Chronic Diseases: Diabetes Patients (Polypharmacy)

Use of multiple medications in the same patients (Polypharmacy) nowadays is a common practice all over the world to treat chronic disorders like diabetes mellitus (DM) and hypertension. These practices are acceptable to treat single and multiple disorders, which occur simultaneously. Polypharmacy sometimes unavoidable. Recently, the standard of healthcare in most chronic conditions achieved by given that multiple drug therapy. The comorbidities of diabetes usually contain hypertension, dyslipidemia, heart failure, and coagulopathies, each of these diseases may need one or more drugs to suitable control. Polypharmacy is predictable in treating a common chronic disease such as diabetes. The possible for polypharmacy will continue to increase
with time, when other therapeutic choices become available. (Austin, 2006) In this case, one drug may affect another drug causing drug-drug interactions (DDI). In high-risk disorders like diabetes and hypertension, these interactions are more dangerous and may be lead to serious conditions. (Kumar et al., 2012) A drug-drug interaction (DDI) defined as an interaction between one or more coadministered medications that lead to the change of the effectiveness or toxicity of any of the coadministered medications. Drug interactions can occur with prescription and over-the-counter (OTC) drug, herbal, foods, vitamins, diseases, and genetics. A high number of medications become a suitable therapy when patients diagnosed with diabetes mellitus. These consist of medications for dyslipidemia, hypertension, and glucose control. Therefore, many medications can be overwhelming, and it is authoritative that patients are carefully educated about their drug regimen. Patients have several concerns when multiple medications are started, including prescribing errors, the cost of medications, and possible adverse reactions. (Triplitt, 2006) Diabetes and hypertension are both lead to cardiovascular disease, especially when the nephropathy is present. Angiotensin converting enzyme (ACE) inhibitor considers first choice drugs for hypertension associated with diabetes. Diabetic patients who used anti-diabetic needs to continuous monitoring of blood glucose levels to prevent the occurrence of complications of diabetes, such as cardiovascular disease and many other complications such as retinopathy, and neuropathy. In addition, we must avoided hypoglycemia because it is dangerous too, and can cause convulsions, coma and even death; hence, we must study drug-drug interactions -various drugs- with oral anti-diabetic medications.
Knowledge in this field makes physicians and pharmacists capable to prevent or even reduce these risks from occurrence through doses adjustment or by using alternative drugs. (Agrawal et al., 2013) 1.1. Diabetes mellitus: Diabetes Mellitus is a most common disease in the world, especially in third world countries such as Yemen. Diabetes mellitus is a chronic metabolic disorder characterized by an increase in blood glucose (hyperglycemia) (fasting blood sugar (FBS > 126 mg/dl, or blood glucose >200 mg/dl 2 h after a meal). Diabetes mellitus characterized by hyperglycemia because of a defect in the secretion of the insulin from the pancreas, frequently coexists with insulin resistance. Hyperglycemia happens due to uncontrolled glucose output in hepatic and decrease uptake of glucose by skeletal muscle with reduced glycogen synthesis. Inside renal, when reabsorption of glucose is exceeded, glucose spills through into the urine, which results in glycosuria and triggered an osmotic diuresis (polyuria) which, in turn, lead to dehydration, thirst and increased drinking
(polydipsia). Reduced Insulin level causes muscle wasting because increased breakdown and decrease protein synthesis. Moreover, the insulin deficiency cause diabetic ketoacidosis, this effect appears because of the faster breakdown of fat to acetyl-CoA, in lack of aerobic carbohydrate metabolism, is converted to acetoacetate and β-hydroxybutyrate (which cause acidosis) and acetone (a ketone).
(Rang et al., 2015) The most common types of diabetes are type I (insulin-dependent diabetes mellitus, IDDM) and type II (non-insulin-dependent diabetes mellitus, NIDDM); either insulin resistance or a defect in insulin secretion or both causes Type II diabetes. (Imamura et al., 2013). In the type II of diabetes mellitus chronic hyperglycemia can lead to serious complications in the organs, especially in eye, nerves, heart and blood vessels. Therefore, the prevalence of hypertension in type-2 diabetes, may be as high as 50%. (Cantrill and Wood, 2003). Furthermore, the incidence of diabetes mellitus over the world is increasing every year. (IDF, 2014), the high incidence rate of DM in the world may because the consequence of changing patterns of diet and physical activity, increases in obesity, and ageing
populations. (Ugarte et al., 2012) ‏ There are an estimated on 2014, 387 million people worldwide have diabetes, and this number will be become 592 million people on 2030, over that 175 million people with diabetes are undiagnosed, people that have diabetes are between 40 and 59 aged, 77% of people with diabetes live in low- and middle-income countries. Diabetes caused 4.9 million deaths in 2014 that meant; every seven seconds a person dies by diabetes. Additionally, Diabetes consume at least 612 billion dollars in health consumption in 2014. (IDF, 2014) Nowadays, Diabetes mellitus considered a vascular disease (Safinaz and Sherine, 2008). Diabetic patients undergo to complications in the cardiovascular system (CVS) more than non-diabetic individuals. Cardiovascular complications among diabetics is responsible for 80% of deaths that occur in diabetic patients, Hypertension disease is a major co-morbidity of diabetes and modifiable risk factor that hastening the development and progression of microvascular and macrovascular complications (Parati et al., 2011). Many complications develop because of the metabolic disorders in diabetes, many of these are the because of disease of blood vessels, either small (microvascular disease) or large (macrovascular disease). Dysfunction of vascular endothelium has an early and important role in the progress of vascular complications in DM. Other factor such as oxygen-derived free radicals, protein kinase C and non-enzymatic products of glucose have been implicated. Macrovascular and its thrombotic complications are common and more severe in diabetic patients. Malfunction of microvascular in diabetes mellitus patients may particularly affect the retina, kidney and peripheral nerves. The commonest cause of chronic renal failure is diabetes mellitus. Concomitant hypertension encourages progressive renal damage, and proper management of hypertension reduces the pro¬gression of diabetic nephropathy and decrease the risk of myocardial infarction. ACE inhibitors or angiotensin receptor blockers (ARBs) are most effective in precluding diabetic nephropathy, possibly because they prevent fibroproliferative actions of angiotensin II and aldosterone. (Rang et al., 2015) Diabetes mellitus need to control blood glucose to decrease risks of diabetic complications. A Patient with type I diabetes must be using an insulin, while in Type II we have a lot of options, one of them is medications which called oral hypoglycemic agents (OHA), which used orally to return the blood glucose at the set point, these agents such as Sulphonylureas, Biguanides, Thiazolidinediones, α-Glucosidase inhibitors and many others. However, treatment of type II diabetes mellitus with metformin or sulfonylureas well-validated core therapies, as it has been in clinical use for more than 50 years. Likewise, lifestyle change programs consider an important requisite in the prevention or manage type II diabetes besides the pharmacological treatment. Some clinical trials demonstrated that the importance of exercise as a strategy for the prevention of diabetes and obesity. The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) recommended that lifestyle change in conjunction with drug therapy to get to the tight control over type II diabetes and its complications. Moreover, another study has shown that intervene to modify lifestyle as exercise and diet, or both reduces the incidence of type II diabetes. (Somineni et al., 2014). 1.2. Hypertension: The most common problem in type 1 and type 2 diabetic patients is hypertension. (Epstein et al., 1992) Cardiovascular disease is the most common type of diabetes complication of type II diabetes and represent 50-80% of the deaths among patients with diabetes. Therefore, prevention of this complication is an important goal for treatment of diabetes (Li, Y et al., 2014).‏ Hypertension is a risk factor for coronary artery disease, heart failure (HF), stroke, and chronic kidney disease. (Lithovius et al., 2013) ‏When hypertension is coexisted with diabetes is not only an indication of the increase risk of mortality, but it also contributes to the development of diabetes. (Goyal et al., 1996) Co-existence of hypertension and diabetes may implicated by insulin resistance, and reactive oxygen species (ROS) production, leading to endothelial dysfunction, high tissue renin– angiotensin–aldosterone system (RAAS) and activation of sympathetic nervous system (SNS). These entire factors have been implicated in the pathophysiology of diabetes and hypertension. (Richey et al., 1999) Additional possible causes of hypertension with diabetes include increased sodium retention in renal tubular, increase intracellular calcium concentration, proliferation of vascular smooth muscle cell and atherosclerosis, and impaired nitric oxide (NO) metabolism in skeletal muscle.(Sowers, 2004) When hypertension identified, both non-pharmacological and pharmacological treatment should be applied. Starting lifestyle changes is principal, beside medical therapy at the earliest detection of the pre-hypertensive patient. These lifestyle changes should include an improved diet, regular physical activity, weight control and stop of smoking. Weight management has shown to be an effective treatment in hypertension management. The most therapy that used in hypertension when co-existing with diabetes are ACE inhibitor and ARBs, ACE inhibitor consider first choice drugs for hypertension associated with diabetes. (Agrawal et al., 2013) other therapy that used in the management of hypertension are beta-blockers, calcium channel blockers (CCB), and thiazide diuretics. (Wassertheil-Smoller et al., 1992) 1.3. Drug-drug interactions (DDIs): The drug–drug interaction (DDIs) refers to an alteration of the effect of one drug caused by the other one. Or DDIs occur when the effects of one drug are changed by the presence of another drug, food, drink or by some environmental chemical agent, this effect may alter either pharmacokinetic parameter such as absorption, distribution, metabolism or execration or may alter pharmacodynamics parameter (Wolf J. et al., 2003). Major 'descriptive' mechanisms of DDIs include the following: a- Pharmacokinetic interaction b- Pharmacodynamic interaction c- Pharmaceutical incompatibility d- Combination of the above. The drug interaction could be either drug –drug interaction or food-drug interaction; When drug-drug interact together, they are generally interacting in different not by a single mechanism, but frequented by two or more mechanisms, the mechanisms of interactions classified into those which include the pharmacokinetics of a drug and those which are pharmacodynamic. When the absorbed, distributed, metabolized and excreted processes, are affected this called pharmacokinetic interactions. While pharmacodynamic interactions are those where the effects of one drug are altered by the existence of another drug at its receptor without any change in concentration of drug in plasma. (Lennard, 1993)