12-pharm care in ckd
Post on 03-Apr-2018
215 Views
Preview:
TRANSCRIPT
-
7/28/2019 12-Pharm Care in CKD
1/19
Pharmacotherapy
of
Chronic Kidney Diseases
Denpong Patanasethanont., Ph.D.Division of Pharmacy Practice
Faculty of Pharmaceutical Sciences
Khon Kaen University
Advanced Pharmacotherapeutics I/ November 13th 2008
Professional education resources on
management of CKD
l National Kidney Foundation, Kidney Disease OutcomeQuality Initiative (K/DOQI)
www.kidney.org/professionals/doqi/index.cfm
l National Kidney Disease Education Program
www.nkdep.nih.govl Veterans Affairs/Department of Defense clinical practice
guideline on pre-ESRD care
www.oqp.med.va.gov/cpg/ESRD/ESRD-Base.htm
l Nephrology Section of Yale University of Medicine
http://kidney.med.yale.edu/pages/Entry.html
Stage of chronic kidney disease
Stage Description GFR (ml/min/1.73m2)
1 Kidney damage withnormal or increase GFR
>90
2 Kidney damage with
mild decrease GFR
60-89
3 Moderate decrease GFR 30-59
4 Severe decrease GFR 15-29
5 Kidney failure
-
7/28/2019 12-Pharm Care in CKD
2/19
CKD
death
Stages in Progression of Chronic KidneyDisease and Therapeutic Strategies
Complications
Screening
for CKD
risk factors
CKD risk
reduction;
Screening for
CKD
Diagnosis
& treatment;
Treat
comorbid
conditions;
Slow
progression
Estimate
progression;
Treat
complications;
Prepare for
replacement
Replacement
by dialysis
& transplant
NormalIncreased
risk
Kidney
failureDamage GFR
Am J Kidney Dis 39:S1246, 2002
Optimal care by NKF stages of CKD
components Stage
1 2 3 4 5
Dx and Tx yes yes yes yes yes
Tx of comorbid conditions yes yes yes yes yes
Slowing progression yes yes yes yes -
CVD risk reduction yes yes yes yes yes
Estimating progression - yes yes yes yes
Evaluating and treating - - yes yes yes
complications
Preparation for RRT - - - yes -
RRT (if uremia present) - - - - yes
l preparing for end-stage renal disease (ESRD)l initiation of renal replacement therapy (RRT)
l adequate medical and psychological preparation
Critical step in the care of patients with CKD
Timing and quality of care
prior to dialysis
morbidity and mortality of ESRD
Quality-of -life
-
7/28/2019 12-Pharm Care in CKD
3/19
Renal insufficiency
Acute renal failure (ARF)
Chronic kidney disease (CKD)
Drug dosing adjustment ?
Closely monitoring?
Renal excretion of drugs
Glomerular filtration
Tubular secretion
Tubular reabsorption
CASE STUDY
65 y/o male, 42 Kg, 168 cm.
CC: Short of breath, urine
l Underlying mod. MR c MS c chronic AF c CKD stage 3,
no DM, no HTN
l H/O gross hematuria from coumadin overdose last admit
14-21/11/50
l On coumadin(3) 1x1, Simvastatin(20) 1x1, moduretic 1x1
l PE: VS; PR 160, BP 98/66, BT 37.2, RR 24
crepitation both lung, active precordium, heaving thrill
positive
l Imp. 1. Mod. MR c MS c chronic AF
2. Lt. side heart failure
3. CKD stage 3
l Lab.29/11/50
BUN 42, Scr 2.2,
Na 137, K 4.8, Cl 108, Ca 8.9, PO4 4.2, Mg 2.7
Hgb 14, Hct 43.6, PT 36.4, PTT 34.6, INR 3.05
l Medication:
One day Lasix (40) IV stat
Digoxin (0.25) IV stat.
Diltiazem (30) tab, po q 8 h
Continue Coumadin(3)1x1 po hs
Simvastatin(20) 1x1 po hs
Digoxin (0.25) po EOD
Co-morbid condition
CKD stage 3, GFR 30-59 ml/min
l Decrease in Ca absorption
l Lipoprotein activity falls
l
Malnutritionl Onset of LVH
l Onset of anemia (erythropoietin deficiency)
l Hypertension (mild)
-
7/28/2019 12-Pharm Care in CKD
4/19
l improve morbidity and mortality
l
prevent or delay progression ofkidney disease
Current Treatment
Biologic consequences of sustained reduction in GFR
Plasma conc.
Normal range
Total GFR (%of normal)
Overt renal
failureZone of compensation
(adequate renal reserve)
A
B
C
A = creatinine
and urea
B = PO4, urate,
K+, H+
C = NaCl
0 25 50 75 100
CKD and complications
lDecrease in Ca absorption
lLipoprotein activity falls
lMalnutrition
lOnset of LVH
lOnset of anemia
(erythropoietin deficiency)
lHypertension (mild)
30-593
lPTH start to rise
lHypertension possible
60-892
>901
complicationsGFRStage
CKD and complications
lTriglyceride conc. start to rise
lHyperphosphatemia
lMetabolic acidosis
lTendency to hyperkalemia
lHypertension (moderate)
15-304
lAzotemia develops
lHypertension (severe)
-
7/28/2019 12-Pharm Care in CKD
5/19
CASE STUDY
l 32 63 158 type1 DM 15 1 BS > 200, A1C>8%
l Na 143, K 5.3, Cl 106, CO2
18, SCr 2.9 mg/dL,
BUN 63, BS 220, PO4 7.6, Ca 8.8, Mg 2.8, uric
acid 8.8
l Hct. 26, Hgb 8.7, WBC 9600, RBC indices
normal, Plt 170000,
l UA: 4+ proteinuria, Alb 700 mg/day (normal
-
7/28/2019 12-Pharm Care in CKD
6/19
Recommendations for glycemic control in DM
Goal values
Normal
value
Glycemic
measureAmerican college of
EndocrinologyAmerican Diabetes
Association
-
7/28/2019 12-Pharm Care in CKD
7/19
Recommendations from Treatment guidelines
ACEI,ARBProteinuria < 1 g/d:/= 1 g/d:
-
7/28/2019 12-Pharm Care in CKD
8/19
Tobacco Cessation
l Smoking, in a dose- dependent manner,increase urinary excretion of albumin
l There is also evidence that smoking may
accelerate a decline in GFR
l The guidelines recommended that all clinicians,
including pharmacists, provide smokingcessation interventions
l Five As is suggested to provide smoking
cessation counseling
Anemia
l progressive erythropoietin deficiency
l Iron deficiency
l normochromic, normocytic anemia
l Early treatment of anemia
l decreased hospitalizations for CVS
complications (LVH)l improved survival, exercise capacity,
cognitive function, quality of life
l CKD => Left ventricular hypertrophy
l 39% in GFR
-
7/28/2019 12-Pharm Care in CKD
9/19
Erythropoiesis-stimulating agents
Recommended to read;
l Cardiovascular Risk Reduction in Early Anemia
Treatment with Epoetin Beta (CREATE)(Dreke TB et al. N Engl J Med. 2006;355:2071-2084)
l Correction of Hemoglobin and Outcomes in
Renal Insufficiency (CHOIR) trials
(Singh AK et al. N Engl J Med. 2006;355:2085-2098)
Erythropoiesis-stimulating agents
l Epoetin alfa (EPIAO, EPREX, ESPOGEN, HEMAX)l 25 -50 IU/kg iv. or sc. 3X/wk
l Adjust increase 25 IU/Kg q 4 wk then 75 IU/ kg 3X/wk
l Epoetin beta (RECORMON)l Sc. : 20 IU / kg 3x/wk, adjust increase 20 IU / kg q 4 wk.
l iv : 40 IU / kg 3x/wk for 4 wk then adjust increase 80 IU/kg
l Maximum dose : 720 IU/ kg /week
There have been no reports that epoetin alfa differs fromepoetin beta in its clinical efficacy
l Darbepoetin ARANESP
l Half-life: 3x of Epoetin alfa (i.v.)
l 0.45 g/kg once a week.
l 0.75 g/kg q 2 weeks
Administration of Epoetinl The dosage of epoetin is individual with more than
tenfold variability among individuals
l no clinical parameters of predicting the necessarydosage.
l Therapeutic range is very wide (up to 100.000IU/week.)
l The HB concentration, along with the reticulocytecount, must be checked
l Initiation: weekly
l Maintenance: monthly
l stable dose-response: every 2-3 months
l The target Hb concentration 11-12 g/dL ismaintained in 90-95% of the patients by
administering
l 1.000-30.000 IU of epoetin per week or
l 5-150 mcg darbepoetin alpha per weekin the presence of adequate reserves of iron.
l Higher dosages define a state of resistance.
Administration of Epoetin (cont.)
-
7/28/2019 12-Pharm Care in CKD
10/19
Erythropoiesis-stimulating agents
l For all patients:l Adhere to dosing to maintain the recommended target
hemoglobin range of 10 to 12 g/dL.
l Measure hemoglobin twice a week for 2 to 6 weeksafter any dosage adjustment to ensure thathemoglobin has stabilized in response to the dosechange.
l Decrease the dose of the ESA if the hemoglobinincrease exceeds 1 g/dL in any 2-week period.
l For CKD patients:l Measure hemoglobin twice a week after initiating
treatment until hemoglobin has stabilized
US FDA Issues Safety Warning on Erythropoietin
Hyperparathyroidism
and Renal Osteodystrophy
l CKD => hypocalcemia => increase in parathyroidhormone levels => bone metabolism abnormality=> renal osteodystrophy
l Inability of kidney to activate vitamin D needed for
calcium absorption from the gut=> phosphate retention
l complications ; soft tissue calcification, pruritus,proximal myopathy, skin ulceration, soft tissuenecrosis
=> impaired pulmonary & heart
Frequency of Measurement of
PTH, Ca, PO4
Every moEvery 3 mo
-
7/28/2019 12-Pharm Care in CKD
11/19
Phosphate Binder
l Calcium product
l Aluminium hydroxide
l Calcium-Aluminum free
Phosphate Binderl Calcium carbonate (40% elemental calcium)
l
l > 6 g/day
l 20-30% absorbed
l 39 mg phosphate bound per 1 g CaCO3
l Try to limit daily intake 1.5 g of elemental Ca per day
l Calcium acetate (25% elemental calcium)l 3 g/dayl
l Absorption with meal: 20%, between meal 40%
l
l Do not exceed 1.5 g of elemental Ca per day
l 45 mg phosphate bound per 1 g Ca acetate
l GI side effects, constipation, hypocalcaemia, extraskeletal calcification
Phosphate Binderl Aluminium hydroxide
l Calcium-Phosphate product > 55 mg2/mL2
l Reserve for short-term 4 weeks
l Do not use concurrently with citrate-containing products
l ADR:
l Constipation/fecal impaction
l Bone mineral defects
lAnemia, Dementia
l Chalky taste, GI distress, N/V
l Liquid: (6.1% suspension)
l Mean binding 22.3 mg phosphate per 5 mL(320 mg/5mL)
l Tablets (500 mg)
l Mean binding 15.3 mg per pill
Phosphate Binder
l Calcium-Aluminum freel Sevelamer hydrochloride (Renagel)
l Sevelamer carbonate (Renvela) less GI S/E
l Poly (allylamine hydrochloride),
l a polymeric amine oral administration
l No absorption
l no hypercalcemia
l Lowers LDL cholesterols, uric acid
l more expensive
-
7/28/2019 12-Pharm Care in CKD
12/19
Sevelamer Hydrochloride
l Renagell film-coated tablet 800 mg or 400 mg
l indicated for the control of serum
phosphorus in patients with chronic kidneydisease (CKD) on dialysis
l 80 mg Phosphate bound per mgSevelamer (animal data only)
l Decrease bioavailability of Ciprofloxacin50%
Sevelamer Hydrochloride
4 tablets three times
daily with meals
2 tablets three times
daily with meals 9.0 mg/dL
3 tablets three times
daily with meals
2 tablets three times
daily with meals
7.5 and
< 9.0 mg/dL
2 tablets three times
daily with meals
1 tablet three times
daily with meals
> 5.5 and
< 7.5 mg/dL
400 mg800 mgSerum Phosphorus
Product information
Sevelamer Hydrochloride
5 tablets3 tablets3 tablets
3 tablets2 tablets2 tablets
2 tablets1 tablet1 tablet
400 mg
(Tablets per meal)
800 mg
(Tablets per meal)
Calcium Acetate
667 mg
(Tablets per meal)
Product information
Sevelamer Hydrochloride
Decrease 1 tablet per meal< 3.5 mg/dL
Maintain current dose3.5 - 5.5 mg/dL
Increase 1 tablet per meal
at 2 week intervals> 5.5 mg/dL
DoseSerum
Phosphorus
Product information
The average dose in a Phase 3 trial designed to
lower serum phosphorus to 5.0 mg/dL or less was
approximately three of 800 mg tablets per meal.
The maximum average daily dose studied was 13 g.
-
7/28/2019 12-Pharm Care in CKD
13/19
Vitamin D
l PTH > 110 pg/mL
l and/or Ca < 9.5 mg/dL
l and/or PO4 < 4.6 mg/dL
l Alfacalcidal (0.25 g, 0.5 g , 1 g)
l (Alpha D3, One-alpha , Bon-One )
l 0.25-1 g OD X3/wk
l Calcitriol (0.25 g)
l (Rocaltrol, Calcit SG, Decostriol, Osteo D)
l 2-4 g OD x3/wk
Vitamin D
Dosing recommendations for calcitriol
in stage 5 CKD on hemodialysis
If Ca < 9.5 mg/dL, PO4 < 5.5 mg/dL, Ca x PO4 < 55 mg2/dL2
3-7 oral
or 3-5 g IV
>1000
1-4 g oral
or 1-3 g IV
600-1000
0.5-1.5 g oral or IV300-600
IV and oral Calcitriol
Dose per HD
iPTH (pg/mL)
Eknoyan G, Am J Kidney Dis 2003;42:1-201
Protein Diet
l RDA = 0.8 g/kg/day
l Thai RDA = 50 g/day
Recommended for CKD patients (USA)l GFR > 30 mL/min/1.73 m2
(or plus proteinurea >3g/day)
l Protein intake 0.75 g/kg/day
l ( )
l GFR < 30 mL/min/1.73 m2
l Not more than 0.6 g/kg/day
Protein Diet (cont.)
l High biological value protein
l ,l 60%
l l 1 = 2 2
l 0.6-0.75 g/kg/day 1 1 (3 )
-
7/28/2019 12-Pharm Care in CKD
14/19
Protein Diet (cont.)
l l l l
l
l () () l ()l l ( )
l l
Salt (NaCl)
According to JNC VII
l Normal BP with
l Type 2 DM, CKD, RRT, Pitting edema, including of
Nephrotic syndrome
l NaCl not more than 6 g/day
l Hypertension
l Not more than 4 g/day (or 5 g/day)
l Avoid instant food, seasoning, Food in restaurant
Salt (NaCl)
Recommend for normal people102.542358.96
Recommended by ESH and ESC 2007
for Hypertension
85.471965.85
Recommended by JNC VII
for Hypertension
68.371572.64
Remark
Na
(mEq)
Na
(mg)
NaCl
(g)
15
10
MW Na = 23
Cl = 35.5
Sodium bicarbonate
l When HCO3- < 17 mEq/L
l Supplement 0.5-1.0 mEq/kg/day
l Titrate to bicarbonate level 18-20 mEq/L
l !! ! Sodium content!!!!
l Sodamint (Sodium bicarbonate) (Sodamint 300 mg)l 1 mEq NaHCO3 = 84 mg (sodium content 23 mg)
l 300 mg = HCO3- ~ 3.7 mEq (sodium content ~82 mg)
l 650 mg = HCO3- ~ 8 mEq (sodium content ~178 mg)
l Shohls solution (Sodium citrate)
l 140 g citric acid and 98 g hydrated crystalline salt ofsodium citrate, distilled water to make 1000 ml;
l 1 mL = 1 mEq
l
-
7/28/2019 12-Pharm Care in CKD
15/19
Renal insufficiency
Effect to Pharmacokinetics
l Absorptionl Uremic gastroparesis can alter rate of drug absorption
l Gastric pH
l
Gastrointestinal tract edemal Vomitting and diarrhea
l Antacid or cholestyramine
l Distributionl Edema or ascites
l increase Vd of water soluble drugs
l Uremic statesl alter plasma protein binding
l Tissue protein binding is reduced decrease Vd
l Metabolism
l Hepatic biotransformation may be altered
l Excretion
l
Most important pharmacokinetic parameters alteredl Creatinine clearance is the guiding factor for drug
dosage
l Clinical pharmacokinetics approach for narrow
therapeutic index may be altered
Renal insufficiency
Effect to Pharmacokinetics (cont.)
Steps to Adjust Drug Dosages
for Patients with Renal Insufficiency
Important points for patient with dialysis
Dialysis can remove drug?
Dosing supplementation is necessary?
Resources for More Information
About Dosing Adjustments
in Patients with Chronic Kidney Disease
-
7/28/2019 12-Pharm Care in CKD
16/19
Determination of renal function
Clcrusing Cockcrof&Gaults equation**
Clcr= (140-age)(LBW) (0.85 if female)72 Scr
*Unit = mL/min/1.73 m2, A 70 kg/1.73 m2BSA is assumed
MDRD study equation**
GFR = 186 (Scr)-1.154 (Age)-0.203(0.742 if female)
(1.210 if African-American)
l **MDRD: Modification of diet in renal disease
l Age >18 year-old
l **Unit = mL/min/1.73 m2, > 60 mL/min/1.73m2 is not exact number
Equations for Predicting Creatinine Clearance
or GFR in Adults with Kidney Disease
Estimated baseline creatinine
base on MDRD formula
age male female
20-24 1 . 3 1 . 0
25-29 1 . 2 1 . 0
30-39 1 . 2 0 . 9
40-54 1 . 1 0 . 9
55-65 1 . 1 0 . 8
>65 1 . 0 0 . 8
24 hour urine collection (mL/min)CrCl = Ucr V
Scr T
l CrCL= creatinine clearance (mL/min)
l Ucr = urinary creatinine conc. (mg%)l V= Volume of urine during collection period (mL)
l Scr = serum creatinine concentration (mg%)
l T = collection time (min) (if 24 hr = 1440 min)
Determination of renal function (cont.)
-
7/28/2019 12-Pharm Care in CKD
17/19
24 hour urine collection
CrCl = Ucr(g/Vol) X Vol (L)
Scr(mg/dL) x T(day)
= Ucr(g/Vol) X Vol (L) x 103
Scr(g/L) x T(min) x (24x60)(102)
CrCl = 6.94(Ucr/Scr)
CrCl ~ 7(Ucr/Scr)
l Protein report g volume (L) Urine
ACEI
25-5050-75100Lisinopril
5075-100100Enalapril
5075100Captopril
50
25-5050-75100Ramipril
7575-100100Quinapril
75-100100100Fosinopril
% of usual Dose
based on GFR mL/min/1.73 m2Drug
American Family Physician Web site atwww.aafp.org/afp
Case Study
l 60 y/o male 90 kg; infected CAPD
l PDF : staphylococcus coagulase negative
sensitivity: Vancomycin
on Vancomycin 1 G + D5W 200 ml IV in 2 hr.
q 96 hr. start 25/10/50
l Vancomycin conc. on 29/10/50 = 7.19 mg/L
Target Vancomycin trough
l For MRSA with MIC 2 mcg/ml
l 50% Protein binding
l Target trough => 4-5 times the MIC
l Target trough = 15-20 mcg/ml
l 20% lower response rate in pt. who did not
achieve target trough initially(76% vs 56%,
p=.05; Hidayat et al. 2006)
http://www.aafp.org/afphttp://www.aafp.org/afp -
7/28/2019 12-Pharm Care in CKD
18/19
l Predicted Cmax after 1st dose
Cmax1 = [1000mg/59.5L] x e -0.0056x2
= 16.64 mg/L
l Cmin1 = 7.19 mg/L (measured level)
l Cmax2 = 7.19 + 16.64 = 23.83 mg/Ll Cmin2 = 23.83 x e -0.0056x96
= 13.82 mg/L
l Cssmax = 39.62 mg/L
l Cssmin = 23.21 mg/L
16.64
7.19
23.83
13.82
39.62
23.21
30
15
Time
Conc.
40
l To help reduce drug-induced CKD in
primary care
l comprehensive drug histories
l prescribing of appropriate dosages
l avoidance of nephrotoxins in pt with underlying
renal problems
l monitoring of nephrotoxic drug therapies
Many pharmacologic agents
can cause kidney damage
Avoidance/Precaution
for patient with CKD
l Pharmacologic agents
l IV radiographic contrast agents
l selected antimicrobials : AMGs, amphotericin B
l NSAIDs (including COX-2 selective inhibitors)
l cyclosporine and tacrolimus
l Volume depletion
l Obstruction of the urinary tract
l The benefits of ACEI and ARB outweigh the
risks; titrating dosage will minimize the risk
of kidney damage
-
7/28/2019 12-Pharm Care in CKD
19/19
Assessment of nephrotoxicity
Identification of drug-induced nephrotoxicity
l a change in Scr of at least 0.5 mg/dL for subjects with a baseline
Scr 2 mg/dL, whencorrelated temporally with the initiation of drug therapy
l Serum creatinine or BUN concentrations and urine
collection for creatinine
l intrasubject between-day variability of Scr (20% within thenormal range).
Potential roles and responsibilities
l Attainment of blood pressure goal
l Attainment of glycemic goals in those with diabetes
l Early evaluation and treatment for proteinuria
l Early evaluation and therapy for anemia
l Early evaluation and therapy for secondaryhyperparathyroidism
l Attainment of lipid goals, where appropriate
l Appropriate drug dosing adjustments
l Minimization of drug-related nephrotoxin exposure
l Provision of drug therapy instruction
l Screening for ability to afford drugs
l Education regarding smoking cessation, whereappropriate
top related