DRUG RELATED PROBLEM EVALUATION

TO THE ASITES PATIENT WITH DISESASES COMPLICATION OF CHF AND CKD

AT CENTRE OF ARMY HOSPITAL GATOT SOEBROTO DITKESAD

Abstract

Asites is liquid accumulation in the peritoneum cavity because of porta hypertension and

hipoalbuminemia. Edema is the number of excessive liquid and natrium, increase the osmotic

pressure, the result is the liquid flew out of the cell so it causes the accumulation of liquid in

interstisial cavity. Congestive Heart Failure (CHF) is a condition where the heart fails to pump

the blood to fulfill the need of nutrient and oxygen for the body cell adequately. Chronic Kidney

Disease (CKD) is the damage of kidney > 3 months in the disorder of kidney structure, can or

can not be with the decrease of glomerulus filtration rate signed by patologi disorder, dan there

is a sign of the kidney damage with glomerulus filtration rate < 60 mL/minute/1.73 m 2. The

patient was hospitalized in RSPAD Gatot Soebroto on June 9 th, 2015 with diagnosis of CHF f.c

II-III, CKD stage V, HT stage I. The medical therapy which was got during in RSPAD Gatot

Soebroto was lasix inj, ceftriaxone inj, CaCO3, folat acid, Vitamin B12, amlodipine, valsartan,

ketosteril, and laxadine syrup. From the observation of drug therapy of the patient, it is got that

there were some DRPs (Drug Related Problem), they were drug interaction and

contraindication, the dose was too low and the drug reaction which did not want to be (ROTD).

Keywords: Drug Related Problem, asites, SHF, CKD, RSPAD Gatot Soebroto Ditkesad

Introduction Chronic Kidney Disease (CKD) is the damage of kidney > 3 months in the type of kidney

structure disorder, can or can not be with decrease of glomerolous filtration rate which is signed

by the damage of kidney with glomerulus filtration rate < 60 mL/minutes/1.73 m2 1. CKD also

cause the asidose of metabolic which happen because of the incapability of kidney to secrete of

acid (H-), ammonia (NH3-), and unable to absorb the excessive bikarbonat natrium (HCO3) and

besides that, CKD also cause the anemia which happen because of the unequal of eritropoietin

production.

CHF (Congestive Heart Failure) is the complex clinic syndrome as the effect of

structural and functional disorder of heart which disturbs the ventrikel ability to be fulfilled with

blood or to pump the blood. The heart is just able to pump the blood in a short time and the heart

muscle wall which becomes weak is unable to pump strongly. The decrease of cardiac output is

caused by the increase of simpatic activity. The simpatic effect can cause the decrease of

circulation and the pressure of artery in kidney. It will cause the decrease of glomerular

filtration rate which will increase the retention of natrium and water. The decrease of blood flow

to kidney will activate the rennin-angiotensin system that one of the effects will increase the

retention of natrium and water. This process causes the increase of blood volume to more than

30% and it causes edema. Edema is caused by the blood flow which flow out from the heart

become slowly, so the return blood to the heart through blood vessel is blocked. It causes the

accumulation of liquid in the tissue. The damage of kidney which is unable to secrete natrium

and liquid also cause the retention of liquid in the tissue. The accumulation of liquid in the tissue

can be seen from the puffy foot or dilation of stomach.

Hypertension is the situation of the same blood pressure more than 140 mmHg and/or

same with diastolic mmHg for somebody who does not consume the anti hypertension drug.

According to JNC VII, blood pressure of 140-159/90-99 mmHg is categorized as Hypertension

stage 1 and blood pressure > 160/100 mmHg is categorized as hypertension stage II. Goal

therapy for the patient of CKD and CHF is <130/80 mmHg6.

Case Study

Mr. D was 48 years old patient who hospitalized on June 9th, 2015 with grievance of the puffing stomach

since about 2 weeks before hospitalized, there was also asphyxia (it was higher when activity did), fever, especially in the

evening, a little piss, and the feces was brown. The patient have ever hospitalized in RSPAD in the last 3 months because

of puffing, cardiomegali, kidney disease, hypertension, since 2 years ago and the patient had DM for 20 years. The

patient was hospitalized with asites observation diagnosis of Stage V CKD with anemia and CHF f.c II-III, HT stage I.

The patient got the treatment of lasix inj, cetriaxone inj, CaCO3, folat acid, Vitamin B12,

amlodipine, valsartan, katosteril, and laxadine syrup.

Clinic Evaluation

During he was in the hospital, he was given the treatment therapy: lasix 2 times a day 20

mg/2ml ampul given every 6-8 hours because lasix was very effective to cope edema with the

given through rute IV.

The initial dose for udem was 20 – 40 mg. Daily dose was 40 – 240 mg7. The side effect of lasix

was hyphokalemia.

Cefriaxone was given once a day 2 gr IV as empiric antibiotic before the thorax rontgen

result finished.

Ceftriaxone was chosen for therapy because ceftriaxone was sefalosporin category which had

wide spectrum with longer break time (t1/2 5 – 9 hours) compared with another sefalosporin so it

was enough to be given just once a day. Normal dose for kidney function which its GFR is 10 –

20 is 1 gr a day (serious infection is 2 – 4 gr a day).

Carbonat calcium was given 3 times a day 500 mg to control metabolic asidose.

Carbonat calcium 500 mg was given every 8 hours.

Folat acid was given once a day 5 mg, it was needed for nucleoprotein synthesis and

normal eritropoiesis maintenance, folat acid stimulated the red blood cell production and white

blood cell. Maintenance folat acid: 5 mg every 1-7 days.

Vitamin B12 was given 3 times a day 50 mg, it was important for the formation of red

blood cell through folat acid koenzim activity. Dose of B12 Vitamin was 50 – 150 mcg/day given

in the food every 8 hours.

Valsartan was given once a day 80 mg as hypertension therapy which can be combined

with another anti hyperthension, valsartan can be given to the CHD patient, homodialisis

patient, low natrium patient, this category do not block the splitting up of bradykinin so it do not

cause the dry cough. Dose for valsartan to CHF, valsartan is given as initial dose 40 mg 2 times

a day. The dose should be increased because of tolerance, 160 mg 2 times a day.

Amlodipine was given once a day 10 mg as anti hypertension, amlodipine can reduce

the miokard contractility and do not cause the damage for heart failure with longer worktime so

can be given once a day. Amlodipine dose for hypertension, the initial dose is 5 mg once a day,

and it increase to 10 mg once a day.

Ketosteril was given 3 times a day 600 mg for kidney vitamin as cronic kidney

insufficient therapy (glomerolus filtration rate 5 – 50 mL/minutes).

Laxadine syrup was given 3 times a day 15 cc for the constipation patient where if it ss

difficult, it will increase the work burden of heart when the muscles are contracting strongly,

while straining, stomach muscle will have a contraction and it increase intra abdomen pressure.

The dose for laxadine syrup is for adult: 5 – 15 ml/days, maximum giving 30 ml/day 2-4 times a day.DRUG RELATED PROBLEM

1. Dosis terlalu rendah the dose is too low

According to Martindale pg. 1214, dose of amlodipine for hypertension is 5 – 10 mg once a

day.

Pharmacy intervention: interaction of amlodipine +CaCO3 cause the decrease of amlodipine

effect through pharmacodinamic so it can not be coped by giving the space time to take the

medicine and it needs the increasing of amlodine dose. Amlodipine given dose is 5 mg but

because of the 5 mg dose has not capable to control the blood pressure yet, so it should be

increased to 10 mg once a day.

2. Undesired drug reaction

Hypersensitivity reaction happened; it was the allergy and asphyxia after injected of

ceftriaxone antibiotic

Pharmacy intervention: ceftriaxone antibiotic is stopped.

3. Potential interaction

Ceftriaxone + CaCO3 (contraincication )

It caused the toksik effect. Ceftriaxone bind the calcium and make fused precipitate in lung

and kidney.

Pharmacy Intervension: it is given with interval time 48 hours after giving ceftriaxone.

4. Drug interaction

CaCO3 + amlodipine (moderate)

CaCO3 decrease the amlodipine effect.

Pharmacy intervention: increase the amlodipine dose to 10 mg. It could be cleared from the

observation result of patient’s blood pressure which still increased.

Conclusion

The continued diagnosis stated that Mr. D had asites with CHF and CKD.

During the treatment, the patient was given drug therapy: lasix inj, ceftriaxone inj, CaCO3, folat

acid, B12 vitamin, amlodipine, valsartan, ketosteril, and laxadine syrup. During the giving of

drug therapy, there was drug interaction which was given together: amlodipine interaction +

CaCO3 caused the decrease of amlodipine effect through farmakodinamik, so it could not be

coped by giving interval time to take the medicine and it needed to increase the amlodipine dose.

Amlodipine dose for hypertension is 5 – 10 mg once a day. Amlodipine given dose was 5 mg but

it was seen from the blood pressure observation, dose of 5 mg had not been able to control the

blood pressure so it needed to increase the dose to 10 mg once a day. The patient was given

ceftriaxone antibiotic as empiric antibiotic to lung infection but when it was injected,

hypersensitivity reaction happened, that was allergy and asphyxia so it was stooped.

DRUG RELATED PROBLEM EVALUATION

TO THE DIABETES MELLITUS PATIENT TYPE II WITH ULKUS DIABETIKUM

PEDIS SINISTRA + SEPSIS + OSTEOMYELITUS + TUBERCULOSIS + CHF

(Congestive Heart Failure)

AT CENTRE OF ARMY HOSPITAL GATOT SOEBROTO DITKESAD

Abstract

Diabetes mellitus is a one of metabolic group of diseases with hyperglikemia

characteristic which happen because of insulin secretion disorder, work of insulin or both. DM

type II is the type of DM that is frequently happen because of insulin resistance (insulin receptor

has not been active anymore because it is reputed that the blood content is still high) will cause

the deficiency of insulin relative. Ulkus dibetikum pedis sinistra is complication of diabetes

mellitus chronic where there is an ulkus in the left leg because of some factors, they are because

of mechanic changing to the structure and architect of leg bone, neuropati perifer, and or there

is perifer artery disease which have the quality of sklerotik. Sepsis is the group of clinic symptom

as the inflammation response systemically (systemic inflammatory response syndrome/SIRS)

because of infection of bacteria, virus, fungus, and protozoa. Osteomyelitis is the infection at

bone marrow which is caused by bacteria, virus, or specific process. Tuberculosis is a disease

which is caused by infection of toberculosis mycobacterium. Congestive Heart Failure (CHF) is

a complex clinic syndrome because of heart functional and structural disorder which disturbs

the ventricle ability to be fulfilled with blood or to pump the blood. Drug related problem,

correlation between drugs therapy and the disease, appropriate drug chosen, interaction and

contraindication.

Keywords: DM type II, Ulkus Diabetikum Pedis Sinistra, Sepsis, Osteomyelitus, Tuberculosis,

CHF, RSPAD Gatot Soebroto Ditkesad.

INTRODUCTION

Diabetes mellitus is a metabolic disease group with hyperglikemia characteristic which

happens because of insulin secretion disorder, insulin’s work, or both. Hyperglikemia is defined

as fasting blood sugar higher than 110 mg/Dl. The normal fasting glucose serum is 70-110

mg/Dl2. Clinic diagnosis of DM is applied if there is special indication of DM such as poliuria,

polidipsia, olifagia, and the decrease of body weight with unknown cause. If there is a special

indication and random blood glucose ≥ 200 mg/dl, DM diagnosis can be applied. The checking

results of GDP ≥ 126 mg/dl can also be used as the guide of DM diagnosis.

In 2000, according to WHO, estimated at least 171 people in the world suffer Diabetes

Mellitus, and estimated at 2030 this number will be 366 million people. DM appears in all over

the world, 90% is the type of DM type II happens in developing country in Asia and Africa. In

Indonesia itself, according to Riskesdas (2007) from 24,417 respondents in the age of more than

45 years, but lately the sufferer of DM type II in adolescent and children, the population

increase. Genetic and environment influence factor are quite big in causing the DM type II, such

as obesity because it is related to insulin resentence, so it seems appear of failure tolerance of

glucose that cause DM type II.

For sufferer of DM type II, there is hyperinsulinemia but the insulin can not bring the

glucose to the tissue because of the insulin resistance that is the decrease of insulin’s ability to

stimulate glucose taking by perifer and to block the glucose production by the heart. So the

insulin resistance (insulin receptor has not been active anymore because of the content is still

high in the blood) will cause the relative deficiency of insulin. It can cause the decrease of

insulin secretion to glucose together with another insulin secretion material so the beta pancreas

cell will get desenticiation to glucose. Onset of this type of DM happens slowly because its

symptom is asimtomatic. The slowly resistance will cause the receptor sensitivity of glucose

decrease. This type of DM is always diagnosed after complication happens.

Ulkus dibetikum pedis sinistra is diabetes chronic complication where there is ulkus in the

left leg because of some factors, they are mechanic changing of leg bone structural and

architect, neuropati perifer and or there is sclerotic perifer artery disease. Ulkus is the red black

wound in the leg and in bad smell because of the block which happen in the middle or big artery

in the leg.

Sepsis is the group of clinic syndrome as systemic inflammatory response syndrome

(SIRS) because of infection of bacteria, virus, fungus, and protozoa. Serious sepsis is sepsis

related to disfunction of hipoperfution organs or hipotention.

Osteomyelitis is the infection of spinal cord caused by bacteria, virus, or specific process.

The cause of osteomyelitis is :

1. Bacteria according to Joyce and Hawks (2005), the cause of osteomyelitis is staphylococcus

aureus (70-80%), besides that, it also can be caused of Escherichia coli, Pseudomonas,

Klebsiella, Salmonella, and Proteus.

2. virus

3. fungus

Tuberculosis adalah penyakit yang disebabkan infeksi mycobacterium tuberculosis adalah

kuman bentuk batang bersifat aerob yang memperoleh energi dari oksidasi beberapa senyawa

karbon sederhana dan tidak membentuk spora6.

Tuberculosis is the disease which is caused by mycobacterium infection. Tuberculosis is

a aerob micrope in the rodding shape which get energy from the ocsidate of some simple carbon

compound and do not make spore.

CHF (Congestive Heart Failure) / gagal jantung adalah suatu sindroma klinik yang kompleks akibat kelainan

struktural dan fungsional (disfungsi) jantung yang mengganggu kemampuan ventrikel untuk diisi dengan darah atau

untuk mengeluarkan darah. Jantung hanya mampu memompa darah untuk waktu yang singkat dan

dinding otot jantung yang melemah tidak mampu memompa dengan kuat7.

CHF (Congestive Heart Failure) is a complex clinic syndrome because of heart

functional and structural disorder which disturbs ventricle ability to be fulfilled with blood or to

pump the blood. Heart is just able to pump the blood in short time and heart wall which become

weak can not pump strongly.

CASE STUDY

Mr. M, 59 years old, was hospitalized on March 29th, 2015 with grievance of asphyxia for

1.5 months, unsputum cough, and ulkus at the left leg. The patient before has ever got the

treatment in RSUD Dr. Soedarso Pontianak with DM type II with CHF and chronic ulkus pedis

sinistra since 1.5 months ago. The patient said that he used novorapid to control his blood

glucose. But he did not control his eating system, and did not check his blood glucose routinely

so his blood glucose was high. He was diagnosed with ulkus pedis sinistra, osteomyelitis, CHF

f.c III, tuberculosis and DM type II. On May 20th, 2015 he went home in conscious condition, his

left leg ulkus ran dry, could actuate the body organs well, and he felt queasy. In his way to the

airport of Halim, the patient passed away because of bleeding in the left leg, estimated that it

was caused by the pressure when he set his foot on.

The drug therapy given to the patient was lantus, novorapid, ISDN, spironolactone,

metronidazole, sulbactam ampicillin, clopidogrel, Bisoprolol, meropenem, ramipril, aspilet,

atorvastin, 4 FDC, Vitamin B6, streptomycin, digoxin, lasix, bisoprolol, domperidone,

omeprazole, ciprofloxacin.

CLINIC EVALUATION

The therapy given to the patient: Lantus once in 5 units given in the evening during

treatment until the patient went home. It was to decrease the blood glucose.

Side effect: hipoglikemia. Lantus is a long acting, start to work about 4 – 6 hours, the climax is

14 – 20 and the work period is 24 hours.

Range dose for lantus is 5 x 3 ml (2 – 40 units).

Novorapid was given 3 times 6 units for therapy of decreasing the blood glucose, it is given

during treatment until the patient went home.

Side effect: hipoglikemik. Novorapid is a short acting, start to work at 0 – 5 hours, the climax is

1 – 4 hours, and work period is 6 – 8 hours.

The calculation for novorapid dose is : a + b = c

Range dose for novorapid is 0.05 – 0.1 unit/KgBB/hour = 2 – 40 units.

ISDN 2 times 5mg in the morning and afternoon, given during the treatment until the patient

went home for therapy of profilaksis and angina medicine; left heart failure.

The dose for ISDN was PO 5 – 20 mg/6 hours. Maintenance dose is 20 – 40 mg/6 hours.

Sublingual: 2.5 mg/2-3 hours based on the need.

Spironolactone once 25 mg in the morning given during treatment until the patient went

home for asites therapy, CHF. Side effect: hiperkalemia.

Dose for spironolactone was 25 – 100 mg/days.

Metronidazole 3 times 500 IV in the morning, at noon, and evening, given 14 days since

March 29th – May 12th 2015, and than stopped. This therapy was for infection caused by anaerob

bacteria. The dose for metronidazole was 500 mg every 6 – 8 hours and not more than 4 g/days.

Sulbactam ampicillin 4 time 1.5 gr given IV since May 29 th in the skin test and given

started from May 1st – 12th for 12 days and on May 13th it was stopped. It was for wide spectrum

anti bacteria; skin infection.

Dose for sulbactam ampicillin was 1.5 – 3 gr every 6 – 8 hours.

Clopidogrel once 75 mg was given in the morning for unstable angina therapy; infark

miokard; stroke iskemik. Clopidogrel was given during treatment and when he went home, the

drugs was stopped.

The dose of clopidogrel was 75 mg – 325 mg/day.

Bisprolol once 2.5 mg in the morning given during treatment until the patient went home for

standard therapy in stable CHF, it meant he was not having hospitalized in ICU or was not

having therapy with inotropic drug (+). It is a kind of beta blocker that its side effect is

hipotention.

The dose for bisoprolol was the initial dose 1,25 mg/day, the dose was increased 2.5 mg, 3.75 mg

– 5 mg/day every week. Next, the dose was increased 7.5 – 10 mg/days every month.

Ramipril 2 times 5 mg given in the morning and afternoon, it is a kind of ACE-I for CHF

first line therapy and drug of choice for the hypertension and DM patient. It was given during

treatment until the patient went home.

Dose of ramipril was 2.5 mg – 5 mg.

Meropenem 3 times 500 given IV in the morning, at noon, and in the evening. It was just

given on May 11th – 12th in the skin test and on May 13 th – 19th for infection therapy which was

caused by pathogen bacteria, sepsis, bone, skin, and skin tissue.

The dose for meropenem was 500 mg every 6 – 8 hours.

Aspilet once 80 at noon was given during treatment until the patient went home for treatment

therapy and avoiding pectoris angina and infark miocard.

Atorvastatin 1 kali 40 mg malam hari untuk terapi kolestrol. diberikan selama perawatan

sampai pasien pulang

Dosis untuk atorvastatin adalah 10 mg-80 mg/hari11.

Atorvastatin once 40 mg in the evening for cholesterol therapy, given during the

treatment until the patient went home.

4 FDC is filled by rifampisin 150 mg, Isoniazid 75 mg, pyrazinamide 400 mg, Ethambutol

HCL 275 mg once 4 tablets, it was just given on May 13 th – 20th for handling of TBC and

microbacteria infection.

The dose for 4 FDC was ≥ 75 g given 5 tab/days, 55-70 g given 4 tab/day, 38-54 g given 3

tablets/days and 30-37 g given 2 tablets/day.

Vitamin B6 once 10 mg, it was just given on May 13 th – 20th 2015 to prevent queasy and

vomit.

The dos of vitamin B6 was 10 mg/day.

Strepomicyn once 750 mg was given at noon. It was just given on May 11th – 20th for

therapy of TBC.

Dose for streptomicyn was 15 mg/kg/day

Dogoxin once 0.125 mg was given in the morning. It was just given on May 15th - 20th for

CHF therapy.

The dose of digoxin was 0.125- 0.25 mg once a day.

During the treatment, lasix was given 240 mg/24 hours and when he went home, he was

given oral lasix once 40 mg for CHF therapy.

Initial dose for drip lasix was 40 mg IV, continued to 20 – 40 mg after 20 minutes.

Beginning dose for oral lasix was 20 – 80 mg.

Domperidone once 10 mg was given when he patient went home for therapy of queasy.

The dose for domperidone was 10 – 20 mg for 3 – 4 hour/day.

Omeprazole once 40 mg was given for short time therapy of gastric ulcer and duodenum

which was not responsive to H2 antagonic.

The doze for omeprazole was 20 – 40 mg/day.

Ciprofloxacin once 500mg was for skin, bone, hinge, and ISK therapy.

The dose for ciprofloxacin was 250 – 500 mg every 8 hours.

Kalipar 3 times 300 mg in the morning, at noon, in the afternoon for Mg and K

supplement therapy to heart and liver, hipokalemia and hipomagnesia because of the long usage

of diuretic which was given on May 9th – 19th, 2015.

The dose for kalipar was 300 mg every 8 hours.

DRUG RELATED PROBLEM

1. Corelation between drug therapy and the disease

There was no supported data about laboratory checking about cholesterol content but it

used atorvastatin drug.

Pharmacy Intervention: atorvastatin is used in the evening as cardioprotective to heart

failure sufferer so it does not make the heart function become worse.

The patient went home and got ciprofloxacin while according to microbiology checking,

resistance of patient to fluroquinolon drug group that was levofloxacin and ciprofloxacin.

Pharmachy intervention: it is better to give intermediate antibiotic drug or sensitive to the

patient.

2. Appropriate Drug Chosen

The giving of multidrug for half udem therapy for CHF such as ISDN, spironolactone,

HCT, lasix.

Pharmacy intervention: to the patient of CHF, there was output cardiac decreasing so

vasokontrisi happen. Vasokontriksi will activate the rennin-angiotensin system that one of the

effects will increase retention of water and natrium. This process causes the increasing of

blood volume so it is more than 30% and edema is made so he got asphyxia. Edema is

caused by the blood flow out of the heart become slower so the return blood to the heart

through blood vessel is blocked. For half udem, it is better to be given one of or 2

combinations of drugs. Drug of choice is diuretic loop group such as lasix which can be

combined with digoksin.

3. Interaksi dan kontraindikasi

Ramipril + spironolactone → hiperkalemia

Pharmacy intervension: ramipril with spironolactone causes hiperkalemia so the taking of

this medicine should have interval about 2 hours where ramipril have 6 hours and

spirolactone have 8 hours.

Metronidzole + Atovastation → nerve function disorder and liver function disorder.

Pharmacy intervension: atorvastatin do not be secreted through kidney but atorvastatin is

disgested in the liver and have the risk to be piled up in patient’s plasm with the decrease

of liver function. Half time of metronidazol in plasm is reported about 6 – 8 hours for

adult people and the kidney and hepar function is normal so it just need to give the break

time to take the medicine.

CONCLUSION

The diagnosis of patient said that the patient had DM Type II, ulkus diabetikum pedis

sinistra, osteomyelitis, tuberculosis, and CHF with the history of patient was DM type II and

CHF. The patient got drug therapy: lantus, novorapid, ISDN, spironolactone, ramipril, aspilet,

atorvastatin, 4FDC, Vitamin B6, streptomycin, digoksin, lasix, bisoprolol, domperidone,

omeprazole and ciprofloxacin. The drug giving which was together with ramipril +

spironolactonel and metronidazole + atorvastatin should have the break time to take. The patient

went home in conscious condition, his leg wound ran dry, he could actuate his organs well and

he has queasy grievance.