PERAN GINJAL-SAL.

KEMIH
pada PHARMACOKINETIK (PK) &
PHARMACODYNAMIC (PD)
OBAT

SULANTO SALEH-DANU R., dr., SpFK.

BAGIAN FARMAKOLOGI dan TERAPI
DIV. FARMAKOLOGI-KLINIK FK-UGM.

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OBJEKTIF.
SETELAH MENGIKUTI TATAP MUKA INI.
DIHARAPKAN MAHASISWA :

MENGERTI, MEMAHAMI PERAN & FUNGSI SERTA

MEKANISME KERJA GINJAL & SAL.KEMIH;

PERAN GINJAL TERHADAP FARMAKOKINETIK (PK) &

FARMAKODINAMIK (PD) SUATU OBAT / SUBSTANSI
YANG MASUK DALAM DAN DIGUNAKAN TUBUH;

MENGERTI OBAT / SUBSTANSI YANG DIGUNAKAN PADA

SISTEM SALURAN KEMIH (UROGENITAL);

MAMPU MENGGUNAKAN, MENILAI MANFAAT

dan BAHAYA OBAT / SUBSTANSI YANG DIGUNAKAN
PADA SISITEM SALURAN KEMIH (UROGENITAL)
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KIDNEY & GENITOURINAY TRACT :

ANATOMICAL
PHYSIOLOGICAL
KIDNEY & UROLOGIC
DISORDERS
PK & PD
PHARMACOTHERAPY
ADR
(Adverse Drug Reactions)

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 KIDNEY & GENITOURINAY TRACT :

SEX ORGAN / GENITAL URINARY TRACT

FEMALE MALE KIDNEY

URETER
OVARIUM PENIS BLADER
TUBA PROSTATE URETHRA
UTERUS TESTIS ORIFICIUM
VAGINA EPIDIDYMIS

LOBUS ANTERIOR HYPOPHYSE

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 GINJAL &
SALURAN GENITOURINARIA
GINJAL, ORGAN TUBUH DENGAN BERAT 0.5 % DARI
BERAT BADAN KITA ;
BERFUNGSI :
- PRODUKSI URINE (25% DARI CARDIAC OUTPUT)
- EKRESSI / ELIMINASI METABOLIT dan ZAT LAINNYA
DARI TUBUH KITA;

PENGGUNAAN OBAT, NUTRISI (SUBSTANSI LAINNYA)

HARUS MEMPERHATIKAN FUNGSI GINJAL;
KARENA GINJAL PEGANG PERANAN DALAM
EKSKRESI ELIMINASI OBAT / NUTRISI / SUBSTANSI LAINNYA
YANG MASUK KEDALAM TUBUH.
TERUTAMA PADA PENDERITA DENGAN GANGGUAN GINJAL

FEMALE SEX ORGAN REPRODUCTIVE SYSTEM

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 OBSTETRICS &
FEMALE GYNAECOLOGY
UROGENITAL ----------------------
SYSTEM Reproductive
System

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 Male
Urogenital
System

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 Male
Urogenital
System

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FUNCTIONS OF KIDNEYS :
1ST . REGULATION OF WATER,INORGANIC ION BALANCE, and
ACID-BASE BLANCE.
2ND. REMOVAL OF METABOLIC WASTE PRODUCTS FROM THE
BLOOD AND THEIR EXCRETION IN THE URINE.
3RD. REMOVAL OF FOREIGN CHEMICALS FROM THE BLOOD
AND THEIR EXCRETION IN THE URINE
4TH. GLUCONEOGENESIS.
5TH. PRODUCTION OF HORMONES / ENZYMES :
A. ERYTHROPOIETIN, WHICH CONTROL ERYTHROCYT
PRODUCTION;
B. RENIN, AN ENZYMES THAT CONTROLS THE FORMATION
OF ANGIOTENSIN, WHICH INFLUENCES BP. AND
SODIUM BALANCE;
C. CONVERSION OF 25 HYDROXYVITAMIN D TO
1, 25 HYDROXYVITAMIN D, WHICH INFLUENCES
CALCIUM BALANCE.
(WIDMAIER, E P, et al, 2014)
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 kidney urine production
PROBLEMS ??

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

CONGENITAL
TRAUMA
INFECTION/
bladder urine collector INFLAMATION
prostate TUMORS
DEGENERATIVES,
gland secretion etc.

urethra urine outlet

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CARDIAC
FAILURE
HYPERTENSION

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ANATOMI &
NOMENCLATUR
OF NEHRON
(Goodman & Gilman ,
12th ed.2011)

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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
ELIMINATION
Pharmacologic
effect Drug Metabolized or Excreted

Clinical response PHARMACODYNAMICS

Toxicity Effectiveness
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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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 Dose of drug
Administration
PHARMACOKINETICS
ABSORPTION

Drug Concentration
In systemic circulation
ORGANS :

Drug in tissues of GASTROINTESTINAL

DISTRIBUTION
Distribution LUNG
SKIN & GLANDS
Drug concentration
at Site of action KIDNEY
METABOLISM

Drug Metabolism ELIMINATION

Drug Metabolized or
Excreted

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 PHARMACOKINETIK & KIDNEY (NEHRON)

FUNCTION : - BLOOD FILTRATION

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

DRUG CONCENTRATION IN THE BODY

Pharmacologic
effect TOXIC
PHARMACODYNAMICS effect
Clinical response

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 DISORDERS IN KIDNEY :
- RENAL FAILURE
- NEPHROPATHIA, etc LOOKING :
RENAL FUNCTION
RENAL by
FUNCTION LABORAT.:
-UREUM
-CREATININE ,etc
DRUG CONCENTRATION IN THE BODY
Pharmacologic
effect

Clinical response

Toxicity Effectiveness

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PARAMETERS IN PHARMACOKINETICS

1. VOLUME DISTRIBUTION (Vd)

2. CLEARANCE (Cl)

3. HALF-LIFE (t)

4. Etc, etc.

( Katzung , 11th , 2009 )

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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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 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)22
t = Waktu paruh,
waktu yang menunjukkan dimana
konsentrasi obat dalam darah
tinggal 50%.

0,7 x Vd
t =
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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24
Steady state

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 Therapeutic
window

Changes in dosage or Changes in rate of removal of the drug from the body
determines whether it will disappear from, or accumulate in the patients blood
It can be life threatening
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Prescribing in Kidney Disease

Patients with renal impairment

Patients on Dialysis
Patients with multiple systemic
diseases

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 Principles
Establish type of kidney disease
Most patients with kidney failure will already be
taking a number of drugs
Interactions are common
Care needed to avoid drug toxicity
Patients with renal impairment and
renal failure
Antihypertensives
Phosphate binders

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 Dosing in renal impairment
Loading dose does not change (usually)
Maintenance dose or dosing interval does

T often prolonged
Reduce dose OR
Increase dosing interval

Some drugs have active metabolites that are

themselves excreted renally
Warfarin, diazepam

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Agent Usual Dosage Renal Dosing
AMPICILLIN Mild to moderate >50/ q6h || 10-50/ q6-12h
infection: 500mg to 2g || <10/ q12-24 hours ||
ivpb q6h. Severe Hemodialysis: Dose after
infection: 2g ivpb q4h dialysis || PD: 250mg
(150-200mg/kg/day) q12h.
AMPICILLIN Usual dose: 250mg to 1g
>50/ no changes || 10-50/
(Oral) po q6h (50-100mg/kg/
q6-12h || <10/ q12h
day).
AMPICILLIN
- SULBACTAM Usual dose: 1.5 to 3g >30/ q6-8h || 15-29/ q12h
(UNASYN) ivpb q6h || 5-14/ q24h

AUGMENTIN
(Oral) Usual dose: 875mg po >30/ no change || 10-30/
q12h or 250-500mg po 250-500mg q12h || <10/
q8h 250-500mg po q24h

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CEFEPIME >60/ 0.5-2g q12h ||
(MAXIPIME) Mild to moderate 30-60/ 0.5g-2g q24h
|| 11-29/ 0.5g-1g
infection: 500mg to
q24h || <10/ 250-
2g ivpb q12h.
500mg q24h or 0.5-2g
Severe: 2g ivpb q8h.
q48h. || HD: 1g AD ||
PD: 1-2 grams q48h
CEFOTETAN >30/ Usual dose ||
(IV) 10-30/ 50% of dose
Usual dose: 1g ivpb
q12h || <10/ 25% of
q12h.
dose q12h.||
Severe: 2-3g ivpb
Hemodialysis or PD:
q12h. (Max 6g/day)
50% of usual dose
q24h
CEFOXITIN Mild infection: 1g
10-50/ q8-12h ||
(IV) <10/ q24-48h || HD:
ivpb q6-8h
give 1g after Dialysis:
Moderate-severe: 1g
e.g. Give Cefoxitin 1g
ivpb q4h or 2g ivpb
ivpb M-W-F after
q6-8h. Life-
dialysis + a
threatening: 2g ivpb
supplemental dose on
q4h or 3g ivpb q6h.
Sunday. 31
CEFOTAXIME Mild infection: 1-2g
(IV) ivpb q12h.
>50/ Usual dose || 10-
Moderate: 1-2g ivpb
50/ q8-12h || <10/
q8h; Severe: 2g ivpb
q24h || HD: 0.5 to 2g
q6-8h; Life
ivpb q24h AD. || PD: 1g
threatening: 2g ivpb
ivpb q24h.
q4h (Max
dose/day= 12g)
CEFUROXIME >20/q8h || 10-20/ q12h
(IV) Usual: 750mg to || <10/ 750mg q24h. ||
1.5g ivpb q8h. Hemodialysis: Give
Severe: 1.5g ivpb single dose after dialysis
q6-8h. or give 750mg q12h. ||
PD: 750mg-1.5g q24h
CEFTIN
(ORAL) No changes req'd (usual
Usual dose: 250-
oral doses are not
500mg po q12h
significant).

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CEFTRIAXONE (IV) Usual dose: 1-2g ivpb No dosage adjustments
q24h. Severe: 2g req'd in renal failure. PD:
ivpb q12h 750mg ivpb q12h
CEFTAZIDIME (IV) Usual dose: 1g ivpb
q8-12h. Severe: 2g Crcl 30-50/ q12h || 10-
ivpb q8-12h. (Max 30/ q24h || <10/ q48h
dose/day= 6 grams).

CEPHALEXIN Keflex: 10-50/ q6-12h ||

KEFLEX/VELOSEF Usual dose: 250- <10/ q12-24h . Velosef:
500mg po q6h; >20/ no change || 5-20/
500mg-1g q12h. 250mg q6h || < 5/ 250mg
q12h
CIPROFLOXACIN
(CIPRO) >50/ no change || 10-50/
Oral dosing: 250- 50-75% of usual dose q12h
750mg po q12h; || <10/50% of usual dose
cystic fibrosis: q12. Alternatives: [200mg
750mg po q8h. IV ivpb or 250mg po q12h] or
dosing: 200-400mg [400 mg ivpb or 500mg po
ivpb q12h. Febrile q24h]. || HD/PD: 250-
neutrapenic pt: 500mg po or 200-400mg
400mg ivpb q8h ivpb q24h AD or 200mg ivpb
or 250mg po q12h.
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IMIPENEM Mild to moderate
31-70/ 500mg q6-8h ||
(PRIMAXIN) infection: 250-500mg
21-30/ 500mg q8-12h
ivpb q6-8h. Severe
max || 0-20/ 250-500mg
infection: 500mg to 1g
q12h max. || HD: 250 mg
ivpb q6-8h. Max
AD + q12h. || PD: max
dose/day=
dose= 1gram/day i.e.
50mg/kg/day or
500mg ivpb q12h.
4g/day
LEVOFLOXACIN >50/ no change || 20-
Usual dose: 500mg po
(LEVAQUIN) 49/ 500mg x 1 then
or ivpb q24h. UTI or
250mg q24h ||
pyelonephritis: 250mg
<19/HD/PD: 500mg x 1
po/ivpb q24h.
then 250mg q48h
METRONIDAZOLE IV: 1 gram or 15
(FLAGYL) mg/kg load IV, then
500mg or 7.5 mg/kg
q6h (range: q6-12h -- > 10/ no change || <10/
long T ). Oral: 250- 500mg ivpb q12h.
750mg po tid.
(occasionally bid). Max
4g/day.

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 Elimination Normal Dose Adjustment
dose
Half Life (t ) interval Creatinine Clearance
(hour) (ml/min)
Normal ESRD > 50 10 - 50 < 10

Captopril 1.9 21 - 32 12 Unch Unch 50

Lisinopril 12 - 36 36 - 48 24 Unch 75 50
Atenolol 6-9 15 - 35 24 Unch 50 25
Propranolol 2 -6 1-6 6 - 12 Unch Unch Unch

Diclofenac 1-2 1-2 6 12 Unch Unch Unch

Ibuprofen 2 -5 Unch 12 Unch Unch Unch

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 Elimination Normal Dose Adjustment
dose
Half Life (t ) interval Creatinine Clearance
(hour) (ml/min)
Normal ESRD > 50 10 - 50 < 10

Phenobarbital 60 -150 117 -160 8 - 24 Unch Unch Unch

Lorazepam 6 - 25 32 - 70 8 - 24 Unch Unch 50
Glibenclamide 10 - 16 ? 24 Unch Unch Unch
Insulin reguler 2 - 3 prolonged 8 Unch 75 50
Carbamazepine 20 - 36 ? 8 - 12 Unch Unch 75
Chloroquine 2-4 5 h 50 days 12 Unch Unch 50
Cisplatine 2 -72 1 - 240 24 Unch 75 50
Cimetidine 2 5 8 Unch 75 50

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 UROLOGIC DISORDERS
GANGGUAN UROLOGIK

RETENSI URINE
ENURESIS & INCONTINENSIA
OBAT-OBAT UNTUK NYERI UROLOGIK
TINDAKAN / PEMBEDAHAN UROLOGIK
DISFUNGSI EREKSI

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RETENSI URINE
TERTAHANNYA URINE
PADA KANDUNG KEMIH
HAMBATAN / OBSTRUKSI
PADA SALURAN OUTLET
VESICA URINARIA

FUNGSI MUSKULER TERGANGGU

SUMBATAN SALURAN URETHRA (BATU dll )
PENEKAN URETHRA DARI PROTAT
( BPH; Ca PROSTAT )

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PHARMACOTHERAPY :
- alpha 1 blockers : - afuzosin
- doxazosin
- indoramin
- prazosin
- tamusulsin
- terazosin

-Parasympathomimetics : - betanechol
- distigmine bromide

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 Mode of actions alpha 1 adrenoceptor
antagonist

Blockade of the motor sympathetic

adrenergic nerve supply of the smooth
muscle prostate & bladder neck reduces
urethral pressure

Functional predominance of
1-adrenoreceptors in human prostatic
muscle

F.M.J Debruyne, Medical treatment of BPH. ACU 2002

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 Mode of actions alpha 1 adrenoceptor
antagonist
BPH causes Bladder Outlet Obstruction
(BOO) by two mechanisms

Mechanical compression by the adenoma

Dynamic obstruction by prostatic smooth
muscle which corresponds to 40% of the
volume of the prostate

F.M.J Debruyne, Medical treatment of BPH. ACU 2002

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Pharmacokinetic of TERAZOSIN

Terazosin hydrochloride ( Hytrin )

* Quinazoline compound
* Completely absorbed on oral
administration
* Peak plasma levels : 1 hour
* Long half time : 12 hours
* Metabolized : in liver
* Excretion : not altered by renal
insufficiency

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Pharmacodynamic of TERAZOSIN
Terazosin hydrochloride ( Hytrin ):

blocks symphatetic nerve impulse to the

adrenoceptors

Smooth muscle & bladder neck relaxation

decrease obstruction

increase urine flow rate
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Treatment of asymtomatic bacteriuria

Treatment recommended :
Neonates and pre-school children
Pregnant women
Men
Known or presumed acquired or congenital uropathy
Necessary intermittent catheterization
Before urologic instrumentation

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Treatment justified :
Diabetics
Mechanical prothesis
Valvular heart disease
Imunocompromised and organ transplant patient
Renal failure and dialysis patients
Urea-splitting organism

Treatment controversial :
Short-term indwelling catheter
Ileal conduits or urologic diversion

Treatment nor recommended :

Long-term indwelling catheter

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 Treatment and prophylaxis of Lower UTI
DRUG DOSE INTERVAL
TREATMENT
Trimethoprim-sulfamethoxazole 160/800 mg 12 hr
Trimethoprim 200 mg 12 hr
Ciprofloxacin 250 mg 12 hr
Norfloxacin 400 mg 12 hr
Ofloxacin 200 mg 12 hr
Amoxillin 250-500 mg 8 hr
Amoxillin-clavulanate 250-500/2 mg 8 hr
Nitrofurantoin 100 mg 12 hr

PROPHYLAXIS
Trimethoprim-sulfamethoxazole 100 mg daily
Trimethoprim 40/200 mg daily
Nitrofurantoin 100 mg daily
Norfloxacin 200 mg daily
Trimethoprim 100 mg single dose*
Trimethoprim-sulfamethoxazole 40/200 or 320/1600 mg single dose
Nitrofurantoin 100 mg single dose
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Selected initial therapeutic regimens for upper UTI

Parenteral (recommended for the majority):

First choices Ampicilline + amoniglycoside
First-generation cephlosporin + aminoglycoside
Second choices Third-generation sephalosporin
Extended-spectrum penicillin
Aminoglycoside
Aztreonam
Imipenem
Penicillin + beta-lactamase inhibitor
Trimethoprim-sulfamethoxazole
Quinolone
Enteral (only if mild symptoms) :
Trimethoprim-sulfamethoxazole
Trimethoprim
Quinolone
Penicillin or cephalosporin if proven efficacy against the organism
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DRUGS USE IN RENAL & URINARY TRACT SYSTEM :
CHOLINOMIMETIC
ANTIMUSCARINIC
ALPHA-RECEPTOR BLOCKING DRUGS
DIURETICS
CARBONIC ANHYDRASE INHIBITORS
OSMOTIC DIURETICS
ANTIDEPRESSANTS
URINARY ANALGESIC ( phenazopyridine)
ANTIINFECTIVES :
- sulfonamides, trimethoprim & quinolone
- nitrofurantoin; methenamine mandelate/hippurate
- beta-lactam
- cefalosporin
- tetracyclin
- erythromycine
HORMONAL
VASOACTIVE

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 KIDNEY DISORDERS

ACUTE - CHRONIC RENAL FAILURE

GLOMERULONEPHRITIS
INTERSTSTIAL NEPHRITIS
CHRONIC RENAL DISEASES
GLOMERULONEPHROPATHIA
NEPHROTIC SYNDROME
Etc.

Details diagnosis, Preventive & Curative

please looking others lecture
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 DIETARY MANAGEMENT IN
CHRONIC RENAL FAILURE ( CRF )

NUTRISI PENDERITA CRF :

-RESTRIKSI PROTEIN
-RESTRIKSI GARAM & AIR
-RESTRIKSI POTASSIUM
-RESTRIKSI PHOSPHORUS
-RESTRIKSI MAGNESIUM

(DETAIL BESARAN & DOSIS/TAKARAN lihat pada topik MANAJEMEN KLINIS)

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Referensi :

1. Katzung, B G., Masters, S B., Trevor, A J., Basic and Clinical

Pharmacology; 12th Ed., 2011, Lange Mc Graw Hill-New York.

2. Speight, T M., Holford, N H G., Averys Drug Treatment ; 4th Ed.,1997;

Adis International; Auckland.

3. Brunton, Chabner & Knollman., Goodman & Gilamans The

Pharmacological Basis of Therapeutics, 12th Ed., 2011, Mc Graw Hill.,
New York.

4. McPhee., Papadakis & Rabow.; CMDT 2011, Current Medical

Diagnosis & Treatment., 50th Ed. 2011., Mc Graw Hill New York.

5. Widmaier, E P.; Raff, H.;Strang, K T., Vanders Human Physiology, 4th

Ed., 2014., McGraw-Hill International Edition., New York.

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