Pentazocine and naloxone
Pentazocine and naloxone Uses, Dosage, Side Effects, Food Interaction and all others data.
Naloxone is a pure opioid antagonist that acts competitively at opioid receptors. While the mechanism of action of naloxone is not fully understood, the preponderance of evidence suggests that naloxone antagonizes the opioid effects by competing for the same receptor sites, especially the opioid mu receptor. Recently, naloxone has been shown to bind all three opioid receptors (mu, kappa and gamma) but the strongest binding is to the mu receptor.
Naloxone is an opioid receptor antagonist indicated in the reversal of opioid overdoses. Naloxone has a shorter duration of action than opioids and multiple doses may be required. The therapeutic window of naloxone is wide, as it has no effect if a patient has not taken opioids. Patients treated with naloxone may experience opioid withdrawal and a person administering naloxone should be aware that reversal of opioid overdoses may not resolve all the symptoms a patient is experiencing if other drugs are involved.
Pentazocine is a benzomorphan derivative with mixed opioid agonist and antagonist actions. It alters perception of and response to pain and produces generalised CNS depression by binding to opiate receptors in the CNS and acting as a partial agonist/antagonist.
Pentazocine is a potent analgesic which when administered orally in a 50 mg dose appears equivalent in analgesic effect to 60 mg (1 grain) of codeine. Onset of significant analgesia usually occurs between 15 and 30 minutes after oral administration, and duration of action is usually three hours or longer. Onset and duration of action and the degree of pain relief are related both to dose and the severity of pretreatment pain. Pentazocine weakly antagonizes the analgesic effects of morphine and meperidine; in addition, it produces incomplete reversal of cardiovascular, respiratory, and behavioral depression induced by morphine and meperidine. Pentazocine has about 1/50 the antagonistic activity of nalorphine. It also has sedative activity.
| Trade Name | Pentazocine and naloxone |
| Generic | Naloxone + pentazocine |
| Type | Oral |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Naloxone is used for the complete or partial reversal of opioid depression, including respiratory depression, induced by natural and synthetic opioids, including propoxyphene, methadone and certain mixed agonist-antagonist analgesics: nalbuphine, pentazocine, butorphanol, and cyclazocine. Naloxone is also used for diagnosis of suspected or known acute opioid overdosage. Naloxone may be useful as an adjunctive agent to increase blood pressure in the management of septic shock
For the relief of moderate to severe pain. Pentazocine may also be used for preoperativeor preanesthetic medication and as a supplement to surgical anesthesia.
Pentazocine and naloxone is also used to associated treatment for these conditions: Opioid Dependence, Opioid Overdose, Pruritus, Respiratory Depression, Septic Shock, Severe Pain, Moderate Pain, Suspected Opioid OverdoseMild pain, Severe Pain, Moderate Pain, Preanesthetic medication therapy
How Pentazocine and naloxone works
Naloxone is a competitive inhibitor of the µ-opioid receptor. Naloxone antagonizes the action of opioids, reversing their effects. If a patient has not taken opioids, naloxone does not have a significant effect on patients.
The preponderance of evidence suggests that pentazocine antagonizes the opioid effects by competing for the same receptor sites, especially the opioid mu receptor.
Dosage
Pentazocine and naloxone dosage
Reversal of central depression from opioid use during surgery:
- Adult:100-200 mcg at intervals of 2-3 minute, titrate dose according to response while maintaining analgesia.
- Child:5-10 mcg IV at 2-3 min intervals.
Opioid overdosage:
- Adult:0.4-2 mg repeated if necessary at 2-3 min intervals. If there is no response after a total of 10 mg has been given, consider the possibility of overdosage with other drugs. Reduce dose for opioid-dependent patients: 0.1-0.2 mg. IM/SC routes may be used (at IV doses) if IV admin is not feasible.
- Child:Initially 10 mcg/kg IV followed by 100 mcg/kg IV if necessary. Alternatively, 0.4-0.8 mg IM or SC, repeated as necessary, if IV admin is not feasible.
Opioid-induced depression in neonates due to obstetric analgesia:
- Child:10 mcg/kg IV, IM or SC repeated at 2-3 min intervals if necessary or 60 mcg/kg as a single IM dose.
Tablet:
Adults: The usual initial adult dose is 1 tablet every three or four hours. This may be increased to 2 tablets when needed. Total daily dosage should not exceed 12 tablets.
Injection:
Adults, Excluding Patients in Labor: The recommended singleparenteraldose is 30 mg byintramuscular, subcutaneous, or intravenous route. This may be repeated every 3 to 4 hours. Doses in excess of 30 mg intravenously or 60 mg intramuscularly or subcutaneously are not recommended. Total daily dosage should not exceed 360 mg. Elderly patients may be more sensitive to theanalgesiceffects of Pentazocine than younger patients. Elderly patients generally should be started on low doses of Pentazocine and observed closely.The subcutaneous route of administration should be used only when necessary because of possible severe tissue damage at injection sites. When frequent injections are needed, the drug should be administered intramuscularly. In addition, constant rotation of injection sites (e.g., the upper outer quadrants of the buttocks, mid-lateralaspects of the thighs, and thedeltoidareas) isessential.
Patients in Labor: A single, intramuscular 30 mg dose has been most commonly administered. An intravenous 20 mg dose has given adequate pain relief to some patients in labor when contractions become regular, and this dose may be given two or three times at two- to three-hour intervals, as needed.
Pediatric Patients Excluding Patients Less Than One-Year-Old: The recommended single parenteral dose as premedication for sedation is 0.5 mg/kg by intramuscular route.
Intravenous:
- Reversal of central depression from opioid: Stable in 0.9% sodium chloride and 5% dextrose inj at 4 mcg/ml for 24 hr.
- Opioid overdosage: Stable in 0.9% sodium chloride and 5% dextrose ing at 4 mcg/ml for 24 hr.
Parenteral: Stable in 0.9% sodium chloride and 5% dextrose inj at 4 mcg/ml for 24 hr.
Side Effects
Occur secondarily to reversal (withdrawal) of narcotic analgesia and sedation. Mental depression, apathy, inability to concentrate, sleepiness, irritability, anorexia, nausea, and vomiting in high oral doses during initial treatment of opiate addiction.
Physical dependence; sedation, dizziness, euphoria, lightheadedness, alterations of mood; respiratory depression; visual hallucinations, disorientation, confusion; hypertension, tachycardia, circulatory depression; shock; hypotension; nausea, vomiting, constipation; seizures, diaphoresis; rash; blood dyscrasias; local tissue damages (SC), muscle fibrosis (IM).
Toxicity
If a patient has not taken opioids, naloxone does not have a significant effect on patients.
The oral LD50 in mice and rats is >1 g/kg. The intraperitoneal LD50 is 80 mg/kg in mice and 239 mg/kg in rats. The subcutaneous LD50 is 286 mg/kg in mice and 500 mg/kg in rats.
Precaution
Patients physically dependent on opioids, or who have received large doses of opioids (acute withdrawal syndrome may be precipitated). Pregnancy and lactation.
May precipitate withdrawal in narcotic addicts. Impaired respiratory, renal and hepatic function; morbidly obese patients; thyroid dysfunction; prostatic hyperplasia or urinary stricture; biliary tract impairment; adrenal insufficiency (including Addison's disease); abdominal conditions. Elderly or debilitated patients; seizure-prone patients; children and infants (safety and efficacy not established in less than 1 yr); lactation. May impair ability to drive or operate machinery. Administer IM rather than SC (when frequent inj are needed) and inj sites should be varied.
Interaction
Decreased effect of opioid analgesics.
Depressant affects potentiated by alcohol, CNS depressants; concurrent use with fluoxetine may lead to diaphoresis, ataxia flushing and tremor associated with serotonin syndrome.
Volume of Distribution
The volume of distribution of naloxone is 200 L. Naloxone distributes into tissues rapidly. It can also cross the placenta and blood-brain barrier.
Elimination Route
An intranasal dose of naloxone is 42-47% bioavailable. An 8 mg dose of nasal naloxone reaches a Cmax of 12.3-12.8 ng/mL, with a Tmax of 0.25 hours, and an AUC of 16.7-19.0 h*ng/mL. A 0.4 mg intramuscular dose reaches a Cmax of 0.876-0.910 ng/mL, with a Tmax of 0.25 hours, and an AUC of 1.94-1.95 h*ng/mL. A 2 mg intravenous dose reaches a Cmax of 26.2 ng/mL with an AUC of 12.8 h*ng/mL.
Well absorbed from the gastro-intestinal tract.
Half Life
The mean half life of naloxone hydrochloride is 1.8-2.7 hours intranasally, 1.4 hours intramuscularly, and 1.2 hours intravenously. In neonates, the mean half life is 3.1 ± 0.5 hours.
2 to 3 hours
Clearance
The clearance of naloxone is 2500 L/day.
Elimination Route
After oral or intravenous administration, naloxone is 25-40% eliminated in the urine within 6 hours, 50% in 24 hours, and 60-70% in 72 hours. The metabolites naloxone-3-glucuronide, noroxymorphone, and naloxol are all detected in the urine.
Pregnancy & Breastfeeding use
Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.
Safe use of Pentazocine during pregnancy (other than labor) has not been established. Animal reproduction studies have not demonstrated teratogenic or embryotoxic effects. However, Pentazocine should be administered to pregnant patients (other than labor) only when, in the judgment of the physician, the potential benefits outweigh the possible hazards. Patients receiving Pentazocine during labor have experienced no adverse effects other than those that occur with commonly used analgesics. Pentazocine should be used with caution in women delivering premature infants.
Contraindication
Pentazocine should not be administered to patients who are hypersensitive to it.
Special Warning
Pediatric Use: The safety and efficacy of Pentazocine as preoperative or preanesthetic medication have been established in pediatric patients 1 to 16 years of age. Use of Pentazocine in these age groups is supported by evidence from adequate and controlled studies in adults with additional data from published controlled trials in pediatric patients. The safety and efficacy of Pentazocine as a premedication for sedation have not been established in pediatric patients less than one year old. Information on the safety profile of Pentazocine as a postoperative analgesic in children less than 16 years is limited.
Geriatric Use: Elderly patients may be more sensitive to the analgesic effects of Pentazocine than younger patients. Clinical data indicate that differences in various pharmacokinetic parameters of Pentazocine may exist between elderly and younger patients. Sedating drugs may cause confusion and oversedation in the elderly; elderly patients generally should be started on low doses of Pentazocine and observed closely.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Storage Condition
Store at 25° C. Protect from light.
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