Key non-adrenergic cardiovascular drugs include vasopressin (and its analogues, terlipressin and ornipressin), phosphodiesterase III inhibitors such as milrinone, and calcium sensitisers such as levosimendan.
|Class||Natural nonapeptide||Phosphodiesterase III inhibitor||Calcium sensitiser and phosphodiesterase inhibitor|
|Uses||Haemorrhage, DI, catecholamine-sparing vasopressor||Refractory CCF and low CO states||Severe acute heart failure||50μg/kg loading dose over 10 minutes (often omitted), followed by infusion titrated to haemodynamic effects, up to 75μg/kg/min|
|Dosing||5-10 units IV bolus, up to 4U/hr infusion||Load 12-24mcg/kg over 10min, then infusion at 0.05-2mcg/kg/min|
|Presentation||Clear solution||Yellow solution at 1mg/ml||2.5mg/mL in 5ml & 10ml vials|
|Distribution||70% protein bound||Very high protein binding >90%|
|Metabolism||t1/2 10 minutes. Metabolised by tissue peptidases and renal elimination.||t1/2 1-2.5 hours, prolonged in patients with cardiac or renal disease||t1/2 1 hour. Hepatic to active metabolite with a t1/2 ~70 hours|
|Elimination||80% of drug is excreted unchanged, making it highly dependent on renal blood flow|
|Mechanism of action||V2 receptors (kidney, platelets) are adenylate cyclase mediated. V1 (vascular smooth muscle) and V3 receptors (pituitary) are phospholipase C/inositol triphosphate mediated||Inhibits phosphodiesterase breakdown of cAMP, increasing intracellular Ca2+ levels. Also increases speed of Ca2+ uptake into cardiac muscle, increasing lusitropy.||Binds to troponin C increasing myofilament Ca2+ sensitivity. Also opens K+ channels causing vasodilation. It may also have some PD III inhibition effect.|
|CVS||↑ SVR through vasoconstriction||Increased inotropy, increased lusitropy, decreased SVR and PVR (PVR decreases more than SVR). Increased dysrhythmias.||Increased CO without increased O2 demand, vasodilation, prolonged QTc with risk of arrhythmia|
|GIT||GIT smooth muscle contraction|
|Renal||↑ Aquaporin insertion into the apical membrane of collecting ducts which ↑ water reabsorption|
|Haematological||↑ Coagulation factor mobilisation and ↑ platelet aggregation|
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