Methods and pharmaceutical compositions to treat drug overdose
Methods and compositions are provided for treating individuals exhibiting opioid withdrawal symptoms with opioid, benzodiazepine and other drugs of abuse by administering an opioid receptor antagonist agent together with a respiratory stimulant to reverse the effects of opioid withdrawal symptoms, including respiratory depression, sedation, and hypotension. Methods and compositions are also provided for treating stimulant overdose with a benzodiazepine and beta-adrenergic blocking agent. Methods and compositions are also provided for treating concurrent stimulant and opioid overdose comprising administering to a patient in need thereof a benzodiazepine and an opioid antagonist. Methods and compositions are also provided for treating individuals exhibiting opioid withdrawal symptoms or prophy tactically treating individuals for opioid withdrawal symptoms from opioid, benzodiazepine and other drugs of abuse by administering an opioid receptor antagonist agent together with a respiratory stimulant to reverse the effects of withdrawal, including respiratory depression, sedation, and hypotension.
1 . A method of treating opioid overdose comprising administering to a patient in need thereof an opioid receptor antagonist selected from the group consisting of naltrexone, naloxone, nalmefene, and a pharmaceutically-acceptable salt thereof and a respiratory stimulant selected from a compound of the following formula or a salt thereof:
wherein:
R 1 and R 2 are independently alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, phenyl, substituted phenyl, phenylalkyl, substituted phenylalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroarylalkyl, substituted heteroarylalkyl, heteroaryl or substituted heteroaryl; or R 1 and R 2 combine as to form a biradical selected from the group consisting of 3-hydroxy-pentane-1,5-diyl, 6-hydroxy-cycloheptane-1,4-diyl, propane-1,3-diyl, butane-1,4-diyl and pentane-1,5-diyl;
X is a bond, O or NR 4 ,
R 3 is alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, or substituted alkenyl;
R 4 is H, alkyl, or substituted alkyl;
and
R 5 is alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, or acyl.
2 . The method of claim 1 , where the opioid overdose is accompanied by respiratory depression.
3 . The method of claim 1 , wherein the antagonist and the stimulant are administered simultaneously or sequentially.
4 . The method of claim 3 , wherein the antagonist and the stimulant are administered by the same route of administration.
5 . The method of claim 3 , wherein the antagonist and the stimulant are administered by different routes of administration.
6 . The method of claim 3 , wherein the antagonist and the stimulant are administered in the same pharmaceutical composition.
7 . The method of claim 3 , wherein the antagonist and the stimulant are administered in different pharmaceutical compositions.
8 . The method of claim 1 , wherein the respiratory stimulant is selected from the group consisting of N-(4,6-bis-n-propylamino-[1,3,5]triazin-2-yl)-N,O-dimethyl-hydroxylamine, and a pharmaceutically-acceptable salt thereof.