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Chronic Kidney Disease
Medication review Warren Prokopiw Pharmacy Resident Chronic Kidney Disease
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Outline Case intro Renal failure issues Application to case Questions
Hypertension, lipids, glucose, anemia Renal bone disease, potassium, acid-base GI Disorders, nutrition, puritis, gout Nervous system disorders Application to case Questions
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Meet Mr Smith 80 year old gentleman with chronic renal failure eGFR = 20 Managed at renal clinic Previous medical history DM 2 x 15 years hypertension osteoarthritis glaucoma psoriasis gout
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Current medication list
Enalapril 5 mg po Daily Insulin (Glargine and lipsro Triferrex 300 mg po QHS Allopurinol 300 mg po Daily Zopiclone 7.5 mg po QHS Alendronate 70 mg q2weekly Rabeprazole 20 mg po Daily Docusate sodium 200 mg po BID Tylenol #3 1-2 po QID PRN Domperidone 10 mg TID AC & 20 mg po QHS Sennosides 8.6 mg po HS PRN Nitroglycerin 0.6 mg/hr patch on at 08/ off 2000H Furosemide 20 mg po BID Lactulose 15 mL BID PRN Clonidine 0.1 mg po Daily Calcium Carbonate (Tums) 2 ac meals, 1 ac snacks Replavite 1 tab po Daily Sidenafil 1 tab PRN Sevelamer 800 mg po TID AC meals Zinc 50 mg po Daily Mirtazepine 15 mg po daily Atorvastatin 20 mg po QHS Alfacalcidol 1 mcg po “TIW” Cosopt drops 1 drop each eye daily Felodipine 5 mg po Daily Darbopoeitin 40 mcg SC Q2W Bimatopost Drops 1 drop each eye at bedtime Why is he on all these meds?
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Hypertension Common association – 75% of patients
Cause and consequence of CKD Target is 130/80 – slow decline to target Medications ACEI/ARB and CCB Diuretics - loop, thiazide, combination Beta blockers (pts < 60) Second or third line agents Nitroglycerin, hydralazine, clonidine, Rapid falls to normotensive levels may be acutely bad to renal function. Achieve target slowly to allow adaptation to reduced perfusion pressures Diuretics help with water balance ACEI/ARBs and CCBs help preserve renal fucntion NTG – venodilator, hydralazine – vasodilator, clonidine – central alpha agonist
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Hyperlipidemia High prevalence in CKD patients
Major risk factor for progression of disease Targets LDL < 2.0; TC/HDL ratio < TG < 10 Medications Statins for high LDL/low HDL Gemfibrozil or nicacin for elevated TG With protienuria, the kidney body is losing its oncotic pressure – it compensates by producing higher VLDL in the liver giving rise to high cholesterol
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Diabetes Risk factor for CKD and cardiovascular events
Tight control reduces diabetic nephropathy HbA1C < 7.0% Fasting glucose 4-7 mmol/L Medications Gliclazide over glyburide Avoid metformin when GFR < 30 ml/min Part of multifactorial strategy promoting BP control and CV risk
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Anemia Due to erythropoetin deficiency
Target 110 g/L – start if Hg < 100 g/L Medications Erythropoetin and darbepoetin Takes 64 days to reach new steady state Reassess dose in 4 weeks Require adequate iron, folic acid and B12 stores for synthesis Darbepoetin is the newer erythroposis stimulating agent – has longer half life than erythropoetin Is given SUBCUT and allows for once weekly or even every second week dosing Erythropoetin can be given SC or IV, usually three times weekly – IV when on HD as have venous access 64 days as opposed to 120 – loss due to uremia
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Iron Supplements Targets - Tsat > 20% Ferretin > 100 ng/ml.
Oral - preferred ferrous fumarate ferrous gluconae ferrous sulfate IV – when patients fail/not tolerate oral iron gluconate iron sucrose iron dextran Triferrex is a polysaccharide ion complex that designed to slowly release iron – I sexpsnive an not tolerated any differently than thy usual mes listed.
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Renal Bone Disease Reduced renal function → PO4 retention
Elevated PO4 → lowered Ca++ → less activation of Vit D → less Ca++ absorption → direct binding PO4 to Ca++ in blood Parathyroid gland stimulated ↑ renal Ca++ and PO4 reabsorption ↑ Ca++ mobilization from bone
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RBD Prevention Goal – keep in normal range Dietary PO4 restriction
PO mmol/L, Ca mmol/L Dietary PO4 restriction PO4 Binder if no hypercalcemia Calcium carbonate, calcium acetate, aluminum hydroxide, sevelamer, lanthanum, cinacalet Ca++ supplement if hypocalcemic Po4 binders taken just before meals as opposed to Ca++ supplements are taken between meals Ca acetate binds 4x the PO4 than carbonate, but more costly AL OH use can lead to aluminum toxicity - bone disease, encephalopathy, epo resistance Sevelamer is a medical grade plastic – non Ca++ binder – costly Lanthanum another costly PO4 binder Cinacalet is a calcium mimic that binds to the PTH calcium receptors and lovers PTH production - $10 per pill
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RBD Prevention Vitamin D supplement if PTH > 53 pmol/L
Alfacalcidol, calcitriol Used TIW pluse therapy Reduce Ca++ and Vit D if hypercalcemia Cholecalciferol, (sometimes called calciol) is an inactive, unhydroxylated form of vitamin D3) 25 OH added in liver – 1 OH added in kidney 1 alpha is activated (has 1-OH) – still must be activated in the liver with 25 OH – is cheaper than calcitriol Calcitriol is fully activated thus useful in patients with liver disease Pulse therapy inhibits PTH production and minimizes PO4 and Ca++ gut absorption
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Hyperlakemia Potassium usually 90% renally eliminated
In CRF, the DCT compensates with increased secretion Aldosterone plays and important role Further decrease in renal function Increased secretion by the colon Management Dietary potassium restriction – avoid constipation Monitor if on ACEI, avoid K+ sparing diuretics Sodium polystyrene sulfonate dialysis Distal convoluted tubule – pts at high risk for hyperkalemia – usual miss a dialysis session – land in emerg. Kayexalate is a sodium – potassium exchange resin that binds K+ in the colon It can be used between dialysis sessions if necessary
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Acid Base Renal PO4 excretion provides buffer for elimination of H+ ions ↓ PO4 excretion → metabolic acidoisis Medication Sodium bicarbonate Sodium citrate Monitor water balance due to sodium content
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GI Disorders Most CDK patients are diabetic Taking high calcium loads
Diabetic gastopariesis Taking high calcium loads Constipation Medications Prokinetics Domperidone and metoclopramide Laxatives Docusate sodium, Senna, Lactulose AVOID Fleet enemas and Fruitlax Dopamine and metoclopramide are dopamine and serotonin antagonists metoclopramide enters CNS – hdeps with nausea on the CTZ Fleet are high in sodium and PO4, Fruitlax is high in potassium
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Nutritional Deficiencies
Dialysis removes water soluble vitamins and zinc Deficient in vitamin B1, B2, B6, B12, niacin, pantothenic acid, niacinamide, folic acid and vitamin C Medication Replavite Zinc Supplement
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Puritis Occurs in up to 86% of dialysis patients Cause unknown
Dry skin, hyper PTH, increased Vit A and histamine Medications Hydroxyzine Diphenhydramine 10% uremol in glaxal base
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Gout Renal failure leads to hyperuricemia
Diuretics used for volume overload compound problem Medications Allopurinol – prevention Colchicine – short term treatment prednisone
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Nervous System Disorders
Affect 50% of patients with EDRD uremic polyneuropathy is axonal in nature Restless legs syndrome Occurs in 50% of ESRD patients due to uremia Medictions sinemet, clonidine, clonazepam The restless leg syndrome refers to a persistent and extremely uncomfortable sensation in the lower extremities that can only be relieved by movement of the legs. Sinemet - Can be used prn – up to 80% get worsening of RLS symptoms in the course of therapy. Symptoms may be more severe and start earlier in the day (e.g., afternoon rather than evening) than before treatment began and may spread to different parts of the body Clondine – good double bang in hypertensive patients Clonazepam - Helpful in some patients when other medications are not tolerated
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Nervous System Disorders
Leg cramps May occur during dialysis Associated with large volume draws Medication Quinine Neuropathic pain Typical pain agents Desipramine, nortryptyline, carbamazepine, gabapentin FDA warning that quiine use can lead to thrombocytopenia, which can cause serious bleeding, or hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura, which may lead to permanent kidney damage… you are already there. TCAs affect NE and SE in the pain transmission gateway up to CNS
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Current medication list
Enalapril 5 mg po Daily Insulin (Glargine and lipsro Triferrex 300 mg po QHS Allopurinol 300 mg po Daily Zopiclone 7.5 mg po QHS Alendronate 70 mg q2weekly Rabeprazole 20 mg po Daily Docusate sodium 200 mg po BID Tylenol #3 1-2 po QID PRN Domperidone 10 mg TID AC & 20 mg po QHS Sennosides 8.6 mg po HS PRN Nitroglycerin 0.6 mg/hr patch on at 08/ off 2000H Furosemide 20 mg po BID Lactulose 15 mL BID PRN Clonidine 0.1 mg po Daily Calcium Carbonate (Tums) 2 ac meals, 1 ac snacks Replavite 1 tab po Daily Sidenafil 1 tab PRN Sevelamer 800 mg po TID AC meals Zinc 50 mg po Daily Mirtazepine 15 mg po daily Atorvastatin 20 mg po QHS Alfacalcidol 1 mcg po “TIW” Cosopt drops 1 drop each eye daily Felodipine 5 mg po Daily Darbopoeitin 40 mcg SC Q2W Bimatopost Drops 1 drop each eye at bedtime Work the solution Ca carbonate and Sevelamer – commonly done – max out tums use due to low cost, and then add sevelamer titrate to PO4 load Triferrex – expsnive – can do just as well with ferrous gluconate Alendronate – CI in poor renal function – renla bone loss is a difffernt process than osteoporosis Sildenafil – lifestyle – DI with NTG – one has to go
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Can J Hosp Pharm. 2009 May-Jun; 62(3): 244
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Questions
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