Drug Related Problems of Diabetic Nephropathy Patients in a Tertiary Hospital in Malaysia

Patients with diabetic nephropathy (DN) are particularly vulnerable to drug related problems (DRPs) due to complex medication regimen and renal dysfunction. However, there was limited information regarding prevalence of DRPs among patients with DN in Malaysia. This research was conducted to determine the prevalence of DRPs among hospitalized patients with DN at tertiary hospital in Malaysia during June 2014-May 2015. This was a retrospective observational descriptive study that used patients medical records as data source. There were 104 subjects included in this study. The prevalence of DRPs among the included subjects was 74%. Most DRPs observed were from two categories, namely non-compliance to medication and adverse drug reactions (20.93% for both categories). These categories were followed by the category of unnecessary drugs (16.28%), too low dose (15.81%), inappropriate drugs (11.16%), untreated indication (10.23%) and too high dose (4.65%). The prevalence of DRP was high among DN patients, thus pharmacists are encouraged to perform comprehensive medication review to improve health outcomes and enhance patients safety.


Introduction
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia caused by either a lack of insulin or the body's inability to use insulin efficiently.The chronic hyperglycemia is associated with long-term damage and dysfunction of various organs. 1,22DM increases the risk of microvascular complication, such as diabetic nephropathy (DN). 3abetic nephropathy (DN) is a major cause of chronic kidney disease and end-stage renal failure worldwide.Its clinical syndromes include the presence of pathological quantities of urine albumin excretion, diabetic glomerular lesions, and loss of glomerular filtration rate (GFR) in diabetics.Poor control of blood gluce is one of the risk factors of DN. 4,5 Patients with DN often receive complex medication regimen.This condition may increase the risk of drug related problems (DRPs) among DN patients.DRPs represent the categorization of clinical problems related to the use of medications, including inappropriate drugs, non-compliance, adverse drug reaction (ADR), etc. [6][7][8][9][10] However, there was limited information regarding the prevalence of DRPs among DN patients in Malaysia.This study was conducted to investigate the prevalence of DRPs and the most common DRPs categories in hospitalized DN patients in a tertiary hospital in Malaysia.

Methods
This retrospective study involved hospitalized DN patients at a tertiary hospital in Malaysia from June 2014 to May 2015.The data source was the medical records of the patients.We included DN patients whose age ≥ 18 years old and those who received at least two drugs for the treatment of DN.The exclusion criteria was incomplete patient data From each record, the following data were extracted; medical prescriptions and patient data, i.e., name, age, sex, duration of illness, duration of treatment, the results of treatment, diagnosis, number of drug doses, type of drug administered, concomitant drugs, and laboratory tests data.The data obtained were transferred and summarized in data collection sheet.
DRPs were further analyzed using standard literature of appropriate drug use such as the British National Formulary, Monthly Index of Medical Specialities, Drug Information Handbook and Drug Interaction Facts.

Results and Discussion
104 participants were included in this study.Data regarding patient profile and DRPs were obtained.

Patient profile
The number of female patients was dominant compared to the male patients (61%).Previous study showed that both men and women had the same prevalence and risk of DN. 11 Most patients were in the age of 45 to 64 years (61%).American Diabetes Association (ADA) stated that one of the risk factor in developing complication among T2DM patients is ≥ 45 years old. 2 The average duration of hospitalization was 1-3 days which was related to the effectiveness of treatment and comorbidities.About 54% of the patients had improved condition when discharged from the hospital.45% of the patients have been diagnosed with T2DM for 11-15 years.Duration of disease was related to the development of complication. 5e most widely use antidiabetic drugs was insulin group.Insulin is the most appropriate drug therapy for DN patients. 12The use of metformin should be given in a controlled Untreated indication 17 patients had symptoms of health problem with no drugs were given to address such issue.For example, the patient had a fever but an antipyretic was not prescribed.In other 15 cases, patients were not given additional medication for the prevention of side effects that arise when taking medication.

Unnecessary drugs
The main cause of such cases were due to redundant effects from duplication of treatment whose mechanism of actions were similar (22 cases).Another cause was the administration of drugs without indication (13 cases).

Inappropriate drugs
There were three main causes of inappropriate drugs given in this study.First, patients received the drug but not the most effective.For example, metoprolol, a beta blocker, was given to patients.However, the more appropriate drug for DN patients was ACEI, such as perindropil.Previous study showed that ACEI could reduce the symptoms of albuminuria with a higher percentage from beta blocker. 15Second, the patients received the drugs that were effective, but not safe.Gliclazide was not appropriate for patients who had renal impairment. 16Third, the patients received the right type of drug, but it was inapproriate for patients condition.Irbesartan 300mg can only be used in T2DM patients who had a serum creatinine > 300 mg/ml. 17(Table 3)

Too low dose
The most frequent DRPs in this category came from biguanide group.Metformin should be given in a dose of 500 mg, but it was given in a dose of 250 mg twice daily.Irbersartan, an ACEI, was prescribed with a dose of 150 mg 1x/day which is not sufficient because the required dose for nephropatic complication is 300 mg 1x/day. 17(Table 4)

Too high dose
Glicazide was often given in the dose of 160 mg 1x/day, while the appropriate dose for DN patients was 80 mg 1x/day. 18(Table 5)

Non-compliance
Patient compliance to medication is necessary to achieve the optimum therapeutic effect.Non-compliance could be resulted from the administration of too many combinations of drugs and inconvenience frequency and dosing.Besides, error in taking medication was also one of the causes of the noncompliance.It was found that most patients stored drugs in wrong and incompatible container for example Telmisartan 80 mg medication stored in the Ranitidine 150 mg container.Poor adherence was associated with development of complications. 19,20

ADR
We found that most frequent ADR observed were associated with the use of ACEI, such as dry cough and hyperkalemia.Hypoglicemia was also one of the side effects of antidiabetic drugs that was frequently reported by patients (Table 4).Drug interactions occur when one drug alters the pharmacological effect of another drug.The pharmacological effect of one or both drugs may be increased or decreased, or a new and unanticipated toxicity may be produced.[23][24]

Conclusion
The prevalence of DRP was high among DN patients, thus pharmacists are encouraged to perform comprehensive medication review to improve health outcomes and enhance patients safety.

Introduction
The use of antioxidants derived from plants have widely improved around the world.Many plants contain various phytochemicals which possess antioxidant activity to protect cells from damaging effects of reactive oxygen species (ROS), such as superoxides, peroxyl radicals, hydroxyl radicals and peroxinitrins. 1,2 human, production of ROS as the result of biochemical process might increase with several factors, including toxins and chemicals in food, pollutants, radiations, etc. Antioxidants compounds are needed to tackle this problem.However, synthetic antioxidant compounds such as butylated hydroxytoluene and hydroxyanisole might cause various side effects. 3This encourage researchers to find