icu presentation - hannah bond and kim treier

Drugs and Dosing in Renal Patients

Kimberly Treier and Hannah BondPharm.D. Candidates 2016

Albany College of Pharmacy- VT campus17 September 2015

Outline

• Kidney Anatomy• Common Drugs Affecting the Kidney• Renal Dosing Calculations• Chronic Kidney Disease – Brief Overview• Acute Kidney Injury – Brief Overview • Drug Induced Nephrotoxicity – Brief

Overview

Kidney AnatomyHannah Bond

Common Drugs Acting on the

KidneysKimberly Treier

Afferent ArterioleNSAIDs- Ibuprofen- Ketoprofen- Naproxen- Indomethacin- Celecoxib- Ketorolac- others

Vasoconstriction

Efferent ArterioleACEIs- Lisinopril- EnalaprilARBs- Losartan- ValsartanAldosterone antagonists- Spironolactone- Eplerenone

Vasodilation

BOTH ArteriolesDopamine agonists*- Bromocriptine- Ropinirole

Alpha-1 blocker- Prazosin- Doxazosin

Vasodilation

BOTH ArteriolesDirect-acting vasodilators- Hydralazine

Nitrates- Nitroglycerine- Nitroprusside- Isosorbide

dinitrate

Vasodilation

Proximal TubuleCarbonic Anhydrase Inhibitors- Acetazolamaid

e- Methazolamid

e

Promotes diuresis and urinary alkalinization

Proximal Tubule + Descending LoopOsmotic diuretics- Mannitol- Isosorbide

urine osmolarity (unable to be reabsorbed) draws H2O into lumen

Ascending LoopLoop diuretics- Furosemide- Torsemide- Bumetanide

Na+ and Cl- reabsorption

Distal TubuleThiazide diuretics- HCTZ- Indapamide- Metolazone- Chlorthalidone

Na+ and Cl- excretion

Distal Tubule + Collecting DuctK+-sparing diuretics- Spironolactone- Eplerenone- Triamterene- Amiloride

Aldosterone-mediated Na+ and water reabsorption, and K+ excretion

Collecting DuctADH agonists- Desmopressin

Renal H2O reabsorption

ADH antagonists- Conivaptan- Tolvaptan- Oxytocin??

Renal H2O reabsorption

Proximal TubuleSGLT2 inhibitors- Canagliflozin- Dapagliflozin- Empagliflozin

reabsorption of filtered glucose

Juxtaglomerular cellsDirect renin inhibitor- Aliskiren

Release of renin

Direct-acting vasodilators- Hydralazine

Release of renin

Renal Dosing Calculations

Hannah Bond

• Step 1: Obtain the following information • Age• Height• Current weight• Most recent SCr

• Step 2: Calculate Ideal Body Weight (IBW)• Male: 50 + (2.3 X inches over 60 inches in

height)• Female: 45.5 + (2.3 X inches over 60 inches

in height)

Creatine Clearance

• Step 3: Determine dosing weight• Use total body weight to calculate CrCl if

TBW< IBW• Use adjusted body weight for obese

patients• TBW > 1.3 times IBW• AdjBW: IBW + 0.4 (TBW – IBW)

• Step 4: Calculate estimated Creatine Clearance• Male: [(140-age) X IBW] / (72 X SCr)• Female: [(140-age) X IBW] / (72 X SCr) X

0.85

Creatine Clearance

• A 57 year old African American female with a PMH of CKD, HTN, and DM is admitted to ICU for IV antibiotics to treat an infected ulcer on her right foot. Dr. Johnson has ordered Ceftazidime 1 g every 12 hours and vancomycin 1 g every 12 hours.• SCr: 2.51 mg/dL• Height: 65 inches• Weight: 68 kg

Creatine Clearance Example

• Step 1: Obtain the following information • Age: 57 • Height: 65 inches• Actual current weight: 68 kg• Most recent SCr: 2.51 mg/dL

• Step 2: Calculate Ideal Body Weight (IBW)• Male: 50 + (2.3 X inches over 60 inches in

height)• Female: 45.5 + (2.3 X inches over 60 inches in

height) • IBW = 45.5 + (2.3 X 5) = 57 kg


• Step 3: Determine dosing weight• Use total body weight to calculate CrCl if TBW< IBW

• 68 kg /57 kg = 1.19• Use adjusted body weight for obese patients• TBW > 1.3 times IBW• AdjBW: IBW +0.4 (TBW – IBW)

• Step 4: Calculate estimated Creatine Clearance• Male: [(140-age) X IBW] / (72 X SCr)• Female: [(140-age) X IBW] / (72 X SCr) X 0.85 • CrCl = [140-57) X 57 kg]/(72 X 2.51 mg/dL) X 0.85 =

26.55 mL/min


• Ceftazidime renal dosing• CrCl 31-50 mL/min: 1-2 g every 12 hours• CrCl 10-30 mL/min: 1-2 g every 24 hours• CrCl < 10 mL/min: 1-2 g every 48 hours

• Based on the above information and her CrCl of 26.55 mL/min, did the doctor prescribe the correct dose of ceftazidime (1 g every 12 hours)?


• Most drug dosing recommendations are based on CrCl

• There are many equations to calculate CrCl• Cockcroft-Gault (adults)• Schwartz Equation (children)

Using CrCl

• Limitations:• CrCl is just an estimate (“eCrCl”)• Creatinine levels dependent on many factors• Age• Sex• Muscle mass• Diet• Renal creatinine secretion (overestimation of kidney function)• Fluctuating renal function (e.g. ICU)

• Multiple equations • Lack of standardization among manufacturers (FDA

labeling and institution-specific implementation)

Using CrCl

• Step 1: Obtain the following information • Age• Sex• Ethnicity• Most recent SCr

• Step 2: Calculate eGFR• GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 ×

(Age)-0.203 × (0.742 if female) × (1.212 if African American)

Estimated Glomerular Filtration Rate (eGFR)

• A 57 year old African American female with a PMH of CKD, HTN, and DM is admitted to ICU for IV antibiotics to treat an infected ulcer on her right foot. Dr. Johnson has ordered Ceftazidime 1 g every 12 hours and vancomycin 1 g every 12 hours.• SCr: 2.51 mg/dL• Weight: 68 kg• Height: 65 inches

eGFR example

• Step 1: Obtain the following information • Age: 57 • Sex: Female• Ethnicity: African American• Most recent SCr: 2.51 mg/dL

• Step 2: Calculate eGFR• GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-

0.203 × (0.742 if female) × (1.212 if African American)

• = 175 × (2.51)-1.154 × (57)-0.203 × (0.742 if female) × (1.212 if African American)= 25 mL/min/1.73m2

eGFR Example

• Some drug dosing recommendations are based on eGFR

• Basis for chronic kidney disease staging• Multiple equations:• Modification of Diet in Renal Disease (MDRD)• Chronic Kidney Disease Epidemiology

Collaboration (CKD-EPI)

• Limitations:• Less accurate in very large/small patients• Multiply eGFR by BSA

Using eGFR

Chronic Kidney Disease

Hannah Bond

What is Chronic Kidney Disease?

• Presence of kidney damage or a reduction in glomerular filtration rate for three months or longer

• As CKD progresses, wastes can build to high levels in your blood.

• Complications: high blood pressure, anemia, weak bones, poor nutritional health and nerve damage

CKD stagingGFR category GFR

(mL/min/1.73m2)Terms

G1 ≥90 Normal to high

G2 60-89 Mild decreased

G3a 45-59 Mild to moderate decrease

G3b 30-44 Moderate to severe decrease

G4 15-29 Severe decrease

G5 <15 Kidney failure

Acute Kidney InjuryKimberly Treier

What is AKI?• Abrupt loss of kidney function • Accumulation of urea and nitrogenous waste• Inability to effectively regulate fluid and electrolytes

• ICU patients considered high-risk for AKI• Occurs in up to ⅔ ICU patients

• Consequences:• Prolonged hospital stay• Hospital-related adverse events• Development of CKD• Acute/chronic renal replacement therapy

What is AKI?

Drug-Induced Nephrotoxicity

Kimberly Treier

Risk factors for drug-induced nephrotoxicity in the ICUChronic risk factors- Older age (> 65 years)- CKD- Diabetes mellitus- Malignancy- Cardiovascular disease- Liver disease- Chronic pulmonary disease- HTN- Peripheral vascular diseaseAcute risk factors- Sepsis/infection- Volume depletion (true and effective)- Acute decompensated heart failure- Hypotension- Complex/major surgery- Trauma- Mechanical ventilation

Perazella MA. Drug use and nephrotoxicity in the intensive care unit. Kidney International (2012) 81, 1172-1178; doi: 10.1038/ki.2010.475


• Tubular epithelial cell damage• Hemodynamically-mediated kidney damage• Obstructive nephropathy• Glomerular disease• Tubulointerstitial disease• Renal vasculitis, thrombosis, and cholesterol

emboli

Tubular epithelial cell damageAcute tubular necrosis **Most common in inpatient setting**- Aminoglycoside antibiotics- Radiographic contrast media- Cisplatin, carboplatin- Amphotericin B- Cyclosporine, tacrolimus- Adefovir, cidofovir, tenofovir- Pentamidine- Foscarnet- ZoledronateOsmotic nephrosis- Mannitol- Dextran- Radiocontrast media- IV immunoglobulin- Drug vehicles (e.g. sucrose, polyethylene glycol)


Aminiglycoside nephrotoxicity• Gentamycin, tobramycin, streptomycin,

amikacin

• 10-25% of patients treated with aminoglycoside• Critically ill: up to 58%

• Accumulation of drug in proximal tubular epithelial cells reactive oxygen species cell apoptosis and proximal tubular necrosis


Dose adjustment example:• Gentamycin:• Traditional dosing – increase dosing interval: • Initial dose given every [SCr x 8] hours

• Traditional dosing – decrease dose: • Give usual initial dose, then reduce dose: [initial

dose/SCr] and give every 8 hours• Once-daily dosing:• Give usual mg/kg dose and adjust initial interval based

on CrCl (i.e. CrCl > 60 mL/min: every 24 h; CrCl 40-60 mL/min: every 36 h; CrCl 20-40 mL/min: every 48 h)


Thank you!Any questions?

References• Santiago C, et. al. Renal Dopamine Receptors, Oxidative Stress, and Hypertension. International

Journal of Molecular Science. 2013 Sep: 14(9): 17553-17572• Schmitz JM, et. al. Renal alpha-1 and alpha-2 adrenergic receptors: biochemical and

pharmacological correlations. J Pharmacol Exp Ther. 1981 Nov;219(2):400-6.• Chunling Li, et. al. Molecular Mechanisms of Antidiuretic Effect on Oxytocin. Journal of the

American Society Nephrology. 2008 Feb; 19(2):225-232• Micromedex. Truven Health Analytics Inc. (online) Available at

<http://www.micromedexsolutions.com.acphs.idm.oclc.org/micromedex2/librarian/ND_T/evidencexpert/ND_PR/evidencexpert/CS/613E30/ND_AppProduct/evidencexpert/DUPLICATIONSHIELDSYNC/2F559D/ND_PG/evidencexpert/ND_B/evidencexpert/ND_P/evidencexpert/PFActionId/pf.HomePage?navitem=Logo#> (accessed 16 Sep 2015)

• CKD and Drug Dosing: Information for Providers. National Kidney Disease Education Program. Revised Apr 2015. Available online at: www.nkdep.nih.gov

• Perazella MA. Drug use and nephrotoxicity in the intensive care unit. Kidney International (2012) 81, 1172-1178; doi: 10.1038/ki.2010.475

• DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, Ninth Edition: www.accesspharmacy.com

• KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl. 2012 Dec;2(5):337-414.

http://www.accesspharmacy.com/

Radiographic contrast media-induced nephrotoxicity (CIN)• 3rd leading cause of hospital-acquired AKI• <2% in patients with normal renal function• Up to 50% in patients with CKD or diabetes

• Systemic hypotension (i.e. renal hypoperfusion) + acute vasoconstriction increased contrast media remaining in tubules cytotoxicity


Prevention of radiographic CIN:• Minimize contrast dose• Use non-iodinated and low-/iso-osmolar

contrast media• Hydration! – before, during and after • Avoid other nephrotoxic drugs


Tubular epithelial cell damageAcute tubular necrosis- Aminoglycoside antibiotics (gentamycin, tobramycin,

etc.)- Radiographic contrast media- Cisplatin, carboplatin- Amphotericin B- Cyclosporine, tacrolimus- Adefovir, cidofovir, tenofovir- Pentamidine- Foscarnet- ZoledronateOsmotic nephrosis- Mannitol- Dextran- Radiocontrast media- IV immunoglobulin- Drug vehicles (e.g. sucrose, polyethylene glycol)


Hemodynamically-mediated kidney injury- ARBs (lisinopril, enalopril, etc.)- ARBs (valsartan, candesartan, etc.)- NSAIDs- Cyclosporine, tacrolimus- OKT3


Obstructive neuropathyIntratubular obstruction- Acyclovir- Sulfonamides- Indinavir- Foscarnet- MethotrexateNephrolithiasis- Sulfonamide- Triamterene- IndinavirNephrocalcinosis- Oral sodium phosphate solution


Glomerular disease- Gold- Lithium- NSAIDs, COX-2 inhibitors (i.e. celecoxib)


Tubulointerstitial diseaseAllergic interstitial nephritis- Penicillins- Ciprofloxacin- NSAIDs, COX-2 inhibitors (i.e. celecoxib)- PPIs- Loop diuretics (furosemide, torsemide, bumetanide)Chronic interstitial nephritis- Cyclosporine- Lithium- Aristolochic acidPapillary necrosis- NSAIDs- Caffeine analgesics (e.g. Fiorecet, Fiorenol, Excedrin)


Renal vasculitis, thrombosis and cholesterol emboliVasculitis and thrombosis- Hydralazine- Propylthiouracil- Allopurinol- Penicillamine- Gemcitabine- Mitomycin C- Methamphetamines- Cyclosprine, tacrolimus- Adalimumab- BevacizumabCholesterol emboli- Warfarin- Thrombolytic agents


icu presentation - hannah bond and kim treier

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