American Nephrology Nurses
Association (ANNA)
PHARMACOLOGY IN RENAL
DISEASE
Timothy V. Nguyen, BS, PharmD, CCP, FASCP
Assistant Professor of Pharmacy Practice
Arnold & Marie Schwartz College of Pharmacy, LIU
Adjunct Pharmacology Professor
Saint Peter’s College
May 7, 2011
1
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
PHARMACOLOGY IN RENAL DISEASE
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.
3
DISEASE STATES OF THE KIDNEY


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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.
4
PHARMACOLOGY IN RENAL DISEASE
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
5
PHARMACOLOGY IN RENAL DISEASE
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
6
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
7
Renal Function – processes of




Filtration
Secretion
Reabsorption
Endocrine &
Metabolic Fx’s
8
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
9
NEPHRON (1 million)/kidney
Is the functional unit
of the kidney
Regions of the
nephron





Glomerulus
Proximal tubule
Loop of Henle
Distal Tubule
Collecting Duct
10
PHARMACOLOGY IN RENAL DISEASE




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.
11
Reabsorbed Fluids & Solutes in the Kidney
Filtered/day
Excreted/day
%
Reabsorbed
20,000mEq
110mEq
99+
NaHCO3
5000mEq
2mEq
99+
K+
700mEq
50mEq
93+
170 L
1.5 L
99+
NACl
H20
12
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
13
Mechanism of Kidney Clearance
Substances

Kidney

Creatinine Clearance
(~GFR)
(Filtration Process)




Measurement of GFR
Serum creatinine
level, eCrCl
MDRD
Cystatin C
14
PHARMACOLOGY IN RENAL DISEASE


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.
15
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
16
PHARMACOLOGY IN RENAL DISEASE
Calculating the CrCl
 79 YO, Female


Serum creatinine =1.2 mg/dL
(140-79)(65)x 0.85
(1.2)(72)
65 Kg
Important to note there is
a normal loss of
nephrons due to the
aging process.
Est. CrCl = 39
mL/min
17
Modification of Diet in Renal Disease
(MDRD) Study Formula
GFR
(mL/min/1.73m2) = 186x(Scr) -1.154 x (age)
(0.742, if female) x (1.212, if black)


-0.203
x
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…
18
Renal Disease Classifications
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
National Kidney Foundation. Am J Kidney Dis. 2002;39(suppl)
19
PHARMACOLOGY IN RENAL DISEASE
Pharmacokinetics

measures rise and fall
of drug concentrations
in the serum and tissue


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
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
20
Pharmacokinetic alterations in CKD
PK Parameters
Absorption
Distribution
Metabolism
Elimination
Alteration in CKD
, believed to be reduced
, reduced plasma protein binding
, accumulation of active metabolites
, decrease in nonrenal clearance
, increased accumulation
, increased toxicity
21
Pharmacotherapeutics


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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.
22
 Especially in pts with compromised organ function
PHARMACOLOGY IN RENAL DISEASE
DRUGS significantly
effected by Renal
Failure
 Aminoglycosides

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
Gentamicin
Tobramycin
Amikacin
Ganciclovir
Vancomycin
DRUGS exhibiting
sensitivities to Renal
Insufficiencies
 Sedatives


Narcotic analgesics


Barbituates
Meperidine (Demerol)
Antihypertensives
23
Drug dosing in CKD

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Anticipate problems
Minimize polypharmacy
Strategies
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Decrease dose
Increase Dosing Interval or BOTH
Methods
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Estimate CrCl
Consult Dosing recommendations – guidelines
Individualize Dose
Monitor Serum Drug Concentrations
24
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
25
Drug Dosing In Dialysis



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Maintenance dose based on anephric
status
Supplemental Dose - Replace amount of
lost drug
Establish Serum Drug Concentration
Monitoring
Water-soluble vitamins are dialyzable
26
COMPLICATIONS FROM CKD
Complications
Anemia
(see Table for anemia
management target
parameters recommended
by the NKF-KDOQI)
Cardiovascular Problems
(accounts for approximately
50% of all deaths)
Bone Metabolism
Renal Osteodystrophy
Dialysis Related
Electrolyte Disorders
Fluid Retention
Gastrointestinal Problems
Hepatitis
Nguyen TV. Consult Pharm. 2007
Possible Associations
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
Ischemic heart disease
Congestive heart failure
Hypertension
Pericarditis
Calcium, phosphate and vitamin D abnormalities (hypocalcemia,
decreased vitamin D production, hyperphosphatemia)
Vascular calcification
Hypotension
Dialyzer reactions
Dialysis technical problems
Metabolic acidosis
Hyperkalemia and electrolytes abnormality
Hypertension
Gastritis
Duodenitis
Peptic ulcer disease
Colonic arteriovenous malformations
B or C virus
COMPLICATIONS FROM CKD (con’t)
Increased bleeding tendency
Hematologic
Vascular access
Infection
Weaken immune system
Hypotension
Intradialytic
Muscle cramps
Complications
Dialysis disequilibrium syndrome
Arrhythmias and angina
Cardiac arrest
Occurs up to 50% of ESRD patients
Malnutrition
Diabetic peripheral neuropathy (may respond to
Neurologic
Problems
tricyclic antidepressants, carbamazepine, or
topical capsaicin)
Altered mental status
Uremic seizures
Sexual Dysfunction Impaired libido
Impotence
and Pregnancy
Infertility
Fatigue
Uremia symptoms
Nausea
Pruritis
Amyloidosis
Diabetes care
Special Issues
(other
Acquired Immunodeficiency Syndrome
complications)
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


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
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



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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
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
33
Beta Adrenergic Blocking Drugs

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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








Amlodipine (Norvasc)
Nifdipine (Adalat,
Procardia)
Isradipine (Dynacirc)
Felodipine (Plendil)
Nnisoldipine (Sular)
Verapamil (Calan,
Isoptin)
Diltiazem (Cardizem)
Others



Also used as:
antiangina,
arrhythmias
Cause negative
inotropic
Dizziness, HoTN
35
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
Dyslipidemias Management in CKD
LDL >100 mg/dL
or 3 months postlifestyle
modification
HMG CoA
Reductase
Inhibitor (Statin)
CKD stage 5,
fasting TG >500
mg/dL
Non-HDL >130
mg/dL
Fibrates or Niacin Lifestyle
(Gemfiprozil,
modification +
DOC)
Statin
(Fibrate if not
tolerate Statin)
Monitor: LFT, myopathy
NKF-K/DOQI. Am J Kidney Disease. 2003;41(suppl 3)
37
38
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
39
NKF-KDOQI Guidelines
NKF-KDOQI Target Treatment Goals for CKD Stage 5
Male: <13 g/dL
Anemia by Hgb
Female: <12 g/dL
Generally 11 to 12 g/dL
Target Hgb
Should not be >13 g/dL
Serum Ferritin: >200 ng/mL (insufficient
Target Iron Indices
evident for routine administration if sFerr
>500 ng/mL)
TSAT: >20%
Or
CHr >29 pg/mL
Monitor: Hb at least monthly
Iron Indices at every 1-3 months
NKF-KDOQI. Am J Kidney Dis. 2006;47(5):suppl 3., Am J Kidney Dis. Sept. 2007
40
ESA: EPO & Darbepoetin alfa
Revolutionized anemia management in CKD
Stimulate the production of RBC
Epoetin alfa, EPO (Epogen, Procrit)
Darbepoetin alfa (Aranesp)
 Similar to EPO but not identical
 Nearly identical structure to
chemical structures
endogenous erythropoietin
 Differs by an addition of two sialic acid
 Subcut administration > IV Push
components at the N-glycosylation site
 Usually TIW administration
 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
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
42
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
43
Recognizing Iron Deficiency in the HD Patient
Form
Indicator
Probable Cause
Absolute Iron
TSAT <20% and
’ed blood loss
Deficiency
sFerritin <100 ng/mL
’ed iron absorption
Functional Iron TSAT may be <20%
’ed stimulation of RBC
Deficiency
and sFerritin may be Production of EPO thx outstrips
100 – 700 ng/mL
iron supply
May develop even when storage
iron appears normal
RE Blockade
Acute or chronic inflammation
Dramatic  in
often seen in HD patient
sferritin along with
Blocks release of iron stores
drop in TSAT
from RES
NKF-KDOQI. Am J Kidney Dis. 2006; Fishbane. Am J Kidney Dis. 1997;29:319-333
IV Iron administration
Oral – not effective (HD)
Drug
Iron Dextran
Iron Gluconate
Iron Sucrose
Ferumoxytol
Anaphylactic Risk
Yes
Low
Low
Low
Test Dose
Yes
No
No
No
IV Push
Yes
Yes
Yes
Yes
Total Dose
Yes
No
No
510 mg
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
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 months
May monitor during iron maintenance schedule, no
need to interrupt dosing
Usually 1-2 wks after course completed

46
Hyporesponsive Issues
Comobidities: DM, HTN, Cardiovascular disease,
Frequent hospitalizations, blood loss, CA, AIDS
Infection, Inflammation
Iron deficiency (Absolute & Functional)
Aluminum toxicity
Pure Red Cell Aplasia (PRCA)
Hypoalbuminemia
Elevated C-reactive protein level
Temporary & permanent catheter insertions
47
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 evidence
Not recommended: Androgens
48
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
49
NKF-KDOQI Target Treatment Goals for
CKD Stage 5
Serum
Phosphorus
3.5 – 5.5
mg/dL
Corrected
serum
Calcium
8.4 – 9.5
mg/dL
Ca x P
Product
Intact
plasma PTH
<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)
50
The New KDIGO
Ca, P, PTH, Alk Phos – should be monitored regularly; adjust according to trends rather than
specific target values
iPTH
Above the assay’s upper limit
CKD
3
4
5
Ca & P
Q6-12months
Q3-6months
Q1-3months
CKD stages 3-5
Evaluate for hyperP, hypoCa,
& vit D deficiency
Treatment w/vitamin D is
suggested if progressively
rises & remains above the
upper-normal limit
Monitoring Intervals
PTH
Baseline & CKD progression
Q6-12months
Q3-6months
Dialysis
Maintain ~2-9 times uppernormal limit (~130-600
pg/mL)
Alk Phos
Q12months, or more frequently
if PTH is elevated
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
51
Mineral & Bone Metabolism

Vitamin D’s




Calcitriol - Calcijex
Paricalcitol - Zemplar
Doxercalciferol - Hectorol
Monitoring


Ca, Phosphorus
Ca x PO4 products
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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
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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
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Antimicrobial: Cefazolin (Ancef, Kefzol)
SOA: sensitive staph & strep
Dose: nl 0.5-1.5 g, q8-6h, crcl <10 mL/min, q2448h.
PKs: renal excretion (56-100%), t1/2 1.5-2.5 hrs
(nl), 11-13 hrs (renal failure), 40-70 hrs
(anephric)
Dialyzable: Yes
HD: moderately dialyzable (20-50%), dose postHD, or 0.5-1 g supplemental dose post-HD
PD: 0.5 g, q12h
CAVH/CAVHD: removes 30 mg/liter of filtrate/day
AE’s & Precautions: GI (diarrhea), renal impairment
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Antimicrobial: Vancomycin
SOA: MRSA, Staph & Streph PCN allergic patients
Dose:q12hq24hq48h72hq96hq5-7days.
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-HD
Not 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 necrosis
Precautions: avoid IM, presence of renal impairments/drugs, preexisting hearing loss, slow IV infusions
Monitor: Trough, Random levels (avoid level w/in 6hr post-HD; wait
~20hrs)
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Vancomycin Serum Levels in Patients
Receiving High flux Dialysis
20 mg/kg QWeek
20 mg/kg Load, 500 mg QDialysis
Concentration, mg/L
50
40
30
20
10
0
0
2
4
6
8
10
12
14
16
18
20
Time, days
Matzke G. ACCP 2007 Spring Meeting
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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
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Unadjusted Associated ADRs
Drugs
ADEs Associated with Unadjusted Dosage
Regimens in CKD
Bleeding, seizures, tremors, thrombocytopenia
CNS toxicity, seizures
Bleeding complications, prolonged PTT
Bleeding complications
CNS toxicity, lethargy, seizures
Seizures, confusion, renal damage
Cefazolin
Imipenem
Cefotetan
Ceftriaxone
Penicillin
Acy-/Ganci clovir
Ketorolac
Nephropathy, ARF
Nitrofurantoin
Peripheral neuropathy
Fluoroquinolones Torsades de Pointes, Achille tendonitis with ruptures,
hepatitis
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CKD & Hypoglycemic Agents
CKD
 Decreased clearance
 Impaired glucogenesis
Risk
 Hypoglycemia
 Active metabolites
 Lactic acidosis
 Worsen fluid retention
What to do?
 Initiate low dose
 Monitor closely
 Avoid (many agents)
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CKD & HYPOGLYCEMIC AGENTS
DRUG
DOSING RECOMMENDATION
CKD Stages 3, 4, or
Dialysis
Kidney Transplant
nd
2 -Generation Sulfonylureas
Preferred
Preferred
Glipizide (Glucotrol)
Initiate at Low Dose
Avoid
Glimepiride (Amaryl)
Not available in USA
Gliclazide
Other Agents
Thiazolidinediones:
Meglitinides:
Incretin:
Pioglitazone (Actos),
Repaglinide (Prandin)
Exenatide (Byetta)
Rosiglitazone (Avandia)
(reduce dose)
Amylin: Pramlintide
Nateglinide (Starlix)
(Symlin) (HD?)
(reduce dose-CKD; HDDDP-4 inh: Sitagliptin
avoid)
(Januvia) (reduce dose)
AVOID
st
nd
1 generation
2 -gen SU:
Biguanides:
sulfonylureas:
Glyburide (Micronase)
Metformin (Glucophage)
Acetohexamide
Alpha-glucosidase inh:
Chlorpropamide
Acarbose (Precose)
(Diabinese)
Miglitol (Glyset)
Tolazamide (Tolinase)
Tolbutamide (Tol-Tab)
Insulin
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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
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Multidisciplinary Care of CKD Patients
Joy et al. Am J Kidney Dis. 2005;45(6):1105-1118
63
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.
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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.
65
ANNA’s Jersey North: CNN Certification
Review Course
QUESTIONS ???
Timothy Nguyen, BS, PharmD, CCP, FASCP
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