Non-Adrenergic Vasoactives
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.
| Property | Vasopressin (ADH) | Milrinone | 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 |
| Dosing | 5-10 units IV bolus, up to 4U/hr infusion | 50μg/kg loading dose over 10 minutes (often omitted), followed by infusion titrated to haemodynamic effects, up to 75μg/kg/min | Load 12-24mcg/kg over 10min, then infusion at 0.05-2mcg/kg/min |
| **Route | **IV/SC/IM | IV | IV |
| 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. ↑ Speed of Ca2+ uptake into cardiac muscle, ↑ 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 | ↑ Inotropy, ↑ lusitropy, ↓ SVR and PVR (PVR ↓ more than SVR). ↑ Dysrhythmias. | ↑ CO without ↑ 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 | ||
| Metabolic | Hyponatraemia |
References
- Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
- Smith S, Scarth E, Sasada M. Drugs in Anaesthesia and Intensive Care. 4th Ed. Oxford University Press. 2011.
- Brunton L, Chabner BA, Knollman B. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 12th Ed. McGraw-Hill Education - Europe. 2011.