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Therapeutics #3 - Renal 2 - CKD
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64
Pharmacology
10/31/2009

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Term
Chronic Kidney Disease (CKD)
Definition
kidney damage and/or decreased GFR lasting > or = 3 months; GFR < 60 mL/min/1.73 m^2; most commonly causes cardiovascular disease (most common cause of death)
Term
Initiating Factors of CKD
Definition
DM; HPN; glomerulonephritis; polycystic kidney disease; we can target to prevent these from occurring
Term
Progression Factors of CKD
Definition
proteinuria; HPN; hyperglycemia; smoking; obesity; anemia; targets of therapy in pts with the disease
Term
Drug-induced CKD
Definition
caused by cyclosporine & tacrolimus; analgesics containing APAP, caffeine, or codeine; lithium (acute intoxication)
Term
Symptoms of Stage 3 and higher CKD
Definition
cold intolerance, shortness of breath, palpitations, muscle cramping, depression, anxiety, fatigue, sexual dysfunction
Term
Signs of Stage 3 or higher CKD
Definition
edema, worsening HPN, left ventricular hypertrophy, GERD, weight loss, hyperparathyroidism, decreased vitamin D activation, Ca & PO4 disorders, gout, anemia, bleeding, hyper- or hyponatremia, hyperkalemia, metabolic acidosis
Term
Stage 1 CKD
Definition
kidney damage, GFR is normal (> or = to 90 mL/min/1.73 m^2)
Term
Stage 2 CKD
Definition
kidney damage, mild decrease in GFR (60 - 89 mL/min/1.73 m^2)
Term
Stage 3 CKD
Definition
moderate decrease in GFR (20 - 59 mL/min/1.73 m^2)
Term
Stage 4 CKD
Definition
severe decrease in GFR (15 - 29 mL/min/1.73 m^2)
Term
Stage 5 CKD (ESRD - end-stage renal disease)
Definition
kidney failure (GFR < 15 or on dialysis)
Term
Goal of Managing CKD
Definition
delay progression of ESRD: control risk factors --> initiate disease-modifying therapies; avoid/minimize exposure to nephrotoxic agents
Term
Antihypertensive Therapy to Manage CKD
Definition
modifying effect: reduces BP, some reduce proteinuria; GOAL BP: <130/80 mmHg; Primary Treatment: use ACEIs or ARBS, possibly in combination; 2nd line therapy: ACEIs + ARBs in combo, Ca Channel Blockers, or Beta-blockers; Non-pharmacologic Therapy: dietary protein restriction to 0.6-0.75 g/kg/day
Term
Proposed Mechanisms for Hemodynamic Benefits of ACEIs or ARBs in treatment of CKD
Definition
decreased angiotensin II; vasodilation of efferent arterioles; decreased systemic BP; decreased capillary pressure
Term
Proposed Mechanisms for Non-hemodynamic Benefits of ACEIs or ARBs in treatment of CKD
Definition
decreased angiotensin II; decreased transforming growth factor B; renal blood flow maintained; slowed progression to proteinuria
Term
ACEIs in AntiHPNive therapy for CKD
Definition
all have reduced clearance in renal insufficiency; start at lower doses in moderate-severe renal impairment or low BP; ADRs: acute worsening of renal function, hyperkalemia; Monitor: SCr (a rise >30% over 24-48 hrs --> d/c drug), serum K (cause increase), BP
Term
Combination Therapy: ACEIs + ARBs
Definition
emerging therapeutic choice for AntiHPNsive treatment of CKD; may reduce proteinuria beyond max doses of each agent alone
Term
Ca Channel Blockers & Beta-blockers
Definition
2ndary antiHPNsive therapy for CKD; decreases BP; may decrease severity of proteinuria
Term
Other Pharmacologic Therapies for antiHPNsive treatment of CKD
Definition
treat hyperlipidemia, anemia, smoking cessation, & blood glucose control
Term
Fluid & Electrolyte Imbalances found in CKD
Definition
hyperkalemia; hyperphosphatemia; hypocalcemia; nocturia (decreased abiility to concentrate urine); fluid retention (edema or systemic HPN)
Term
Hyperkalemia
Definition
complication of CKD; occurs in later stages (3 or 4) of CKD; ESRD pt can tolerate K levels on higher end of normal; adverse effect of ACEI/ARB therapy
Term
Fluid Retention
Definition
complication of CKD which usually occurs during later stages; may present as edema or systemic HPN; Diuretic Therapy Goal: maintain hemodynamic stability while maintaining normal serum Na; use thiazide or loop diuretics, carbonic anhydrase inhibitors, or K-sparing diuretics
Term
Thiazide Diuretics (HCTZ, metolazone)
Definition
used to treat fluid retention in CKD; not effective at CrCl <30 mL/min; may be useful in combination with loop diuretics in pts with diuretic resistance;
Term
Loop Diuretics (furosemide)
Definition
used to treat fluid retention in CKD; useful for controlling HPn in pts with renal insufficiency; useful for treating edema associated with renal failure
Term
Carbonic Anhydrase Inhibitors (acetazolamide)
Definition
used to treat fluid retention in CKD; MoA: inhibits Na reabsorption in proximal tubule by inhibiting carbonic anhydrase; useful for treatment of edema refractory to other diuretics in pts with renal failure; Caution: may cause metabolic acidosis
Term
K+-sparing Diuretics (spiranolactone, triamterene, amiloride)
Definition
used as add-on therapy for treatment of fluid retention in CKD; aldosterone antagonists; C/I in pts already on high range of normal for K
Term
ADRs of Acetazolamide
Definition
hypOkalemia; ACIDOSIS
Term
ADRs of Thiazides
Definition
hypOkalemia; ALKALOSIS
Term
ADRs of Loop Diuretics
Definition
hypOkalemia; ALKALOSIS
Term
ADRs of K+-sparing Diuretics
Definition
HYPERkalemia; ACIDOSIS
Term
Bone Metabolism Disorder & Hyperparathyroidism in CKD
Definition
decreased renal excretion of PO4 --> hyperphosphatemia --> + increase PTH --> normally increases excretion of PO4 but doesn't do to CKD --> Ca-PO4 may precipitate in tissues/blood causing vascular calcification; decreased renal excretion of phosphorus --> hyperphosphatemia --> inhibits activation of Vitamin D3 --> hypocalcemia --> increased PTH --> hyperparathyroidism; may occur as early as Stage 3; leads to renal osteodystrophy
Term
Non-pharmacological Therapy of Hyperparathyroidism & Bone Metabolism Disorder
Definition
dietary restriction of PO4 (DON'T eat/drink beer, dark sodas, meat, beans, dairy); parathyroidectomy (last-line)
Term
Initiate Therapy Based on Biochemical Markers when Hyperparathyroidism is cause
Definition
hyperphosphatemia or hypocalcemia; PTH > 495 pg/dL; Ca x PO4 > 55
Term
Target Ranges of Biochemical Markers in CKD with Hyperparathyroidism
Definition
Stage 3: corrected Ca - normal, PO4 - 2.7-4.6, Ca x P product - <55; Stage 4: corrected Ca - normal, PO4 - 2.7-4.6, Ca x P product - < 55; Stage 5: corrected Ca - normal or slightly lower, PO4 - 3.5-5.5, Ca x PO4 < 55
Term
Treatment Therapy for Hyperparathyroidism in CKD
Definition
phosphate binders (calcium salts & non-Ca phosphate binders); vitamin D therapy; active vitamin D3 used in stage 5; calcimimetics
Term
Phosphate Binders
Definition
used to treat hyperparathyroidism & bone metabolism disorder in CKD; MoA: binds dietary PO4 and lowers serum PO4 concentration; Ca salts & non-Ca binders
Term
Caclium Salts
Definition
1st line therapy used to treat hypocalcemia in hyperparathyroidism & bone metabolic disorder in CKD; inexpensive; ADRs: constipation, hypercalcemia, drug-drug interactions; Ex: CaCarbonate (TUMS) & CaAcetate (PhosLo)
Term
Non-calcium Phosphate Binders (sevelamer (Renagel, Renvela), lanthanum (Fosrenol))
Definition
used in treatment of hyperparathyroidism & bone metabolism disorder when Ca salts are ineffective or pts are in HYPERcalcemia; sevelamer HCl (Renagel), carbonate (Renvela); lanthanum (Fosrenol)
Term
Vitamin D Therapy
Definition
used in stages 3, 4, & 5 of CKD; check PTH levels; if PTH is elevated, check vitamin D levels; when PTH remains elevated despite adequate 25-hydroxyvitamin D levels, therapy should be initiated; use ergocalciferol or active Vitamin D3 proucts (calcitriol, paricalcitol, doxercalciferol)
Term
Active Vitamin D products
Definition
used in Stage 5 CKD; final activation of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D3 is impaired; dosing based on PTH concentration; use calcitriol (Rocaltrol), paricalcitol (Zemplar), doxercalciferol (Hectorol)
Term
Calcimimetics (cincalcet [Sensipar])
Definition
used for 2ndary hyperparathyroidism with or without vitamin D therapy or phosphate binders; increases sensitivity of Ca-sensing receptor on parathyroid gland --> decreases PTH release; DO NOT USE if corrected Ca < 8.4 mg/dL; ADRs: hypocalcemia, nausea, vomiting
Term
Treatment of Hyperlipidemia in CKD
Definition
at high risk for developing atherosclerotic CVD - major cause of mortality in pts with CKD; goal LDL: < 100 mg/dL
Term
Treatment of Metabolic Acidosis in CKD
Definition
kidneys unable to excrete H+ in later stages of CKD; mild form usually does not need treatment if pt is asymptomatic; SAG acidosis is usually present; treat with bicarb in IV fluids or altering dialysis fluids
Term
Treatment of Anemia in CKD
Definition
most of body's erythropoietin (90%) produced by kidneys; production decreased in CKD --> anemia --> activates RAAS; treatment: synthetic erythropoietic agents (epoetin [Epogen, Procrit], darbepoetin [Aranesp]); iron supplementation (TSAT% must = 20%, IV therapy with dialysis); target Hgb: 11-12 g/dL
Term
TSAT%
Definition
[serum Fe/total Fe binding capacity (TIBC)]*100
Term
Adjusting Drug Regimens in Reduced Renal Function
Definition
1) Obtain relevant hx including hx of renal disease; 2) estimate CrCl; 3) review current meds & identify ones to be adjusted; 4) Individualize regimen by considering dose adjustment recommendations & pharmcokinitic info of each drug; 5) monitor for drug response, toxicity, & blood levels; 6) Revise regimen based on drug response or changes in renal fcn
Term
Indications for Renal Replacement Therapy (RRT)
Definition
CKD: CrCl = 10 mL/min, uncontrolled BP or HF, neurologic deficits; AKI: acidosis electrolyte imbalances, intoxication, overload, uremia, critical illness with hemodynamic instability, sepsis (AEIOU)
Term
Advantages & Disadvantages of Hemodialysis
Definition
A's: technique failure is low, closer monitoring of pt, better defined efficacy parameters; D's: multiple visits per week, hypotension, muscle cramps, higher risk of infection, vascular access compromised, residual renal fcn declines more quickly
Term
Advantages & Disadvantages of Peritoneal Dialysis
Definition
A's: more hemodynamic stability, better preservation of residual renal fcn, pt is more ambulatory, no heparinization needed, convenient route of administration of some drugs; D's: reduced appetite, risk of peritonitis, high rate of technique failure, non-compliance, risk of obesity, protein & amino acid losses through peritoneum, catheter malfunction
Term
Hemodialysis
Definition
blood is taken from arterial system & pushed through a dialyzer; dialyzer consists of semipermeable membrane that allows for removal of substances like water, urea, Cr, uremic toxins, & drugs; removal of these substances facilitated by dialysate; dialysate = liquid that contains differing conc. of solutes normally found in blood; removal of substances occurs by passive diffusion or ultrafiltration, heparin flushes used to keep blood from clotting during process
Term
Vascular Access for HD to be performed
Definition
1st choice: arteriovenous (AV) fistula - surgical connection of artery to a vein allowing for vein to grow thicker so repeated penetration can occur; 2nd choice: arteriovenous (AV) graft - surgical placement of plastic tube between artery & a vein allowing for puncture at tube site rather than vein; 3rd choice: venous catheter - temporary only, greater risk for thrombosis & infections
Term
Methods of HD
Definition
IHD: intermittent hemodialysis; SLED/EDD: slow low efficiency dialysis/extended daily dialysis; CVVH: continuous venovenous hemofiltration; CVVHD: continuous venovenous hemodialysis; CVVHDF: continuous venovenous hemodiafiltration; SCUF: slow continuous ultrafiltration
Term
Conventional Membranes
Definition
in dialyzer, small pore holes limiting removal to smaller molecules
Term
High-efficiency membranes
Definition
in dialyzer, larger surface area allowing more removal of water, urea, & small molecules; allows for shorter dialysis times
Term
High-flux membranes
Definition
in dialyzer, larger pore holes allowing for removal of larger molecules (certain drugs & proteins); allows for shorter dialysis times
Term
Goals of HD
Definition
achieve "dry weight" (euvolemia); removal of endogenous waste products
Term
Peritoneal Dialysis
Definition
pt's peritoneum acts as dialyzer membrane; dialysate dwells within peritoneal cavity for period of time; methods: CAPD & APD
Term
Peritoneal Dialysis
Definition
pt's peritoneum acts as dialyzer membrane; dialysate dwells within peritoneal cavity for period of time; methods: CAPD & APD
Term
CAPD (continous ambulatory peritoneal dialysis)
Definition
dialysate instilled by gravity; three dwell during day (4-6 hrs each) + overnight dwell (8-10 hrs); once dwell time is over, dialysate is drained & reinstilled
Term
APD (automated peritoneal dialysis)
Definition
dialysate instilled by machine; occurs overnight; once dwell time is over, dialysate is drained & reinstilled
Term
Complications of HD
Definition
hypotension & muscle cramps (most common), nausea/vomiting, HA, chest & back pain, pruritus, fever/chills; thrombosis of access site - more common in fistulas or grafts, saline flushes used initially, use thrombolytics (alteplase); infections (Gram + skin bacteria); dialyzer reactions (anaphylactic or due to complement activation [fever & chills])
Term
Complicatoins of PD
Definition
anorexia, diabetes, cardiovascular disease, peritonitis
Term
Pharmacotherapy Considerations when on HD or PD
Definition
dosing is typically NOT based on CrCl or GFR (drug info); drug characteristics determine removal by dialysis; if <30% of drug is cleared by kidneys then dose adjustment is UNNECESSARY; replace drugs that are cleard by dialysis AFTER dialysis
Term
Nutrition Considerations with HD
Definition
albumin, B vitamins, trace elements (Zn, Se, Mn, Cd, CHr)