Download Advanced Pharmacology Renal Agents The Kidneys

Advanced Pharmacology
Renal Agents
Thomas W. Barkley, Jr., PhD, ACNP‐BC, FAANP
President, Barkley & Associates
www.NPcourses.com
and
Professor of Nursing
Director of Nurse Practitioner Programs
California State University, Los Angeles
Robert Fellin, PharmD, BCPS
Faculty, Barkley & Associates
Pharmacist, Cedars‐Sinai Medical Center
Los Angeles, CA
©2014 Barkley & Associates
Unit 4
The Kidneys
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Unit 4
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
©2014 Barkley & Associates
Unit 4
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
Unit 4
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Functions of the Nephron: Summary
Unit 4
http://www.as.miami.edu/chemistry/2086/chap26/chapter%2026-new_part1.htm
©2014 Barkley & Associates
Management of Renal Disease
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Unit 4
Pharmacologic:
 Volume overload
Sodium and water hemostasis
 Electrolyte disturbances
Potassium and magnesium homeostasis
 Mineral and bone disorders
Calcium and phosphorous hemostasis
 Acid-Base imbalances
 Anemia
 Dose adjust/remove/avoid nephrotoxic agents
 Manage comorbid conditions
HTN, hyperlipidemia, DM
Nonpharmacologic:
 Renal replacement therapy: (HD, PD, CVVHD)
 Transplant
©2014 Barkley & Associates
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Diuretics: Mechanisms of Action
 Most
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
©2014 Barkley & Associates
Unit 4
Carbonic Anhydrase Inhibitors
Agents:
Acetazolamide (Diamox), methazolamide (Neptazane)
Site of action:
Proximal convoluted tubule; blunt sodium bicarbonate
reabsorption
Hyperchloremic metabolic acidosis, renal stones,
hypokalemia, drowsiness, paresthesias
Adverse
Effects:
Comments:
Unit 4
Rarely used as diuretics
Other applications: glaucoma, urinary alkalinization,
metabolic alkalosis, acute mountain sickness
Contraindication: hyperammonemia, hepatic
encephalopathy
©2014 Barkley & Associates
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Loop Diuretics
Agents:
Site of action:
Adverse
Effects:
Comments:
Bumetanide (Bumex), ethacrynic acid (Edecrin),
furosemide (Lasix), torsemide (Demadex)
Block sodium absorption at the ascending Loop of Henle
Electrolyte disturbances, dehydration, thirst, dry mouth,
weight loss, headache, hypotension, hyperuricemia,
hypercalcemia, ototoxicity (rare)
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
©2014 Barkley & Associates
Unit 4
Thiazide/Thiazide-Like Diuretics
Agents:
Site of action:
Adverse
Effects:
Comments:
Unit 4
Chlorothiazide (Diuril), chlorthalidone (Thalitone),
hydrochlorothiazide (Microzide), indapamide (Lozol),
metolazone (Zaroxolyn)
Block sodium absorption at the distal tubule
Electrolyte disturbances, dehydration, thirst, dry mouth,
weight loss, headache, hyperglycemia, ototoxicity (rare)
Primary use: HTN
Less efficacious than loop diuretics
Not effective in severe renal impairment
In certain situations may combine with loop diuretic to
provide synergistic diuresis
Chlorothiazide: only parenteral thiazide available
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Potassium-Sparing Diuretics
Agents:
Amiloride (Midamor), triamterene (Dyrenium),
eplerenone* (Inspra), spironolactone* (Aldactone)
Site of action:
Reduce sodium absorption in the collecting tubules
and ducts; aldosterone antagonist
Gynecomastia (spironolactone), hyperkalemia
Adverse Effects:
Comments:
Least effective diuretics
Most commonly used in combination with other
diuretics to reduce potassium loss
Caution use in renal impairment or pre-existing
hyperkalemia
Overuse: hyperchloremic metabolic acidosis
©2014 Barkley & Associates
Unit 4
Osmotic Diuretics
Agents:
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
Unit 4
©2014 Barkley & Associates
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Vasopressin Antagonists
Agents:
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
©2014 Barkley & Associates
Unit 4
Renal Agents: Sites of Action
Unit 4
http://accessmedicine.mhmedical.com.mlprox.csmc.edu/content.aspx?bookid=388&sectionid=45764235
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Sodium Imbalances
Normal Range:
135-145 mEq/L
Hypo Na:
Fluid restriction, 0.9% saline, 3% saline, conivaptan,
tolvaptan
Hyper Na:
Comments:
diuretics, hydration
Determine and treat underlying cause
Assess osmolality
Assess fluid status
Calculate total Na deficit
Maximum rate of correction: 8-12 mEq/24 hours
Monitor Na levels q2h during correction
Many medications implicated as the cause
©2014 Barkley & Associates
Unit 4
Potassium Imbalances
Normal Range:
3.5-5.0 mEq/L
Hypo K:
Hyper K:
Comments:
KCl, Kphosphate, Kacetate
sodium polystyrene sulfonate (Kayexalate), HD
Determine and treat underlying cause
Primary concern: life threatening arrhythmias
Check for ECG changes
Check serum Mg level; replete if necessary
Hypomagnesemia can cause refractory hypokalemia
Max rate: 10 mEq/hour**
Max Conc: 10 mEq/50 mL**
Oral repletion: no more than 40 mEq at once
Monitor potassium level q2-4 hours or after each 80
mEq
Unit 4
©2014 Barkley & Associates
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Magnesium Imbalances
Normal Range:
1.5-2.5 mEq/L
Hypo Mg:
Hyper Mg:
Magnesium sulfate, magnesium oxide
diuretics, HD, calcium chloride
Comments:
Determine and treat underlying cause
Primary concern: life threatening arrhythmias
Check for ECG changes
Max rate: 1 gram (8 mEq)/hour**
Max Conc: 1 gram/50-100 mL**
Hypomagnesemia can cause refractory hypokalemia
©2014 Barkley & Associates
Unit 4
Calcium Imbalances
Normal Range:
Hypo Ca:
Hyper Ca:
Comments:
Unit 4
8.5-10.5 mEq/L (iCa: 1.12-1.30 mmol/L)
Calcium gluconate, calcium chloride, others
hydration, loop diuretics, bisphosphonates
Regulated by parathyroid hormone, vitamin D, and calcitonin
99% of total body Ca found in bones, less than 1% in the
serum
40-50% of Ca in the blood is bound to albumin
Must correct for hypoalbuminemia
Free or ionized Ca level may be more reliable
Max rate: 1 gram (4.65 mEq)/hour**
Max Conc: 1 gram/50-100 mL**
Preferred agent: Ca gluconate
Ca chloride used for emergent situations
©2014 Barkley & Associates
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Phosphorus Imbalances
Normal Range:
2.5-4.5 mg/dL
Hypo Phos:
Hyper Phos:
Comments:
Na phosphate, K phosphate
hydration, oral phosphate binders, HD
Majority of Phos found in bones
Max rate: 15 mmol over 5 hours**
Max Conc: 15 mmol/100 mL**
Infused slowly to reduce/avoid the risk of
thrombophlebitis and calcium-phosphate precipitation
Watch the salt (Na vs. K) content:
30 mmol Phos = 44 mEq K or 40 mEq Na
Weight based dosing guidelines available
©2014 Barkley & Associates
Unit 4
Acid-Base Imbalances
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Unit 4
Evaluate the patient
 What is occurring physiologically
Assess the pH
 If the pH < 7.4 = ACIDOSIS
 If the pH > 7.4 = ALKALOSIS
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
©2014 Barkley & Associates
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Contrast Induced Nephropathy
 No
specific treatment once contrast-induced acute kidney
injury (AKI) develops
 Patients at increased risk:
 serum
creatinine ≥ 1.5 mg/dL, eGFR < 60/1.73 m2
 Management:
best treatment of contrast-induced kidney injury
is prevention
 Avoid
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
©2014 Barkley & Associates
Unit 4
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
Unit 4
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The End
Unit 4
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