Statins Diuretics

All ACE-I + diuretic or ARB blood pressure lowering Peridopril 2-8 mg daily Indapamide 1.25-5 mg daily Statin therapy ... 

This is not the only example. Recently, polymorphisms in the G protein p3-subunit gene have been shown to predict response to hydrochlorothiazide (Turner et al., 2001). Psaty et al. identified a subset of patients with a variant of the a-adducin gene that were associated with a lower risk of myocardial infarction and cerebral hemorrhage with diuretic therapy (Psaty et al., 2002). In addition, Genaissance has indicated that it has identified markers that predict the response to the statins, a class of drugs used to lower cholesterol. 

Receptors can mediate the action of endogenous signalling compounds and may therefore be viewed as regulatory proteins. Such receptors are the physiological targets for neurotransmitters and hormones. Other types of receptors include enzyme proteins, transport proteins and structural proteins. For example, statins inhibit an enzyme catalysing the synthesis of cholesterol and loop diuretics inhibit an enzyme that facilitates the re-uptake of salt in primary urine. 

PUFAs suppress HMG-CoA reductase and ACE activities, inhibit platelet aggregation, enhance parasympathetic activity and, thus, enhance heart rate variabihty (and thus, have actions similar to that of fS-blockers), and possess diuretic properties either by themselves and/or by increasing the formation of PGAs and PGEs that have been shown to increase renal blood flow and augment diuresis. These actions of PUFAs are similar to that of the polypill that is a combination of aspirin, fS-blockers, statins, and ACE inhibitors, which is expected to reduce cardiovascular diseases by over 70-80% (92). This suggests that PUFAs could function as an endogenous polypill the evidence for this is detailed below. 

All ACE inhibitor + diuretic or ARB blood pressure lowering Statin ... 

Various classes of drugs, such as thiazide diuretics, proton-pump inhibitors, androgens, PTH, statins, and human monoclonal antibody, have been shown to have beneficial effects in treatment of diseases associated with abnormal calcium homeostasis through various mechanisms. 

In clinical studies, the safety and efficacy of statins were not altered by concurrent use of diuretics. 

The MADIT II trial addressed some of the issues raised by the MADIT. The MADIT II trial evaluated patients with ischemic cardiomyopathy (history of myocardial infarction > 1 month before entry). New York Heart Association Functional Class I-III congestive heart failure, and left ventricular ejection fraction < 0.30 (documented within 3 months), with or without ventricular ectopy. The study enrolled 1,232 patients to assess if an ICD improve total mortality compared to optimal therapy alone. No Holter or electrophysiology test criteria were required for enrollment. Optimal medical therapy included angiotensin-converting-enzyme inhibitors, beta-blockers, diuretics, and lipidlowering statin drugs (172). 

Drug interactions The extent to which vitamin D supplementation alters drug effectiveness and toxicity in humans has been systematically reviewed. Bile acid sequestrants and lipase inhibitors were found to inhibit the absorption of vitamin D from the gut. Statins, rifampicin, isoniazid, hydroxychloroquine, antiepileptics, corticosteroids, immimo-suppressive and chemotherapeutic agents, antiretroviral drugs and H2 receptor antagonists interfered with vitamin D metabolism. The interaction between vitamin D and thiazide diuretics could result in hypercalcaetnia. Vitamin D supplementation decreases concentrations of atorvastatin, and could cause hypercalcaetnia in elderly individuals or tixose with compromised renal function or hyperparathyroidism [84 ]. 

HMG-CoA reductase, whilst in other situations the enzyme S5 tems are involved in a variety of functions, e.g. phosphodiesterases. The following sections detail aspects of lipid-lowering dmgs including the action of statins with HMG-CoA reductase, the suiphonamide diuretics and carbonic anhydrase activity and their involvement with the Na/Q/K symporter, ACE inhibitors, a number of different pbospbcxUesterase inbibitors involved in erertile dysfunction and cbronic obstructive pulmonary disease and tbe proton pump inbibitors used in tbe treatment of gastric ulcers. 

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