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. Overview.
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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
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.
End Stage Renal Disease In The United States *:
A profile of kidney failure patients in the U.S. follows: (2000)
* National Kidney Foundation 2005
Leading causes of kidney failure in the US *
National Kidney Foundation data 2003
Is the functional unit
of the kidney
Regions of the nephron
Intermittent availability, high cost, invasiveness, sample preparation, & assay variability limits its use in the clinical setting.
(140-age)(body weight in kg)
Women x 0.85
(140-79)(65)x 0.85 (1.2)(72)
Est. CrCl = 39 mL/min
Calculating the CrCl
Important to note there is a normal loss of nephrons due to the aging process.
GFR (mL/min/1.73m2) = 186x(Scr)-1.154 x (age) -0.203 x (0.742, if female) x (1.212, if black)
Other Methods: CKD-EPI, Cystatin, etc…
National Kidney Foundation. Am J Kidney Dis. 2002;39(suppl)
measures rise and fall of drug concentrations in the serum and tissue
T1/2 : the time it takes to eliminate 50% of the drug from the body
What the drug does to the body
integrates microbiological activity focusing on biological effects, particular growth inhibition and killing of pathogens
DRUGS significantly effected by Renal Failure
DRUGS exhibiting sensitivities to Renal Insufficiencies
Johnson et al. 2005 Dialysis of Drugs
Nguyen TV. Consult Pharm. 2007
Nguyen TV. Consult Pharm. 2007
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).
(In the treatment AKI, large randomized trials have failed to prove diuretics to be effective)
NKF-K/DOQI. Am J Kidney Disease. 2003;41(suppl 3)
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
NKF-KDOQI. Am J Kidney Dis. 2006; Kalantar-Zadeh, et al. Nephrol Dial Transplant. 2004;19:141-149
NKF-KDOQI. Am J Kidney Dis. 2006; Fishbane. Am J Kidney Dis. 1997;29:319-333
Oral – 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
Monitor: every 1 to 3 months
May monitor during iron maintenance schedule, no need to interrupt dosing
Usually 1-2 wks after course completed
Comobidities: DM, HTN, Cardiovascular disease,
Frequent hospitalizations, blood loss, CA, AIDS
Iron deficiency (Absolute & Functional)
Pure Red Cell Aplasia (PRCA)
Elevated C-reactive protein level
Temporary & permanent catheter insertions
Vitamin C (Ascorbate)
Conclusion: Insufficient evidence
Not recommended: Androgens
NKF-KDOQI. Am J Kidney Dis. 2003;42(suppl 3)
Kidney Int. 2009;76(suppl 113s):S1-130
Dosages must be adjusted for renal failure
SOA: sensitive staph & strep
Dose: 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)
HD: moderately dialyzable (20-50%), dose post-HD, 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
SOA: MRSA, Staph & Streph PCN allergic patients
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, pre-existing hearing loss, slow IV infusions
Monitor: Trough, Random levels (avoid level w/in 6hr post-HD; wait ~20hrs)
Matzke G. ACCP 2007 Spring Meeting
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
What to do?
Initiate low dose
Avoid (many agents)
Worsen fluid retention
Joy et al. Am J Kidney Dis. 2005;45(6):1105-1118
Timothy Nguyen, BS, PharmD, CCP, FASCP