Isoprenaline (also called isoproterenol) is a non-selective beta-adrenergic agonist. It is administered via IV or oral inhalation and is used to treat conditions including mild or transient episodes of heart block that do not require pacing, serious episodes of heart block and Adams-Stokes attacks (except when caused by ventricular tachycardia or fibrillation), cardiac arrest until electric shock or pacemaker therapy is available, bronchospasm occurring during anesthesia, and as an adjunct to in the treatment of hypovolemic and septic shock, low cardiac output states, congestive heart failure, and cardiogenic shock. The actions of isoprenaline are mostly observed in heart muscle, where it binds to beta-1 adrenergic receptors, and smooth muscle (bronchi, blood vessel, GI tract and uterus), where it exerts it’s effects via beta-2 adrenergic receptors. In the heart, isoprenaline binds to and activates the beta-1 adrenergic receptor, which is coupled to the G-protein signaling cascade. Activation of the receptor activates the signaling cascade which leads to activated protein kinase. Protein kinase activates calcium channels in the membrane, causing them to open and allow Ca2+ to enter the cell. Due to this effect, there is high concentration of Ca2+ in the cell. Ca2+ activates the ryanodine receptor on the sarcoplasmic reticulum, which transports Ca2+ from the sarcoplasmic reticulum into the cytosol. the high concentration of Ca2+ in the cytosol binds to troponin to cause muscle contraction. The high concentration of Ca2+ means that more Ca2+ binds to troponin, increasing inotropy. In non-cardiac myocytes, an increase in intracellular Ca2+ increases the slop of phase 4 of the action potential. The threshold is reached faster, therefore, the heart rate is increased. In the smooth muscle, Ca2+-calmodulin complex activates myosin-LC kinase which activates myosin-LC. The activated myosin-LC causes contraction. Isoprenaline binds to and activates beta-2 adrenergic receptor, activating the G-protein signaling cascade. The G-protein signaling cascade produces cAMP, which inhibits myosin-LC kinase. This prevents the activation of myosin-LC and as a result, decreases smooth muscle contraction. Possible side effects from taking isoprenaline include headache, dizziness, upset stomach, flushing, fatigue, nervousness, angina, hypotension, hypertension, palpitations, ventricular arrhythmia, tachycardia, adams-stokes syndrome, dyspnea, edema, blurred vision, nausea, vomiting, tremor, weakness.

Isoprenaline B1-Adrenergic Cardiac Muscle Contraction Pathway References