Naloxone has two isomers, (+)naloxone and (-)naloxone, with the latter being active. The liver metabolizes naloxone. It has very low oral bioavailability, which is why it is administered intravenously, intramuscularly or intranasally. Small amounts of naloxone are often added to opioids like buprenorphine and pentazocine to prevent abuse. This is because of the bioavailability difference; injecting the isolated ingredients from the pill will also inject naloxone.
Naloxone has been noted to block a placebo based analgesic effect. For example, if an individual has been administered something that they were told was morphine and had an analgesic response to it, naloxone will block that response.
Naloxone also has a lower affinity as an antagonist at the κ-opioid and δ-opioid receptors.
If naloxone is administered in the absence of concomitant opioid use, no functional pharmacological activity occurs, except the inability for the body to combat pain naturally. In contrast to direct opiate agonists, which elicit opiate withdrawal symptoms when discontinued in opiate-tolerant people, no evidence indicates the development of tolerance or dependence on naloxone. The mechanism of action is not completely understood, but studies suggest it functions to produce withdrawal symptoms by competing for opiate receptor sites within the CNS (a competitive antagonist, not a direct agonist), thereby preventing the action of both endogenous and xenobiotic opiates on these receptors without directly producing any effects itself.
When taken by itself and outside the context of an opioid overdose, naloxone causes relatively comfortable sedation and general suppression of emotions.
When administering naloxone, it is important to understand which formulation it is coming in and what that means. In the United States, naloxone primarily comes in four formulations. Narcan is a prescription nasal spray that is inserted and administered into the nose.Evzio is an autoinjector with voice instruction capabilities similar to many epinephrine autoinjectors. Naloxone may come in a pink or orange box that reads "Naloxone Hydrochloride, INJ., USP" or a green box that reads the same thing. The main difference between these two is that the green ones come with a needle built in and is meant for intramuscular injection specifically.
- Common Brands (United States)
- Narcan** is one of the most common brands containing naloxone. To use it, these steps are followed:
- Peel the device out of the packaging
- Hold the device with the thumb on the bottom of the plunger and 2 fingers on the nozzle
- Place and hold the tip of the nozzle in either nostril until one's fingers touch the bottom of the patient’s nose
- Press the plunger down, which will release the medication.
Narcan is not a substitute for professional medical care. On brand Narcan will deliver 4mg of naloxone. Narcan does not last as long as many opioids, so before or after administering Narcan, one should call for emergency services.
- Evzio** is one of the most common brands containing naloxone. To use it one can follow these steps: 1) Pull the device out of the case 2) Pull off the red safety guard 3) Place the black end of the device against one's outer thigh 4) Ensure there are no solid objects between the black end and their skin -- the needle can go through clothes if necessary 5) Press firmly down on the device until distinct click is heard and hold it there for 5 seconds to ensure all the naloxone is released from the device.
Evzio is not a substitute for professional medical care. Evzio does not last as long as many opioids, so before or after administering Evzio, one should call for emergency services.
To use orange/pink box naloxone, one can follow these steps: 1) Take the device out of the box 2) If the device is not assembled, assemble it 3) Remove the yellow caps off the cylinder 4) On the narrow end, put the cylindrical cap 5) Take the vial of the medication and put it into the chamber, with the colored end pointing towards the patient 6) The dosage for adults is 2 mg of naloxone and the device comes with 2 mg 7) Put the device in either nostril and press down on the vial of medication until half of it is dispersed into that nostril 8) Then, take the device and put it in the other nostril and administer the rest of the medication.
If the patient is under 5 years of age, only administer 1 mg total, or a quarter of the total medication in each nostril. Each naloxone should be administered with the goal of restoring ventilation (breathing) but not necessarily consciousness. Naloxone should not be administered in the field to patients under 28 days of age.
Boxed naloxone is not a substitute for professional medical care. Naloxone does not last as long as many opioids. So before or after administering naloxone, one should call for emergency services.
Naloxone is often combined with otherwise frequently abused Opioids like "Tilidin" (Synthetic Opioid which is 5 times weaker than Morphine; almost only used in European Countries) which is produced in composition of 50mg (Tilidin) / 4mg (Naloxone), 100/8 and 200/16 and given out in extended-elease Tablets.
It should be noted that this doesn't prevent abuse since Naloxone's Oral Bioavailability is around 1%, which therefore requires dosages of around 400mg of Naloxone alone (Oral) for it to show its antagonistic effects.
not habit-forming. When naloxone is administered in an opioid overdose, the individual will go through immediate withdrawal. Sudden opioid withdrawal may be life-threatening in extreme cases. Symptoms of opioid withdrawal may include, but are not limited to agitation, nausea, psychosis, temperature regulation suppression, anxiety, physical fatigue, excessive yawning, sweating, dehydration, and pupil dilation.
It has been noted that naloxone may be needed in higher dosages depending on the opioid that was consumed. It is not uncommon for several doses of naloxone to be administered in overdose cases involving fentanyl or one of its many analogs. If an individual does not have opioids in their system when naloxone is administered, it may cause dehydration and nausea.
It is strongly recommended that one use harm reduction practices when using this substance.
Throughout the world, naloxone is not considered a controlled substance. It is a prescription drug in most countries.
Australia: In Australia, naloxone is considered an over the counter drug and is available at most pharmacies
Canada: In Canada, naloxone kits are distributed at many emergency rooms, clinics, and some pharmacies.
Germany:** Naloxone is a prescription medicine, according to Anlage 1 AMVV.
Switzerland: Preparations containing only naloxone are listed as "Abgabekategorie B" pharmaceuticals, which require a prescription to obtain.
Turkey: Naloxone is only sold as an addictive to buprenorphine to deter abuse, which is prescription only.
United States: At a federal level, naloxone is a prescription drug. Many states have programs that make naloxone over the counter and available at request at most pharmacies. In the United States, most jurisdictions have programs to deploy naloxone to law enforcement and fire and rescue services.
United Kingdom: In the United Kingdom, naloxone is considered a prescription drug, but drug services can supply it without a prescription. And anyone can use it to save a life in an emergency.
Responsible use
Safer injection guide
Opioids
Heroin
Fentanyl
Codeine
Morphine
Naloxone (Wikipedia)
Naloxone (Erowid Vault)
Naloxone (TiHKAL / Isomer Design)
Combatting America's Opioid Crisis: Heroin's Antidote (Vice)
Naloxone can be administered via insufflated, intramuscular, intravenous, oral. The route of administration can influence both the onset and intensity of pain relief.