NALOXONE HCL
Chemistry - An opiate antagonist, naloxone HCl is structurally related to oxymorphone. It occursas a white to slightly off-white powder with a pKa of 7.94. Naloxone is soluble in water andslightly soluble in alcohol. The pH range of commercially available injectable solutions are from 3-4.5. Naloxone HCl may also be known as N-allylnoroxymorphone HCl.
Sterile water for injection is the recommended diluent for naloxone injection. When given as an IVinfusion, either D5W or normal saline should be used. Naloxone HCl injection should not bemixed with solutions containing sulfites, bisulfites, long-chain or high molecular weight anions orany solutions at alkaline pH.
The drug apparently has its highest affinity for the mu receptor.
Naloxone reverses the majority of effects associated with high-dose opiate administration(respiratory and CNS depression). In dogs, naloxone apparently does not reverse the emetic actionsof apomorphine.
Naloxone also has other pharmacologic activity at high doses, including effects on dopaminergicmechanisms (increases dopamine levels) and GABA antagonism.
The duration of action usually persists from 45-90 minutes, but may act for up to 3 hours.
Naloxone is distributed rapidly throughout the body with high levels found in the brain, kidneys, spleen, skeletal muscle, lung and heart. The drug also readily crosses the placenta.
Naloxone is metabolized in the liver, principally via glucuronidative conjugation with metabolitesexcreted into the urine. In humans, the serum half-life is approximately 60-100 minutes.
P/M® Naloxone HCl Injection¯P/M; Mallinckrodt)
Naloxone is generally considered to be non-teratogenic in animals, but has precipitated withdrawalin opioid-dependent human fetuses.
Because the duration of action of naloxone may be shorter than that of the narcotic being reversed, animals that are being treated for opioid intoxication or with symptoms of respiratory depressionshould be closely monitored as additional doses of naloxone and/or ventilatory support may berequired.
Storage, Stability, Compatibility
Naloxone HCl for injection should be stored at room temperature (15-30°C) and protected from light.Sterile water for injection is the recommended diluent for naloxone injection. When given as an IVinfusion, either D5W or normal saline should be used. Naloxone HCl injection should not bemixed with solutions containing sulfites, bisulfites, long-chain or high molecular weight anions orany solutions at alkaline pH.
Pharmacology - NALOXONE HCL
Naloxone is considered to be a pure opiate antagonist and it has basically noanalgesic activity. The exact mechanism for its activity is not understood, but it is believed that thedrug acts as a competitive antagonist by binding to the mu, kappa, and sigma opioid receptor sites.The drug apparently has its highest affinity for the mu receptor.
Naloxone reverses the majority of effects associated with high-dose opiate administration(respiratory and CNS depression). In dogs, naloxone apparently does not reverse the emetic actionsof apomorphine.
Naloxone also has other pharmacologic activity at high doses, including effects on dopaminergicmechanisms (increases dopamine levels) and GABA antagonism.
Uses, Indications
Naloxone is used in veterinary medicine almost exclusively for its opiate reversal effects, but the drug is being investigated for treating other conditions (e.g., septic, hypovolemic or cardiogenic shock). Naloxone may also be employed as a test drug to see if endogenousopiate blockade will result in diminished tail-chasing or other self-mutilating behaviors.Pharmacokinetics - NALOXONE HCL
Naloxone is only minimally absorbed when given orally as it is rapidly destroyed in the GI tract. Much higher doses are required if using this route of administration for anypharmacologic effect. When given IV, naloxone has a very rapid onset of action (usually 1-2minutes). If given IM, the drug generally has an onset of action within 5 minutes of administration.The duration of action usually persists from 45-90 minutes, but may act for up to 3 hours.
Naloxone is distributed rapidly throughout the body with high levels found in the brain, kidneys, spleen, skeletal muscle, lung and heart. The drug also readily crosses the placenta.
Naloxone is metabolized in the liver, principally via glucuronidative conjugation with metabolitesexcreted into the urine. In humans, the serum half-life is approximately 60-100 minutes.
Contraindications, Precautions, Reproductive Safety
Naloxone is contraindicated in patientshypersensitive to it. It should be used cautiously in animals that have preexisting cardiac abnormalities or in animals that may be opioid dependent. The veterinary manufacturer states to use thedrug "...cautiously in animals who have received exceedingly large doses of narcotics. ... mayproduce an acute withdrawal syndrome and smaller doses should be employed." (Package Insert;P/M® Naloxone HCl Injection¯P/M; Mallinckrodt)
Naloxone is generally considered to be non-teratogenic in animals, but has precipitated withdrawalin opioid-dependent human fetuses.
Adverse Effects, Warnings
At usual doses, naloxone is relatively free of adverse effects in nonopioid dependent patients.Because the duration of action of naloxone may be shorter than that of the narcotic being reversed, animals that are being treated for opioid intoxication or with symptoms of respiratory depressionshould be closely monitored as additional doses of naloxone and/or ventilatory support may berequired.