Analgesic formulations and methods for reduced postoperative nausea and vomiting and enhanced postoperative pain relief

Abstract

A multimodal antiemetic anesthetic/analgesic formulation for pain control not limited to postoperative pain control is described herein. The opioid-free/sparing anesthetic/analgesic formulation comprises a local anesthetic, an N-methyl-D-aspartate (NMDA) receptor antagonist, and a cyclooxygenase (COX) inhibitor such as Bupivacaine Hydrochloride, Ketamine Hydrochloride, and Ketorolac Tromethamine, which is effective to significantly reduce postoperative nausea and vomiting and enhance postoperative pain relief as compared to existing prior art anesthetics/analgesics. The formulation is administered to a mammal in need of anesthesia/analgesia and can be used as a preemptive and preventative multimodal analgesic. The formulation may have a buffer to enhance its shelf life and improve pharmacokinetics. The formulation may further comprise an alpha agonist, a steroid, a Transient Receptor Potential Channel agonist or antagonist, a beta-lactam antibiotic, a protein kinase inhibitor, a competitive or non-competitive glycine or glutamate antagonist, a glutamate or glycine inhibitor, a cyclooxygenase 3 inhibitor, or combinations thereof.

What is claimed: 
     
         1 . A method of treating pain, said method comprising administering, by subcutaneous injection, intramuscular injection, intrafascial plane injection or intradermal injection, an effective amount of a formulation to a mammal in need of such treatment, the formulation comprising about 0.01%-0.5% of a local anesthetic comprising bupivacaine, ropivacaine, or levobupivacaine; 1.0-3.0 mg/cc of an N-methyl-D-aspartate (NMDA) receptor antagonist comprising MgSO 4  or ketamine; and 0.2-1.2 mg/cc of a cyclooxygenase (COX) inhibitor comprising meloxicam or ketorolac. 
     
     
         2 . The method in  claim 1 , wherein the formulation further comprises: an antifibrinolytic, an antibiotic, a steroid, an alpha agonist, a cyclooxygenase 3 inhibitor, a Transient Receptor Potential Vanilloid (TRPV) receptor agonist or antagonist, a Transient Receptor Potential channel agonist or antagonist, a protein kinase inhibitor, a competitive or non-competitive glycine or glutamate agonist, a glutamate or glycine inhibitor, a neurokinin-1 receptor antagonist, or combinations thereof. 
     
     
         3 . The method of  claim 2 , wherein the antifibrinolytic is tranexamic acid. 
     
     
         4 . The method of  claim 2 , wherein the alpha agonist is clonidine, dexmedetomidine, tizanidine, guanfacine, or medetomidine. 
     
     
         5 . The method of  claim 2 , wherein the alpha agonist is epinephrine. 
     
     
         6 . The method of  claim 2 , wherein the cyclooxygenase 3 inhibitor is acetaminophen or paracetamol. 
     
     
         7 . The method of  claim 2 , wherein the steroid is dexamethasone, methylprednisolone, betamethasone, a mineralocorticosteroid, or a glucocorticosteroid. 
     
     
         8 . The method of  claim 2 , wherein the antibiotic is a beta lactam antibiotic. 
     
     
         9 . The method of  claim 2 , wherein the antibiotic is vancomycin. 
     
     
         10 . A method of treating pain, said method comprising administering, by subcutaneous injection, intramuscular injection, intrafascial plane injection or intradermal injection, an effective amount of a formulation to a mammal in need of such treatment, the formulation comprising about 0.01%-0.5% of a local anesthetic comprising bupivacaine, ropivacaine, or levobupivacaine; 1.0-3.0 mg/cc of an N-methyl-D-aspartate (NMDA) receptor antagonist comprising MgSO 4 , ketamine, trilamine, meperidine, or tramadol; and 0.2-1.2 mg/cc of a cyclooxygenase (COX) inhibitor comprising meloxicam or ketorolac. 
     
     
         11 . The method in  claim 10 , wherein the formulation further comprises an antifibrinolytic, an antibiotic, a steroid, an alpha agonist, a cyclooxygenase 3 inhibitor, a Transient Receptor Potential Vanilloid (TRPV) receptor agonist or antagonist, a Transient Receptor Potential channel agonist or antagonist, a protein kinase inhibitor, a competitive or non-competitive glycine or glutamate agonist, a glutamate or glycine inhibitor, a neurokinin-1 receptor antagonist, or combinations thereof. 
     
     
         12 . The method of  claim 11 , wherein the antifibrinolytic is tranexamic acid. 
     
     
         13 . The method of  claim 11 , wherein the alpha agonist is clonidine, dexmedetomidine, tizanidine, guanfacine, medetomidine, or epinephrine. 
     
     
         14 . The method of  claim 11 , wherein the steroid is dexamethasone, methylprednisolone, betamethasone, a mineralocorticosteroid, or a glucocorticosteroid. 
     
     
         15 . A method of treating pain, said method comprising administering, by subcutaneous injection, intramuscular injection, intrafascial plane injection or intradermal injection, an effective amount of a formulation to a mammal in need of such treatment, the formulation comprising about 0.01%-0.5% of a local anesthetic comprising bupivacaine, ropivacaine, levobupivacaine, lidocaine, prilocaine, amethocaine, procaine, cinchocaine, mepivacaine, or etidocaine; 1.0-3.0 mg/cc of an N-methyl-D-aspartate (NMDA) receptor antagonist comprising MgSO 4 , ketamine, trilamine, meperidine, or tramadol; and 0.2-1.2 mg/cc of a cyclooxygenase (COX) inhibitor comprising meloxicam, ketorolac, acetaminophen, paracoxib, or ibuprofen. 
     
     
         16 . The method in  claim 15 , wherein the formulation further comprises an antifibrinolytic, an antibiotic, a steroid, an alpha agonist, a cyclooxygenase 3 inhibitor, a Transient Receptor Potential Vanilloid (TRPV) receptor agonist or antagonist, a Transient Receptor Potential channel agonist or antagonist, a protein kinase inhibitor, a competitive or non-competitive glycine or glutamate agonist, a glutamate or glycine inhibitor, a neurokinin-1 receptor antagonist, or combinations thereof. 
     
     
         17 . The method of  claim 16 , wherein the antifibrinolytic is tranexamic acid. 
     
     
         18 . The method of  claim 16 , wherein the alpha agonist is clonidine, dexmedetomidine, tizanidine, guanfacine, medetomidine, or epinephrine. 
     
     
         19 . The method of  claim 16 , wherein the steroid is dexamethasone, methylprednisolone, betamethasone, a mineralocorticosteroid, or a glucocorticosteroid.