LAPORAN PRAKTIKUM FARMASI KLINIS: GANGGUAN PADA SISTEM SIRKULASI DARAH

 I.  THEORETICAL BASIS

Diseases of the circulatory system are the major cause of illness, disability, and death in Canada. The most common of these diseases are ischemic heart disease (which includes acute myocardial infarction or heart attack), congestive heart failure, and cerebrovascular disease (stroke). A heart attack is typically caused by a blockage (usually a blood clot) in a coronary artery that severely restricts or cuts off the blood supply to a region of the heart. If this lasts more than a few Minutes, heart tissue dies. Congestive heart failure occurs when the heart can no longer pump blood at the rate needed by the body’s tissues. A stroke involves loss of brain function when a clot or piece of atherosclerotic plaque breaks away from another area of the body and blocks a blood vessel in the brain (ischemic), or when a blood vessel in the brain bursts (hemorrhagic), thereby allowing blood to leak into an area of the brain and destroy it (Johansen dkk., 2005).

The main physiological role of red blood cells (RBCs), or erythrocytes is to transport of gases (O2, CO2) from the lung to the tissues and to maintain systemic acid/ base equilibria. In addition, RBCs are well equipped with antioxidant systems, which essentially contribute to their function and integrity. Damage of red cell integrity, defined as hemolysis, has been shown to significantly contribute to severe pathologies, including endothelial dysfunction. Recent clinical and experimental evidence indicates that RBCs may be directly involved in tissue protection and regulation of cardiovascular homeostasis by exerting further noncanonical functions, including nitric oxide (NO) metabolism and control of blood rheology, as well as erythrocrine function (i.e., by releasing bioactive molecules, including NO, NO metabolites, and ATP). Anemia is a pathological condition characterized by a decreased number of circulating RBCs and defined by hemoglobin (Hb) concentrations in whole blood below 12 g/dL in females and 13 g/dL in males. There is clinical evidence that anemia is also associated with a series of severe complications in cardiovascular disease (CVD) such as thromboembolic events (e.g., venous thrombosis and stroke). However, therapeutic interventions aimed to increase the circulating number of RBCs (e.g., by transfusion of blood or by administration of erythropoiesis-stimulating agents [ESAs] to stimulate the production of RBCs by the bone marrow), were not always effective in the tested cohorts. One possible explanation is that these treatments have side effects and therefore may contribute themselves to the negative outcome, for example, treatment with ESAs was associated with increased thromboembolic events (Kuhn dkk., 2017).

II. ALGORITHM THERAPY

a.    Heart Failure Therapy Algorithm

b.   Lymphoma Therapy Algorithm

 

 

 d. FARM

 

Community Acquired Pneumonia (CAP)

Community-acquired pneumonia is a leading cause of death. Risk factors include older age and medical comorbidi­ties. Diagnosis is suggested by a history of cough, dyspnea, pleuritic pain, or acute functional or cognitive decline, with abnormal vital signs (e.g., fever, tachycardia) and lung examination findings. Diagnosis should be confirmed by chest radiography or ultrasonography. Validated prediction scores for pneumonia severity can guide the decision between outpatient and inpatient therapy. Using procalcitonin as a biomarker for severe infection may further assist with risk stratification. Most outpatients with community-acquired pneumonia do not require microbiologic testing of sputum or blood and can be treated empirically with a macrolide, doxycycline, or a respiratory fluoroquinolone. Patients requiring hospitalization should be treated with a fluoroquinolone or a combination of beta-lactam plus mac­rolide antibiotics. Patients with severe infection requiring admission to the intensive care unit require dual antibiotic therapy including a third-generation cephalosporin plus a macrolide alone or in combination with a fluoroquinolone. Treatment options for patients with risk factors for Pseudomonas species include admin­istration of an antipseudomonal antibiotic and an aminoglycoside, plus azithromycin or a fluoroquinolone (Kaysin & Viera, 2016).

 

 

Finding	Assessment	Resolution and Monitoring
Patient progress notes: ·       14-17/6/2017: S = cough with phlegm yellow, shortness of breath ·       14/6/2017: O = (H): leukosit, BUN, Srcr, PCO2, HCO3 ·       15-17/6/2017: HR increases ·       17-6-2017 hematemesis dan melena   Clinical signs: ·       Tgl 14/6: 130/70 Tgl 16/6: 130/70 Tgl 17/6: 130/80 ·       Pulse Tgl 14-17: above normal   Lab data: ·       Leukosit= 15.980 ·       Ureum/BUN= 1,53 ·       Kreatinin= 1,49 ·       pCO2= 51,3 ·       HCO3= 34,9 ·       Base excess= +10,5	Community Acquired Pneumonia (CAP)   Cefoperazon ·       Cephalosporin class of antibiotics, which are antibiotics for the treatment of gram-negative bacterial infections (third generation). ·       This drug works by inhibiting the formation of bacterial cell walls thereby preventing bacterial growth.   Levofloxacin ·       Quinolone class of antibiotics which are broad spectrum antibiotics for the treatment of gram-negative and gram-positive bacterial infections. ·       This drug works by cause bacterial cell death due to inhibition and increased concentration of the gyrase and topoisomerase enzymes.	·       Because of the importance of bacterial infection in most AECOPD episodes, the Global Obstructive Lung Disease and American Thoracic Society COPD guidelines recommend antibiotic use during these episodes. ·       It is recommended to use levofloxacin because of a broad-spectrum antibiotic. ·       The dose is correct: 750 mg every 48 hours (i.v.), adjusted for the patient's GFR value of 26.17 ·       GFR values ​​must be calculated because it is related to kidney function. The lower the GFR value means that the kidney condition is getting worse. ·       For all patients with kidney disorders, care should be taken to take the dosage of the drug to be given. ·       Antibiotics given (levofloxacin) are in accordance with first line therapy.     Side effects: Headache, nausea (Lacy, 2009)   Normal value: ·       Leukosit= 3200 – 10.000/mm3 ·       Ureum/BUN= 10-50 mg/dL ·       Kreatinin= 0,7 – 1,2 mg/dL ·       pCO2= 35-45 ·       HCO3= 21-28 ·       Base excess: (-)3 – (+) 3

 

Chronic Obstructive Pulmonary Disease (COPD) AE III

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) describe the phenomenon of sudden worsening in airway function and respiratory symptoms in patients with COPD. These exacerbations can range from self-limited diseases to episodes of florid respiratory failure requiring mechanical ventilation. Although bacterial infections are the most common causes of AECOPD, viral infections and environmental stresses are also implicated. Bacterial infections are implicated in the majority of AECOPD episodes. This is not surprising because the patient with COPD has airways that are prone to infections, with impaired local defenses and frequent bacterial colonization. Sputum and bronchoscopy data have shown that Moraxella catarrhalis, Haemophilus influenza, and Streptococcus pneumonia are the most common organisms associated with AECOPD episodes (MacIntyre, N. & Huang, C.Y., 2007).

 

 

Finding	Assessment	Resolution and Monitoring
Patient progress notes: ·       14-17/6/2017: S = cough with phlegm yellow, shortness of breath ·       14/6/2017: O = (H): leukosit, BUN, Srcr, PCO2, HCO3 ·       15-17/6/2017: HR increases ·       17-6-2017 hematemesis dan melena   Clinical signs: ·       Tgl 14/6: 130/70 Tgl 16/6: 130/70 Tgl 17/6: 130/80 ·       Pulse Tgl 14-17: above normal   Lab data: ·       Leukosit= 15.980 ·       Ureum/BUN= 1,53 ·       Kreatinin= 1,49 ·       pCO2= 51,3 ·       HCO3= 34,9 ·       Base excess= +10,5	Chronic Obstructive Pulmonary Disease (COPD) AE 3   Combivent ·       Contains Ipratropium Bromide, Salbutamol Sulphate. Salbutamol ·       Function as a bronchodilator. ·       Mechanism of action for muscle relaxation in the respiratory tract so that it stimulates adrenergic beta 2 receptors. Ipratropium bromide ·       It has a bronchodilating effect.     Pulmicort ·       Contains Budesonide. ·       Budesonide is a corticosteroid class of drugs.       NAC (Acetylcysteine) ·       Mechanism of Action: Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering mucous viscosity. ·       Serves to reduce the viscosity of mucus, so it is expected that mucus can be eliminated.       Metil prednisolon ·       Corticosteroid drugs, which function to inhibit prostaglandins so it can treat inflammation of the lungs.	·       This drug is suitable for the treatment of COPDAE 3 (MacIntyre, N. & Huang, C.Y., 2007). ·       Frequency of drug use can be increased if needed. ·       The amount of puff applied depends on the strength of the active substance.                         ·       Corticosteroid therapy improved pulmonary function testing more rapidly and shortened the length of the exacerbation period (MacIntyre, N. & Huang, C.Y., 2007). ·       The dosage is correct.     ·       During an AECOPD episode, other modalities that are useful include mucolytics/chest physical therapy in selected patients who have copious retained secretions MacIntyre, N. & Huang, C.Y., 2007). ·       The dosage is correct.                         ·       Dose: 125 mg methylprednisolone every 6 hours for 72 hours followed by 60 mg prednisone daily tapered for 2 weeks (MacIntyre, N. & Huang, C.Y., 2007)                     Theophylline ·       Needs to be added in pharmacological therapy in COPDAE 3 patient (MacIntyre, N. & Huang, C.Y., 2007). ·       Pharmacologic Category: Theophylline Derivative ·       Mechanism of Action: causes bronchodilatation, diuresis, CNS and cardiac stimulation, and gastric acid secretion by blocking phosphodiesterase which increases tissue concentrations of cyclic adenine monophosphate (cAMP) which in turn promotes catecholamine stimulation of lipolysis, glycogenolysis, and gluconeogenesis and induces release of epinephrine from adrenal medulla cells ·       I.V. dose: 4.6 mg/kg loading dose (5.8 mg/kg hydrous aminophylline) (Lacy, 2009).     Normal value: ·       Leukosit= 3200 – 10.000/mm3 ·       Ureum/BUN= 10-50 mg/dL ·       Kreatinin= 0,7 – 1,2 mg/dL ·       pCO2= 35-45 ·       HCO3= 21-28 ·       Base excess: (-)3 – (+) 3

 

 

 

HF stage C FC III

Class III (Moderate) Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or anginal pain.

 

Finding	Assessment	Resolution and Monitoring
Patient progress notes: ·       14-17/6/2017: S = cough with phlegm yellow, shortness of breath ·       14/6/2017: O = (H): leukosit, BUN, Srcr, PCO2, HCO3 ·       15-17/6/2017: HR increases ·       17-6-2017 hematemesis dan melena   Clinical signs: ·       Tgl 14/6: 130/70 Tgl 16/6: 130/70 Tgl 17/6: 130/80 ·       Pulse Tgl 14-17: above normal   Lab data: ·       Leukosit= 15.980 ·       Ureum/BUN= 1,53 ·       Kreatinin= 1,49 ·       pCO2= 51,3 ·       HCO3= 34,9 ·       Base excess= +10,5	Heart Failure (HF) stage C FC III   Captopril ·       Pharmacologic Category: Angiotensin-Converting Enzyme (ACE) Inhibitor ·       Mechanism of Action: Competitive inhibitor of angiotensin-converting enzyme (ACE); prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor; results in lower levels of angiotensin II which causes an increase in plasma renin activity and a reduction in aldosterone secretion. ·       A persistent, dry cough in a patient using captopril as medical treatment, should be considered as an adverse effect.   Lisinopril ·       Mechanism of Action: Competitive inhibitor of angiotensin-converting enzyme (ACE); prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor; results in lower levels of angiotensin II which causes an increase in plasma renin activity and a reduction in aldosterone secretion. ·       Labeled Indications: Treatment of hypertension, either alone or in combination with other antihypertensive agents; adjunctive therapy in treatment of heart failure (HF).       Amlodipine ·       Pharmacologic Category: Calcium Channel Blocker. ·       Mechanism of Action: Inhibits calcium ion from entering the slow channel or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization, producing a relaxation of coronary vascular smooth muscle and coronary vasodilation; increases myocardial oxygen delivery in patients with vasospastic angina. Furosemide ·       Pharmacologic Category:  Loop Diuretic. ·       Mechanism of Action: Inhibits reabsorption of sodium and chloride in the ascending loop of Henle and distal renal tubule, interfering with the chloride-binding cotransport system, thus causing increased excretion of water, sodium, chloride, magnesium, and calcium.	·       The patient has a history of COPD, which coughs, so if given captopril it will worsen the cough disease. ·       A suggestion is to stop using captopril, and only lisinopril is given.                                               ·       Lisinopril dose given to patients with kidney disorders is appropriate.                                               ·       Amlodipine selection is appropriate because it is selective in blood vessels and rarely causes tachycardia. ·       The dose of amlodipine given by p.o. route already right.                                   ·       Labeled Indications: Management of edema associated with congestive heart failure and hepatic or renal disease; alone or in combination with antihypertensives in treatment of hypertension. ·       The purpose given furosemide is for fluid retention. ·       The dose of furosemide given by i.v. route already right.                     Spironolactone ·       Needs to be added in pharmacological therapy in HF stage C FC III patient (American Heart Association). ·       Pharmacologic Category: is a specific pharmacologic antagonist of aldosterone. ·       Mechanism of action: acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Causes increased amounts of sodium and water to be excreted, while potassium is retained. ·       Acts both as a diuretic and as an antihypertensive drug by this mechanism. ·       It may be given alone or with other diuretic agents which act more proximally in the renal tubule. ·       Spironolactone can be given to patients because patients do not experience hyperkalemia. ·       Patients are asked to monitor potassium in blood levels. ·       Dose: CHF, severe (with ACE inhibitor and a loop diuretic, digoxin): 12.5-25 mg/day; maximum daily dose 50 mg (Lacy, 2009).                     Digoxin ·       Needs to be added in pharmacological therapy in HF stage C FC III patient (American Heart Association). ·       Pharmacologic Category: Antiarrhythmic Agent, Class IV; Cardiac Glycoside ·       Mechanism of action: Inhibition of the sodium/potassium ATPase pump which acts to increase the intracellular sodium-calcium exchange to increase intracellular calcium leading to increased contractility ·       Dose: Daily maintenance dose: Give once daily to children >10 years of age and adults. Oral: 0.125-0.5 mg I.V. or I.M.: 0.1-0.4 mg (Lacy, 2009) ·       Patients are asked to monitor potassium in blood levels.     Normal value: ·       Leukosit= 3200 – 10.000/mm3 ·       Ureum/BUN= 10-50 mg/dL ·       Kreatinin= 0,7 – 1,2 mg/dL ·       pCO2= 35-45 ·       HCO3= 21-28 ·       Base excess: (-)3 – (+) 3

 

All patients were required to be taking a loop diuretic and, if tolerated, an ACE inhibitor (FDA)

Dosis digoxin (Lacy, 2009)

 

Finding	Assessment	Resolution and Monitoring
Patient progress notes: ·       14-17/6/2017: S = cough with phlegm yellow, shortness of breath ·       14/6/2017: O = (H): leukosit, BUN, Srcr, PCO2, HCO3 ·       15-17/6/2017: HR increases ·       17-6-2017 hematemesis dan melena   Clinical signs: ·       Tgl 14/6: 130/70 Tgl 16/6: 130/70 Tgl 17/6: 130/80 ·       Pulse Tgl 14-17: above normal   Lab data: ·       Leukosit= 15.980 ·       Ureum/BUN= 1,53 ·       Kreatinin= 1,49 ·       pCO2= 51,3 ·       HCO3= 34,9 ·       Base excess= +10,5	Lanzoprazole ·       Pharmacologic Category: Proton Pump Inhibitor. ·       Mechanism of Action: Decreases acid secretion in gastric parietal cells through inhibition of (H+, K+)-ATPase enzyme system, blocking the final step in gastric acid production. Aspirin (ASA) ·       Pharmacologic Category: Salicylate (NSID). ·       Mechanism of Action: Irreversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which result in decreased formation of prostaglandin precursors; has antiplatelet, antipyretic, analgesic, and anti-inflammatory properties.	·       A PPI is often prescribed with the combination of aspirin to prevent gastrointestinal bleeding. A number of PPIs are available and include esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole (Lacy, 2009). ·       Lanzoprazole dose given is appropriate.             DRP: ·       May be used as prophylaxis of myocardial infarction; prophylaxis of stroke and/or transient ischemic episodes ·       Aspirin causes hematemesis. ·       Dose: 75 to 162 mg/day, unless contraindicated

 

 

 

Stable CAD

 

Stable coronary artery disease (CAD) is defined as an established pattern of angina pectoris, a history of myocar­dial infarction (MI), or the presence of plaque documented by catheterization. CAD results when coronary artery plaque develops, reducing the oxygen supply to the myocardium.

Finding	Assessment	Resolution and Monitoring
Patient progress notes: ·       14-17/6/2017: S = cough with phlegm yellow, shortness of breath ·       14/6/2017: O = (H): leukosit, BUN, Srcr, PCO2, HCO3 ·       15-17/6/2017: HR increases ·       17-6-2017 hematemesis dan melena   Clinical signs: ·       Tgl 14/6: 130/70 Tgl 16/6: 130/70 Tgl 17/6: 130/80 ·       Pulse Tgl 14-17: above normal   Lab data: ·       Leukosit= 15.980 ·       Ureum/BUN= 1,53 ·       Kreatinin= 1,49 ·       pCO2= 51,3 ·       HCO3= 34,9 ·       Base excess= +10,5	Simvastatin ·       Pharmacologic Category: Antilipemic Agent, HMG-CoA Reductase Inhibitor. ·       Mechanism of Action: Simvastatin is a methylated derivative of lovastatin that acts by competitively inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the rate-limiting step in cholesterol biosynthesis.	·       Prophylaxis of atrial fibrillation among patients with stable coronary artery disease (Stable CAD). ·       Secondary prevention of cardiovascular events in hypercholesterolemic patients with established coronary heart disease (CHD) or at high risk for CHD: To reduce cardiovascular morbidity (myocardial infarction, coronary revascularization procedures) and mortality; to reduce the risk of stroke and transient ischemic attacks.                   DRP: ·       Simvastatin and amlodipine: rhabdomyolysis. ·       Amlodipine increases levels of simvastatin. Benefit of combination therapy should be carefully weighed against the potential risks of combination. Potential for increased risk of myopathy/rhabdomyolysis. ·       Plan: limit simvastatin dose to not more than 20 mg/day when use concurrently. ·       The dose of simvastatin given is appropriate.     Beta Blockers ·       Beta blockers are first-line antihypertensive agents for patients with CAD. ·       These drugs block β1 and β2 adrenergic receptors, causing a decrease in heart rate, an increase in diastolic filling time, and a decrease in cardiac contrac­tility. This negative inotropic and chronotropic effect decreases myocardial oxygen demand (Pflieger, 2011). ·       Heart failure (HF): Use with caution in patients with compensated heart failure and monitor for a worsening of the condition. Patients should be stabilized on heart failure regimen prior to initiation of beta-blocker. Beta-blocker therapy should be initiated at very low doses with gradual and very careful titration. ·       Although beta blockers are the first line of CAD treatment, in this case beta blockers cannot be used because the patient has heart failure (Lacy, 2009).

 CONCLUSION:

1.     Therapy is appropriate, but it is necessary to add some type of drug which is expected to further improve the patient's condition due to the patient's poor condition.

2.     First-line drugs in CAD cannot be used because the patient has HF.

3.     Therapy monitoring.

 

SUGGESTION

1.     Increase cooperation between health workers such as doctors, pharmacy, nurses and nutrition to support the effectiveness of therapy and help improve the quality of life of patients.

 

2.      

DAFTAR PUSTAKA

 

Inamdar, A.A. & Inamdar, C.A., 2016, Heart Failure: Diagnosis, Management and Utilization, Journal of Clinical Medicine, University Medical Center, Hackensack, NJ 07601, USA.

 

Kaysin, A. & Viera, J.A., 2016, Community-Acquired Pneumonia in Adults: Diagnosis and Management, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Kemenkes RI, 2007, Pharmaceutical Care Untuk Penyakit Hati, Ditjen Bina Kefarmasian dan Alat Kesehatan, Departemen Kesehatan Republik Indonesia, Jakarta.

Kementerian Kesehatan Republik Indonesia, 2011, Pedoman Interpretasi Data Klinik, Jakarta.

Johansen, H., Thillaiampalam, S., Nguyen, D. & Sambell, C., 2005, Diseases of The Circulatory System-Hospitalization and Mortality, Health Reports, Vol. 17, No. 1, Canada.

 

Kementrian Kesehatan Republik Indonesia, 2015, Panduan Nasional Penanganan Limfoma Non-Hodgkin, Jakarta.

 

Kuhn,V., Diederich, L., Keller, S., Kramer, M.C., Lu, W., Panknin, C., Suvorava, T., Isakson,B., Kelm, M. & Krott, C.M., 2017, Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia, Antioxidants & Redox Signaling,  Volume 00, Number 00.

 

Lacy, F.C., 2009, Drug Information Handbook 17^th Edition, Lexi Comp., New York, Amerika.

MacIntyre, N. & Huang, C.Y., 2007, Acute Exacerbations and Respiratory Failure in Chronic Obstructive Pulmonary Disease, Duke University Medical Center, Durham, North Carolina.

Pflieger, M., Winslow, T.B., Mills, K. & Dauber, M.I., 2011, Medical Management of Stable Coronary Artery Disease, American Family Physician, Volume 83, Number 7 .

Somayana, G., 2017, Pankreatitis Akut, Fakultas Kedokteran Universitas Udayana, Bali.