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Clinical Experience with Purinergic Analgesia

Clinical Experience with Purinergic Analgesia. 1992 – 200 4. ADENOSINE. Purine nucleotide Natural metabolite Metasympathetic autonomous mediator Interacts with adenosine (purinergic) receptors А 1 , А 2 , А 3. Adenosine Medicines. Adenosine ( pure nucleoside )

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Clinical Experience with Purinergic Analgesia

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  1. Clinical Experience with Purinergic Analgesia 1992 – 2004

  2. ADENOSINE • Purinenucleotide • Natural metabolite • Metasympathetic autonomous mediator • Interacts with adenosine (purinergic) receptors А1, А2 , А3

  3. Adenosine Medicines • Adenosine (purenucleoside) • Adenosine Monophosphate (АМP, Adenocard®) • Diadenosine Tetraphosphate (2АTP) • Sodium Adenosinetriphosphate (АТP) • R-phenylisopropyladenosine(R-PIA)

  4. ATP

  5. Adenosine Derivatives Metabolism

  6. Adenosine: Main Effects • Vasodilation, especiallyPulmonary • Negativechrono-, dromo-, batmo- &inotropicaction • GI Motility Inhibition • Bronchial Constriction • Central Analgesia • Anti-Inflammatory action • Sedation ???

  7. Influences on Inflammation: • Suppressesfree O-radical effluxfrom neutrophils (A2) • DecreasesTNF- productionin reperfusion/reoxygenation • ReducesIL-6 release • But:maylead to direct histaminerelease (А3)!

  8. Adenosine Catabolism T1/2<10 s!

  9. N.B.! Any Adenosine drug acts only as a direct agonist at specific cell membrane receptors, butdoes not deliver any energy supply!

  10. Adenosine EffectsModulation + POTENTIATION • Dipyridamole – BLOCKING • Theophylline • Pentoxiphylline • Caffeine

  11. Adenosine: Routine Clinical Use • Supraventricular Antiarrhythmic • Vasodilator, esp. Pulmonary • Test Bronchoconstrictor

  12. Marta Segerdahl Alf Sollevi Karolinska Institutet, Stockholm 1992 - 1995

  13. Alf Sollevi:Adenosine infusion during isoflurane-nitrous oxide anaesthesia: indications of perioperative analgesic effect // Anesthesia& Analgesia. – 1992. – Vol. 80. – P. 595-599.Gomaa AA:Characteristics of analgesia induced by adenosine triphosphate // Pharmacology and Toxicology. – 1987. – V. 61. – P. 199-202.

  14. Zarate E, Sa Rego MM, White PF et al.:Comparison of adenosine and remifentanil infusions as adjuvants to desflurane anesthesia // Anesthesiology. – 1999. – Vol. 90. – P. 956-963.Fukunaga AF, Alexander GE, Stark CW: Characterization of the analgesic actions of adenosine: comparison of adenosine and remifentanil infusions in patients undergoing major surgical procedures // Pain. – 2003. – Vol. 101. – P. 129-138.

  15. Adenosine:analgetic per se,analgetic adjuvant or just direct autonomous corrector?

  16. ComparativeStudy I

  17. Surgery and AnaesthesiaControl Points 1. Starting Point before Induction 2. On Anaesthesia Induction 3. On Skin Cutting 4. During Mobilization 5. Restorative Phase (Anastomosis) 6. Recovery from Anaesthesia

  18. CARDIAC INDEX l / m2 · min

  19. SVR INDEX dyn · s · cm-5 · m2

  20. Two-component Modelof Respiratory Mechanics • P – full Circuit Pressure, kPа • R – Airways aerodynamicResistance, kPа·s/l • С - «Thorax-Lungs» System Compliance, l/kPа P = R·dV/dt + V/C, whereV - Volume, t - Time.

  21. AIRWAYS RESISTANCE kPа·s/l

  22. THORAX& LUNGS COMPLIANCE l/kPа

  23. DEAD VOLUME (VDСО2 ) ml/kg

  24. METABOLIC RATE(Indirect Calorimetry) cal/m2 ·min

  25. ComparativeStudy II

  26. Surgery and AnaesthesiaControl Points 1. Starting Point before Induction 2. On BladderSeparation 3. Just beforeRecovery

  27. Surgery Spectrum

  28. Specific Cases of Adenosine Use • Surgery in Myasthenia Gravis – 6 • Fast Opiate Detoxification under General Anaesthesia with Naloxone – 49 • Anaesthesia in Opiate Addicts – 12 • Test in Full Consciousness – 1

  29. Adenosine Infusion Official 1% Sodium-ATP solution: Infusion Rate = 1…5 mg/kg per hour No Bolus Infusion! Precision Syringe Pump!!! ECG Monitoring!!! !

  30. DETAILS &… COMPLICATIONS ! • Bradycardia • Bronchospasm • SА- or АV-block exacerbation • SpO2 decrease (vasodilation, V/Q mismatch) • Hyperuremic metabolic acidosis

  31. CONTRAINDICATIONS • Allcases of bronchial obstruction • SА- or АV-conduction disturbances • Weak sinus syndrome • Hyperuricemia?

  32. ADVANTAGES • GoodAnalgesiawithoutSedation • Excellent Controllability • Stimulates Breathing • Mild Hemodynamic Effects • No Postoperative Hyperalgesia • Treats Pulmonary Hypertension • May be used in Opiate Addicts • No Law Restrictions

  33. ANALGESIC SPECTRUM:BETWEEN HYSTORY & FUTURE… • OPIATES • 2-ADRENOPOSITIVE AGENTS • PURINE DERIVATIVES • SEROTONINE (5-HT) AGONISTS

  34. FUTURE ANALGESIC SET • PREEMPTIVE (ANTI-INFLAMMATORY) ANALGESICS: NSAIDs, PROTEINASE INHIBITORS, GLUCOCORTICOIDS • INTRAOPERATIVE ANALGESICS – DIRECT AUTONOMOUS CORRECTORS: 2-ADRENOPOSITIVE AGENTS, PURINE DERIVATIVES, -BLOCKERS, Ca++-CHANNEL BLOCKERS, etc. • “FULL-CONSCIOUSNESS” ANALGESICS: OPIATES, NMDA-ANTAGONISTS

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