American Nephrology Nurses Association (ANNA)

1

American Nephrology Nurses Association (ANNA)

PHARMACOLOGY IN RENAL DISEASE

Timothy V. Nguyen, BS, PharmD, CCP, FASCPAssistant Professor of Pharmacy Practice

Arnold & Marie Schwartz College of Pharmacy, LIUAdjunct Pharmacology Professor

Saint Peter’s CollegeJanuary 31, 2010

Overview Effect of CKD on Metabolism and

Elimination of Pharmacologic Agents Classifications of Drugs to Treat

Patients with Chronic Kidney Disease Hypoglycemic Agents Interdialytic Agents Effect of Dialysis on Drug Therapy

2

3


Diseases of the kidney are among the most common and complex of all

diseases of man.

The kidneys are 0.5% of the body weight, but consume 7% of total body

oxygen.

4

DISEASE STATES OF THE KIDNEY

Acute Kidney Injury Acute Nephritis Chronic Kidney Disease Nephrotic syndrome Urinary Tract Infections & Obstructions Renal Tubule Effects – medication induced

Acyclovir, MTX, triamterene, indinivir, sulfonamides

Hypertension Nephrolithiasis End stage renal failure

End stage renal failure is defined as the condition in which the kidneys fail to remove metabolic waste products, regulate pH, or control fluid balance.

5


End Stage Renal Disease In The United States *: More than 20 million Americans (1in 9 adults), have chronic kidney

disease 470,000 Americans receiving treatment for ESRD

335,000 dialysis patients 136,000 with a functioning kidney transplant Each year about 70,000 Americans die from kidney failure

A profile of kidney failure patients in the U.S. follows: (2000) There are approximately 3,600 dialysis facilities and 255 transplant

facilities in the U.S. Only 260 dialysis units are hospital-based. The current annual cost of treating kidney failure in the U.S. is

approximately $17.9 billion.

* National Kidney Foundation 2005

6


Leading causes of kidney failure in the US * Diabetes –

44% new cases 36% of all cases

Uncontrolled or poorly controlled high blood pressure

Glomerulonephritis & inflammatory diseases

National Kidney Foundation data 2003

7

PHARMACOLOGY IN RENAL DISEASE: Kidneys Main Function

Maintain water & electrolyte balance Secrete renin by the cells of the

juxtaglomerular apparatus Important regulatory mechanism for

controlling blood flow Production & metabolism of

prostaglandins & kinins Production & secretion of erythropoietin

by the interstitial cells in response to decreased 0xygen in the blood

8

Renal Function – processes of

Filtration Secretion Reabsorption

Endocrine & Metabolic Fx’s

9

Renal physiologic functions affecting Pharmacology

Filtration Occurs at the glomerulus Determinants of a drug’s capacity to be filtered Most drugs are small enough for filtration except

for high molecular weight dextrans i.e. volume expanders

Protein Binding Displacement of highly bound drugs Only free drug can pass through the glomerulus

10

NEPHRON (1 million)/kidney

Is the functional unit

of the kidneyRegions of the

nephron Glomerulus Proximal tubule Loop of Henle Distal Tubule Collecting Duct

11


At the nephron is where we see the passing of anions & cations through active & passive diffusion.

Na+, K+, Cl-, HCO3-, & H20. Reabsorption denotes transport from

the urine back to the blood. Secretion is the movement of solutes or

water from the blood to the nephron tubule lumen.

12

Reabsorbed Fluids & Solutes in the Kidney

Filtered/day Excreted/day

% Reabsorbed

NACl 20,000mEq 110mEq 99+

NaHCO35000mEq 2mEq 99+

K+ 700mEq 50mEq 93+

H20 170 L 1.5 L 99+

13

Measurement of Renal Function

Quantify renal fx to use as a diagnostic indicator to monitor therapy. success vs. failure

Measurement of renal function is an indicator of the body’s ability to eliminate drugs from the body.

Single best measure of renal fx = GFR Volume of plasma filtered across the glomerulus

per unit of time Responsible for keeping the renal blood flow

constant Normal GFR = 120 mL/min/1.73m2

14

Mechanism of Kidney Clearance

Measurement of GFR Serum creatinine

level, eCrCl MDRD Cystatin C

Substances Kidney Creatinine Clearance (~GFR)

(Filtration Process)

15


Measurement of GFR Inulin clearance

fructose polysaccharide obtained from plant tubers of the Jerusalem artichoke, chicory & dahlia plants.

Urine & blood samples Iothalamate clearance

I-Iothalamate radiolabeled form

Intermittent availability, high cost, invasiveness, sample preparation, & assay variability limits its use

in the clinical setting.

16

Estimation of Creatinine Clearance

CrCl is the single most common clinical test for the assessment of renal fx.

Cr is a product of creatinine metabolism on muscle mass.

Normal Cr = 0.5 – 1.5 mg/dL Cockcroft and Gault Formula:

(140-age)(body weight in kg)(72)(serum creatinine)

Women x 0.85

17


Calculating the CrCl 79 YO, Female Serum creatinine =1.2

mg/dL 65 Kg

Important to note there is a normal loss of nephrons due to the aging process.

(140-79)(65)x 0.85 (1.2)(72)

Est. CrCl = 39 mL/min

18

Modification of Diet in Renal Disease (MDRD) Study Formula

GFR (mL/min/1.73m2) = 186x(Scr) -1.154 x (age) -

0.203 x (0.742, if female) x (1.212, if black)

Does not require weight as a variable More accurate for patients whose GFR

is less than 90 mL/min

Other Methods: CKD-EPI, Cystatin, etc…

19

Renal Disease Classifications

National Kidney Foundation. Am J Kidney Dis. 2002;39(suppl)

Stages of Chronic Kidney Disease

Estimate Glomerular Filtration Rate

(mL/min)

1 90* 2 60 – 89 3 30 – 59** 4 15 – 29 5 <15

*Kidney damage with normal or GFR **CKD: kidney damage for ≥3 months with or without GFR or GFR <60 mL/min/1.73 m2 for ≥3 months with or without kidney damage

8183-11U Master

20


Pharmacokinetics measures rise and fall

of drug concentrations in the serum and tissue

Absorption Distribution Metabolism Elimination

T1/2 : the time it takes to eliminate 50% of the drug from the body

Pharmacodynamics What the drug does

to the body incorporates kinetics integrates

microbiological activity focusing on biological effects, particular growth inhibition and killing of pathogens

21

Pharmacokinetic alterations in CKD

PK Parameters Alteration in CKD Absorption , believed to be reduced Distribution , reduced plasma protein binding Metabolism , accumulation of active metabolites

, decrease in nonrenal clearance Elimination , increased accumulation

, increased toxicity

22

Pharmacotherapeutics Establish a therapeutic outcome for a specific patient Monitor patient’s therapy for effectiveness & clinical

responses Evaluate potential side effects Drug Interactions:

Additive effect Synergistic effect Incompatibility Adverse drug events

All drugs are potentially toxic & can have cumulative effects. Knowledge of organs responsible for metabolizing & elimination will allow us to dose appropriately. Especially in pts with compromised organ function

23


DRUGS significantly effected by Renal Failure

Aminoglycosides Gentamicin Tobramycin Amikacin

Ganciclovir Vancomycin

DRUGS exhibiting sensitivities to Renal Insufficiencies

Sedatives Barbituates

Narcotic analgesics Meperidine

(Demerol) Antihypertensives

24

Drug dosing in CKD Anticipate problems Minimize polypharmacy Strategies

Decrease dose Increase Dosing Interval or BOTH

Methods Estimate CrCl Consult Dosing recommendations – guidelines Individualize Dose Monitor Serum Drug Concentrations

25

Drug Dosing in Dialysis

Influencing factors Protein Binding – unbound drug for diaysis Volume of Distribution-lge VD less dialyzable Molecular Weight – MW > 500 not dialyzable Dialyzer Membrane Permeability – allow

passage of drugs Dialyzer Surface Area – larger areas achieve

greater clearance Blood Flow Rate – fast BFR may allow

increased clearance

Johnson et al. 2005 Dialysis of Drugs

8183-11U Master

8183-11U Master

26

Drug Dosing In Dialysis

Maintenance dose based on anephric status

Supplemental Dose - Replace amount of lost drug

Establish Serum Drug Concentration Monitoring

Water-soluble vitamins are dialyzable

COMPLICATIONS FROM CKD Complications Possible Associations Anemia (see Table for anemia management target parameters recommended by the NKF-KDOQI)

Acute and Chronic Blood loss, decrease erythropoietin production, decreased red blood cell lifespan, inadequate dialysis, inadequate iron store due to iron loss and decrease intake, and multiple co-morbid complications Hyporesponsive to erythropoiesis stimulating agents

Cardiovascular Problems (accounts for approximately 50% of all deaths)

Ischemic heart disease Congestive heart failure Hypertension Pericarditis

Bone Metabolism Renal Osteodystrophy

Calcium, phosphate and vitamin D abnormalities (hypocalcemia, decreased vitamin D production, hyperphosphatemia) Vascular calcification

Dialysis Related Hypotension Dialyzer reactions Dialysis technical problems

Electrolyte Disorders Metabolic acidosis Hyperkalemia and electrolytes abnormality

Fluid Retention Hypertension Gastrointestinal Problems Hepatitis

Gastritis Duodenitis Peptic ulcer disease Colonic arteriovenous malformations B or C virus

Nguyen TV. Consult Pharm. 2007

COMPLICATIONS FROM CKD (con’t) Hematologic Increased bleeding tendency Infection Vascular access

Weaken immune system Intradialytic Complications

Hypotension Muscle cramps Dialysis disequilibrium syndrome Arrhythmias and angina Cardiac arrest

Malnutrition Occurs up to 50% of ESRD patients Neurologic Problems

Diabetic peripheral neuropathy (may respond to tricyclic antidepressants, carbamazepine, or topical capsaicin) Altered mental status Uremic seizures

Sexual Dysfunction and Pregnancy

Impaired libido Impotence Infertility

Uremia symptoms Fatigue Nausea Pruritis Amyloidosis

Special Issues (other complications)

Diabetes care Acquired Immunodeficiency Syndrome Hyperlipidemia Rehabilitation Depression Perioperative Management Cancer Screening Noncompliance Kidney Transplantation Insurance, medical and prescription coverage

Nguyen TV. Consult Pharm. 2007

Antihypertensive in CKD: ACEIs & ARBs(HTN, a common complication of CKD)

Angiotensin Converting Enzyme Inhibitors

Captopril (Capoten), enalapril (Vasotec), enalaprilat (Vasotec IV), lisinopril (Prinivil, Zestril), ramipril (Altace), benazepril (Lotensin), quinapril (Accupril), fosinopril (Monopril), moexipril HCl (Univasc), spirapril (Renormax), trandolapril (Mavik), perindopril (Aceon).

29

ACEIs Beneficial in pts with HTN & diabetic damage to the

kidneys & heart. HF – ↓ systemic vascular resistance, BP (afterload),

preload; also ↑ CO & exercise tolerance time; Also block the sympathetic nervous system & therefore prevent ventricular remodeling (?end stage HF after an MI) (↓’ed mortality from CHF by 25 to 31%)

Preventing diabetic nephropathy – ↓’ed GFR, improved renal hemodynamics, ↓’ed proteinuria, retarted glomerular hypertrophy, & a slower rate of decline in GFR.

Excreted primarily by the kidney Half-life is prolonged in RD

30

ACEIs: Precautions

First dose effect (a profound drop in BP); used in 2nd & 3rd trimesters of pregnancy is associated with fetal injury & death; cautious in RD (~20% associated with nephrotic syndrome); hyperkalemia.

CI: bilateral renal artery stenosis, angioedema, pregnancy

AE’s: orthostatic hotn, angioedema Dry, hacking cough (15 – 20%) (seem to be

related to bradykinin & substance P) Elevations of liver enzymes, BUN/SrCr, K DI: Potassium-sparing diuretics, NSAIDs

31

Angiotensin Receptor Blockers (ARBs)

Losartan potassium (Cozaar), candesartan (Atacand), eprosartan (Teveten) , irbesartan (Avapro), olmesartan (Benicar), telmisartan (Micardis), valsartan (Diovan)

MOA: Blocks the vasoconstriction & aldosterone effects of angiotensin, selectively blocking the binding of angiotensin II to angiotensin receptors.

Have no effect on bradykinin metabolism & therefore more selective blockers of angiotensin effects than ACEIs; potentially have a more complete inhibition of angiotensin action compared with ACEIs b/c there are enzymes other than ACE that are capable of generating ACEII

AE’s: angioedema, diarrhea, dizziness, cough (less than ACE inhibitors)

32

33

HTN: Diuretics

Thiazides – early renal failure(In the treatment AKI, large randomized trials have failed to prove diuretics to be effective)

Loop diuretics – effective in pts with residual renal fx Furosemide (Lasix), Torsemide (Demadex)

Thiazide-like Diuretics – potent, use in CKD/ESRD Indapamide (Lozol), metolazone (Zaroxoline)

Osmotic – Mannitol K-Sparing – spironolactone (Aldactone), amiloride

(Midamor) [avoid in hyperKalemia] Monitor: I/O, kidney function, lytes, ototoxicity, lipid

profiles, uric acid, allergy

Beta Adrenergic Blocking Drugs Propranolol HCl (Inderal) Acebutolol (Sectral) Metoprolol (Lopressor) Nadolol (Corgard) Atenolol (Tenormin) Pindolol (Visken) Betaxolol (Kerlone) Acarteolol (Cartrol) Penbutolol (Levatol) Timolol (Blocadren) Carvedilol (Coreg) Esmolol (Brevibloc) Sotalol (Betapace) Nebivolol (Bystolic)

↓ HR Bronchospasm Masked

hypoglycemia ↑ triglycerides

w/↓HDL

34

Calcium Channel Blockers

Also used as: antiangina, arrhythmias

Cause negative inotropic

Dizziness, HoTN

35

Amlodipine (Norvasc) Nifdipine (Adalat,

Procardia) Isradipine (Dynacirc) Felodipine (Plendil) Nnisoldipine (Sular) Verapamil (Calan,

Isoptin) Diltiazem (Cardizem) Others

Analgesics in CKD

Mild (1-4): APAP, +/- adjuvants prn Moderate (5-6): Tramadol (Ultram),

Hydromorphone (Dilaudid)? Severe (7-10): Fentanyl, Methadone, +/-

adjuvants Not recommended: Codeine,

Oxycodone, Morphine, NSAIDs AVOID: Meperidine, Propoxyphene

36

37

Dyslipidemias Management in CKD

NKF-K/DOQI. Am J Kidney Disease. 2003;41(suppl 3)

LDL >100 mg/dL or 3 months post-lifestyle modification

CKD stage 5, fasting TG >500 mg/dL

Non-HDL >130 mg/dL

HMG CoA Reductase Inhibitor (Statin)

Fibrates or Niacin (Gemfiprozil, DOC)

Lifestyle modification + Statin (Fibrate if not tolerate Statin)

Monitor: LFT, myopathy

8183-11U Master

39

CKD & Anemia Management Transfusions Androgen tx – 1970

Modest success Only 50% of pts respond with a 5%

increase in HCT’s Recombinant erythropoietin

EPO, Darbepoetin alfa Iron Therapy

Iron dextran (Infed), Sodium ferric gluconate (Ferrlecit), Iron Sucrose (Venofer)

Adjuvants

40

NKF-KDOQI GuidelinesNKF-KDOQI Target Treatment Goals for CKD Stage 5 Anemia by Hgb Male: <13 g/dL

Female: <12 g/dL Target Hgb Generally 11 to 12 g/dL

Should not be >13 g/dL Target Iron Indices Serum Ferritin: >200 ng/mL (insufficient

evident for routine administration if sFerr >500 ng/mL) TSAT: >20% Or CHr >29 pg/mL

NKF-KDOQI. Am J Kidney Dis. 2006;47(5):suppl 3., Am J Kidney Dis. Sept. 2007

Monitor: Hb at least monthlyIron Indices at every 1-3 months

ESA: EPO & Darbepoetin alfa Revolutionized anemia management in CKD

Stimulate the production of RBC Epoetin alfa, EPO (Epogen, Procrit) Nearly identical structure to

endogenous erythropoietin Subcut administration > IV Push Usually TIW administration

Darbepoetin alfa (Aranesp) Similar to EPO but not identical

chemical structures Differs by an addition of two sialic acid

components at the N-glycosylation site

Results with enhance molecular weight & increase half-life (~3x longer compared to EPO)

Usually Weekly or Q2W Administration Onset of action: several weeks Avoid rapid rise in Hb (>1 g/dL in any 2-wk period) Common AE’s: infection, HTN/HoTN, myalgia, H/A, diarrhea, fever, chest pain Serious AE’s: vascular access thrombosis, CHF, sepsis, cardiac arrh, PRCA Black Boxed WARNINGS: ’ed the risk for death & serious CVS events when Hb >12 g/dL Iron supplementation: TSAT >20%, sFerritin >200 ng/mL (HD)NKF-KDOQI 2007

42

FDA Public Health Warning Issued for ESAs

Hb target >12 g/dL may risk of CV events & death

Lowest dose of ESAs should be used Hb should be gradually raised to

avoid need for transfusion Monitor Hb during dose titration Withhold the dose if the Hb exceeds

12 g/dL or rises by 1 g/dL in any 2-wk period

43

Iron Physiology Is a key constituent of Hb & necessary as adjunctive thx to

enhance the effectiveness of ESA Ferritin: Liver is the main storage site of Fe & in the form of

ferritin Acute-phase reactivity (’ed in acute/chronic

inflammation, malnutrition, liver disease) Transferrin (TSAT): immediate iron on board is essential for

erythropoiesis Acute-phase reactivity (significant fluctuations, low in

malnutrition/chronic disease) Reticulocyte hemoglobin content

“Real time” assessment of Fe status Measures immediated incorporation of Fe into

reticulocytes (in circulation for only 1 day) Less variable/more accurate than sferritin/TSAT

NKF-KDOQI. Am J Kidney Dis. 2006; Kalantar-Zadeh, et al. Nephrol Dial Transplant. 2004;19:141-149

Recognizing Iron Deficiency in the HD Patient Form Indicator Probable Cause

Absolute Iron Deficiency

TSAT <20% and sFerritin <100 ng/mL

’ed blood loss ’ed iron absorption

Functional Iron Deficiency

TSAT may be <20% and sFerritin may be

100 – 700 ng/mL

’ed stimulation of RBC Production of EPO thx outstrips

iron supply May develop even when storage

iron appears normal RE Blockade Dramatic in

sferritin along with drop in TSAT

Acute or chronic inflammation often seen in HD patient

Blocks release of iron stores from RES

NKF-KDOQI. Am J Kidney Dis. 2006; Fishbane. Am J Kidney Dis. 1997;29:319-333

IV Iron administrationOral – not effective (HD)

Iron Dextran: anaphylactic risk (0.6-2.3%), ~0.7% w/life-threatening rxns

Iron Sucrose & Gluconate: better safety profile, similar efficacy

Iron & Infection: microbes synthesize iron transport proteins that compete with transferrin for free iron; Depress sIron values have been documented during infectious diseases

Drug Anaphylactic Risk Test Dose IV Push Total Dose Iron Dextran Yes Yes Yes Yes Iron Gluconate Low No Yes No Iron Sucrose Low No Yes No Ferumoxytol Low No Yes 510 mg

46

NKF-K/DOQI Guideline: Fe Administration

If TSAT <20% and/or Ferritin <100 ng/mL, give IV iron 100-125 mg qHD x8-10 doses

Repeat TSAT & Ferr 1-2 weeks later, if still <20% and/or <100 ng/mL, repeat IV Fe course

Once TSAT 20% & Ferr 100 ng/mL, give IV Fe 50-100 mg qweek MD

Monitor: every 1 to 3 monthsMay monitor during iron maintenance schedule,

no need to interrupt dosingUsually 1-2 wks after course completed

47

Hyporesponsive IssuesComobidities: DM, HTN, Cardiovascular disease, Frequent hospitalizations, blood loss, CA, AIDSInfection, InflammationIron deficiency (Absolute & Functional)Aluminum toxicityPure Red Cell Aplasia (PRCA)HypoalbuminemiaElevated C-reactive protein levelTemporary & permanent catheter insertions

48

Overcoming Hyporesponsive Issues?

L-Carnitine A carrier involved in the transport of fatty acid HD patients may have low level No pathogenic mechanism that may contribute

to anemia

Vitamin C (Ascorbate) May help the release of Fe from ferritin & the

reticuloendothelial system, which Fe utilization during heme synthesis

Conclusion: Insufficient evidenceNot recommended: Androgens

49

Mineral & Bone Disorders

Severe Hyperparathyroidism (sHPT) Vitamin D’s analogs Phosphate-binding drugs Cinacalcet (Sensipar)

Calcium sensing receptors Decrease PTH hormone Lowering serum calcium levels Dose sHPT – 30mg po daily; increase q2-4w,

prn AE’s: N/V, hypocalcemia, seizures

50

NKF-KDOQI Target Treatment Goals for CKD Stage 5

Serum Phosphorus

Corrected serum

Calcium

Ca x P Product

Intact plasma PTH

3.5 – 5.5 mg/dL

8.4 – 9.5 mg/dL

<55 mg2/dL2 150 – 300 pg/mL

Ca-based binder: 1500 mg/day (elemental Ca)

NKF-KDOQI. Am J Kidney Dis. 2003;42(suppl 3)

51

The New KDIGO Ca, P, PTH, Alk Phos – should be monitored regularly; adjust according to trends rather than

specific target values

iPTH CKD stages 3-5 Dialysis Above the assay’s upper limit Evaluate for hyperP, hypoCa,

& vit D deficiency Treatment w/vitamin D is suggested if progressively rises & remains above the upper-normal limit

Maintain ~2-9 times upper-normal limit (~130-600 pg/mL)

Monitoring Intervals

CKD Ca & P PTH Alk Phos 3 Q6-12months Baseline & CKD progression 4 Q3-6months Q6-12months Q12months, or more frequently

if PTH is elevated 5 Q1-3months Q3-6months Which binder? “Any one will do”, Dr. Martin KJ, Work Group for KDOQI Lowering elevated P levels toward the normal range

Kidney Int. 2009;76(suppl 113s):S1-130

52

Mineral & Bone Metabolism Vitamin D’s

Calcitriol - Calcijex Paricalcitol - Zemplar Doxercalciferol - Hectorol

Monitoring Ca, Phosphorus Ca x PO4 products

53

Mineral & Bone Metabolism Phosphate Binding Agents

Aluminum base binders Calcium base binders (1500 mg/day) Non Calcium/Aluminum binders

Sevelamir HCl (Renagel) Lanthanum Carbonate (Fosrenol)

Monitoring Ca, PO4

54

Antimicrobials

Gram positives coverage: Cefazolin, nafcillin, vancomycin, linezolid (Zyvox), quinupristin/dalfopristin (Synercid), daptomycin (Cubicin), Tigecycline (Tygacil), others

Gram negative coverage: aminoglycosides, fluoroquinolones, 3rd gen cephalosporins, others

AntiFungals: e.g. Amphotericin, Fluconazole AntiVirals: e.g. Acyclovir

Dosages must be adjusted for renal failure

55

Antimicrobial: Cefazolin (Ancef, Kefzol)

SOA: sensitive staph & strepDose: nl 0.5-1.5 g, q8-6h, crcl <10 mL/min, q24-

48h. PKs: renal excretion (56-100%), t1/2 1.5-2.5 hrs (nl),

11-13 hrs (renal failure), 40-70 hrs (anephric)Dialyzable: YesHD: moderately dialyzable (20-50%), dose post-

HD, or 0.5-1 g supplemental dose post-HDPD: 0.5 g, q12hCAVH/CAVHD: removes 30 mg/liter of filtrate/dayAE’s & Precautions: GI (diarrhea), renal impairment

56

Antimicrobial: VancomycinSOA: MRSA, Staph & Streph PCN allergic patientsDose:q12hq24hq48h72hq96hq5-7days.PK: Renal excretion, t1/2 4-6hrs (nl RF), 7.5 days (avg anephric

pts)Dialyzability: Conventional membranes - not dialyzable (0-5%),

no longer used.Newer high-flux filter – dialyzable, dose post-HDNot significantly removed by CAPD, Clearance ~10-15 mL/min (CAHD)

AE’s: rash (red neck), chills, drug fever.Slow infusion, not exceeding 10 mg/min, extremely irritating

& may cause tissue necrosisPrecautions: avoid IM, presence of renal impairments/drugs,

pre-existing hearing loss, slow IV infusionsMonitor: Trough, Random levels (avoid level w/in 6hr post-HD;

wait ~20hrs)

57

Vancomycin Serum Levels in Patients Receiving High flux Dialysis

0 2 4 6 8 10 12 14 16 18 200

10

20

30

40

50 20 mg/kg QWeek20 mg/kg Load, 500 mg QDialysis

Time, days

Co

ncen

trati

on

, m

g/L

Matzke G. ACCP 2007 Spring Meeting

58

Aminoglycosides: Gentamycin, Tobramycin, Amikacin

SOA: serious infections, gram negative, staph

PK: Renal excretions (60-85%), t1/2 1.6-3 hrs (nl), 53 hrs (anephric)

Dialyzable (HD, PD, Hemoperfusion): Yes, dose post-HD

AE’s: ototoxicity, nephrotoxicity, neurotoxicity, edema, rash, GI’s

Precautions: other nephro/ototoxicity agents, impair renal function.

Monitor: Peak & trough, random levels

59

Unadjusted Associated ADRs

Drugs ADEs Associated with Unadjusted Dosage Regimens in CKD

Cefazolin Bleeding, seizures, tremors, thrombocytopenia Imipenem CNS toxicity, seizures Cefotetan Bleeding complications, prolonged PTT Ceftriaxone Bleeding complications Penicillin CNS toxicity, lethargy, seizures Acy-/Ganci -clovir

Seizures, confusion, renal damage

Ketorolac Nephropathy, ARF Nitrofurantoin Peripheral neuropathy Fluoroquinolones Torsades de Pointes, Achille tendonitis with ruptures,

hepatitis

CKD & Hypoglycemic Agents

What to do? Initiate low dose Monitor closely Avoid (many

agents)

60

CKD Decreased clearance Impaired

glucogenesisRisk Hypoglycemia Active metabolites Lactic acidosis Worsen fluid

retention

61

CKD & HYPOGLYCEMIC AGENTS

DRUG DOSING RECOMMENDATION CKD Stages 3, 4, or Kidney Transplant

Dialysis

2nd-Generation Sulfonylureas Glipizide (Glucotrol) Preferred Preferred Glimepiride (Amaryl) Initiate at Low Dose Avoid Gliclazide Not available in USA

Other Agents Thiazolidinediones: Pioglitazone (Actos), Rosiglitazone (Avandia)

Meglitinides: Repaglinide (Prandin) (reduce dose) Nateglinide (Starlix) (reduce dose-CKD; HD-avoid)

Incretin: Exenatide (Byetta) Amylin: Pramlintide (Symlin) (HD?) DDP-4 inh: Sitagliptin (Januvia) (reduce dose)

AVOID 1st generation sulfonylureas: Acetohexamide Chlorpropamide (Diabinese) Tolazamide (Tolinase) Tolbutamide (Tol-Tab)

2nd-gen SU: Glyburide (Micronase) Alpha-glucosidase inh: Acarbose (Precose)

Miglitol (Glyset)

Biguanides: Metformin (Glucophage)

Insulin

Interdialytic Agents

Hypertonic Solutions: 23.5% NS, 5%, NS, 3% NS Warning – JC Patient Safety High Alert

Normal Saline (NS) Plasma expanders: Albumin, Mannitol Sympatholytics: Midodrine

Alpha agonist, activates phospholipase C, effects smooth muscle contraction increasing BP

62

63

Multidisciplinary Care of CKD Patients

Joy et al. Am J Kidney Dis. 2005;45(6):1105-1118

8183-11U Master

64

PHARMACOLOGY IN RENAL DISEASE:

IN CONCLUSION

The kidney is the major excretory organ for many therapeutic agents and their metabolites.

It is imperative to consider renal function when reviewing drug therapy. Maximize therapeutic effects while

minimizing toxicity. Estimated CrCl is the only clinical tool

available for renal function.

65

Nurse’s Roles The processes of assessments, implementation, &

monitoring should be reassessed regularly The treatment plan (pharmacotherapy) should be

changed to accommodate the needs of the patient Neglecting may results in ineffective tx Nurse’s Role: More than just memorization of the

names or pharmacologic agents, their use, but requires a sound comprehension & application of the knowledge to a variety of clinical situations.

66

ANNA’s Jersey North: CNN Certification Review Course

QUESTIONS ???

Timothy Nguyen, BS, PharmD, CCP, FASCP

American Nephrology Nurses Association (ANNA)

Documents

Transcript of American Nephrology Nurses Association (ANNA)