Patient 3 is a 45 year old Malay male currently on dialysis and has penicillin allergy. Some of his lab readings include: A1c – 4.7%, Hb – 7.4, K+ 5.1. Patient 3 presented with a prescription of the following from the Renal Department:
1. calciTRIOL 0.25MCG CAPSULE
– Take 1 capsule on Monday morning and Thursday morning
2. FERROUS FUMARATE 200MG TABLET
– 2 tablets BD
3. FRUSEMIDE 40MG TABLET
– 2 tablets TDS
4. LOSARTAN POT 50MG TABLET (COZAAR)
– 1 tablet OM
5. niFEdipine 30MG LA TAB
– 1 tablet BD
6. RENALVITE TABLET
– 1 tablet OM
7. SIMVASTATIN 20MG TABLET
– 1 tablet ON
8. SIMVASTATIN 10MG TABLET
– 1 tablet ON
9. PROCHLORPERAZINE MALEATE 5MG TABLET
– 1 tablet TDS prn (nausea, vomiting, giddiness)
10. CALCIUM CARBONATE 1.25G TAB
– 3 tablets TDS with meals
11. INSULIN GLARGINE (LANTUS) 300IU/3ML SoloSTAR
– Inject 8 units every morning
12. ERYTHROPOIETIN BETA 4000IU INJ. 0.3ML
– Inject 4000 units ONCE a week on Thursday
13. SODIUM BICARBONATE 500MG CAPSULE
– 1 tablet TDS
General Overview:
Patient 3 is currently on dialysis treatment, indicating that he has Chronic Kidney Disease (CKD). The Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines define CKD as having either of the following for more than 3 months:
As for the staging of CKD based on the severity of renal impairment is classified by the NKF Kidney Disease Outcomes Quality Initiative (KDOQI) according to a patients GFR (Glomerular Filtration Rate):
Patients with CKD will generally have the following Clinical Presentations, commonly known as Uremic Syndromes:
Mental Confusion, Shortness of Breath, Uremic Breath, Nausea/Vomiting, Appetite Loss, Fatigue, Neuropathy, Itching, Cold Intolerance, Weight gain
Other common signs related to CKD include:
Changes in urine output, edema, abdominal distension, pericardial rub (rubbing sound due to the friction of visceral and perietal pericardial layers), asterixis (flapping hand and tremor when the hand is extended)
Several LAB ABNORMALITIES may occur too.
Decreased: GFR, CrCl, CO2 (metabolic acidosis), Hgb (anemia), iron stores, vitamin D deficiency, albumin (malnutrition), glucose, Ca (early stages of CKD), HDL
Increased: SCr, BUN, K, P, PTH, Blood pressure, Glucose, Lipids, Ca (especially when on vitamin D therapy)
CKD patients are usually on many medications, simply because quite a number of complications are associated with CKD. These include:
1. Cardiovascular diseases (Hypertension, Dyslipidemia, Atherosclerosis, Vascular calcification)
2. Fluid and electrolyte abnormalities (increased P, Mg, K, water causing edema)
3. Metabolic acidosis
4. Malnutrition
5. Anemia
6. Secondary parathyroidism causing mineral and bone disorder (CKD-MBD)
7. Glycemic control (insulin is cleared renally, hence reducing insulin requirement due to reduced excretion in CKD patients)
8. Depression
We know that Patient 3 is currently on dialysis. According to KDOQI guidelies, dialysis should be started when:
1. Non-diabetics : GFR < 15ml/min/1.73m2
2. Diabetics (Patient 3 is diabetic) : GFR < 20ml/min/1.73m2
CKD Complication 1: Cardiovascular Disease (CVD)
CVD complications is one of the most prevalent complications associated with CKD, especially Hypertension (HTN), Dyslipidemia. Approximately 50-70% CKD patients will have concurrent hypertension problems. Management of HTN in CKD patients is described in the 2013 KDIGO Guidelines:
1. Individualize BP targets according to Age, CVD, Comorbidities, Risk of CKD progression, Presence of retinopathy due to Diabetes Melitus (DM) and Tolerance of treatment.
2.Check for dizziness and postural hypotension (especially in elderly. If there is, target BP can be less aggressive)
3. Target BP for DM and non-DM patients are i) < 140/90 mmHg if AER (Albumin Excretion Rate) is < 30 mg/24hr and ii) < 130/80 mmHg if AER is > 30 mg/24hr.
4. ACEI or ARB is recommended in DM CKD patients with AER > 30mg/24hr and in DM or non-DM patients with AER > 300 mg/24hr.
5. Insufficient evidence in recommending combination therapy of ACEI + ARB to prevent CKD progression.
ACEI or ARB are the first line medications for the management of HTN in CKD patients. They have beneficial properties in reducing blood pressure, reducing proteinuria, slowing progression of CKD, prevent CVD events and treat angina as they are both vasculoprotective agents. However, it is prudent to monitor patient’s SCr (Serum Creatinine related to kidney function) and Serum potassium (K) levels (related to control of electrolytes). Therapy can be continued if these values are within an: Increase in SCr < 25-30% from baseline value (due to changes in efferent arteriole in kidneys) and Serum K < 5.5 mmol/L (important to avoid K-containing food).
Diuretics are also frequently used together with ACEI/ARB to potentiate antihypertensive effects, while reducing hyperkalemia risk. Although the JNC (Joint National Committee) VII recommends thiazide-type diuretics (eg: Hydrochlorothiazide) in patients at risk of CHD based on the ALLHAT trial, Loop diuretics (eg: Furosemide) is preferred if a patient’s Creatinine Clearance (CrCl) is below 30 ml/min (Thiazides are ineffective in these patients as it works in the Distal Convoluted Tubule (DCT). However, at such low CrCl, drug cannot reach into the DCT hence it cannot help to reduce edema or fluid accumulation). Monitoring parameters for diuretic therapy include Volume depletion (hypotension or decreased GFR), Hypokalemia, Hyperglycemia, Hyperuricemia and hyper/hypocalcemia.
Dyslipidemia increases risk of atherosclerosis, leading to CVD and higher mortality. Statins should be started when LDL > 130mg/dL with a target goal of LDL < 100mg/dL. However, if LDL levels are between 100-129mg/dL after 3 months of Therapeutic Lifestyle Changes (TLC), statins can also be started. Care should be taken to avoid concurrent fibrates and statins therapy due to the increased risk of rhabdomyolysis. If fibrates are required for the treatment of high triglycerides in patients with CKD, Gemfibrozil is the fibrate of choice.
CKD Complication 2: Fluid and Electrolyte Abnormalities
Fluid balance is an important consideration in CKD patients. As renal failure progresses the upper and lower limits of water excretion narrow gradually as well. Retaining excessive water leads to edema and hypertension, while too little water may lead to dehydration and further deterioration of renal failure. Fluid overload can be managed by diuretic therapy (Thiazide or Loop diuretic depending on CrCl value). Fluid intake of 1-1.5L/day is usually acceptable for most CKD patients, while 800ml-1L water is usually acceptable for CKD Stages III and IV patients. It is also important to educate patients that this ‘fluid intake’ includes all kinds of beverages including those available in foods.
Sodium levels should be maintained within the range of 135-150mmol/L. Excretion of sodium is reduced in CKD patients. Hence, there is an increased risk of hypernatremia, which can lead to increased intravascular volume, circulatory overload, edema, hypertension and coronary heart failure (CHF). To prevent these complications, sodium intake needs to be restricted to less than 2g a day according to KDIGO recommendations.
Potassium levels should be maintained within the range of 3.5-5.0mmol/L. CKD patients have higher risk of hyperkalemia due to impaired renal excretion of potassium. Hyperkalemia can also be caused by catabolic states (infections, trauma, surgery), dietary indiscretion (banana, papaya, potato, durian), salt substitutes, sudden decrease in urine output and drugs. The following drugs may cause hyperkalemia:
1. Penicillin (contains K)
2. Beta-blockers (block K entry into cells)
3. Succinylcholine (release muscle K)
4. K-sparing diuretics (reduce urinary K excretion)
5. ACEI or ARB (inhibit angiotensin/aldosterone [secretes K in distal renal tubule])
6. Digoxin (compete with K for Na-K-ATPase, decreasing K excretion)
Hyperkalemia may lead to neuromuscular and cardiovascular complications. Hyperkalemia causes and initial increase in excitability of neural/muscle cell membranes, followed by a decrease in muscular excitability and conduction. Consequently, initial muscle twitching may begin at K levels > 6.5mmol/L, while muscle weakness begins from lower extremities first and progressively towards the trunk, upper extremities and respiratory muscles. Cardiac disturbances are observed when K levels > 7 mmol/L with signs and symptoms such as bradycardia, hypotension, ventricular fibrillation and cardiac arrest. Only Dialysis and Resonium (Sodium polystyrene sulfonate) are definitive ways of removing potassium from the body. Other management methods (glucose and insulin, beta-adrenergic agonist, sodium bicarbonate) only shifts K intracellularly. IV Calcium Carbonate is the first line drug to use if patient has ECG changes due to hyperkalemia. It works by antagonizing deleterious and life-threatening effects of high K on heart.
CKD patients are also prone to hyperuricemia due to impaired renal excretion of uric acid. Urate lowering drugs such as allopurinol and colchine can be used for the management of uricemia. However, renal dosing adjustment is required as these drugs are also primarily excreted renally. Uricosuric agents (drugs that increase the excretion of uric acid in urine in proximal tubule) such as probenecid, benzbromarone and sulfinpyrazone are ineffective as there is no sufficient renal function to begin with in CKD patients.
Another electrolyte to be monitored is Magnesium, as it is renally excreted. Hypermagnesia may result in neuromuscular activities. Hence, CKD patients should avoid taking Mg-containing medications such as those in laxatives, antacids and multivitamins.
CKD Complication 3: Metabolic Acidosis
Metabolic acidosis occurs when serum bicarbonate levels goes below 22 mmol/L (normal range 22 – 31 mmol/L). Acid-base balance tends to be normal until there is >50% reduction in GFR. At GFR <20% of normal, significant acidemia (blood pH < 7.4) may occur. Among other factors besides CKD that can also result in a dramatic fall in arterial pH include: Diarrhea, Dehydration, Sepsis, Excessive catabolism, Fever. Renal failure-induced metabolic acidosis is due to the following mechanisms:
1. Decreased H+ excretion – causing a decrease in pH and serum bicarbonate secretion (serum bicarbonate < 22 mmol/L = metabolic acidosis)
2. Decreased NH3 excretion – NH3 (ammonia) excretion is a mechanism to excrete H+. Hence, this results in an accumulation of H+
3. Decreased PO4 excretion – PO4 (phosphate) excretion is a mechanism to excrete H+. Hence, this results in an accumulation of H+
4. Retention of SO4 and other organic ions
5. CaCO3 is released from bones to buffer the excess H+. This results in weak and brittle bones
Clinical presentations for metabolic acidosis include anorexia, nausea and lethargy. Management of metabolic acidosis is usually started when serum CO2 or bicarbonate levels < 20 mmol/L. The key concept in metabolic acidosis management is the use of alkalinizing salts to replenish bicarbonate stores.
1. Sodium bicarbonate (oral/IV): 500mg to 1g PO BD-TDS
2. Citrate/citric acid preparations – Requires healthy liver function for liver metabolism to bicarbonate, CO2 and water
3. Higher concentrations of bicarbonate or acetate in dialysate for dialysis patients
CKD Complication 4: Malnutrition
Protein-energy malnutrition is common in patients with advanced CKD. Protein requirements in CKD patients is 0.6-0.8g/kg/day for non-dialysis patients and 1.2g/kg/day in dialysis patients due to protein loss from dialysis. Protein requirements are lower in non-dialysis patients due to their inability to excrete nitrogenous wastes, hence preventing nitrogenous waste buildup. The recommended total energy intake for CKD patients is 30-35 kcal/kg/day. This is similar to the total energy intake recommended for healthy individuals. Hence, there is not a need to cut down on calorie intake. Inadequate caloric intake may result in catabolism of body fat and muscle, resulting in decrease in lean body mass. Common causes of malnutrition may include:
1. Poor dietary intake due to anorexia (can be due to metabolic acidosis), altered taste sensation, limited food choices (may be due to dietary and salt restrictions), depression
2. Loss of nutrients from dialysis – Dialysis patients should restrict protein intake before dialysis
3. Loss of blood from dialysis
4. Hypercatabolism and chronic inflammation
Malnutrition also includes that of vitamins and trace elements. Water soluble vitamins (B1, B2, B6, B12, niacin, panthothenic acid, biotin, vitamin C and folic acid) are usually low as these may be cleared by dialysis. Supplementation with renal vitamins such as Renalmin are necessary. However, it shall not be taken in the morning because dialysis will simply clear it out. Hence, it is usually dosed at night in dialysis patients. Conversely, increased amounts of vitamins A and E are observed in End Stage Renal Disease (ESRD) patients. Vitamin D is usually low due to reduced activation by 1-alpha-hydroxylase (enzyme required for conversion from inactive vit D to active vit D. Iron and zinc deficiency is common, whilst Aluminium overload may be observed. It is important to remind CKD patients to avoid Aluminium containing pills as it may cause Al toxicity such as CNS complications, anemia and liver toxicity.
CKD Complication 5: Anemia
CKD-associated anemia (Hgb male < 13 g/dL, Hgb female < 12 g/dL) is due to decreased red blood cell (RBC) production, decreased red blood cell survival, and increased red cell loss. RBC production is reduced due to decreased erythropoietin (EPO) production by the kidneys (kidneys synthesize 90% of EPO in body when it detects and is stimulated by low oxygen concentration in blood, whereas the liver synthesize the other 10%). With such low levels of EPO, erythropoiesis (process by which RBC is produced) in the bone marrow is inhibited or reduced. Erythropoiesis may also be inhibited due to nutritional deficiencies of folate, vitamin B12 or iron. Decreased RBC survival is due to abnormalities of the red cell membrane, which causes it to be fragile, thereby decreasing its life span from 120 days to 60 days. Elevated parathyroid (PTH) hormones in CKD patients also contributes to increased RBC osmotic fragility. Lastly, RBC loss can be caused by GI bleeding or blood loss with dialysis. Laboratory findings may reflect low Hgb, reticulocyte (immature RBC) count, MCV and MCHC. Also, iron status can be monitored via Transferrin Saturation (TSAT) [Indicator of iron immediately available for delivery to bone marrow or circulating iron available for erythropoiesis] and Serum Ferritin [indirect measure of storage iron]. However, serum ferritin is an acute phase reactant and may be elevated in cases of inflammation or infection. Patients with CKD-associated anemia may have negative effects on their Quality Of Life (QoL) such as shortness of breath, weakness, fatigue and pale complexion. Anemia may also precipitate ischemia due to decreased oxygen delivery to organs.
Patients with CKD-associated anemia should have a target goal of Hgb: 10-11.5 g/dL, TSAT: >20-30%, and serum ferritin >100 ng/ml (for stages III and IV CKD and Peritoneal Dialysis patients) or 200-500 ng/ml (for hemodialysis patients). Erythropoietin Stimulating Agents (ESA) is recommended in CKD patients with Hgb < 10g/dL. ESAs (Epoetin alfa, Epoetin beta, Darbepoietin, Mircera) works by stimulating differentiation of erythroid progenitor stem cells and induce release of reticulocytes from bone marrow.
At the same time, ESA treatment often lead to increased Iron (Fe) demands due to stimulation of erythropoiesis. Hence, co-administration of Fe and ESA is common to effectively stimulate erythropoiesis. Oral iron (ferrous fumarate, ferrous gluconate, ferrous sulfonate) may be used in early or pre-dialysis stages of CKD but is usually inadequate to maintain Fe stores in hemodialysis patients. IV Fe preparations (iron dextran, ferric gluconate, iron sucrose, ferumoxytol) are usually required.
CKD Complication 6: CKD-associated-Mineral and Bone Disorder (CKD-MBD)
This systemic disorder of mineral and bone metabolism due to CKD has its pathophysiology related to abnormalities in Calcium (Ca), Phosphate, Parathyroid hormone (PTH) and vitamin D. Generally, renal failure causes hyperphosphatemia and Vitamin D deficiency (as stated previously in this article). Increased phosphates binds to circulating Ca, while low concentrations of vit D reduces Ca absorption in the gut causing a decrease in circulating Calcium concentrations. These combined effects stimulates the parathyroid gland to increase PTH secretion, resulting in bone diseases such as fractures, bone pain, marrow fibrosis and erythropoietin resistance. Consequently,the primary goal in CKD-MBD therapy is to maintain normal levels of serum P, Ca, Ca x P, vit D and PTH. Among the management strategies include dietary P restriction, Phosphorous Binders, Vit D therapy and Calcimimetics.
Patient Specific Therapy:
1. calciTRIOL 0.25MCG CAPSULE (Rocaltrol 0.25mcg Capsule)
Information: Calcitriol is the fully active form of vitamin D3 (1,25-dihydroxycholecalciferol). It has 2 functions: Firstly to increase gastrointestinal absorption of Calcium and secondly, to suppress PTH secretion and synthesis. In CKD patients, vitamin D therapy is primarily used to maintain normal bone formation and reducing fracture risk. This is exceptionally important in the elderly. Other Vitamin D therapy agents include Alfacalcidol (not fully active form of vitamin D, hence requiring functioning liver for full activation) and Paracalctol (synthetic analog of calcitriol but having selective activation of vitamin D receptors in PTH glands inhibiting PTH synthesis and secretion, with less hypercalcemia and hyperphosphatemia). Starting doses of calcitriol is usually 0.25mcg 3 times weekly and can be increased to daily dosing for pre-dialysis CKD patients. In hemodialysis (HD) patients, the dose of calcitriol is usually 3 times a week through intravenous route. One major limitation of Vitamin D therapy is the risk of hypercalcemia and hyperphosphatemia, which will cause or worsen vascular calcification, hence narrowing of arteries. Consequently, a group of drugs called Calcimimetics, such as Cincacalcet, can be used as an alternative to Vitamin D analogs. Calcimimetics increases the sensitivity of Calcium-sensing receptors (CaSR) [principal regulator of PTH secretion] on the parathyroid gland to extracellular Calcium, resulting in reduced PTH and serum Calcium concentrations. Although Calcimimetics have a shorter onset and less hypercalcemia and hyperphosphatemia risk, it does not possess peripheral health benefits brought together by Vitamin D analogs. These health benefits include reducing risk of cardiovascular disease, protecting and preserving kidney function, improving immune function and reducing morbidity and mortality. In general, a sufficient serum 25-hydroxyvitamin D level and target goal is >30 ng/ml or mcg/L.
Counseling: Calcitriol is a medication used to maintain sufficient levels of vitamin D in your body and ensure strong and healthy bones. Take 1 capsule once in the morning and once in the evening before or after food, every Monday and Thursday. If you experience minor stomach discomfort when you take it before food, you can try taking the calcitriol after food. If you experience any symptoms such as rashes on the face or around the eyes or lips, excessive weakness, headaches, nausea, vomiting, dry mouth, constipation, bone or muscle pain, or a constant metallic taste in your mouth, please alert your doctor to it. As much as possible, try to maintain a consistent diet without any sudden excessive intake of calcium-containing food such as milk, egg whites or soy beans. Also, avoid taking any supplements that contains vitamin D or calcium, except the medications provided for you. We are already providing calcium products for you.
2. FERROUS FUMARATE 200MG TABLET
Information: Ferrous fumarate is often used together with ESAs to stimulate erythropoiesis in CKD-associated anemia. It is important to know the contents of elemental iron (Fe) in oral iron preparations. For example, Ferrous fumurate contains 33% elemental Fe, Ferrous sulfate contains 20% and Ferrous gluconate contains 12% elemental iron. Daily doses of Fe should be at least 200mg elemental Fe, administered in 2-3 divided doses. Also, absorption is optimum when taken without food or medications. However, it can also be taken after food if GI discomfort occurs. Concurrent medications such as Calcium salts (take note of administration time because patient is also prescribed with calcium products), quinolones, H2-Receptor Antagonists (eg: cimetidine, ranitidine [Zantac]) and Proton-pump Inhibitors (eg: omeprazole) will decrease its absorption.
Counseling: Ferrous fumarate is a medication to ensure you have sufficient iron and healthy red blood cells in your body. Take 2 tablets of Ferrous fumarate in the morning and evening before food. You may experience some common side effects such as nausea, constipation or abdominal pain. These should be mild. If however, these side effects worsen and discourages you from taking the medication any longer, please alert your doctor to it. Please do take note that you may observe dark colored stools when you take this medication. Do not be alarmed as this is normal. As much as possible, try to avoid eating dairy products 1 hour before or 2 hours after taking this medication. The most common side effect is constipation. As such, try to take more fruits and vegetables, at least one serving for your lunch and dinner.
3. FRUSEMIDE 40MG TABLET
Information: Frusemide is a loop diuretic that is commonly prescribed to most CKD patients. The JNC VII recommends thiazide type diuretics for all patients at risk of coronary heart disease. However, loop diuretics are generally preferred in patients with CrCl < 30 ml/min (severe renal function). Also, thiazide diuretics can be used to lower BP but is less effective than loop diuretics in reducing fluid accumulation. Diuretics have 4 distinct benefits with the acronym CABS:
1. Cardiovascular – Reduce risk of Cardiovascular Disease in CKD patients
2. ACEI/ARB effect – Potentiate effects of ACEI and ARBs with reduced hyperkalemia risk
3. Blood pressure – Lowers BP
4. Swelling and Shortness of Breath – Reduces extracellular volume, hence reducing swelling especially at the extremities (ankles and legs) and shortness of breath due to congestion (fluid accumulation in lungs)
Frusemide and loop diuretics are usually dosed once to twice daily (prn basis if only for heart failure management). At a three times daily dosing as prescribed for this patient, it probably means that the patient has persistent fluid overload. Another thing to note is to advise patient to take the last dose of frusemide in the early evening by 4pm, instead of taking it just before bedtime. The latter might cause sleep disturbance due to the need to urinate after taking frusemide. Administration of loop diuretics are often associated with hypotension and dizziness. Hence, there is a need to remind patients to stand up slowly from a sitting or lying down position. It is also important to monitor patient’s weight. If patient is at dry weight, the diuretic dose may be reduced by 50% or be treated intermittently. If however, patient’s weight increases for >0.44 – 0.88kg in one day or 2kg/week, with increased swelling and returning of shortness of breath, diuretic dose can be increased temporarily until the patient is stable or asymptomatic. Also, if a certain diuretic is refractory, a diuretic of a different mechanism of action can be added after non-adherence (failure to restrict water/salt intake) is ruled out. Monitoring of uric acid and glucose levels is important as frusemide may cause hyperuricemia and hyperglycemia (especially in this patient, who is taking insulin for diabetes management). The use of diuretics also increases the risk of hypokalemia (normal range for serum potassium concentration 3.5 – 5.0 mmol/L). Patient 3 has K+ concentrations of 5.1 mmol/L, hence not at high risk for hypokalemia.
Counseling: Frusemide is a medication used to reduce fluid accumulation that causes swelling and shortness of breath, while reducing your risk of having heart problems. Take 2 tablets of Frusemide three times daily, preferably before your breakfast, lunch and dinner. As much as possible, try not to take the last dose just before your bedtime as you may need to urinate, hence disturbing your sleep. Frusemide may cause dizziness. Do not operate heavy machinery or activities that require coordination after taking this medication. Also, always remember to stand up slowly from a sitting or lying down position to avoid falling down. If you notice any rashes such as red patches and itch on your face or skin, please alert your doctor about it. As you may expel more fluid after taking this medication, please take note to record your weight at the same time every morning in a piece of paper or diary. Your doctor may ask you to notice any changes in body weight and adjust the amount of Frusemide to be taken. Lastly, refrain from alcohol while being on this medication. (Can advise patient to increase intake of potassium containing foods such as banana. However, the serum potassium level of patient is already above the normal range.)
4. LOSARTAN POT 50MG TABLET (COZAAR)
Information: Losartan is an Angiotensin II Receptor Blocker (ARB) that blocks the activation of angiotensin II AT1 receptors. This blockage of AT1 receptors directly causes vasodilation and reduces the production as well as secretion of aldosterone (acts on distal renal tubules and collecting ducts of the nephron to cause the conservation of sodium, secretion of potassium, increased water retention, and increased blood pressure), thereby reducing blood pressure. ARB is usually used when ACE (angiotensin-converting enzyme) inhibitor causes dry cough in patients. Both ACEI and ARBs are considered a 1st line drug for CKD patients with Diabetes Mellitus. Similar to Diuretics, ACEI and ARBs also helps in preventing Cardiovascular diseases. There is insufficient data to support the concurrent use of ACEI and ARBs. However, it is important to take note that both ACEI and ARBs may cause further renal failure and increase in serum potassium (K) levels. In general, therapy can be continued if the increase in Serum Creatinine is less than 25-30% of baseline value and Serum K levels are < 5.5 mmol/L (it is still used in Patient 3 as we know his Serum K level is 5.1 mmol/L and has also been given Frusemide to control serum K levels). Hypotension, diarrhea and fatigue are common side effects with Losartan. However, it is important to remind patients to look out for rare but serious adverse effects such as angioedema (swelling of the face and neck possibly due to hypersensitivity) and Rhabdomyolysis (unexplained general muscle ache). Both ACEI and ARBs cannot be used in pregnancy (not related to Patient 3, male).
Counseling: Losartan is a medication used to lower your blood pressure and reduce your risk of having cardiovascular disease. Take 1 tablet of Cozaar once in the morning with or without food. Some common side effects include diarrhea and fatigue but should be quite mild. You may experience some dizziness after taking this medication. So, please avoid operating any heavy machinery or do any activities that require coordination after taking this medication. Also, stand up slowly from a sitting or a lying down position to avoid dizziness and falls. If you experience any persistent dry cough that affects your quality of life, please let the doctor know. There are some rare but serious adverse effects to take note of while taking this medication. If you experience any swelling on your face or neck, or have any unexplained generalized muscle ache with accompanying fever, please refer to the doctor immediately.
5. niFEdipine 30MG LA TAB (Adalat LA)
Information: Nifedipine is a short acting dihydropyridine belonging to the class of Calcium Channel Blockers (CCB). [Non-dihydropyridines are Dilitiazem and Verapamil, Long acting dihydropyridines are Amlodipine and Felodipine] CCB block the transmembrane influx of calcium ions into cardiac muscles and vascular smooth muscles by binding to L-type calcium channels. This decreases myocardial contractility hence decreasing cardiac output (contributing to lowering of BP) and reduced oxygen requirement. It also relaxes or decreases vascular smooth muscle tone, hence causing coronary and peripheral vasodilation, resulting in a further lowering of BP. Nifedipine, being a SHORT-ACTING CCB has increased adverse effect (dizziness, headache, flushing [due to vasodilation], peripheral edema, tachycardia, gingival hyperplasia) and increased morbidity and mortality (do note that Nifedipine, although is a short acting drug, as a long-acting (LA) preparation, such as in this patient). CCBs are usually only used with patient has high risk of coronary heart disease and an add-on to ACEI or ARB in diabetes patients.
Counseling: Nifedipine is a medication used to lower your blood pressure, while reducing your risk of heart diseases. Take 1 tablet of Nifedipine 30mg twice a day, preferably in the morning and evening BEFORE meals. This medication may cause dizziness. So, do not operate any heavy machinery or do any activities that require coordination after taking this medication. Stand up slowly from a sitting or lying down position to avoid falls. Also, there are some common side effects related to this medication such as headache, flushing and swelling. If these side effects persist or worsen with use of this medication, please alert your doctor to it. Additionally, if you notice any swelling on your lips or gums, please refer to your doctor immediately.
6. RENALVITE TABLET
– 1 tablet OM
Information: Renalmin is a multivitamin supplement consisting mostly of vitamins B and C complex and is commonly used in dialysis patients or patients with azotemia due to chronic renal failure. Note that these vitamins are water soluble. Water soluble vitamins are eliminated during dialysis, hence the need arises to replenish them. Vitamin B complex is generally important for cell metabolism and healthy nerve function. Vitamin C acts as an antioxidant and helps to strengthen immune finction
a. Thiamine nitrate (B1)
b. Riboflavin (B2)
c. Pyridoxine HCl (B6)
d. Cyanocobalamin (B12)
e. Ascorbic acid (C)
f. Folic acid (B9) – normal cell division, especially during pregnancy and infancy, which are times of rapid growth. Folate also aids in ERYTHROPOIESIS, the production of red blood cells (RBC).
g. Biotin (B7)
h. Niacinamde (B3)
i. Calcium pantothenate (B5)
Counseling: Renalmin is a multi vitamin supplement consisting of vitamin B and C complex. It is given to replenish the vitamins lost primarily during dialysis. Vitamin B generally maintains healthy nerve function and cell metabolism whereas vitamin C helps to strengthen your immune function. Take 1 tablet of Renalmin in the morning with your breakfast.
7. SIMVASTATIN 20MG TABLET (Zocor 20mg Tablet)
8. SIMVASTATIN 10MG TABLET (Zocor 10mg Tablet)
Information: Simvastatin is a vasculoprotective drug. Statins are the only class of lipid-lowering agents that has consistently demonstrated a reduction in overall mortality. Simvastatin is a HMG-CoA reductase inhibitor. HMG-CoA reductase catalyzes the rate limiting step in hepatic intracellular cholesterol synthesis. Inhibition of HMG-CoA reductase will cause increased cellular uptake of LDL molecules and lower the intravascular (blood) circulating LDL concentration effectively. Dosing for statins can be derived from the Rule of Six. However, the Rule of Six is just an estimation, as LDL reduction is highly dependent on a patient’s lifestyle changes, such as diet and exercise. Statins and cholesterol reducing medications should be taken at night as our body produces cholesterol at night.
Contraindications to HMG-CoA reductase inhibitor includes active liver disease (hepatitis, cirrhosis, hepatic encephalopathy), alocoholism, pregnancy and breastfeeding mothers. Among notable side effects of this class of drugs include:
a. Gastrointestinal discomfort, which will usually go away when medication is continuously taken – abdominal pain, flatulence, constipation.
b. Hepatotoxicity – This is because statin is cleared through the liver. If AST or ALT increase to > 3 times the UNL and persist, dose reduction or drug withdrawal is recommended. Hence, monitoring of LFT 6-12 weeks after initiation or increase in dose, then at least once annually is required. If LFT > 3x UNL, it is recommended to stop statin therapy and only be reintroduced at a lower dose when LFT is normalized.
c. Myopathy and Rhabdomyolysis (Increase in Creatinine Kinase > 10 times UNL with Creatinine elevation) – Usually presented with brown urine and described by general unexplained muscle pain. Higher risk in patients on high statins dose, old age, renal impairment, and LDL-lowering agent combination therapy such as nicotinic acid and fibrates.
Counseling: Simvastatin is a medication used to reduce the levels of bad cholesterol in your body. Take 1 tablet of Simvastatin 20mg and 1 tablet of Simvastatin 10mg every night as our body produces cholesterol at night. Do not take this medication with alcohol as it will severely damage your liver. You may experience some common side effects such as stomach discomfort and flatulence while taking Simvastatin. These side effects should go away as you continue with this medication. However, do take note of symptoms such as brown coloured urine, yellowing of eyes or skin, and generalized, unexplained muscle ache accompanied by fever. If these symptoms arise, stop your medication and visit a hospital’s emergency department immediately. Lastly, please include a reminder on you and your caregiver’s phone or calendar for the date of your next doctor’s appointment. This is important for us to be able to monitor the effect of Simvastatin on your cholesterol control and liver function.
9. PROCHLORPERAZINE MALEATE 5MG TABLET (Dhaperazine 5mg Tablet)
Information: Prochlorperazine is a piperazine phenothiazine with antidopaminergic effects. Prochlorperazine blocks the postsynaptic dopamine receptros in the mesolimbic system as well as in the chemoreceptor trigger zone (CTZ). Blocking of dopaminergic effect in the CTZ is the primary mechanism of action for its anti-emetic effects. Prochlorperazine also blocks anticholinergic and alpha-adrenergic receptors resulting in sedation, muscle relaxation and hypotension. Prochlorperazine toxicity may lead to cardiovascular abnormalities such as arrythmias and EKG changes. Tardive dyskinesia, convulsions and somnolence may also occur.
Counseling: Prochlorperazine is a medication used to alleviate symptoms of nausea, vomiting and giddiness. Take 1 tablet of prochlorperazine three times a day when you feel any nausea or giddiness or when you experience any episodes of vomiting.
10. CALCIUM CARBONATE 1.25G TAB
– 3 tablets TDS with meals
Information: Calcium Carbonate at such a high dose of 3.75g TDS suggests that it is intended to act as a phosphorus binder. This is due to CKD-MBD as explained in the description above. Renal failure causes an increase in serum phosphate as phosphates are renally excreted. Calcium ions are supposed to bind to these phosphates. However, serum calcium levels are low because absorption of calcium is impaired due to low vitamin D levels (vitamin D levels are low because of the decrease in production of enzyme 1-alpha-hydroxylase by kidneys. High levels of serum phosphate together with low levels of serum calcium results in secondary hyperparathyroidism, which causes bone diseases such as fractures, bone pain, marrow fibrosis and erythropoietin resistance. Calcium salts such as Calcium carbonate combines with dietary phosphates to form insoluble calcium phosphate, which will be excreted through feces. Hence, it is important to administer calcium salts with meals to exert its mechanism of action. It is generally ineffective as Calcium replacement when given alone. Hence, vitamin D is given together in this patient to avoid limitations of oral calcium absorption. Calcium carbonate has 40% elemental calcium (Ca acetate has 25% elemental Ca). Side effects for calcium salts include hypercalcemia, constipation, nausea, vomiting and loss of appetite. KDOQI guidelines recommends that elemental Ca is limited to 2.0g daily. Due to the risk of hypercalcemia, there are other alternatives for phosphorus binders such as Sevelamer, Lanthanum, and Aluminium based binders.
Counseling: Calcium carbonate is a medication to maintain healthy bones in CKD patients. Take 3 tablets of calcium carbonate 1.25g three times a day WITH your MEALS. This is very important in order for this medication to be effective. You may experience some common side effects such as constipation, nausea, vomiting and loss of appetite. If these symptoms persist or worsen after continuous administration of the medication, please alert your doctor to it. In terms of dietary changes, you can consider reducing intake of foods with high phosphorus contents such as beer, ales, dark colas, milk drinks, cheese, ice cream, proteins, beans and peas, nuts, wheat products and preservatives in fast foods and processed foods.
11. INSULIN GLARGINE (LANTUS) 300IU/3ML SoloSTAR
Information: Insulin Glargine is used for the management of Diabetes Mellitus. Diabetes can be caused by impaired insulin secretion by the pancreas, increased hepatic glucose production, and/or decreased muscle glucose uptake in the body, resulting in hyperglycemia. Symptoms of hyperglycemia include extreme thirst, frequent urination, dry skin, hunger, blurred vision, drowsiness and nausea. It is also more commonly thought of as the 3P’s – Polydipsua, Polyuria, and Polyphagia. On the other hand, it is also important to know the symptoms of hypoglycemia to know when the patient has too low blood glucose levels. These include shakiness, fast heartbeat, sweating, dizziness, anxiousness, hunger, blurred vision, fatigue, headache and irritable. In the management of DM, the optimal goal for DM patients are A1C of 6.5-7.0%, Preprandial glucose levels of 6.1-8.0 mmol/L and 2 hours postprandial glucose levels of 7.1-10.0 mmol/L. DM patients also require monitoring at regular intervals. These include their A1C levels (every 6 months), Lipid panel (every year), microalbuminuria (every 6 months), eye exam (every year), blood pressure (every doctor’s visit) and foot exam (every day by patient). In the management of DM by insulin, it works by mimicking the physiologic, pancreatic insulin secretion from the beta cells to maintain normal plasma glucose levels. Firstly, it stimulates glucose uptake and storage. Secondly, it reduces hepatic glucose output, lipolysis and ketone production. Thirdly, it increases amino acid incorporation into proteins. The stability of insulin is vital, especially when given to patients. Remember to remind patients that:
1. unopened insulin vials are good until expiration IF stored in a refrigerator.
2. unopened insulin vials are good for only ONE MONTH (28 DAYS) if NOT stored in the refrigerator.
3. OPENED insulin vials are good for ONE MONTH REGARDLESS of refrigeration.
With regards to terms used, 1ml of insulin is equivalent to 100 units. Insulin Glargine is specifically a long-acting insulin with an onset of 1.1 hours and a duration of 24 hours without any peaks in concentration. It has a clear appearance. In choosing injection areas, remember to remind patients that insulin requires subcutaneous administration, hence requiring an area of the body with more fatty tissues present. Common areas include abdomen (2 inch circle around the navel), top and outer thighs (to avoid bony area above the knees) and outer upper arms.
Counseling: Insulin glargine is a long acting insulin to help maintain normal blood glucose levels throughout the day. Your blood glucose level is well controlled (A1C at 4.7%) and you should keep up the good work. Prior to using the pen, please check if the solution in the pen is clear. If it is cloudy or coloured, do NOT use the pen. In order to inject insulin, here are a couple of steps for you to follow:
1. Use an alcohol swab to wipe your injection spot in one direction.
2. Keep the pen STRAIGHT and attach the needle.
3. Dial 2 units and remove the protective cap from the needle.
4. If you are using a newly-opened pen, a safety test is required. Hold the pen with the needle pointing upwards. Tap the pen and slowly eject any air bubbles trapped in it. Check if insulin comes out from the needle top. Also check that the dose window shows “0”.
5. Set your dose, then pinch your abdomen and hold the pen at 90 DEGREES. Release before pressing the injection button all the way in. The number in the dose window will return to “0” as you inject.
6. Count to 10 before withdrawing the needle to ensure that the full dose is delivered. DO NOT RUB the injection spot. Dispose the needle in a container.
7. Remember to rotate injection sites to reduce any bruising or scarring.
8. Please do not freeze your insulin pens.
For this prescription, your doctor has instructed you to inject 8 units every morning. Do remember that low blood sugar is a very DANGEROUS condition. You can recognise this condition if you experience symptoms such as increased heart rate, dizziness and cold sweat. If these occur, eat some sweets to raise your blood sugar quickly and wait for 15 minutes. f your symptoms persist, take another 5-6 pieces of candy. You may also drink fruit juice or coke. However, milo should be avoided because it releases sugar slowly and will not help with your condition.
12. ERYTHROPOIETIN BETA 4000IU INJ. 0.3ML (Recormon 4000IU INJ 0.3ML)
Information: Recormon belongs to the group of drugs called Erythropoiesis Stimulating Agents (ESA) and is a mainstay of therapy for CKD-induced anemia. It works by stimulating the differentiation of erythroid progenitor stem cells and induce release of reticulocytes from bone marrow in order to increase red blood cells and hemoglobin levels in the body. Anemia is presented by symptoms such as shortness of breath, weakness, tiredness and pale complexion, In fact, decreased oxygen delivery to vital organs such as the heart may increase risks of cardiovascular complications. Target Hgb levels for hemodialysis patients should be within the range of 10-11.5 g/dL. ESAs require individualized dosage titrations and it can be summed up as follows:
1. Rate of Hgb increase should be 1-2 g/dL per month
2. If Hgb increase < 1 g/dL over 4 weeks, increase EPO dose by 25%
3. If Hgb approaches 11-12 g/dL, reduce dose by 25%
4. If Hgb increase >1 g/dL over 2 weeks, reduce EPO dose by 25%
5. If Hgb > 13 g/dL, hold EPO until Hgb < 11-12, then restart at lower dose with monitoring
6. The minimum interval between dose adjustments is 2-4 weeks to allow time to work
A very common adverse effect of ESAs is hypertension. In scenarios where systolic BP > 160 mmHg, EPO might need to be witheld with an increase in hypertensives to reduce blood pressure to normal values before restarting ESA. Other adverse effects include increased blood viscosity, seizures and flu-like syndrome. It is also prudent to know that ESAs alone is not sufficient to build red blood cells if there is iron deficiency. Hence, iron supplement (ferrous fumarate in this case) needs to be given concurrently to avoid ESA resistance.
Counseling: Recormon is a medication used to increase your number of red blood cells to prevent you from feeling tired, weak and having shortness of breath. This is usually administered into your vein and therefore you cannot administer this yourself. Your doctor as instructed you to use 1 injection every week on Thursday, which is the day that you go for dialysis. So, remember to bring along 1 injection every Thursday when you go for your dialysis. You may experience some flu-like symptoms such as fever and tiredness while being on this medication.
13. SODIUM BICARBONATE 500MG CAPSULE
Information: Sodium bicarbonate is usually given to CKD patients who experience metabolic acidosis, whereby their serum bicarbonate level drops below 20 mmol/L (as stated above in the article).
Counseling: Sodium bicarbonate is a medication used to make your blood less acidic due to renal impairment (causing decreased in H+, NH3 and PO4 excretion), hence alleviating presentations of metabolic acidosis such as loss of appetite, nausea and lethargy. Take 1 capsule 3 times a day. You might feel slightly bloated after taking this medication. As such, you can eat smaller meals to reduce the bloatedness.
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