Effect of Atenolol on Hepatic Dysfunction by Evaluating Level of AST

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In control group of 20 people of random age and gender with normal blood pressure have AST levels in normal range for males lies within <35U/L and for females <31 U/L (Table  1).
for some side effects including hepatic dysfunction. It causes damage to the liver cell and produce a variety of symptoms but the main problem originates from glucose insu cient supply to the brain leading to functions impairment. Liver function tests (LFTs) are performed in clinical biochemistry which indicate the condition of patient's liver [10,11]. Abnormal liver function tests (LFTs) have been reported in people with high blood pressure [12]. AST (Aspartate transaminase) is a sensitive indicators of liver damage or injury from different forms of diseases. The elevated level of AST indicates the damaged liver however there could also be some others factors responsible for this increase in AST level e.g., muscle damage also causes an increase in AST level in blood its normal range for male lies within <35U/L and for females <31 U/L [13]. This study was based on nding the effect of atenolol on hepatic functions by measuring the AST level in hypertension patients after they are treated with atenolol alone or in combination with other anti-hypertensive drugs. In this study, total of 80 subjects were selected with hypertension taking atenolol alone or in combination and 20 subjects with normal blood pressure were taken as control. Patients were selected from Punjab Institute of Cardiology, Lahore for the evaluation of hypertension status. Those with hypertension taking atenolol alone or in combination were selected and their AST levels were checked. All positive hypertensive patients were included and those on multidrug therapy and with concomitant disorder were excluded in this study. Those with normal blood pressure were taken as control for comparison. After collection of blood from the patients, blood was centrifuged, and serum were separated. The AST level was determined by measuring the change in absorbance with + time due to the conversion of NADH to NAD which was measured by using a by using a photometer 5010plus at 340/400nm rate technique. Addition of pyridoxal-5phosphate (P-5-P), recommended by IFCC, stabilizes the activity of transaminases and avoids falsely low values in sample containing insu cient endogenous P-5-P, from patients with hypertension.

R E S U L T S
The effect of atenolol on liver was studied by measuring the level of AST in blood of hypertensive patients. Figure 1 indicates the signi cant change (increase) in AST level in patients treated with atenolol alone (mean value = 49.9) as compared to patients treated with atenolol in combination with other anti-hypertensive drugs (mean value = 42.2) and while the mean value in control patients was 32.  The group of patient's takings atenolol alone having random age and gender have signi cant disturbance in AST levels as compared to control group (Table 2). applying standard deviation and standard error. In case of AST values evaluation, the signi cant results with 0.049 value were obtained (Table 4). Hypertension is a medical condition attributed to high blood pressure in blood vessels (140/90 mmHg or higher). According to world health organization ~1.28 billion adults with age between 30 to 79 years have hypertension across the world, with almost two-thirds of them living in low and middle economic countries. Some common factors include; age, genetics, obesity, non-active lifestyle, diet with high salt content and alcohol consumption [14]. Different anti-hypertensive drugs have developed to control blood pressure which targets different systems of the body that control and regulates the blood pressure. These anti-hypertensive drugs include; alpha blockers, ACE inhibitors, angiotensin receptor blockers, beta blockers, calcium channel blockers, central alpha agonists, diuretics, renin inhibitors and vasodilators [15]. Among beta blocker, a known drug is Atenolol (2-{4-[2-Hydroxy-3-(propan-2-ylamino) propoxy] phenyl} acetamide), which is a beta-adrenergic agent that blocks beta receptors on the heart and slow it down and decreases the blood pressure [9]. Some side effects of atenolol have been found when it is used in treatment of hypertension including; indigestion, dry mouth, depression, hepatic dysfunction, constipation, confusion, insulin level disturbance, central nervous system side effect, gastrointestinal and cardiovascular dysfunction [16]. Among these side effects the main focus of study is to study the effect of atenolol on hepatic dysfunction. As it is reported to cause damage to the liver cells. Liver function tests (LFTs) are important clinical assay used in clinical laboratory to give information about the condition of patient's liver [17]. Aspartate transaminase (AST) also known as serum glutamic oxaloacetic transaminase (SGOT) is an important biomarker among these LFTs but it doesn't indicate the absolute dysfunction of liver as its value can also be increase in some other in ammatory conditions such as muscle damage [13]. However, it is most commonly used test in clinical laboratories. In this study the effect of atenolol is studies on liver dysfunction by measuring AST level from blood of 80 patients either treated with atenolol alone or with atenolol in combination with other hypertensive drugs. While 20 persons with random age and gender with blood pressure within normal range were taken as control. After   33  35  40  40  41  43  44  45  45  48  48  50  50  50  50  50  54  54  55  55  56  57  58  58 1 year 8 years 2 months 3years 3 months 8 months 1 year 3 months 1 month 5 years 4 months 9 months 5 months 1 week 4 years 5 months 1 week 6 years 1 week 1 year 1 week 3 years 3 months 2 months 9 years 4 years 3 months 1 year 1 month 4 years 3 months 1 year 5 months 10 years 100  100  100  50  100  50  50  100  50  100  50  100  100  100  50  50  100  50  50  100  100  100  50  50   58  35  29  41  53  54  36  58  56  45  28  38  44  26  60  46  60  61  63  52  29  39  32  46   16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43   Female  Male  Male  Male  Female  Female  Female  Female  Female  Female  Female  Male  Male  Male  Female  Female  Female  Female  Female  Female  Male  Female  Male  Female  Male  Female  Female  Male   48  48  50  50  50  50  50  50  51  52  54  56  60  60  60  60  60  60  60  60  61  62  65  67  70  70  70  77 1 year 1 month 7 months 1 year 3 months 1 year 1 month 3 years 1 year 2 months 6 months 5 months 7 months 9 months 1 year 3 months 2 years 1 month 1 month 6 years 1 months 10 months 2 years 2 months 1 year 9 months 5 months 7 years 7 years 4 months 2 years 7 months 6 months 1 year 5 months 1 year 2 months  2 weeks   50  25  100  50  100  50  100  50  20  100  50  50  20  25  50  100  100  50  100  50  100  100  50  50  50  100  50  100   41  28  33  55  52  38  50  51  50  57  35  35  34  37  82  56  27  36  50  42  63  36  58  38  43  36  38  53 While, in the group of patient's takings atenolol in combination with other antihypertensive drugs having random age and gender have lower disturbance in AST levels as compared to group of patients taking atenolol alone (Table 3).

Variations in AST levels between Groups
blood sampling the serum was separated and AST level was measured by measuring the change in absorbance with time due to the conversion of NADH to NAD+ which was measured by using photometer at 340/400nm rate technique. The signi cant results were obtained as there was more increase in level of AST in patients treated with atenolol alone (mean value = 49.9) as compared to patient group treated with atenolol in combination with other antihypertensive drugs (mean value = 42.2) and control (mean value = 32). The effect of atenolol on hepatic dysfunction has found in literature, as one study has reported that out of 76408 people having side effects due to atenolol, 393 (0.15%) have abnormal liver function tests. While in sixty the rate of hepatic dysfunction increases while using atenolol. In females this chance of hepatic dysfunction increases while using atenolol [12]. Many other studies have also reported the hepatic dysfunction due to atenolol treatment for hypertension as one study has reported that in two patient's hepatic dysfunction was reported and in another complicated case the liver cirrhosis (acute hepatitis) was reported on administration of atenolol in hypertensive patient [18,19]. Result of this study supports these previous studies of effect of atenolol on hepatic dysfunction by evaluating the AST value [20,21].
This study has showed that atenolol may have e cacy in controlling hypertension but it also causes disturbance in AST levels so any other drug in combination with atenolol is recommended to use to control hypertension to avoid AST variation. Further this study can be performed on larger patient groups with more cases for validating the outcomes of this study.