Mechanism of Action:
Naloxone is a mu (μ)-opioid receptor competitive antagonist, and also has an antagonist action with a lower affinity, at κ- and δ-opioid receptors. It blocks the action of both exogenous opioids (e.g. morphine, diamorphine) and endogenous opioids on opioid receptors in the central nervous system. Opioid receptors are G-protein-coupled receptors and inhibit adenylate cyclase. They cause hyperpolarisation (by opening potassium channels causing K+ to move out of cells) and prevent transmitter release (by blocking calcium channels).
Naloxone is a derivative of the opioid oxymorphone, with the substitution of the N-methyl group with an allyl (prop-2-enyl) group to give N-allyl oxymorphone.
Indications
- Reversal of opiate toxicity
Lecture and CAL materials: (under review)
- Lecture: Pain and Analgesia (Lecture 2): Analgesics and other drugs used to treat pain
- CAL: G Proteins
Drug specifics
| Alternative drug name | Naloxone Hydrochloride, Narcan® |
| Effects | Used clinically to reduce the life-threatening adverse effects of opioids intoxication (deliberate or accidental) such asespiratory depression, hypotension and coma. Its use is primarily for deliberate large overdosage of opioids (eg morphine, methadone, codeine) by addicts. However, it is also required on occasion in hospital due to excessive opioid effects when morphine is used as analgesia (e.g. post-operatively). Opioid intoxication may be recognized by features such as bradypnoea, hypotension, pinpoint pupils and reduced conscious level. |
| Adverse actions | There is a danger of causing sudden and serious withdrawal reactions with administration of naloxone - most cases of opioid poisoning happen in addicts. Constipation is a predictable complication of the use of opioids that can be seriously troublesome. |
| Dose | Given intravenously. An important practical point is that the half-life of naloxone is much shorter than the opioid agonists and so administration often has to be repeated or followed by an infusion. |
| Interactions | None of note other than the direct antagonism of the effects of opioid analgesics. |
| Contraindications | not specified |
| Comments | Intravenous naloxone is also useful to diagnose the cause of coma – if the patient does not respond promptly to treatment with naloxene, the cause is probably not opioid poisoning. Naloxone has a shorter half-life than most opioids and so repeated administration may be required. Note that naloxone administration will remove the effects of any ongoing analgesia. Naltrexone is structurally similar to opioids but has a slightly increased affinity for κ;-opioid receptors, can be administered orally and has a longer duration of action. It is being used by some in the long-term treatment of opioid addiction. Naloxegol is a modified, oral derivative of naloxone that does not enter the CNS. It antagonises the gastrointestinal effects of opioids acting on enteric μ receptors without reversing the CNS effects. |
| Contributors | Updated by ANT April 2017 |
eDrug by