Therapeutic use of adenosine compounds as surgical anesthetics

• US 5,677,290 A
• Filed: 05/05/1995
• Issued: 10/14/1997
• Est. Priority Date: 05/10/1990
• Status: Expired due to Fees

• Current Assignee: Puref, LLC
• Original Assignee: Atsuo F. Fukunaga
• Inventors: Fukunaga, Atsuo F.
• Primary Examiner(s): Kunz, Gary L.
• Assistant Examiner(s): CRANE, LAWRENCE E
• Application Number:
  US08/437,080
• Time in Patent Office: 893 Days
• Field of Search: 514/46, 514/47, 514/26.23, 514/26.7, 514/26.26, 514/27.6
• US Class Current: 514/46
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

A method of inducing anesthesia, sedation, analgesia, hypothermia, and reduced stress by administering an effective amount of an adenosine compound to a mammal. It also provides a method for preserving donor organs in vivo by contacting them with an adenosine compound, as well as a method for preparing organ recipients for transplant.

Claims

1. A method of performing surgery on a mammal comprising the steps of:

a) determining a baseline value of a physiologic parameter selected from the group consisting of respiratory rate, blood pressure, blood oxygen, blood carbon dioxide, and heart rate;

b) monitoring the physiologic parameter to ascertain deviations from the baseline value;

c) initiating administration of a pharmaceutical composition comprising a compound selected from the group consisting of adenosine, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate;

d) adjusting the rate at which the pharmaceutical composition is administered to said mammal so as to provide a level of said compound sufficient to produce at least two effects selected from the group consisting of sedation, analgesia, inhibition of stress, and skeletal muscle relaxation;

e) initiating surgery; and

f) adjusting the rate at which the pharmaceutical composition is administered to said mammal so as to provide a level of said compound sufficient to maintain said effects, wherein the rate can be adjusted to maintain the blood pressure within about 20% of a baseline value while maintaining said effects or, when said blood pressure differs from said baseline value by more than about 20%, the rate can be adjusted to return the blood pressure to within about 20% of the baseline value while maintaining said effects.

2. The method of claim 1, further comprising the steps of completing surgery and discontinuing the administration after step f).

3. The method of claim 1, wherein the surgery comprises endoscopy, angiography, dental work, laparoscopy, thoracic surgery, cardiac surgery, abdominal surgery, cranial surgery, orthopedic surgery, urologic surgery, neurosurgery, plastic surgery, otolaryngology surgery, ophthalmologic surgery, pediatric surgery, gynecologic surgery, obstetrical surgery, breast surgery, reconstructive surgery, oral surgery, fetal surgery and veterinary surgery.

4. The method of claim 1, wherein the step of initiating administration comprises initiating a continuous infusion of said pharmaceutical composition.

5. The method of claim 1, wherein the step of initiating administration comprises initiating an infusion selected from the group consisting of an intravascular infusion, an intraperitoneal infusion, an epidural infusion and an intrathecal infusion.

6. The method of claim 1, wherein the steps of adjusting the rate at which the pharmaceutical composition is administered prior to and during surgery comprise administering said compound at a rate of from about 1 μ

g/kg/min to about 5500 μ

g/kg/min.

7. The method of claim 1, additionally comprising the step of co-administering a second pharmaceutical composition in at least one of steps c), d) and f), said second pharmaceutical composition comprising a compound selected from the group consisting of an inhalation anesthetic, an intravenous anesthetic and a muscle relaxant.

8. The method of claim 1, wherein the physiologic parameter is blood pressure and is selected from the group consisting of systolic blood pressure and mean arterial blood pressure.

9. The method of claim 1, wherein the pharmaceutical composition is selected from the group consisting of a solution, a suspension, and an emulsion of said compound.

10. The method of claim 1, wherein the steps of adjusting the rate at which the pharmaceutical composition is administered prior to and during surgery comprise administering said pharmaceutical composition at a rate of from about 30 μ

g/kg/min to about 5500 μ

g/kg/min.

11. The method of claim 7, wherein said inhalation anesthetic is selected from the group consisting of nitrous oxide, enflurane, isoflurane, halothane, and methoxyflurane.

12. A method of providing anesthesia to a mammal for surgery, comprising the step of:

administering a pharmaceutical composition to said mammal at a rate sufficient to produce a level of anesthesia in said mammal sufficient to anesthetize said mammal for surgery while maintaining a physiologic parameter of said mammal within a desired range, wherein said pharmaceutical composition comprises an adenosine compound selected from the group consisting of adenosine, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate, and said physiologic parameter is selected from the group consisting of blood pressure, heart rate, respiratory rate, pH, and partial pressure of at least one blood gas.

13. The method of claim 12, further comprising the steps of:

surgically stimulating said mammal following said step of administering said pharmaceutical composition; and

adjusting the rate at which said pharmaceutical composition is administered during said surgical stimulation in order to maintain a desired level of anesthesia in said mammal while maintaining said physiologic parameter within said desired range, whereby said level of anesthesia and said physiologic parameter can be maintained within said desired range during said surgical stimulation.

14. The method of claim 12, wherein said physiologic parameter is blood pressure, and said method further comprises the step of:

adjusting the rate of administration of said pharmaceutical composition to avoid hypotension.

15. The method of claim 12, wherein said physiologic parameter is blood pressure, and said step of adjusting the rate at which said pharmaceutical composition is administered comprises adjusting the rate of administration to avoid hypotension.

16. The method of claim 15, wherein said adenosine compound is administered to said mammal at a rate of about 1 μ

g/kg/min to about 5500 μ

g/kg/min.

17. A method of maintaining anesthesia in an anesthetized mammal, comprising the step of:

administering to an anesthetized mammal a pharmaceutical composition at a rate sufficient to maintain a desired level of anesthesia in said mammal, wherein said pharmaceutical composition comprises an adenosine compound, wherein said adenosine compound is selected from the group consisting of adenosine, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate, and said rate is sufficient to provide an anesthetically effective amount of said adenosine compound without inducing hypotension in said mammal, and wherein said desired level of anesthesia can be maintained and hypotension avoided in said mammal during surgical stimulation by adjustment of said rate of administration, and said desired level of anesthesia can be maintained despite dosage reduction of at least one compound other than an adenosine compound which would be required in the absence of said adenosine compound to maintain said desired level of anesthesia.

18. The method of claim 17, wherein said adenosine compound is administered to said mammal at a rate of about 1 μ

g/kg/min to about 5500 μ

g/kg/min.

19. The method of claim 17, wherein said mammal is a human.

20. A method of anesthetizing a mammal for surgery, comprising:

a first step of administering a first anesthetic agent to said mammal;

a second step of administering to said mammal as an anesthetic adjuvant a composition comprising an adenosine compound, wherein said adenosine compound is selected from the group consisting of adenosine, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate; and

adjusting the rate of said administration of said adenosine compound in order to cause at least two effects selected from the group consisting of sedation, analgesia, inhibition of stress, and muscle relaxation, whereby said mammal is anesthetized sufficiently for surgery by said first and second steps, and said effects are maintained during surgery on said mammal.

21. The method of claim 20, wherein:

said rate of administration of said adenosine compound is adjusted to between about 1 μ

g/kg/min and about 5500 μ

g/kg/min.

22. A method of anesthetizing a mammal for surgery utilizing an adenosine compound, comprising the step of:

administering to a mammal an anesthetically effective amount of a composition comprising an adenosine compound sufficient to anesthetize said mammal for surgery, wherein said compound is selected from the group consisting of adenosine, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate.

23. The method of claim 22, wherein the rate of administration of said compound is adjusted to induce and maintain a desired level of anesthesia while maintaining the blood pressure of said mammal within a desired range.

24. The method of claim 22, wherein between about 30 μ

g/kg/min and about 5500 μ

g/kg/min of said compound is administered to said mammal.