CLINICAL PHARMACOLOGY :

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

BAGIAN FARMAKOLOGI & TERAPI;

DIVISI FARMAKOLOGI-KLINIK;
FAKULTAS KEDOKTERAN - UGM
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CLINICAL PHARMACOLOGY
and
KIDNEY & URINARY TRACT
PROBLEMs

2
 KIDNEY & CLINICAL
URINARY TRACT OUTCOME
PROBLEMs

PHARMACOLOGICAL
RESPONSES : PK & PD

KONGENITAL
INFLAMASI & INFEKSI
TRAUMA
DEGENERATIF
MALIGNANCY, etc
 KIDNEY PROBLEMs
ACUTE RENAL CHRONIC KIDNEY
INJURY / FAILURE (ARF) DISEASE (CKD)

-ONSET : HOURS DAYS -ONSET : MONTHS - YEARS

-SIGN : NITROGEN & -SIGN: LOSS OF RENAL FUNCTION
CREATININ RETENTION BASED : GFR ( < 60 mL/min/
( AZOTEMIA ) 1.73 m ) for more than 3 mo.

CAUSA :
PRE RENAL : renal hypoperfusion ( low GFR )
INTRINSIC RENAL DISEASES : - ACUTE TUBULAR NECROSIS
- ACUTE GLOMERULONEPHRITIS
- ACUTE INTERSTISTIEL NEPHRITIS
POST RENAL (OBSTRUCTION) : obstruction of the URINARY TRACT.
 CHRONIC KIDNEY
DISEASE (CKD)
-ONSET : MONTHS - YEARS
-SIGN: LOSS OF RENAL FUNCTION
BASED : GFR ( < 60 mL/min/
1.73 m for more than 3 mo.

CKD 1 GFR > 90 with other evidence of renal disease

CKD 2 GFR 60 89 with other evidence of renal disease
CKD 3 GFR 30 59
CKD 4 GFR 15 29
CKD 5 GFR < 15 (or dialysis)

Note : GFR (ml/min/1.73m)

(Watnick, S., Morrison, G., 2011)

 CHRONIC KIDNEY
DISEASE (CKD) / FAILURE ( CRF )
MAJOR CAUSES
GLOMERULOPATHIES :
1. PRIMARY GLOMERULAR DISEASES :
focal/segmental glomerulosclerosis
membranoproliferative glomerulonephritis
IgA nephropathy
Membranous nephropathy.

2. SECONDARY GLOMERULAR DISEASES :

DIABETIC NEPHROPATHY
AMYLOIDOSIS
POSTINFECTIOUS GLNPHRITIS.
HIV-associated nephropathy
COLLAGEN VASCULAR disease
SICKLE CELL NEPHROPATHY
HIV- asso membrano proliferative glomerulonephritis 6
 CHRONIC KIDNEY
DISEASE (CKD) / FAILURE ( CRF )
MAJOR CAUSES

TUBULOINTERSTISTIAL NEPHRITIS :

Drug hypersensitivity
Heavy metal
Analgesic nephropathy
Reflux / chronic pyelonephritis
Idiopathic

HEREDITARY DISEASES :

Polycystic kidney disease

Medullary cystic disease
Alports syndrome
 CHRONIC KIDNEY
DISEASE (CKD) / FAILURE ( CRF )
MAJOR CAUSES

OBSTRUCTIVE NEPHROPATHIES :

Prostatic disease
Nephrolithiasis
Retroperitoneal fibrosis / tumor
Congenital

VASCULAR DISEASES :

Hypertensive nephrosclerosis
Renal artery stenosis
 CHRONIC KIDNEY
DISEASE (CKD) / FAILURE ( CRF )

CLINICAL FINDING :

AZOTEMIA (monthly years)

UREMIA (nearing end-stage disease)
HYPERTENSIOAN (mayority)
Urine sediment : ISOTHENURIA & BROAD CASTS
USG : BILATERAL SMALL KIDNEY.

SEVERITY : GFR
BUN and serum CREATININE
COMPLICATION ( + / - )
 CHRONIC KIDNEY
DISEASE (CKD) / FAILURE ( CRF )
COMPLICATIONs :
1. HYPERKALEMIA
2. ACID BASE DISORDERS
3. CARDIOVASCULAR :
Hypertension
Pericarditis
Congestive Heart Failure ( CHF )
4. HEMATOLOGIC :
Anemia
Coagulopathy
5. NEUROLOGIC :
Neuro & Encephalopathy
6. DISORDER of MINERAL METABOLISM :
Bone (mineral disorders of metabolism)
Osteomalacia
Adynamic bone disease
7. ENDOCRINE DISORDERS.
 CHRONIC KIDNEY
DISEASE (CKD) / FAILURE ( CRF )
TREATMENT & MANAGEMENT :
1. MANGEMENT OF NUTRITION :
Makanan cukup TANPA MEMBERATKAN GINJAL
Menurunkan kadar UREUM dan CREATININE
Mencegah / mengurangi GARAM /AIR dalam tubuh
Dengan cara :
a. PROTEIN RESTRICTION
b. SALT & WATER RESTRICTION
c. MINERAL RESTRICTION : POTASSIUM
PHOSPHORUS
MAGNESIUM
2. DIALYSIS : HEMODIALYSIS
PERITONEAL DIALYSIS
3. RENAL TRANSPLANTATION
4. PHARMACOTHERAPEUTIC (depend the cause)
URINARY TRACT PROBLEMs
ACUTE CYSTITIS
ACUTE PYELONEPHRITIS
PROSTATITIS :
- acute bacterial prostatitis
- chronic bacterial prostatitis
- non-bacterial prostatitis
PROSTATODYNA
ACUTE EPIDIDYMISITIS
STONE : URINARY STONE DISEASE
URINARY INCONTENANCE :
- interstistial cystitis
- male erctile & sexual dysfunction
INFERTILITY ( REPRODUCTIVE BLOCK)
BENIGNA PROSTATE HYPERPLASIA (BPH)
KONGENITAL
INFLAMASI & INFEKSI URINARY
TRAUMA
DEGENERATIF TRACT
MALIGNANCY
URINARY TRAC INFECTION ( UTI )
INFEKSI SALURAN KEMIH ( ISK )
KATEGORI UTI / ISK :

TRACT INFECTION : lower UTI

upper UTI
recurrent UTI
ASYMPTOMATIC INFECTION
(asymptomatic bacteriuria)
PROSTATITIS ( MALE : STI )

FEMALE > MALE

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COMMON PATHOGENS MICROORGANISM
IN URINARY TRACT INFECTION :

- Escherichia coli
- Proteus spp.
- Klebsiella spp.
- Enterobacteriaceae (others)
- Pseudomonas aeruginosa
- Enterococcus spp.
- Staphylococcus saprophyticus

- SEXUAL TRANSMITTED INFECTION :

- Gonorrhoea ( N. gonorrhoeae )
- Syphilis ( Trepanoma pallidum )
- Chancroid ( Haemophilus ducreyi )
- Granuloma inguinale ( Calymmatobacterium granulomatis )
- Bacterial Vaginosis (Bacterial vaginitis, Anaerobic vaginosis)
- Trichomonasginalis; Candida albicans.
- etc, etc
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 TERAPI EMPERIK PADA
INFEKSI SALURAN KEMIH / ISK
( URINARY TRACT INFECTION / UTI )

DIAGNOSIS ANTIBIOTIC ROUTE DURATION

ACUTE CYSTITIS cephalexin 250-500mg / 6 hrs p.o. 1 3 days

ciprofloxacin, 250-500 mg/12 hrs p.o 1 3 days
nitrofurantoin 100 mg / 12 hrs p.o. 7 days
norfloxacin 400 mg / 12 hrs p.o. 1 3 days
ofloxacin 200 mg / 12 hrs p.o. 1 3 days
trimethoprim sulfamethoxazole
160/800 mg p.o.
single dose

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DIAGNOSIS ANTIBIOTIC ROUTE DURATION

ACUTE PYELONEPHRITIS ampicillin/amoxycillin 1 gr/6 hrs

& dan gentamycin i.v. 21 days
ACUTE BACTERIAL 1 mg/kg / 6 hrs
PROSTATITIS ciprofloxacin 750 mg p.o. 21 days
/12 hrs
ofloxacin 200-300 mg p.o. 21 days
/ 12 hrs
trimethoprim-
sulfamethoxazole p.o. 21 days
160/800 mg / 12 hrs

DIAGNOSIS ANTIBIOTIC ROUTE DURATION

CHRONIC same as for ACUTE PYELONEPHRITIS,

PYELONEPHRITIS but DURATION of therapy longer is 3 6 mos

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DIAGNOSIS ANTIBIOTIC ROUTE DURATION

ACUTE PYELONEPHRITIS ampicillin 1 gr/6 hrs

& dan gentamycin i.v. 21 days
ACUTE BACTERIAL 1 mg/kg / 6 hrs
PROSTATITIS ciprofloxacin 750 mg p.o. 21 days
/12 hrs
ofloxacin 200-300 mg p.o. 21 days
/ 12 hrs
trimethoprim-
sulfamethoxazole p.o. 21 days
160/800 mg / 12 hrs

DIAGNOSIS ANTIBIOTIC ROUTE DURATION

CHRONIC same as for ACUTE PYELONEPHRITIS,

PYELONEPHRITIS but DURATION of therapy longer is 3 6 mos

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DIAGNOSIS ANTIBIOTIC ROUTE DURATION

ACUTE EPIDIDYMITIS ceftriaxon, 250 mg p.o. 1 3 mo

Sexually transmitted as single dose;
plus:
doxycycline, 100 mg /
12 jam

DIAGNOSIS ANTIBIOTIC ROUTE DURATION

CHRONIC BACTERIAL cyprofloxacine, p.o. 1-3 mo

PROSTATITIS 250-500 mg /12 hrs
ofloxacine,
200-400mg / 12 hrs p.o. 1-3 mo
trimethoprime-
sulfamethoxazole p.o. 1-3 mo
160/800 mg/12 hrs
( Stoller, ML et al ;in CMDT Mc Phee S.J. eds 2007) 19
 Selected initial therapeutic regimens for upper UTI

Parenteral (recommended for the majority):

First choices Ampicilline/Amoxycillin + 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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 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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Prescribing in Kidney Disease

Patients with Renal Failure

Patients on Dialysis
Hypertension
Nephrotic Syndrome
Nephrolithiasis

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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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 International classification of renal disease
CHRONIC RENAL DISEASES /
CHRONIC RENAL FAILURE ( CRF )

CKD 1 GFR > 90 with other evidence of renal disease

CKD 2 GFR 60 90 with other evidence of renal disease
CKD 3 GFR 30 60
CKD 4 GFR 15 30
CKD 5 GFR < 15 ( or dialysis )

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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
AMOXYCILLI infection: 500mg to 2g || <10/ q12-24 hours ||
N 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/
AMOXYCIL. po q6h (50-100mg/kg/
q6-12h || <10/ q12h
(Oral) day).

AMPI
/AMOXY - Usual dose: 1.5 to 3g >30/ q6-8h || 15-29/ q12h
SULBACTAM ivpb q6h || 5-14/ q24h
(UNASYN)
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. 27
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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DRUGS USE IN RENAL & URINARY TRACT SYSTEM :
CHOLINOMIMETIC
ANTIMUSCARINIC
ALPHA-RECEPTOR BLOCKING DRUGS
DIURETICS
CARBONIC ANHYDRASE INHIBITORS
OSMOTIC DIURETICS
ANTIDEPRESSANTS
URINARY ANALGESIC ( phenazopyridine, pH alkalinized, etc )
ANTIINFECTIVES :
- sulfonamides, trimethoprim & quinolone
- nitrofurantoin; methenamine mandelate/hippurate
- beta-lactam
- cefalosporin
- tetracyclin
- erythromycine
URINARY ANTISEPTIC (pipemidic acid;nalidic acid; phenazopyridine
HORMONAL
VASOACTIVE
SOLUTION FOR BLADDER IRRIGATION
dll.
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 UROLOGIC DISORDERS
GANGGUAN UROLOGIK
RETENSI URINE
ENURESIS & INCONTINENSIA
OBAT-OBAT UNTUK NYERI UROLOGIK
TINDAKAN / PEMBEDAHAN UROLOGIK
DISFUNGSI EREKSI

Female BLOK
Urogenital REPRODUKTIF
System

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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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 RETENSI URINE
- retensi urine : ACUTE catheterisation (IGD / EMERGENCY)
CHRONIC
BPH (Benign Prostatic Hyperplasia)

MEDICATION (chronic CONDITION and Painless) :

- Alpha-Receptors Blocking agents : Alfuzosin

Indoramin
Doxazosin
Prazosin
Tamusolusin
Terazosin

- Parasympathomimetics : Betanechol chloride

Distigmine bromide

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