INTRODUCTION:

Stroke is one of the most common cause of death in the world in 2013. Stroke is also the cause of disability, namely hyparesis, paralysis, decreased cognitive ability, and aphasia. In addition, stroke is also the number three cause of death in women and number five in men in America¹.

Meanwhile, stroke cases in Indonesia increased from 8.3 per 1000 in 2007 to 12.1 per 1000 in 2013. Stroke are most common found in people aged 56-64 years and continued to increase in the age group above. This can occur because in the elderly, the risk of chronic bleeding in the brain parenchyma or microbleeds increased².

Risk factors for hemorrhagic stroke are divided into several risk factors. Modifiable risks include hypertension, anticoagulant therapy, thrombolytic therapy, excessive alcohol consumption, and drug use. While the non-modifiable risk factors include age, race, cerebral amyloidosis, coagulopathy, vasculitis, arterio venous malformation (AVM), and brain tumors³. Hypertension is the highest risk factor because it causes structural and functional changes in blood vessels of the brain. One of them is thickening of blood vessels which can increase the risk of stroke⁴.

In systolic of 140-150mmHg, attacks of hemorrhagic strokes can increase the risk of death. Therefore, monitoring of blood pressure in acute hemorrhagic strokes is very important. Even though the patient previously had normal blood pressure, the risk of hypertension become higher and can cause worse effects. This is due to very high blood pressure which is the cause of the hematoma.

To reduce blood pressure, patients are given antihypertensive drugs. Antihypertensive drugs use in stroke patients, especially acute hemorrhagic strokes is not limited to just one class of drugs. There were several drugs of choice in hypertension cases, namely a direct vasodilator group, β-blockers, and calcium channel blocker. The Clinical Practice Guide states that hemorrhagic stroke patients with systolic > 180mm Hg or Mean Arterial Pressure> 130mmHg, and have other comorbidities that endanger the patient's condition, it need to be reducedimmediately using intravenous antihypertensive therapy⁶. In acute phase hemorrhagic stroke patients who have an indication of antihypertensive administration, blood pressure is lowered using intravenous antihypertension. However this should not be more than 25% MAP in 24 hours⁶.

In addition, acute hemorrhagic stroke patients with hypertension who have complications such as heart disease, kidney failure, and other diseases, need more complex medication. This case can lead to interactions of other drugs with antihypertensive drugs. If the ACE inhibitor is given along with potassium-sparing diuretics, it can cause hyperemia. In addition, in patients with diabetes complications of beta blocker administration and oral antidiabetic drugs can cause symptoms of hypoglycemia⁷.

In addition to the problem of drug interactions and drug-related problems, the another important proble is the side effects of the drugs. Some of antihypertensive drugs have the potential to cause side effects in patients, such as calcium channel blocker group which is diltiazem causing bradycardia, nicardipine can cause tachycardia, and other antihypertensive drugs side effects.

Based on the problems related to antihypertensive drugs above, it is necessary to conduct a research aboutpatterns of antihypertensive drugs use in acute hemorrhagic stroke patients in teaching hospitals in Indonesia. The purpose of this study was to examine the patterns of antihypertensive drugs use, the effect of antihypertensive administration on patients' blood pressure, and potential drug-related problems that occur in acute hemorrhagic stroke patients in teaching hospitals in Indonesia.

MATERIAL AND METHODS:

The Method of study:

This research was descriptive study with a retrospective approach. The study was conducted by examining the medical record data of acute hemorrhagic stroke patients with hypertension.

Location and time of the study:

This research was conducted in the Medical Record Unit of Inpatient Installation at Airlangga University Hospital or well known as RSUA. The time of the study was conducted between March and May.

Research Instrument:

The research instrument in this study was medical record data containing the antihypertensive therapy in patients which includes drug selection, route of administration, dosage, frequency of administration, and duration of therapy.

Sample and Population:

The samples were 24 stroke patients from all medical documents of patients, who were diagnosed with acute hemorrhagic stroke with hypertension in RSUA during January 2013 to December 2016. They were selected based on research inclusion criteria, namely patient health documents, diagnosed with hemorrhagic stroke with hypertension and having antihypertensive treatment history.

Inclusion and exclusion criteria:

Health medical documents of patients with final diagnosis of acute hemorrhagic stroke with hypertension and receiving antihypertensive therapy. The exclusion criteria in this study were patients with incomplete data of health medical documents.

RESULTS:

Patient Demographics Data:

Data showed that the number and percentage of hemorrhagic stroke male patients with hypertension were 54.17%. The percentage of female stroke patients was 45.83%. In addition, the number and percentage of hemorrhagic stroke patients with hypertension based on the most commonly occured in 45-65 years age group by 45.83%. There were 41.67% of patients over 65 years old and 12.50% of other patients were less than 45 years old.

Patients who experience a stroke usually do not only suffer from one type of disease. Some of the comorbidities suffered by patients are diabetes mellitus, chonic kidney disease, dyslipidemia, diabetes mellitus nephrophaty, post pneumoni, hemiplegia, pulmonary tuberculosis, pneumonia, ischemia of hepatitis, hemorrhoids, osetoarthritis, ODS glaucoma, susp dermatitis, post hematemesis, and melena. However, the following disease that is often suffered by patients is dyslipidemia.

In addition, the patient's financial status was related to the type of antihypertensive drugs selection. Data showed that 54.17% of patients were registered as national health insurance patients. There were 33.33% of patients registered as general patients. General patients are patients who do not use health insurance. The hospital fee is fully paid by the patient. While 12.50% of other patient's financial status were not listed.

Distribution of antihypertensive administration based on financing status:

Data showed that the distribution of antihypertensive administration to national health insurance patients was 7.69% of intravenous antihypertensive, 61.54% of oral antihypertensive, and 30.77% of intravenous and oral combinations. While the distribution of antihypertensive administration in general patients was oral antihypertensive as many as 75%, mean while intravenous and oral combinations as many as 25%. As for patients who did not their financial status data, the distribution of antihypertensive administration included intravenous and oral combinations by 66.66% and oral antihypertensive by 33.33%.

Distribution of antihypertensive administration by route:

Oral antihypertensive types, both single therapy and combination administration given to hemorrhagic stroke patients, were Amlodipine as much as 62.50%, Nimodipine as much as 8.33%. The Irbesartan, Bisoprolol and Valsartan were given to 16.67% patients. Whereas Canesartan, Captopril, HCT, Furosemide, and Ramipyrene were given as much as 4.17%, Lisinopril was given as much as 12.50%. Whereas oral antihypertension given was 33.33% Nicardipin and 12.50% Diltiazem.

Dosage of Antihypertensive Administration in Patients:

The appropriate dose is one of the determining factors in the success of antihypertensive therapy in hemorrhagic stroke patients. The antihypertensive dose given to hemorrhagic stroke patients and their literature can be seen in table 1.

Table 1 Antihypertensive doses received by the patients

Drugs Name	Doses according to literature	Doses given to the patients	Amount of Patients	Description
HCT	50 mg	1x12.5 mg	1	Appropriate
Captopril	450 mg	3x25 mg	1	Appropriate
Ramipril	2.5-20 mg	5 mg	1	Appropriate
Valsartan	80-320 mg	1x80 mg 1x160 mg Tidak jelas	7 5 1	Appropriate Appropriate -
Candesartan	8-32 mg	1x16 mg	1	Appropriate
Irbesartan	150-300 mg	1x150 mg 2x150 mg 1x300 mg	3 1 3	Appropriate Appropriate Appropriate
Nicardipine	0.5 – 6 mcg/kgBB	0.25 mcg/kgBB 0.5 mcg/kgBB 1.5 mcg/kgBB	1 7 1	Inappropriate Appropriate Appropriate
Diltiazem	5-15 mg/jam 5 mg/mL	15 mg/jam 1 mg/mL 2 mg/mL 5 mg/mL	1 1 1 1	Appropriate Inappropriate Inappropriate Appropriate
Amlodipin	5-10 mg	1x5 mg 2x5 mg 1x10 mg 1x15 mg	7 2 19 1	Appropriate Appropriate Appropriate Inappropriate
Lisinopril	Low Dosage : 5 mg Usualdosage: 10-40 mg	1x5 mg 2x5 mg 1x10 mg	2 1 1	Appropriate Appropriate Appropriate
Nimodipinee	60 mg setiap 4 jam	4x60 mg 6x60 mg	1 1	Appropriate Appropriate
Bisoprolol	2,5-10 mg	1x2,5 mg 1x5 mg	2 2	Appropriate Appropriate
Furosemide	20-80 mg	Tidak jelas	1	-

Information:

- The literature used was AHFS (American Hospital Formulary Service) Drug Information Book, 2011

- Patients can receive more than single dose

Antihypertensive type given to patients who have an indication of antihypertensive administration (on the first 3 days):

In general, acute hemorrhagic stroke patients will be given immediately antihypertension even from the first day of admission to the hospital. But there are some patients who have recently received antihypertension after the third day of hospitalization. The first antihypertensive route for the first 3 days given to patients including oral antihypertension was administered to 57.89% of patients, intravenous antihypertension was administered to 31.57% of patients, and combination antihypertension was given to 10.53% of patients. As for the first 3 days, all patients were given oral antihypertension.

Antihypertensive types given to patients who have an indication of antihypertensive administration include Nicardipin 181/110mmHg with indications of systolic > 180mmHg and MAP>130mmHg, Nimodipine 150/ 90mmHg, Irbesartan 150/100mmHg, Captoprin 200/ 100mmHg with systolic indication > 180mmHg and MAP> 130mmHg, Valsatran 160/90mmHg, Nicardipin 173/101mmHg, Amlodipine 170/100mmHg, Amlodipine 198/98mmHg with indications systolic> 180 mmHg and MAP>130 mmHg, Nicardipin 273/ 119mmHg with indications systolic> 180 mmHg and MAP>130mmHg, Diltiazem 160/100mmHg, Amlodipine 120/100mmHg, Candesartan 158/ 86mmHg, Diltiazem 180/105mmHg with indications of systolic 180mmHg and MAP 130mmHg, Amlodipine 160/100mmHg, and Nicardipine 178/109mmHg with MAP indication>130 mmHg.

In addition, a combination of Amlodipine+Valsartan 235/127mmHg is given with an indication of systolic> 180mmHg and MAP>130mmHg, Amlodipine+ Irbesartan 150/100mmHg, Nicardipin + Irbesartan 209/ 98mmHg with indications of systolic> 180 mmHg and MAP>130mmHg, and Diltiazm+Amlodipine 184/ 118mmHg with indications of systolic> 180 mmHg and MAP>130mmHg. The antihypertensive drugs given a few days after treatment (> third day) is in table 2.

Table 2 Antihypertensive drugs given several days after treatment (> third day)

Patient	Drug’s name	BP pre (mmHg)	Days-	BP post (mmHg)
1	Amlodipine	180/110	9	130/80
2	Valsartan	170/80	5	180/70
3	Amlodipine	120/100	3	150/100
4	Amlodipine	130/90	6	130/90
5	Amlodipine + Valsartan	183/103	4	174/101

Target achievement of antihypertensive drug:

After administration of intravenous antihypertension, theaverage of initial blood pressure is 174/107mmHg or MAP averaging 129 to 160/88mmHg or MAP averaging 112mmHg.

Patients given oral antihypertension had an average initial blood pressure of 156/95 or MAP averaging 115 and a final blood pressure averaging 145/87 or MAP averaging 106. Whereas patients who received intravenous and oral combination antihypertension had blood pressure the average start was 190/107mmHg, or MAP averaged 135, and the final blood pressure averaged 149/87mmHg, or an average MAP of 108 mmHg.

Duration of treatment and Discharged from hospital time:

The duration of treatment for hemorrhagic stroke patients in the study period was 54.17% of patients treated for 10-20 days.

In addition, there were 33.33% of patients treated for less than 10 days. 12.50% of patients were treated for more than 20 days. The reason for the patients was discharged from the hospital was they become outpatients. But there were some patients referred to other hospitals and some of the hospital was already full.

Drug Related Problem:

Treatment given to hemorrhagic stroke patients who are hospitalized does not only consist of antihypertensive therapy, but also other drugs.

This can trigger antihypertensive drug interactions with other drugs. Data showed that 2 patients had increased risk of hypertension due to Valsartan and potassium supplements. There were also 4 patients who experienced an increase in recycomyopathy due to the administration of Amlodipine and Simvastatin together. Giving captopril and antacids can also reduce absorbapaprilril. While for drug side effects, there are 4 patients who experience Tachycardia because of Nicardipine.

DISCUSSION:

First-line antihypertensive therapy in acute hemorrhagic stroke patients according to the guideline is intravenous antihypertension⁶.

However, the selection of oral antihypertensive therapy in patients can be influenced by many things. Some of them were costs incurred and other comorbid conditions found when a patient experiences a stroke. Intravenous antihypertension costs higher than oral antihypertension. This gives a considerable influence in the selection of antihypertension to be given.

Several types of antihypertensive agents, such as nicardipine, diltiazem, amlodipine, irbesartan, valsartan, candesartan, lisinopril and captopril were included in funding by national health insurance. Oral antihypertensive therapy is the most common antihypertensive type given to national health insurancepatients. In addition, some patients were given intravenous antihypertension and some patients were given a combination of oral and intravenous antihypertensive.

Antihypertensive that given to national health insurance patients was in accordance with the guidelines. This was because all types of antihypertensivehave been borne by the government, so patients do not need to pay more for these drugs. As for general patients, most of them receive oral antihypertensive. Some general patients also receive intravenous and oral antihypertension.

In addition those patients, there were also patients whose financial data was unknown. This was because their financing status is not listed in the patient's health document. The types of antihypertension received were 1 person receiving oral antihypertension and 2 people receiving intravenous and oral antihypertension.

The most common used of antihypertensive drugs include labetalol, esmolol, nicardipin, and diltiazem. However, not all intravenous antihypertension is available in Indonesia. In Indonesia, patients were given antihypertensive of nicardipine and intravenous diltiazem to reduce blood pressure if systolic> 180 mmHg with a target of lowering blood pressure <25% MAP in the first 24 hours. Nicardipine is a calcium channel blocker derived from Dihidropyridine which shows strong coronary and cerebral vasodilation activity. Nicardipine is administered intravenously with an initiation dose of 0.5mcg/kgBW. This drug is given at a dose of 0.5mcg/kgBW to 7 people. This dose is in accordance with the dosage stated in the American Society of Health-System Pharmacists 2011. However, one patient received a nicardipine dose of 1.5mcg/ kgBB. This can be caused by the high blood pressure of the patient so that the nicardipine dose is increased. In this patient a tappering off dose was also made to 0.5 mcg/kgBB. On the last day, patients received nicardipine at a dose of 0.25mcg/kg before the administration of nicardipine was stopped.

Other intravenous antihypertensive agents given to hemorrhagic stroke patients are diltiazem. This drug comes from the same group as nicardipine, which is calcium channel blocker. In contrast to nicardipine which is a derivative of dihydropirin. Diltiazem is a calcium channel block of non-hydropyrin derivatives. Intravenous diltiazem has very fast onset of action, which had the effect of decreased heart rate and haemodynamic effects. The duration of action of this drug is about 1-3 hours in decreasing heart rate, while for blood pressure reduction generally does not last long, but can last for 1-3 hours after administration.

Diltiazem is given to patients at a dose of 15mg/hour. This drug is given to 1 patient at a dose of 15mg/hour and according to the dosage stated in the American Society of Health-System Pharmacists 2011. The dose of diltiazem is also available in other units, namely mg/ mL. The dose for diltiazem injection solution is 5mg/ mL⁶. Diltiazem at a dose of 5mg/mL was given to 1 patient. However, other patients receiving diltiazem at a dose of 2mg/mL were then reduced to 1mg/mL. This can be caused by the condition of the patient where at that dose, the patient's blood pressure drops to the target⁸. In the administration of antihypertensive drugs, patients can receive more than one dosage regimen.

After the patient's blood pressure reaches 160/90 mmHg, the administration of intravenousantihypertensive can be replaced with oral antihypertensive as a maintenance phase. Patients with intracerebralpost haemorrhage are given oral antihypertensive recommended by JNC 8. There are 4 groups recommended as first-line therapy between diuretics, ACE inhibitor, ARB, and CCB. There is no difference in the administration of the four antihypertensive groups in the treatment of hypertension in bleeding stroke patients⁹.

However, treatment of hypertension in intracerebral hemorrhage patients who have systolic > 180mmHg cannot use oral antihypertension. They need intravenous antihypertension because the patient's blood pressure must be lowered immediately before causing damage to other organs. In addition, dose control for intravenous antihypertension is related to the magnitude of the decrease in blood pressure produced after administration. This is related to brain autoregulation, where the brain basically has the ability to maintain cerebral blood flow when changes in blood pressure occur. Brain autoregulation generally works well on MAP 50-150mmHg. This will be damaged if the patient's MAP is out of the range. If autoregulation is damaged, then there is a slight change from MAP, it will have an impact on cerebral blood flow and cerebral blood volume pressure. This will endanger the patient's condition¹⁰.

The antihypertensive types given include Almodipine, Nimodipine, Irbesartan, Captopril, Valsartan, Bisoprolol, Bisinopril, HCT, Furosemid, Ramipril, and Candesartan in both single and combination therapies. Nimodipine is given at a dose of 4x60 mg and 6x60mg given to 1 patient each. The administration is in accordance with the literature which is 60mg every 6 hours a day⁸.

Compared to nifedipine, amlodipine is more acceptable in terms of safety profiles. Nifedipine is an antihypertensive type with a shorter duration of action compared to amlodipine. So, nifedipine is given three times a day in the form of conventional tablets and twice a day in the form of slow release. This affects the compliance of patients in taking drugs. Compliance of patients in consuming diododipine is higher compared to nifedipine. In addition to amlodipine, several other antihypertensive agents are given to patients such as irbesartan, valsartan, nimodipine, and other drugs.

Each antihypertensive dose is adjusted to the condition of each patient. Antihypertensive administration starts from the smallest dose and can be increased if the blood pressure target is still not reached. In addition, antihypertensive can be given in single or in combination with other antihypertensive agents. Amlodipine is administered from a dose of 5mg to a maximum dose of 10m per day⁸.

Amlodipine was given with a variety of frequencies and doses. The lowest dose is 1x5 mg given to 7 patients. While the dose of 2x5mg was given to 2 patients. The maximum dose of amlodipine is 1x10mg given to 19 patients. The dose of amlodipine is in accordance with the American Society of Health-System Pharmacists 2011. But there was administration of amlodipine which exceeds the maximum dose per day. This drug is given 15mg in one day. This is caused by the condition of the patient who needs an increase in the dose of amlodipine to reduce his blood pressure.

Lisinopril is given with a minimum dose of 10mg per day with a maximum dose of 40mg per day 8. This drug is given at a dose of 1x5mg to 2 people and is not in accordance with the American Society of Health-System Pharmacists 2011. This can be caused by the condition of the patient, which at a dose of 1x5mg per day can reduce the patient's blood pressure. This drug is also given at a dose of 2x5mg and 1x10mg each to 1 person.

Bisoprol is given to 4 patients. 2 patients received Bisoprolol at a dose of 1x2.5mg and 1x5mg to 2 other patients. The provision is in accordance with the American Society of Health-System Pharmacists 2011 which is 2.5-10mg per day. The Furosemide with a dose of 20-80mg per day was given to 1 patient. However, the patient's health document did not state the dosage of the furosemide tablet, so that it cannot be concluded, the adminstration of the drug was in accordance or not with the American Society of Health-System Pharmacists 2011. Hydrochlorothiazide or HCT is given to 1 patient with a dose of 1x12.5 mg and administration in accordance with the American Society of Pharmacists Health-System 2011, which is a maximum of 50mg per day 8. Captopril was given to 1 patient at a dose of 3x25 mg. Ramipril was administered to 1 patient at a dose of 5 mg once a day, according to the dosage listed in the literature ie 2.5-20 mg per day⁸.

Valsartan is given with a minimum dose of 80 mg and a maximum dose of 320mg per day. A dose of 1x80mg was given to 7 patients and a dose of 1x160mg was given to 5 patients. Another drug given is candesartan which is given to 1 patient at a dose of 1x16mg.

Oral antihypertension which was also given to patients is irbesartan. This drug has a minimum dose of 150mg and a maximum dose of 300mg once a day. A dose of 1x150mg was given to 3 patients, while a dose of 2x150 mg was given to 1 patient, and 3 patients were given irbesartan at a dose of 1x300mg. The administraton of the drug was in accordance with the doses listed in the American Society of Health-System Pharmacists 2011. The drugs above include the angiotensin receptor blocker group given to hypertensive patients accompanied by diabetes mellitus and dyslipidemia⁸.

From 19 patients with antihypertensive administration before the third day of treatment, oral antihypertension was the most administered route, which was 57.89%, then intravenous antihypertensive was 31.57%, and intravenous and oral antihypertensive combinations were 10.53%. There were 11 of the 19 patients receiving antihypertensive byoral routes. The antihypertensive agents included Amododipine, Nimodipine, Irbesartan, Captopril, Valsartan, Bisoprolol, Bisinopril, HCT, Furosemid, Ramipril, and Candesartan both in the form of single and combination therapies in both single and combination therapies.

Patients with intracerebral hemorrhagic stroke with blood pressure below 180mmHg should not need to be given antihypertension, because they were susceptible to a significant reduction in blood pressure. If the patient has a significant decrease in blood pressure or even experiences hypotension, it will cause a decrease in cerebral blood flow^11,12. Therefore, it is necessary to evaluate and confirm antihypertensive indications in patients.The next route that is mostly given to patients is intravenous and oral and intravenous combinations. Changes in antihypertensive therapy from a single therapy to a combination are needed if the patient's blood pressure cannot be reduced if only using a single therapy. Some patients receive combination antihypertension after receiving a single antihypertensive.

In acute hemorrhagic stroke patients who have systolic blood pressure > 200 mmHg or MAP > 150mmHg, and patients who have systolic blood pressure > 180mmHg or MAP> 130mmH, the use of intravenous antihypertensive agent is recommended to reduce blood pressure by monitoring blood pressure reduction. The target of decreasing blood pressure by 160/90 mmHg or MAP is 110mmHg¹³. If the systolic blood pressure reaches 160mmHg it can be replaced using oral antihypertension¹⁴. Patients with hypertension and diabetes or kidney disease have a target blood pressure of 130/80 mmHg. This is to minimize strokes and other cardiovascular diseases¹⁵. Some patients who have blood pressure above 180 mmHg and a decrease in blood pressure cannot only use intravenous antihypertension, then combined with oral antihypertension.

Three of the four patients received combination antihypertension between the CCB and ARB groups. The combination of these two groups was additional measure to decreasing blood pressure. In addition, ARB groups can minimize the increase in heart rate which is generally a side effect of CCB dihropropirin. ARBs can also avoid the risk of peripheral edema.Another combination given to patients is CCB and beta blockers. This combination was also count as additional measure. At low doses, it could suppress renin secretion which can potentiate vasodilatory properties of CCB. However, the combination of beta blockers with non-dihydropirin CCB is not recommended, because it can cause severe bradycardia and arterioventricular block^16,17. The results showed a combination of antihypertensive administration in appropriate and rational bleeding stroke patients.

For intravenous antihypertensive administration, the average initial blood pressure is 174/107 mmHg or MAP an average of 129, and the final blood pressure on average is 160/88 mmHg or MAP an average of 112 mmHg. Patients given oral antihypertension had an average initial blood pressure of 156/95 or MAP mean value of 115, and a final blood pressure mean value of 145/87 or MAP mean value of 106. Whereas patients who received an intravenous and oral combination antihypertensive had a pressure initial blood mean value of 190/107 mmHg, or MAP mean value of 135, and the final blood pressure mean value of 149/87 mmHg, or MAP mean value of 108 mmHg. The largest decrease in blood pressure occurred in patients with intravenous and oral combination antihypertensive administration with a MAP difference of 27mmHg.

The results also showed that there were drug interactions and side effects on antihypertensive agents. The interaction of captopril and antacids can reduce absorbaptopril. This is because antacids can increase gastric pH.

Other drug interactions are valsartan and potassium supplements. This can increase the risk of hypercalcemia because the administration of both drugs can increase serum potassium levels. This interaction included in the major class because it can endanger the patient's condition. If the patient receives both drugs, the patient must be monitored for potassium levels.

Amlodipin and simvastatin which can also interact when given together. The effect that occurs is an increased risk of myopathy and is included in the category of major interactions. If the patient receives both drugs, the patient must be educated. If symptoms such as muscle pain, especially if accompanied by fever, malaise and/or dark urine, the patient must report to the doctor. If the patient is diagnosed with myopathy, the antihypertensive administration is stopped.

The results also show that there were other DRP suspected drug side effects. There were 4 patients who experienced tachycardia. This may be caused by the administration of CCB class antihypertension, nicardipine.

The duration of treatment for each patient was different, depending on the severity of the stroke suffered and other comorbidities. Most of patients were hospitalized for 10-20 days. Some patients were hospitalized for less than 10 days, and the otherwere more than 20 days. Reasons for leaving the hospital were changing into outpatient treatment, the hospitalizatopn goal is achieved or cured, referred to another hospital, and forced to go home respectively. There were also some patients who do not include reasons for discharged form hospital in patient medical records.

CONCLUSION:

Based on these results, it can be concluded that the first antihypertensive given in the acute phase includes nicardipine, diltiazem, nimodipin, irbesartan, valsartan, amlodipine, captopril and candesartan. Changes in single therapy into a combination are done because blood pressure increases and very fluctuating, so combination antihypertensive needs to be given. The most commonly given combination antihypertensive types are amlodipine and valsartan. The administration of intravenous antihypertensive doses in acute bleeding stroke patients at the Hospital is in accordance with the 2011 DOSE guidelines and the American Society of Health-System Pharmacists 2011, and guidelines for hospital clinical practice. However, some patients given antihypertensive exceeds or under the literature dose caused by blood pressure fluctuations and dose titration. The most potential drug interactions occurred in patients, namely the interaction of amlodipine-simvastatin, valsartan-potassium supplements, and captopril and antacids. The drug side effects found in patients were tachycardia which may be caused by nicardipine. Therefore, more complete recording of drug data and clinical data of patients was needed for monitoring the effects of antihypertensive administration on patients' blood pressure.

ETHICAL LEARNING:

This research had been reviewed by the ethics committee of the Airlangga University Hospital in Surabaya and was declared ethically feasible based on a certificate passed the ethical review no. 088 / KEH / 2017.

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

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Received on 15.07.2019 Modified on 18.08.2019

Research J. Pharm. and Tech 2020; 13(2):547-554.

DOI: 10.5958/0974-360X.2020.00103.1