Legal status and availability to law enforcement and emergency personnel
In the United States, naloxone is ostensibly available without a prescription in every state with the exception of Hawaii. In reality, not all pharmacies stock or dispense naloxone. Depending on the pharmacy, a pharmacist may have to write a prescription or not be able to give naloxone to comply with accounting rules, as naloxone is still considered a prescription-only medication under FDA rules. As of mid-2019, officials in 29 states had issued standing orders to enable licensed pharmacists to provide naloxone to patients without the individual first visiting a prescriber. Prescribers working with harm reduction or low threshold treatment programs  have also issued standing orders to enable these organizations to distribute naloxone to their clients. A standing order, also referred to as a "non-patient specific prescription" is written by a physician, nurse or other prescriber to authorize medicine distribution outside the doctor-patient relationship. In the case of naloxone, these orders are meant to facilitate naloxone distribution to people using opioids, family members and friends. Over 200 naloxone distribution programs utilize licensed prescribers to distribute the drug through such orders, or through the authority of pharmacists (as with Californias legal proision, AB1535).Laws and policies in many US jurisdictions have been changed in recent years to allow wider distribution of naloxone. In addition to laws or regulations permitting distribution of medicine to at risk individuals and families, some 36 states have passed laws that provide naloxone prescribers with immunity against both civil and criminal liabilities.
It is capable of blocking a placebo pain-lowering response, if the placebo is administered together with a hidden or blind injection of naloxone. Other studies have found that placebo alone can activate the bodys μ-opioid endorphin system, delivering pain relief by the same receptor mechanism as morphine.Naloxone should be used with caution in people with cardiovascular disease as well as those that are currently taking medications that could have adverse effects on the cardiovascular system such as causing low blood pressure, fluid accumulation in the lungs (pulmonary edema), and abnormal heart rhythms. There have been reports of abrupt reversals with opioid antagonists leading to pulmonary edema and ventricular fibrillation. Hypersensitivities
Naloxone preparations may contain methylparaben and propylparaben and are inappropriate for use by people with a paraben hypersensitivity. If a person is sensitive to nalmefene or naltrexone, naloxone should be used with caution as these three medications are structurally similar. Cross-sensitivity among these drugs is unknown. Preservative-free preparations are available for those with paraben hypersensitivities. Pharmacology
Pharmacodynamics
Naloxone is a lipophilic compound that acts as a non-selective and competitive opioid receptor antagonist. The pharmacologically active isomer of naloxone is (−)-naloxone. Naloxones binding affinity is highest for the μ-opioid receptor (MOR), then the δ-opioid receptor (DOR), and lowest for the κ-opioid receptor (KOR); naloxone has negligible affinity for the nociceptin receptor.If naloxone is administered in the absence of concomitant opioid use, no functional pharmacological activity occurs, except the inability of the body to combat pain naturally.