CLINICAL PHARMACOLOGY :

GINJAL / KIDNEY - I
SULANTO SALEH-DANU R., dr., SpFK

BAGIAN FARMAKOLOGI & TERAPI;

DIVISI FARMAKOLOGI-KLINIK;
FK-KMK – UGM
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OBJEKTIF.
SETELAH MENGIKUTI TATAP MUKA INI.
DIHARAPKAN MAHASISWA :

MENGERTI, MEMAHAMI PRINSIP-2

PERAN GINJAL PADA FARMAKOLOGI – FARMAKOTERAPI;

MENGERTI OBAT-OBAT YANG BERPENGARUH

PADA GINJAL SECARA LANGSUNG MAUPUN DAMPAK
SISTEMIK;

MAMPU MENGIDENTIFIKASI, MENILAI MANFAAT, KEAMANAN

dan BAHAYA OBAT-OBAT YANG DIGUNAKAN ;
SERTA MEWASPADAI DAMPAKNYA TERHADAP GINJAL.

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 ANATOMI
GINJAL

(Silverthorn, D U., 2013 )

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 GINJAL &
SALURAN GENITOURINARIA

 GINJAL, ORGAN TUBUH DENGAN BERAT 0.5 % DARI

BERAT BADAN KITA ;
 SECARA UMUM BERFUNGSI PRODUKSI : URINE
 EKRESSI / ELIMINASI METABOLIT dan ZAT LAINNYA (“SAMPAH”)
DARI TUBUH KITA;
 MENAMPUNG 25% DARI CARDIAC OUTPUT.

 PERESEPAN HARUS MEMPERHATIKAN FUNGSI GINJAL;

KARENA PEGANG PERANAN PADA
PROSES EKSKRESI – ELIMINASI
BAHAN2 & OBAT2 YANG MASUK KEDALAM TUBUH MANUSIA.
 UTAMA : PENDERITA DENGAN GANGGUAN & KELAINAN GINJAL

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 FUNGSI GINJAL :
1. SEBAGAI REGULATOR VOLUME CAIRAN
EXTRASELULER & TEKANAN DARAH
(BERKAITAN DENGAN HEMODINAMIK);
2. REGULATOR OSMOLARITAS CAIRAN TUBUH;
3. MEMELIHARA KESEIMBANGAN CAIRAN DAN
ELEKTROLIT / ION (Na; K; Ca; dll);
4. REGULATOR HOMEOSTATIK;
5. ELIMINASI & EKSKRESSI HASIL METABOLISME
ZAT YANG TIDAK BERMANFAAT BAGI TUBUH
(“ SAMPAH “);
6. MEMPRODUKSI HORMON, MESKIPUN BUKAN
KELENJAR ENDOKRIN ( eg : ERYTHRPOETIN;
RENIN )
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(Silverthorn, D U., 2013 ) 6
PRODUKSI : URINE

FILTRASI : ± 180L/hari
REABSORBSI : 99%
SEKRESI  URINE : 1,5 L /hari

NEPHRON

(Silverthorn, D U., 2013 ) 7

 Male
Urogenital
System

FEMALE 
BLOK : REPRODUKSI
bladder
protate
membr. urethrae

testis
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 Male
Urogenital
System

FEMALE 
BLOK :
REPRODUKSI
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 kidney  urine production
PROBLEMS ??

LOCAL / SYST.
ACUTE / CHRONIC
ADULT / CHILD
ureter  tunnel to urine collecting

CONGENITAL
TRAUMA
bladder  urine collector INFECTION/
prostate INFLAMATION
TUMORS
gland  secretion  DEGENERATIVES
urethra  urine outlet

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 The ROLE of
UROGENITAL SYSTEM on
PHARMACOKINETIC and
PHARMACODYNAMIC
of
DRUGS

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 Dose of drug
Administration
ABSORTION

Drug Concentration
PHARMACOKINETICS
In systemic circulation

DISTRIBUTION
Drug concentration Drug in tissues of
at Site of action Distribution

Pharmacologic
EXCRETION /
effect ELIMINATION
Drug Metabolized
or Excreted
Clinical response

PHARMACODYNAMICS
Toxicity Effectiveness
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 Dose of drug
Administration
PHARMACOKINETICS
ABSORTION

Drug Concentration ORGANs :

In systemic circulation
GASTROINTESTINAL
Drug in tissues of LUNG
DISTRIBUTION
Distribution SKIN & GLANDS
Drug concentration KIDNEY
at Site of action

METABOLISM

Drug Metabolism
EXCRETION /
ELIMINATION
Drug Metabolized or
Excreted
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 The Kidney as Excretory Organ
• Most drugs are eliminated in urine either
chemically unchanged or as metabolites.

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 PHARMACOKINETIK & KIDNEY (NEHRON)

FUNCTION : - BLOOD FILTRATION

- REABSORPTION
- SECRETION (METABOLITES, etc)
- COLLECTION
- EXCRETED

DRUG CONCENTRATION IN THE BODY

Pharmacologic
effect
PHARMACODYNAMICS
Clinical response
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 DISORDERS IN KIDNEY :
- RENAL FAILURE
- NEPHROPATHIA, etc CHECK &
MONITOR:
RENAL
RENAL FUNCTION by
FUNCTION LABORAT.:
-UREUM
-CREATININE ,etc
DRUG CONCENTRATION IN THE BODY
Pharmacologic
effect

Clinical response

Toxicity Effectiveness

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CARDIAC –
FAILURE
HYPERTENSION

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PARAMETERS IN
PHARMACOKINETICS ( PK )

1. VOLUME DISTRIBUTION (Vd)

2. CLEARANCE (Cl)

3. HALF-LIFE (t½)

4. Etc, etc.

( Katzung , 12nd Ed , 2012 )

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 VOLUME OF DITRIBUTION ( Vd ) :
the measure of apparent space in the body available
to contain the drugs

Amount of drug in body

Vd = C

C = the concentration of drug in blood or plasma

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• rate of removal known as ‘Clearance’

the removal of drug by all processes

from the biological system

• Definition: A volume of fluid (could be plasma, blood or

total body fluid) from which a drug is irreversibly removed
in unit time

• Atenolol Cltotal = Clrenal

• Paracetamol Cltotal = Clhepatic + Clrenal
• Ethanol Cltotal = Clhepatic + Clrenal + Cllung

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CLERANCE ( Cl ) = KEMAMPUAN TUBUH UNTUK
MENGELUARKAN (EKRESSI/ELIMINASI)
OBAT DARI TUBUH

Rate of Elimination
Cl
Cl ==
C

C = blood / plasma concentration of drug

Cl systemic = Clrenal + Clliver + Cl others

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t ½ = Waktu paruh,
waktu yang menunjukkan dimana
konsentrasi obat dalam darah
tinggal 50%.

0,7
0,7 xx Vd
Vd
tt ½
½ ==
Cl
Cl
0.7 = konstanta dari ln 2
Vd = volume distribusi
Cl = clearence renal
UxV
Cl = U = konsentrasi pada urine
P P = konsentrasi pada plasma (mg/dL)
V = aliran (flow) urine ( mL/min)
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 CHECK & MONITOR:
RENAL FUNCTION
by
LABORAT.:
-UREUM,
-CREATININE ,etc

FORMULA ;

COCKROFT - GAULT
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Tests of renal function cont.
• 24h Urine sample-Creatinine Clearance
• chromium EDTA Clearance
• gold standard Inulin clearance

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 Calculating Creatinine Clearance
Cockcroft-Gault Equation
CrCl men = (140 - Age) x LBW
Scr x 72
CrCl women = CrCl men x 0.85
Modification of Diet in Renal Disease Equation (MDRD)
CrCl men = (Scr) -1.154 x (age) -0.203
CrCl women = CrCl men x 0.742
CrCl African American = CrCl men x 1.210
Other Formulas Include (but are not limited to):
• Jelliffe Method • Schwartz Formula (children)
• Wright Formula • Counahan-Barratt Equation (children)
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Steady state

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 KONGENITAL
PROBLEM INFLAMASI & INFEKSI
PADA TRAUMA
GINJAL DEGENERATIF
MALIGNANCY

LOKAL:
SYSTEM UROGENITAL

SISTEMIK:
DAMPAK KELAINAN
SISTEM DILUAR
SISTEM U-G.

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FUNGSI GINJAL  PD : RESPON –
EFEK KLINIK

PK : - ABSORPSI
- DISTRIBUSI
TERAPI : - METABOLISME
NON-FARMAKOTERAPI
- EKSKRESI /
FARMAKOTERAPI
ELIMINASI

KONGENITAL
INFLAMASI & INFEKSI
TRAUMA
DEGENERATIF
MALIGNANCY
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FARMAKOKINETIK ( PK ) BERUBAH :
- ELIMINASI ↓↓↓
- IKATAN PROTEIN ↓↓↓
FARMAKODINAMIK ( PD ) BERUBAH
- EFFEK KLINIS  BERUBAH
KONDISI KLINIS  MEMBURUK
ADVERSE DRUG REACTION ↑↑↑

FUNGSI GINJAL

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 KONFIRMASI
FUNGSI GINJAL
&
PENGATURAN DOSIS

FUNGSI GINJAL :
- CREATININ
CLEARANCE
(urine 24 jam)
- CREATININ serum
PENYESUAIAN DOSIS :
- frekwensi / interval
FARMAKOKINETIK ( PK ) BERUBAH : - dosis
- ELIMINASI ↓↓↓ LOADING DOSE
- IKATAN PROTEIN ↓↓↓ MONITOR
FARMAKODINAMIK ( PD ) BERUBAH
KONSENTRASI OBAT
- EFFEK KLINIS
KONDISI KLINIS  MEMBURUK DARAH
ADVERSE DRUG REACTION ↑↑↑ ( obat yg toksis )

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 MEDICINE in RENAL DISEASES

ABSORPTION & BIOAVAILABILITY.

pH CRF (Chronic Renal Failure) :

amonia lambung naik  pH naik
absorpsi ↓ : - cloxacillin; - sulfas ferrosus;
- as folat; - pindolol ; - chlorpropamide .
aluminium hydroxyde : pada CRF sebagai pengikat FOSFAT
tetapi dapat mengikat preparat lain
( fenitoin; preparat FE; asam salisilat/
aspirin; fenotiazin; quinolone;
tetrasiklin; rifampisin dan
ketokonazole. )

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DISTRIBUTION of MEDICINE in RENAL PROBLEMS (1).

DRUG ACTION : blood drug concentration

 unbound drug / free
 bound drug

- Plasma protein terikat

- Albumin

RENAL FAILURE pH ↑ free fatty acids ↑;

indoxyl sulfate ↑.

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DISTRIBUTION of MEDICINE in RENAL PROBLEMS (2).

-Theophylline -Warfarin IKATAN PROTEIN ↓↓

-Phenitoin -Barbiturates
-Methotrexate -Clofibrate
-Diazepam -Morphine
-Prazosin -Salicylate FREE DRUGs
-Furosemide -Dicloxacillin CONCENTR ↑↑

- Plasma protein
terikat
- Albumin

pH ↑ free fatty acids ↑;

RENAL FAILURE
indoxyl sulfate ↑.
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 DISTRIBUTION of MEDICINE in RENAL PROBLEMS (3).

RENAL FAILURE PERUBAHAN pH

KADAR PROTEIN
NEPHROTIC SYNDROME IKATAN PROTEIN/
ALBUMIN/
RENAL INFECTIONs, GLYCOPROTEIN
and Other CONDITION

PENYESUAIAN DOSIS : KONSENTRASI

 DOSIS DIKURANGI
OBAT BEBAS
 FREKWENSI /
INTERVAL PEMBERIAN MENINGKAT

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PROBLEM ACUTE FARMAKO-
PADA TERAPI
GINJAL CHRONIS TERAPI DIET

– CKD 1 – GFR ≥ 90 mL/min/1.73 m² , normal GFR

– CKD 2 – GFR 60 – 90 renal damage with mild GFR
– CKD 3 – GFR 30 – 60 moderatly
– CKD 4 – GFR 15 – 30 severely
– CKD 5 – GFR < 15 FAILURE  DIALYSIS (hemodialysis /
peritoneal dial.)

CKD = Classification (Chronic) Kidney Diseases .

GFR = Glomerular Filtration Rate.
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GFR ( GLOMERULAR FILTRATION RATE ) :

U x V
C = --------------
P

C = Clearance
U = Urine concentration of the substance
( mg/dL )
P = Plasma concentration of the substance
( mg/dL )
V = Urine flow rate ( ml/min )

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DIET – NUTRISI PDRT. GGK / Term.

MEMPERHATIKAN dan MEMBATASI CHRONIS :

INTAKE :  PROTEIN azotemia
progressive ;
 GARAM uremia;
hypertensi;
 AIR bilateral small
 K (potasium) Kidney;
isothenuria blood
 phosphorus cast pada sedimen
 magnesium urine

FUNGSI GINJAL :  LAB TEST

 RADIOLOGIC
 others 37
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