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DRUGS THERAPY

FOR KIDNEY
Budi Raharjo

Function of Kidney
Excretion of waste product
e.g.Hydogen ion, Water

Biosynthesis and Metabolim of


hormone
e.g. Renin, Insulin, Erythropietin

Regulation of homeostasis
e.g. Fluid, Electrolyte and Acid-base
balance

Renal Function Test

Renal Function Test


Serum Creatinine
Creatinine Clearance
Urea (Blood Urea Nitrogen)
Miscellaneous

Serum Creatinine
(Male 0,6-1,2 mg/dL; Female 0,2-0,4
mg/dL)

By product of muscle metabolism


Rate of formation proportional to
muscle mass
Freely filtered by glomerolus (little
secretion or reabsorption by tubule)
Indicator of renal function, but..
Factor affecting serum creatinine:
Diet, time of day, age, sex, exercise,
drugs

Caution in unstable renal function or


acute renal disease

Creatinine Clearance
Measurement of creatinine
clearance give an estimate of GFR
(Glomerular Filtration Rate)
Creatinine clearance varies with
age, sex, and size
Measurement:
Urine collection
Cockroft and Gault Equation

Creatinine Clearance
Normal reference = 120 ml/min
Renal disorder if: 60 < CrCl < 120
ml/min symptomless
Renal insuficiency:

Mild
Moderate
Severe
ESRD
(End State

20 50 ml/min
10 20 ml/min
< 10 ml/min
< 5 ml/min
of Renal Disease)

Urine Collection
Accurate collection of over 24 hour
periode (note problems with patient
compliance)
Plasma sample midway through 24 hour
periode
U x V
Clcr = ------------S
U = Urine Creatinine concentration (mg/dL)
V = Urine flow rate (ml/min)
S = Serum Creatinine concentration
(mg/dL)

Cockroft & Gault Equation


F x (140 age) x IBW
ml/min
CrCl =
Serum Cr (mg/dL) x 72
F = 1,23 (males)
F = 1,04 (females)
IBW (Ideal Body Weight)
Males
TB > 152,5 cm IBW = 50 + [(TB - 152,4) x 0,89]
TB < 152,5 cm IBW = 50 - [(152,4 - TB) x 0,89]

Females
TB > 152,4 cm IBW = 45,5 + [(TB - 152,4) x 0,89]
TB < 152,4 cm IBW = 45,5 - [(152,4 - TB) x 0,89]

Limitation of
Cockroft & Gault Equation
Cannot be used if
Age < 15 years old or age > 90 years old
Renal function is changing rapidly
Pregnancy (GFR + 20 %)
Serum creatinine > 3 x normal range
Amputated limb

Blood Urea Nitrogen


(8 18 mg/dL)
Urea Nitrogen is an end product of
protein metabolism
Produced by the liver, transported in
blood and excreeted by the kidney
Freely filtered by glomerolus, partly
reab-sorbed by the tubules
use as a screening test for renal
disfunction, not quantify the extend of
renal disease

Blood Urea Nitrogen


BUN in:
Acute or chronic renal failure
High protein intake in diet
Increased catabolism (infection, surgery)
Uper GI bleeding or esophageal varices
(blood converted to ammonia by bacteria)
Dehydration or water depletion
BUN in:
End state of liver disease ( formation)
Water axcess (dilution)

Miscellaneous
Increased potassium
Decreased bicarbonate
Increased phosphate
Decreased calcium
Altered sodium levels
Disturbed fluid balance

Implications for Clinical


Pharmacy Practice
Drug choice in patient with renal disease
Pharmacokinetics

General guidelines regarding drug choice


in patient with renal disease
Dosage adjusment in patient with renal
disease

Pharmacokinetics
Absorption
Oral absortion reduce by vomitting, nausea,
diarrhoea, GI oedema & changes in blood pH
Little clinical significance

Distribution
Volume distribution (Vd) due to
oedema/ascites; Vd due to dehydration
(Little clinical significant: Aminoglycoside,
Lithium)
Protein binding (Pb) due to protein loss or Pb
due to uraemia; increase free drugs;
temporary effect; caution in interprete drug
level (Clinical Significant: Phenytoin, Warfarin)

Pharmacokinetics
Metabolism
Hepatic metab. unaffected in renal impairment
Clinical significant of impaired renal
metabolism:
Accumulation of active metabolite
Vitamin D replacement
Insulin requirement

Excretion
Elimination of drug or its metabolites may be
decreased
Most important parameter to consider when
making dosage decissions

General Guidelines
Only use drugs if a definite indication
Choose drugs with minimal nephrotoxic
effect and avoid potentially nephrotoxic
drugs
Increased sensitivity to certain drug
effects
Monitor and act on plasma levels
Check appropriate dosage adjustment
Avoid prolonged courses of potentially
toxic drugs
Monitor for clinical efficacy and evidence
of toxicity

Drugs in Renal Disease:


Clinical Pharmacy Practice
Point
Identification of patient with
renal disease (Acute/Chronic
Renal Disease)
Monitoring of renal function
(including dose adjustment)
Assessment of current and
proposed drug treatment

Dosage Adjustment
Loading dose is usually unchanged (except
for digoxin and gentamycin)
The most common maintenance dosage
changes are to decrease the dosage or
increase the dosage interval or both
Refference sources:
BNF
Data Sheet / Drugs leaflet
Bennett: Drugs and renal desease

Dosage Adjustment
DRrf = DRn x [(1 - Feu) + (Feu x RF)]
Patient creatinine clearance (ml/mnt)
RF =
Ideal creatinine clearance (120ml/mnt)
DRrf = Dosing Rate in renal failure
DRn = Dosing Rate in normal state
RF = the extent of Renal Failure
Feu = Fraction of drugs normally excreting unchage
in the urine

RENAL DISEASE
Acute Renal Failure
Chronic Renal
Failure

Acute Renal
Failure
Pre-Renal ARF

Hipovolemia
sweating,vomiting,
diarhoe,blood loss
Cardiac Output
AMI, CHF
Renal hypoperfusiondrug induce
ARF:Diuretic,ACEI
NSAID (PgE2D2I2)

Intra-Renal ARF

Post-Renal ARF

Acute Tubular Necrosis


(ATN) ichaemic & toxin
(aminoglycosid,cyclosporin,cont
rast media)
Interstitial nephritis drug
hypersensitive: penicillin,cephalosporine,allopurinol,azathioprin
Glomerular lession (glo- Post-renal obstrucmerulnephritis)
tion: urinary stone,
neoplasm,BPH

Examination of ARF
1. Full history, including medication history
2. Physically Examination:
Postural hypotension & skin turgor Pre-Renal
Drug rashes / vasculitic lession Intra-Renal
Sizes of bladder & kidneys Post Renal

3. Examination of The Urine:


Concentrated urine Pre-Renal
Intra-Renal Isotonic urine,Epithel cell (ATN);Proteinuria & Haematuria (Glomerulonephritis)

4. Examination of Blood
5. Radiological Study

Drugs that Alter Renal Hemodynamic


Glomerolus
Arteri Afferent
Aliran Darah

Vasokonstriktor Afferent:
Inhibitor Prostaglandin
- NSAID
- COX-2 inhibitor
Vasokonstriktor langsung
- Cyclosporine
- Amphotericine-B
- Kontras Media (ionik)
- Vasopresor

Tekanan
Hidrostatik
Glomerolus

Ultrafiltrat

Tubulus Proximal

Arteri Efferent
Aliran Darah

Vasodilator Efferent:
Renin-Angiotensin Aldosteron
- ACE Inhibitor
- Angiotensin II Antagonis
Vasokonstriktor langsung
- CCB dihydropiridin
- Diltiazem
- Verapamil

Treatment of ARF
1.Early Management:
Correction of fluid & Electrolide imbalance
If not respons Loop diuretic & Manitol; or Dopamine

2.Establish ARF:
a.Uraemia protein intake + Fat & CH Catabolism
b.Hyperkalaemia (K excresion + Cell damage) Cardiotoxic Ca gluconate i.v.; Soluble insulin + glucose; Ca resin
ion exchange
c.Acidosis H+ excresion Na bicarbonate
d.Hypocalcaemia (Ca malabsorption) Ca Supplement
e.Hyperphosphataemia (retention) Ca carbonat

3.Haemodialysis, Peritonial Dialysis

Chronic Renal
Failure

Causes of CRF:
Chronic Glomerulonephritis (nephrotic
syndro-me): Pitting Oedema; Proteinuria 3-5
gram/day; Hypoalbuminaemia 25-30 gr/L
Hypertension
Chronic Pyelonephritis
Urinary Obstruction: BPH, Renal calculi,
Veico-ureteric reflux, indwelling urinary
cathethers
Interstitial Nephritis
Congenital Abnormalities
Metabolic Disease: DM, Amyloidosis can
lead to chronic glomerulonephritis

Examination of CRF
1. Full history, including medication history
2. Physically Examination: Nocturia, Fatigue,
Breathless, Anemia, Skin coloration with
Hypertension, Oedema
3. Examination of The Urine: Proteinuria
4. Examination of Blood: Creatinine Serum
and/or Clearence, Electrolyte disturbance
(Hyperkalaemia,Serum bicarbonateAcidosis,Hypercalcaemia,Hyperphospataemia
)
5. Radiological Study: Intravenous Urography
(IVU) with Contrast Media

Hypertension
Sodium and
fluid
Retention

Renal Parenchymal
damage
Reduce ability
to excrete Na
ions

Activation
of RAA
System
Cycle of events leading to hypertension
in
Renal
Ischaemic

CRF

R.A.A. System
Perdarahan
Masif

TD

Iskhaemia
Ginjal

Angiotensinogen
RENIN

Juxtaglomerolus App.
Stimulasi

Angiotensin I

Prostaglandin

Angiotensin Converting Enzyme (ACE)


Angiotensin II
Vasopresin

TD

Angiotensin III
Vol.Cairan

Retensi Air

Aldosteron
Retensi Na

Renal Failure
1,25 dihydroxycholecalciferol

Ca
absorption
from GI
tract.

Reduced Mineralization of bone

OSTEOMALACIA

Phosphate excretion
Serum phosphate

Serum calcium

Hyperparathyroidism

OSTEOSCLEROSIS

Disturbance of Calcium and Phosphate Balance


in CRF

Treatment of CRF

Hypertention: Diuretics, Beta blocker, ACE


Inhibitor, AT II Antagonist, Vasodilators
(hydralazin, prazosin, minoxidil)
Anaemia: Trans PRC,Erythropoietin (+Iron
supl)
Oedema: Fluid and Sodium restriction, If
Hypoalbuminemia Albumin i.v., Diuretics
Hyperkalaemia: Resin K binder
Acidosis: Sodium bicarbonate
Osteodystrophy: Phosphat binder AlOH
(toxic syst not recom.), (CaCO3);
Vit.D/pro vit.D

Terima
Kasih