Tumescent contravenom drug delivery
A tumescent contravenom solution including: (a) a vasoconstrictor, (b) a physiological crystalloid solution, and (c) optionally a contravenom agent that neutralizes tissue toxic enzymes present in a venom and/or a drug that impairs or paralyzes lymphatic smooth muscle function and impairs lymphatic transport of venom. Also described are methods of treating an envenomation in a subject, and a kit for performing the method of treating an envenomation.
1. A tumescent contravenom solution comprising:
(a) a vasoconstrictor drug,
(b) a physiological crystalloid solution adjusted to an acidic pH; and
(c) a contravenom agent selected from the group consisting of a protease inhibitor that counteracts a venom protease, a metalloprotease chelating agent, a phospholipase A2 inhibitor, a cellular receptor site blocker that blocks interaction of a venom protein with integrins and a contravenom agent that counters a procoagulation or a coagulation inhibitory property of a venom.
2. The tumescent contravenom solution according to claim 1 , wherein the phospholipase A2 inhibitor is Varespladib or a salt thereof.
3. The tumescent contravenom solution according to claim 2 , wherein the salt of Varespladib is a sodium salt.
4. The tumescent contravenom solution according to claim 1 , wherein contravenom neutralizes a venom from an organism selected from the group consisting of a Cnidarian , a jellyfish, a sea anemone, a hydra, a mollusk, an annelid, an arthropod, a spider, a scorpion, a centipede, a bee, a wasp, an ant, a tick, a horsefly, an echinoderm, a starfish, a sea urchin, and a venomous vertebrate, including a fish, an amphibian, a snake, a lizard and a mammal.
5. The tumescent contravenom solution according to claim 1 , wherein the vasoconstrictor is epinephrine.
6. The tumescent contravenom solution according to claim 5 , wherein the epinephrine is at a concentration of 0.2 to 1.5 mg/L.
7. The tumescent contravenom solution according to claim 1 , further comprising a drug that impairs or paralyzes lymphatic smooth muscle function and impairs lymphatic transport of venom.
8. The tumescent contravenom solution according to claim 1 , further comprising a local anesthetic.
9. The tumescent contravenom solution according to claim 8 , wherein the local anesthetic is lidocaine.
10. The tumescent contravenom solution according to claim 9 , wherein lidocaine is at a concentration of 0.4 mg/ml to 1.2 mg/ml.
11. The tumescent contravenom solution according to claim 1 , further comprising a beta-blocker drug that slows heart rate, thereby limiting systemic distribution of venom.
12. The tumescent contravenom solution according to claim 1 , wherein the concentration of contravenom agent is diluted by a factor of 2 or more by the physiological crystalloid solution, or wherein a volume used to dissolve a lyophilized powder of the contravenom agent is at least twice a minimal amount required to dissolve the contravenom agent.
13. The tumescent contravenom solution according to claim 1 , wherein the physiological crystalloid solution is selected from the group consisting of 0.9% physiologic saline and lactated Ringer's solution.
14. A method of treating an envenomation in a subject comprising locally injecting the tumescent contravenom solution according to claim 1 within and/or around a site of the envenomation.
15. The method according to claim 14 , comprising self-administering of the tumescent contravenom solution by the subject.
16. The method according to claim 14 , wherein the tumescent contravenom solution is injected subcutaneously or intramuscularly.
17. The method according to claim 14 , wherein the contravenom solution is injected within 5-10 minutes following the envenomation.
18. A kit for performing the method according to claim 14 comprising:
(a) a physiological crystalloid solution adjusted to an acidic pH,
(b) a vasoconstrictor that is either in solid or liquid form,
(c) a contravenom agent selected from the group consisting of a protease inhibitor that counteracts a venom protease, a metalloprotease chelating agent, a phospholipase A2 inhibitor, a cellular receptor site blocker that blocks interaction of a venom protein with integrins and a contravenom agent that counters a procoagulation or a coagulation inhibitory property of a venom;
(c) a hypodermic needle or an infiltration cannula, and
(d) a syringe.
19. The kit according to claim 18 , further comprising a contravenom agent and/or a drug that impairs or paralyzes lymphatic smooth muscle function and impairs lymphatic transport of venom.
20. The tumescent contravenom solution according to claim 1 , wherein the physiological crystalloid solution is adjusted to have a pH in the range of 3.8 to 5.0.