Renal RxPrep Book 2022 PDF

RxPREP 2022 COURSE BOOK I RxPREP ©2021, ©2022 Vitamin D Deficiency & Secondary Hyperparathyroidism After controlling hyperphosphatemia, elevations in PTH are treated primarily with vitamin D. Vitamin D deficiency occurs when the kidney is unable to hydroxylate vitamin D to its final active form....

RxPREP 2022 COURSE BOOK I RxPREP ©2021, ©2022 Vitamin D Deficiency & Secondary Hyperparathyroidism After controlling hyperphosphatemia, elevations in PTH are treated primarily with vitamin D. Vitamin D deficiency occurs when the kidney is unable to hydroxylate vitamin D to its final active form. 1125-dihydroxy vitamin D. Vitamin D deficiency worsens bone disease, impairs immunity and increases the risk of cardiovascular disease. Vitamin D occurs in two primary forms: vitamin D3 (or cbolecalciferol), which is synthesized in the skin after exposure to ultraviolet light (e.g., the sun), and vitamin D2 (or e.rgocalciferol), which is produced from plant sterols and is the primary dietary source of vitamin D. Supplementation with oral ergocalciferol or cholecalciferol may be necessary, especially in patients with early CKD (e.g., stage 3 and 4). The vitamin D analogs are used in patients with later stages of CKD, or ESRD, to increase calcium absorption from the gut, raise serum calcium concentrations and inhibit PTH secretion. Calcitriol (Rocaltrol) is the active form of. vitamin D3. Newer vitamin D analogs, such as paricalcitol and doxercalciferol, are alternatives that cause less hypercalcemia than calcitriol. Another method of inhibiting PTH release is by increasing the sensitivity of the calcium receptor on the parathyroid gland. Cinacalcet (Sensipar) is a "calcimimetic" which mimics the actions of calcium on the parathyroid gland and causes a further reduction in PTH. It is only used in dialysis patients. Drugs for the Treatment of Secondary Hyperparathyroidism DRUG SAFETY/SIDE EFFECTS/MONITORING DOSING Vitamin D analogs: i intestinal absorption of Ca, which provides negative feedback to the parathyroid gland. CONTRAINDICATIONS Calcitriol (Rocaltrol) CKD: 0.25-0.5 mcg PO daily Capsule, solution, Dialysis: 0.25-1 mcg PO daily or 0.5-4 mcg IV Hypercalcemia, vitamin D toxicity _i_n1_ ·e_ct_io_n_ __ ___3 _x_w _ ee_k_lY_ _ _ _ _ _ _ _ _ _ _ ____, WARNINGS Calcifediol (Raya/dee) Digitalis toxicity potentiated by hypercalcemia CKD Stage 3 or 4: 30 mcg PO QHS I ! SIDE EFFECTS ER capsule _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ ____,. Hypercalcemia, hyperphosphatemia, NN/D (> 10%) CKD: 1-3.5 mcg PO daily Doxercalciferol (Hectorol) Capsule, injection ---------- Paricalcitol (Zemplar) Capsule, injection i Ca, PO4, PTH, 25-hydroxy vitamin D (calcifediol) ---1 CKD: 1-2 mcg PO daily or 2-4 mcg PO 3x weekly Dialysis: 2.8-7 mcg IV 3x weekly Calcimimetic: MONITORING Dialysis: 10-20 mcg PO 3 x weekly or 4 - 18 mcg IV 3x weekly I NOTES Take with food or shortly after a meal to J. GI upset (calcitriol) Calcifediol is a prod rug of calcitriol sensitivity of the calcium-sensing receptor on the parathyroid gland, which causes .J, PTH, .J, Ca, .J, P04. Clnacalcet (SensiparJ Dialysis: 30-180 mg PO daily with food Take tablet whole, do not crush or chew CONTRAINDICATIONS Hypocalcemia WARNING Caution in patients with a history of seizures SIDE EFFECTS Hypocalcemia, N/V/D, paresthesia, HA, fatigue, depression, anorexia, constipation, bone fracture, weakness, arthralgia, myalgia, limb pain, URTls MONITORING Ca, PO4, PTH Etelcalcetide (Parsabiv) Dialysis: 2.5-15 mg IV 3x weekly WARNINGS Hypocalcemia, worsening HF, GI bleeding, decreased bone turnover SIDE EFFECTS Muscle spasms, paresthesia, NN/D MONITORING Ca, PO4, PTH 299 18 I RENAL DISEASE ANEMIA OF CKD Anemia is defined as a hemoglobin level < 13 g/dL. It is common in CKD and is due to a combination of factors. The primary problem is a lack of erythropoietin (EPO), which is normally produced by the kidneys and travels to the bone marrow to stimulate the production of red blood cells (RBCs). RBCs (which contain hemoglobin) are released into the blood where they transport oxygen. As kidney function declines, EPO production decreases. This leads to reduced hemoglobin levels and symptoms of anemia (e.g., fatigue, pale skin). These processes are exacerbated by CKD, causing an inflammatory state, which contributes to decreased EPO production. Anemia of CKD is sometimes referred to as anemia of chronic disease. Erythropoiesis-stimulating agents (ESAs) can prevent the need for blood transfusions. ESAs include epoetin alfa (Procrit, Epogen, Retacrit) and the longer-lasting formulation darbepoetin alfa (Aranesp). ESAs have risks, including elevated blood p1'essure and thrombosis. They should only be used when the hemoglobin is < 10 g/dL. The dose should be held or discontinued if the hemoglobin exceeds 11 g/dL, as the risk for thromboembolic disease (DVT, PE, MI, stroke) is increased with higher hemoglobin levels. ESAs are only effective if adequate iron is available to make hemoglobin. It is important to assess an iron panel (iron, ferritin and TSAT) and provide supplementation to prevent iron deficiency. In ESRD, iron levels can be low due to reduced GI absorption and blood loss from dialysis treatments. Intravenous (IV) iron is given at the dialysis center. See the Anemia chapter for more information on identifying different types of anemia and use of ESAs and IV iron. HYPERKALEMIA A normal potassium level is 3.5 - 5 mEq/L. Hyperkalemia can be defined as a potassium level> 5.3 or> 5.5 mEq/L (ranges vary), though clinicians will be concerned with any level> 5 mEq/L. Potassium is the most abundant intracellular cation and is essential for life. Humans obtain potassium through the diet from many foods, including meats, beans and fruits. Normal daily intake through the GI tract is about 1 mEq/kg/ day. Excess intake is excreted, primarily via the kidneys and partially via the gut. Renal potassium excretion is increased by the hormone aldosterone, diuretics (loops > thiazides), 300 by a high urine flow (via osmotic diuresis) and by negatively charged ions in the distal tubule (e.g., bicarbonate). High dietary potassium intake does not typically cause hyperkalemia unless there is significant renal damage. With normal kidney function, the acute rise in potassium from a meal would be offset by the release of insulin, which causes potassium to shift into the cells. The most common cause of hyperkalemia is decreased renal excretion due to kidney failure. The risk can be increased with a high dietary potassium intake or use of drugs that interfere with potassium excretion. Patients with diabetes are at a higher risk for hyperkalemia, as insulin deficiency reduces the ability to shift potassium into the cells, and many patients with diabetes take ACE inhibitors or ARBs. Hospitalized patients are at higher risk of hyperkalemia than outpatients, primarily due to the concurrent use of drugs and IV solutions. Rarely, acute hyperkalemia can be due to tumor lysis, rhabdomyolysis or succinylcholine administration. A patient with an elevated potassium level may be asymptomatic. When symptoms are present, they can include muscle weakness, bradycardia and fatal arrhythmias. If the potassium is high or the heart rate/rhythm is abnormal, the patient is usually monitored with an ECG. The risk for severe, negative outcomes increases as the potassium level increases. I' SELECT DRUGS THAT RAISE POTASSIUM LEVELS Others: Glycopyrrolate ACE inhibitors Heparin (chronic use) Aldosterone receptor antagonists NSAIDs Aliskiren ARBs Canagliflozin Drospirenone-containing COCs Potassium-containing IV fluids (including parenteral nutrition) Potassium supplements Sulfamethoxazole/Trimethoprim Transplant drugs (cyclosporine, everolimus, tacrolimus) Pentamidine RxPREP 2022 COURSE BOOK I RxPREP ©2021, ©2022 Treatment of Hyperkalemia All potassium sources must be discontinued. If hyperkalemia is severe, there is an urgent clinical need to stabilize the myocardial cells (to prevent arrhythmias, this is done first) and to rapidly shift potassium intracellulatly or induce elimination from the body. The Study Tip Gal below lists the medication options for management of hyperkalemia. Several medications move potassium from the extracellular to the intracellular compartment. One or more of these methods are used in severe hyperkalemia. These drugs work quickly, but they do not lower total body potassium. Interventions to enhance potassium elimination can be used. These methods take longer to reduce potassium and are only used alone in less severe situations; they are mostly used in combination with a drug that shifts potassium intracellularly. MECHANISM INTERVENTION ROUTE OF ADMINISTRATION ONSET NOTES StablOze the heart Calcium gluconate IV 1-2 minutes Does not decrease potassium. Stabilizes myocardial cells to prevent arrhythmias. Regular insulin IV 30 minutes Co-administered with glucose or dextrose to prevent hypoglycemia. Move It Dextrose IV Shift K intracellularly Stimulates insulin secretion, but does not shift K intra cellularly on its own. Sodium bicarbonate IV Used when metabolic acidosis is present. Albuterol Nebulized Monitor for tachycardia and chest pain. Furosemlde IV 5 minutes I Eliminates Kin the urine. Sodium polystyrene sultanate Oral or rectal 1 hour; do Binds K in the 61 tract. Prevent arrhythmias I -- Monitor volume status. Remove It Ellminate K from the body not use oral for acute emergencies L_ I Patlromer Oral -7 hours Oral may take hours to days to work. Rectal route has a faster onset and can be used in acute (emergency) treatment. Binds Kin the GI tract. Not for acute or emergency use due to delayed onset. I Sodium zirconium cyclosilicate IHemodlalysls Oral 1 hour Binds Kin the GI tract. I Not for acute or emergency use due to delayed onset. Immediate, o ce starte· n d Removes K from the blood. I It takes several hours to set up/complete d1alys1s. . . Other methods are generally used in conjunction. 301 18 I RENAL DISEASE Drugs for Treatment of Hyperkalemia DRUG DOSE SAFETY/SIDE EFFECTS/MONITORING Sodium polystyrene sulfonate (SPS, Kayexalate•, Kionex) Oral: 15 grams 1-4 times/day WARNINGS Rectal: 30-50 grams Q6H ---------- Electrolyte disturbances (hypernatremia, hypokalemia, hypomagnesemia, hypocalcemia), fecal impaction, GI necrosis (i risk when administered with sorbitol; do not use together) Can bind other or!lf medications (check for drug interactions and separate administration) Powder, oral suspension, rectal suspensi on SIDE EFFECTS N/V, constipation or diarrhea Non-absorbed cation exchange resin MONITORING K, Mg, Na, Ca NOTES Do not mix oral products with fruit juices containing K Patiromer (Veltassa) Powder for oral suspension Non-absorbed cation exchange polymer 8.4 grams PO once daily; max dose is 25.2 grams once daily WARNINGS Instructions: measure 1/3 cup of water and pour half into an empty cup; empty the Veltassa packet contents into the water and stir well; add the remaining water to the mixture and stir well (the mixture will be cloudy); drink the mixture right away (if powder remains in the cup, add additional water and drink; repeat as needed) Binds to many oral drugs; separate by at least 3 hours before or 3 hours after Can worsen GI motility, hypomagnesemia SIDE EFFECTS Constipation, nausea, diarrhea MONITORING K,Mg NOTES Delayed onset of action; not for emergency use Store powder in the refrigerator (must be used within 3 months if stored at room temperature) Sodium zirconium cyclosilicate (Lokelma) Powder for oral suspension Non-absorbed cation exchange polymer 10 g PO TID for up to 48 hours Instructions: empty packet contents into a cup with at least 3 tablespoons of water; stir well and drink immediately (if powder remains in t he cup, add additional water and drink; repeat as needed) WARNINGS Can worsen GI motility, edema, contains sodium (may need to adjust dietary sodium intake) Can bind other drugs; separate by at least 2 hours before or 2 hours after SIDE EFFECTS Peripheral edema NOTES Delayed onset of action; not for em rgency use Store at room temperature 'Brand discontinued but name still used in practice. METABOLIC ACIDOSIS The ability of the kidney to reabsorb bicarbonate decreases as CKD progresses. This can result in the development of metabolic acidosis. In the ambulatory care setting, treatment of metabolic acidosis is initiated when the serum bicarbonate concentration is < 22 mEq/L. Drugs to replace bicarbonate include: Sodium bicarbonate (Neut) o Sodium load can cause fluid retention. o Monitor sodium level and use caution in patients with hypertension or cardiovascular disease. Sodium citrate/citric acid solution (Cytra-2, Oracit, Shohl's solution) o Monitor sodium level. o Metabolized to bicarbonate by the liver; may not be effective in patients with liver failure. 302 RxPREP 2022 COURSE BOOK I RxPREP ©2021, ©2022 DIALYSIS If CKD progresses to failure (stage 5 disease), dialysis is required in all patients who do not receive a kidney transplant. The two primary types of dialysis are hemodialysis (HD) and peritoneal dialysis (PD). In HD, the patient's blood is pumped to the dialyzer (dialysis machine) and runs through a semipermeable dialysis filter, which, using a concentration gradient, removes waste products, electrolytes and excess fluid. HD is a 3 - 4 hour process, several times per week (usually three times). Patients who do HD at home can do it more frequently (e.g., 5- 6 times per week). In PD, a dialysis solution (usually containing glucose) is pumped into the peritoneal cavity (the abdominal cavity surrounding the internal organs). The peritoneal membrane acts as the semipermeable membrane (i.e., as the dialyzer). The solution is left in the abdomen to "dwell" for a period of time, then is drained. This cycle is repeated throughout the day, every day. PD is performed by the patient at home. [Qi khawfangenvi16/5hutterstock.com FACTORS AFFECTING DRUG REMOVAL DURING DIALYSIS When a patient receives dialysis, the pharmacist must consider the amount of medication cleared during dialysis in order to recommend the correct dose and interval. Medications that are removed during dialysis (including many antibiotics) must be given after dialysis or may require a supplemental dose following dialysis. Drug removal during dialysis depends primarily on the factors below. FACTOR EFFECT Drug Characteristic Molecular weight/size Smaller molecules are more readily removed by dialysis Volume of distribution Drugs with a large Vd are less likely to be removed by dialysis Protein-binding Highly protein-bound drugs are less likely to be removed by dialysis Dialysis Factors Membrane High-flux (large pore size) and high-efficiency (large surface area) HD filters remove more substances than conventional/low-flux filters Blood flow rate Higher dialysis blood flow rates increase drug removal over a given time interval Select Guidelines/References Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int., Suppl. 2013;3:1-150. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. 2021;99(35):51-587. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2020;98(45):51-5115. 303