Clinical Experience with Purinergic Analgesia

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Clinical Experience with Purinergic Analgesia
1992 2004
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ADENOSINE

• Purine nucleotide
• Natural metabolite
• Metasympathetic autonomous mediator
• Interacts with adenosine (purinergic)
  receptors ?1, ?2 , ?3

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Adenosine Medicines

• Adenosine (pure nucleoside)
• Adenosine Monophosphate (??P, Adenocard)
• Diadenosine Tetraphosphate (2?TP)
• Sodium Adenosinetriphosphate (??P)
• R-phenylisopropyladenosine (R-PIA)

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ATP
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Adenosine Derivatives Metabolism
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Adenosine Main Effects

• Vasodilation, especially Pulmonary
• Negative chrono-, dromo-, batmo- inotropic
  action
• GI Motility Inhibition
• Bronchial Constriction
• Central Analgesia
• Anti-Inflammatory action
• Sedation ???

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Influences on Inflammation

• Suppresses free O-radical efflux from neutrophils
  (A2)
• Decreases TNF-? production in reperfusion/reoxygen
  ation
• Reduces IL-6 release
• But may lead to direct histamine release
  (?3)!

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Adenosine Catabolism
T1/2lt10 s!
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N.B.! Any Adenosine drug acts only as a direct
agonist at specific cell membrane receptors,
butdoes not deliver any energy supply!
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Adenosine EffectsModulation

• POTENTIATION
• Dipyridamole
• BLOCKING
• Theophylline
• Pentoxiphylline
• Caffeine

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Adenosine Routine Clinical Use

• Supraventricular Antiarrhythmic
• Vasodilator, esp. Pulmonary
• Test Bronchoconstrictor

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• Marta Segerdahl
• Alf Sollevi

Karolinska Institutet, Stockholm 1992 - 1995
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Alf SolleviAdenosine infusion during
isoflurane-nitrous oxide anaesthesia indications
of perioperative analgesic effect // Anesthesia
Analgesia. 1992. Vol. 80. P. 595-599.
Gomaa AACharacteristics of analgesia induced
by adenosine triphosphate // Pharmacology and
Toxicology. 1987. V. 61. P. 199-202.
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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.
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Adenosineanalgetic per se,analgetic adjuvant
or just direct autonomous corrector?
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Comparative Study I
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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

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CARDIAC INDEX

• l / m2 min

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SVR INDEX
dyn s cm-5 m2
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Two-component Modelof Respiratory Mechanics

• P full Circuit Pressure, kP?
• R Airways aerodynamic Resistance, kP?s/l
• ? - Thorax-Lungs System Compliance, l/kP?
• P RdV/dt V/C,
• where V - Volume, t - Time.

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AIRWAYS RESISTANCE
kP?s/l
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THORAX LUNGS COMPLIANCE
l/kP?
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DEAD VOLUME (VD??2 )

• ml/kg

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METABOLIC RATE(Indirect Calorimetry)
cal/m2 min
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Comparative Study II
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Surgery and AnaesthesiaControl Points

• 1. Starting Point before Induction
• 2. On Bladder Separation
• 3. Just before Recovery

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Surgery Spectrum
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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

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Adenosine Infusion
Official 1 Sodium-ATP solution Infusion Rate
15 mg/kg per hour No Bolus Infusion!

• Precision Syringe Pump!!!
• ECG Monitoring!!!

!
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DETAILS COMPLICATIONS
!

• Bradycardia
• Bronchospasm
• S?- or ?V-block exacerbation
• SpO2 decrease (vasodilation, V/Q mismatch)
• Hyperuremic metabolic acidosis

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CONTRAINDICATIONS

• All cases of bronchial obstruction
• S?- or ?V-conduction disturbances
• Weak sinus syndrome
• Hyperuricemia?

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ADVANTAGES

• Good Analgesia without Sedation
• Excellent Controllability
• Stimulates Breathing
• Mild Hemodynamic Effects
• No Postoperative Hyperalgesia
• Treats Pulmonary Hypertension
• May be used in Opiate Addicts
• No Law Restrictions

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ANALGESIC SPECTRUMBETWEEN HYSTORY FUTURE

• OPIATES
• ?2-ADRENOPOSITIVE AGENTS
• PURINE DERIVATIVES
• SEROTONINE (5-HT) AGONISTS

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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