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Unit 4 ©2014 Barkley & AssociatesUnit 4 ©2014 Barkley & Associates

Advanced PharmacologyRenal Agents

Thomas W. Barkley, Jr., PhD, ACNP‐BC, FAANPPresident, Barkley & Associates

www.NPcourses.comand

Professor of NursingDirector of Nurse Practitioner ProgramsCalifornia State University, Los Angeles

Robert Fellin, PharmD, BCPSFaculty, Barkley & Associates

Pharmacist, Cedars‐Sinai Medical CenterLos Angeles, CA


The Kidneys Kidneys: primary organs for regulating fluid balance, electrolyte composition and acid-base

balance

Secrete renin, which helps regulate BP

Release erythropoietin, a hormone that stimulates RBC production

Produce calcitriol, the active form of vitamin D, which helps maintain bone homeostasis

Each kidney contains ~ 1 million nephrons

Blood is filtered through the glomerulus

Water and other small molecules readily pass through the glomerulus and enter Bowman’s capsule (the first section of the nephron) and then the proximal tubule

Once in the nephron, the fluid is called filtrate

After leaving the proximal tubule, the filtrate passes through the Loop of Henle and subsequently, the distal tubule

Nephrons empty their infiltrate into collecting ducts and then, into larger structures in the kidney

Fluid leaving the collecting ducts and entering subsequent parts of the kidney is called urine

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Anatomy of the Nephron

http://www.as.miami.edu/chemistry/2086/chap26/chapter%2026-new_part1.htm


Renal Reabsorption, Secretion and Failure As filtrate passes through the nephron, its composition changes

Some substances cross the walls of the nephron to reenter the blood (tubular reabsorption)

GFR: The best marker for estimating kidney function; volume of water filtered through Bowman’s capsule per minute

Excellent compensatory mechanisms with nephrons, so > 50% damage results in a fall in GFR to less than one-half its normal value

More than ½ of all patients with chronic renal failure occur in patients with long standing HTN or diabetes

Kidneys are the primary route of elimination of most drugs or their metabolites

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Functions of the Nephron: Summary

http://www.as.miami.edu/chemistry/2086/chap26/chapter%2026-new_part1.htm


Management of Renal Disease Pharmacologic:

Volume overloadSodium and water hemostasis

Electrolyte disturbancesPotassium and magnesium homeostasis

Mineral and bone disordersCalcium and phosphorous hemostasis

Acid-Base imbalances Anemia Dose adjust/remove/avoid nephrotoxic agents Manage comorbid conditionsHTN, hyperlipidemia, DM

Nonpharmacologic: Renal replacement therapy: (HD, PD, CVVHD) Transplant

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Diuretics: Mechanisms of ActionMost commonly, block Na+ reabsorption in the nephron, thus sending

more Na+ to the urine

Chloride ions follow Na+

Because H2O also travels with Na+, blocking the reabsorption of Na+ will increase the volume of urination/diuresis

May affect the renal excretion of other ions, including Mg, K, phosphate, Ca and HCO3


Carbonic Anhydrase InhibitorsAgents: Acetazolamide (Diamox), methazolamide (Neptazane)

Site of action: Proximal convoluted tubule; blunt sodium bicarbonate reabsorption

Adverse Effects:

Hyperchloremic metabolic acidosis, renal stones, hypokalemia, drowsiness, paresthesias

Comments: Rarely used as diureticsOther applications: glaucoma, urinary alkalinization, metabolic alkalosis, acute mountain sicknessContraindication: hyperammonemia, hepatic encephalopathy

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Loop DiureticsAgents: Bumetanide (Bumex), ethacrynic acid (Edecrin),

furosemide (Lasix), torsemide (Demadex)

Site of action: Block sodium absorption at the ascending Loop of Henle

Adverse Effects:

Electrolyte disturbances, dehydration, thirst, dry mouth, weight loss, headache, hypotension, hyperuricemia, hypercalcemia, ototoxicity (rare)

Comments: Most effective diuretics

May induce urine output even when blood flow to the kidneys is diminished

Overuse: hypokalemic metabolic alkalosis

Sulfa allergy (anaphylaxis): use ethacrynic acid


Thiazide/Thiazide-Like DiureticsAgents: Chlorothiazide (Diuril), chlorthalidone (Thalitone),

hydrochlorothiazide (Microzide), indapamide (Lozol), metolazone (Zaroxolyn)

Site of action: Block sodium absorption at the distal tubule

Adverse Effects:

Electrolyte disturbances, dehydration, thirst, dry mouth, weight loss, headache, hyperglycemia, ototoxicity (rare)

Comments: Primary use: HTNLess efficacious than loop diureticsNot effective in severe renal impairmentIn certain situations may combine with loop diuretic to provide synergistic diuresisChlorothiazide: only parenteral thiazide available

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Potassium-Sparing DiureticsAgents: Amiloride (Midamor), triamterene (Dyrenium),

eplerenone* (Inspra), spironolactone* (Aldactone)

Site of action: Reduce sodium absorption in the collecting tubules and ducts; aldosterone antagonist

Adverse Effects: Gynecomastia (spironolactone), hyperkalemia

Comments: Least effective diureticsMost commonly used in combination with other diuretics to reduce potassium lossCaution use in renal impairment or pre-existing hyperkalemiaOveruse: hyperchloremic metabolic acidosis


Osmotic DiureticsAgents: Mannitol (Osmitrol)

Site of action: Proximal tubule and descending limb of Henle's loop

Adverse Effects:

Expansion of extracellular volume, electrolyte disturbances, dehydration, headache, nausea, vomiting

Comments: Other applications: increased ICP, HD (?)

Not an agent of first choice

Rarely used as diuretic

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Vasopressin AntagonistsAgents: Conivaptan (Vaprisol), tolvaptan (Samsca)

Site of action: Inhibit the effects of ADH in the collecting tubule

Adverse Effects:

Dry mouth, thirst, hypernatremia, hypotension

Comments: Applications: SIADH, hyponatremia

Conivaptan: available as IV only; max dose: 40 mg; max duration 4 days; do not use in severe renal impairment

Tolvaptan: avoid in severe renal impairment


Renal Agents: Sites of Action

http://accessmedicine.mhmedical.com.mlprox.csmc.edu/content.aspx?bookid=388&sectionid=45764235

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Sodium ImbalancesNormal Range: 135-145 mEq/L

Hypo Na:

Hyper Na:

Fluid restriction, 0.9% saline, 3% saline, conivaptan, tolvaptan

diuretics, hydration

Comments: Determine and treat underlying causeAssess osmolalityAssess fluid statusCalculate total Na deficitMaximum rate of correction: 8-12 mEq/24 hoursMonitor Na levels q2h during correctionMany medications implicated as the cause


Potassium ImbalancesNormal Range: 3.5-5.0 mEq/L

Hypo K:Hyper K:

KCl, Kphosphate, Kacetatesodium polystyrene sulfonate (Kayexalate), HD

Comments: Determine and treat underlying causePrimary concern: life threatening arrhythmiasCheck for ECG changesCheck serum Mg level; replete if necessaryHypomagnesemia can cause refractory hypokalemiaMax rate: 10 mEq/hour**Max Conc: 10 mEq/50 mL**Oral repletion: no more than 40 mEq at onceMonitor potassium level q2-4 hours or after each 80 mEq

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Magnesium ImbalancesNormal Range: 1.5-2.5 mEq/L

Hypo Mg:Hyper Mg:

Magnesium sulfate, magnesium oxidediuretics, HD, calcium chloride

Comments: Determine and treat underlying causePrimary concern: life threatening arrhythmiasCheck for ECG changesMax rate: 1 gram (8 mEq)/hour**Max Conc: 1 gram/50-100 mL**Hypomagnesemia can cause refractory hypokalemia


Calcium ImbalancesNormal Range: 8.5-10.5 mEq/L (iCa: 1.12-1.30 mmol/L)

Hypo Ca:Hyper Ca:

Calcium gluconate, calcium chloride, othershydration, loop diuretics, bisphosphonates

Comments: Regulated by parathyroid hormone, vitamin D, and calcitonin99% of total body Ca found in bones, less than 1% in the serum40-50% of Ca in the blood is bound to albuminMust correct for hypoalbuminemiaFree or ionized Ca level may be more reliableMax rate: 1 gram (4.65 mEq)/hour**Max Conc: 1 gram/50-100 mL**Preferred agent: Ca gluconateCa chloride used for emergent situations

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Phosphorus ImbalancesNormal Range: 2.5-4.5 mg/dL

Hypo Phos:Hyper Phos:

Na phosphate, K phosphatehydration, oral phosphate binders, HD

Comments: Majority of Phos found in bonesMax rate: 15 mmol over 5 hours**Max Conc: 15 mmol/100 mL**Infused slowly to reduce/avoid the risk of thrombophlebitis and calcium-phosphate precipitationWatch the salt (Na vs. K) content:30 mmol Phos = 44 mEq K or 40 mEq NaWeight based dosing guidelines available


Acid-Base Imbalances1. Evaluate the patient

What is occurring physiologically

2. Assess the pH

If the pH < 7.4 = ACIDOSIS

If the pH > 7.4 = ALKALOSIS

3. Assess the pCO2 & Assess the HCO3

pH < 7.35 and HCO3 < 22 metabolic acidosis

pH < 7.35 and pCO2 > 40 respiratory acidosis

pH > 7.45 and pCO2 < 40 respiratory alkalosis

pH > 7.45 and HCO3 > 28 metabolic alkalosis

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Contrast Induced NephropathyNo specific treatment once contrast-induced acute kidney

injury (AKI) developsPatients at increased risk:serum creatinine ≥ 1.5 mg/dL, eGFR < 60/1.73 m2

Management: best treatment of contrast-induced kidney injury is preventionAvoid of repetitive studies that are closely spaced (within 48 to 72

hours)

N-Acetylcysteine (Mucomyst)

Hydration with or without sodium bicarbonate (??)

2012 KDIGO Clinical Practice Guideline for Acute Kidney Injury


Assessment of Renal Function Creatinine (estimated GFR)

Intake/output (I/O); urine output

Concurrent diuretic/natriuretic use

Concurrent vasopressor use

Clinical/hemodynamic status

Sepsis, s/p cardiac arrest

Past medical history

CHF

Renal insufficiency vs. chronic kidney disease

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The End

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