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adenosine

adenosine

Introduction:

  • adenosine is a naturally occurring endogenous nucleoside
  • adenosine is rapidly taken up by RBC's & endothelial cells such that almost completely eliminated from circulation after 1st pass → plasma T1/2 < 10secs;
  • hence can expect exaggerated response in anaemic patients, & reduced response if infusion in peripheral vein rather than IV bolus into central vein;

Precautions and contraindications:

  • only use with full resuscitative facilities on hand
  • avoid in severe coronary artery disease as risk of vasodilatation of normal vessels may produce ischaemia in vulnerable territory
  • avoid in severe asthma
  • patients on theophylline may require higher doses
  • dipyridamole potentiates effects of adenosine
  • carbamazepine increases risk of prolonged AV block

Dose and usage for SVT:

  • see also SVT
  • give half these doses if administering via a central venous catheter (CVC).
  • Insert cannulae into a large proximal peripheral vein (the cubital fossa is ideal) with three way tap attached
  • Draw up starting dose of adenosine 0.1-0.2 mg/kg (6 or 12mg for an adult). If necessary dilute to 1 ml with normal saline.
  • Draw up 10 ml saline flush & warn patient they will feel awful!
  • Turn on the ECG trace recorder
  • Administer adenosine as a rapid IV push followed by the saline flush
  • Repeat procedure at 2 minutely intervals, until tachycardia terminated, increasing the dose of adenosine by 0.05mg/kg (6mg for an adult) each time up to a maximum of 0.5 mg/kg (max dose 18mg).
    • adenosine success rates in adults with Rx SVT:
      • 1 dose 43%; 2nd dose 34%; 23% require a 3rd dose although a third of these will fail (ie. 8% of all patients and 23% of those with PH SVT)
      • failure risk score = (age/heart rate on admission) + number of past paroxysmal SVT episodes
        • if score > 1.18 then sens. 96% and spec. 71% for failure of adenosine protocol
        • ref: Am J Emerg Med 2008; 26:304-9.

Adverse Effects:

  • usually last < 2 min. due to short half life
  • facial flushing -18% if IV bolus;
  • SOB -12% if IV bolus;
  • chest pain/pressure - 11% if IV bolus;
  • hypotension
  • occasionally, more prolonged AV block or sinus arrest after IV bolus
  • dose dependent decreased renal blood flow, GFR & urine flow if infusion
  • myocardial ischaemia presumably via coronary steal;
  • AV block - 2nd/3rd degree occurred in 6% with infusion @ 140ug/kg/min for 6min;
  • adenosine used to Rx SVT is said to result in atrial fibrillation in up to 12% of patients (Strickberger et al. Ann.Intern.Med. 1997)
  • adenosine used to unmask flutter waves in atrial flutter has been reported to result in 1:1 conduction with haemodynamic compromise.

Pharmacodymanics and physiology:

  • Effects mediated by adenosine receptors on outer surface of cell membrane:
    • Type A1:
      • activate K channels & inhib. c-AMP accumulation;
      • predominate in myocardium;
    • Type A2:
      • stimulate release of EDRF & the accum. of i/cell. c-AMP;
      • esp. in coronary arteries;
    • Type A3:
    • Type A4:
  • Adenosine may play a key role in the production of, & mediation of anginal PIC;
  • Electrophysiologic effects (mediated by A1):
    • -ve chronotropic effect on sinus node automaticity;
    • -ve dromotropic effect on AV nodal conduction;
    • In supraventricular tissues (sinus node, AV node):
      • activates K outward current in a distinct K channel
        • ⇒ tissue hyperpolarisation;
    • In ventricular tissue:
      • acts primarily by attenuation of catecholamine-stimulated Ca fluxes;
    • Summary:
      • when given as a bolus dose IV, it directly inhibits AV nodal conduction and increases AV nodal refractory period, but has only mild effects on SA nodal function.
  • Cardioprotective effects:
    • Adenosine is released from myocardium when O2 supply:demand ratio falls →:
      • coronary vasodilatation
      • antiadrenergic via:
        • decr. release NA from cardiac symp. Ns;
        • attenuates stimulating effects of catecholamines on heart;
      • antiarrhythmic:
        • exog. adenosine → decr. severity of ischaemia-induced vent. arrhthm.
      • metabolic effects:
        • delays myocardial ATP depletion;
        • incr. myocardial glucose uptake;
        • incr. glycolytic fluxes;
      • attenuation of microvascular injury:
        • ? prevention of neutrophil/platelet aggreg.
        • ? inhib. of free O2 radical release from activated neutrophils;
adenosine.txt · Last modified: 2009/02/16 15:49 (external edit)