opiate and opioid antagonists

short-acting opiate receptor antagonists:

These are usually used in the short-term reversal of the respiratory depressant effects of excess dosing of opiates and opioids, including heroin.

Administer with caution to patients who have received large doses of opioids, or to those physically dependent on opioids, as a too rapid reversal may precipitate an acute withdrawal syndrome. When naloxone hydrochloride is used in the management of an acute opioid overdose, other standard resuscitative measures should be readily available (cardiopulmonary resuscitation and vasopressor agents). A withdrawal syndrome may also be precipitated in newborn infants of opioid dependent mothers.
The signs and symptoms of opioid withdrawal in a patient physically dependent on opioids may include, but are not limited to, the following: body aches, diarrhoea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness and increased blood pressure. In the neonate opioid withdrawal may also include: convulsions, excessive crying and hyperactive reflexes.

These may cause adverse effects in post-operative patients:

Following the use of opioids during surgery, excessive doses of naloxone hydrochloride should be avoided as they may cause excitement, increase blood pressure and reverse analgesia. A too rapid reversal of opioid effects may cause nausea, vomiting, sweating or tachycardia, seizures, ventricular tachycardia and fibrillation, pulmonary oedema and cardiac arrest which may result in death.

see naloxone (Narcan)
a synthetic congener of oxymorphone
a competitive antagonist at opiate receptor sites. It can prevent or reverse the effects of opioids, including respiratory depression, sedation and hypotension. It can also reverse the respiratory depression caused by pentazocine.
When naloxone is administered intravenously, the effects are usually apparent within two minutes; the onset of action is only slightly less rapid when it is administered intramuscularly or subcutaneously. The duration of action is dependent upon the dose and route of administration but is usually in the region of one to four hours. Intramuscular administration produces a more prolonged effect than intravenous administration.
can be given intranasally 1ml into each nostril of 1mg/ml formulation but slower onset compared with IM use
- BestBets.org - IN vs IM naloxone
The elimination half-life in adults is 60 to 90 minutes and 180 minutes in neonates.
formulation: 400mcg per 1 ml ampoule
adult dose:
- heroin OD: 400mcg IV, IM or SC and repeat every 2-3min as needed up to 10mg.
- post-operative: 100-200mcg IV, IM or SC and repeat every 2-3min as needed up to 10mg.
children:
- initially 0.01 mg/kg IVI, IMI or SCI; repeat with 0.1 mg/kg if needed.
neonates:
- initially 0.01 mg/kg IVI, IMI or SCI; repeat every 2-3 mins if nec; OR 0.06 mg/kg stat IMI at birth

a long acting opioid antagonist which is well absorbed orally
a severe withdrawal reaction may be precipitated if the pt has recently taken heroin or another opioid
- thus should not be started until 7-10days after last opioid dose
- see Mx of severe acute opiate withdrawal due to inappropriate use of naltrexone
dose: usually 50mg per day
best results are obtained with “motivated” pts (eg. white-collar professionals, persons on parole, probation or in jail)
if it is taken intermittently & then heroin is taken in the intervening periods, the risk of death from overdose may be INCREASED due to the reduced opioid tolerance.
has also been found useful to decrease craving in chronic alcoholics undergoing withdrawal treatment

a partial mu agonist and weak kappa antagonist taken sublingually as it has a high 1st pass metabolism
half-life 4-5hrs
ceiling effect:
- because it is a partial agonist, its effects plateau at higher doses & then begins to behave more like an antagonist which limits its maximal analgesic & resp. depression effects
  - this confers a high safety profile clinically (better than methadone) although deaths have occurred from overdoses
the high affinity blockade significantly limits the effect of subsequently administered opioid agonists or antagonists
results are comparable to methadone
can be taken on alternate days
more expensive than methadone but may become Rx of choice
pts on large doses of heroin may experience some withdrawal symptoms
dose regimen:
- 8-12mg sublingually daily for 5-7 days then maintenance dose 4-32mg/d will suppress symptoms of withdrawal & reduce illicit opioid use. Dosing can be extended to every 2-3 days.
acute overdose:
- naloxone may be helpful in improving resp. depression although improvement in mental state may be less. Doses of 5-10mg may be needed.
- blog on Mx of buprenorphine ingestion in children
WH intranet ED policy - buprenorphine

these are agents that have limited ability to cross the blood-brain barrier and thus of use in Mx of opioid-induced constipation

introduced in Australia in 2009 as Relistor
related to the opioid antagonist naltrexone but more selective for peripheral receptors as it does not cross the blood-brain barrier well and thus marketed to help reduce opioid-induced constipation in palliative care patients
must be given by s/cut. injection with half-life of 8 hours and tends to allow a bowel movement within 4hrs of injection