FARMAKOLOGI

PADA GAGAL GINJAL

Dra. Widyati, Apt, MClinPharm

PRINSIP DASAR
 GGK ~ POLIFARMASI ~ Adrac
 Renal disease affect PK + PD which may
not predictable
 Uremia induced changing in absorption,
protein binding, distribution, elimination

 [Drug] ↑ plasma or tissue

PERUBAHAN FARMAKOKINETIK

 ABSORBSI:
 Uremia: NH3 pH absorpsi obat
 Uremia: motility + emptying time changing
 Absorbsi I.m, s.c. in ARF tissue
perfussion
 Blood flow to gut absorpsi obat
DISTRIBUSI OBAT PADA CKD
 Plasma protein binding change (e.g. teofilin,
warfarin, furosemide, fenitoin, diazepam
morfin,clofibrate,salisilat) due to alteration in
mol config. Of albumin cause by acidosis,low
alb,competition with acidic compound
 Perubahan Vd karena perubahan ECF,
changing in proportion of fat & muscle.
 Obat yg terpengaruh dg perubahan tsb adalah
yg memiliki sifat highly albumin-bound + low
Vd+high hepatic extraction ratio yaitu acidic
drugs spt: fenitoin, warfarin,
furosemide,salisilat,fenilbutazon
METABOLISME OBAT PADA CKD

 First pass metabolism



 BA ↑ (propanolol, cloxacilin, dihydrocodein, zidovudine)

EKSKRESI OBAT PADA CKD
 Perub. GFR clearance obat

 Akumulasi metabolit aktif, t½

PERUBAHAN FARMAKODINAMIK PADA
UREMIA

 Drug sensitivity :
 perubahan pada distribusi di CNS
→sensitivitas thd antidepressan,
benzodiazepin
 In hypovolemic sensitivity to antihypertensive
agent (ACE, ARB, -blocker)
 Impairment in coagulation increased sens to
anticoagulants
 K+ often → digoxin toxicity
MODIFIKASI DOSIS
 Ketahui rute eliminasi obat
 Eliminasi obat melalui ginjal akan menurun
 Tingkatan gagal ginjal yang mempengaruhi
eliminasi tergantung pada prosentase
‘unchanged drug’ yang dieliminasi lewat ginjal
 Di samping fraksi unchanged drug, perhatikan
metabolit aktif
 Perhatikan ‘therapeutic window’ (TW), TW
sempit terapkan highly specific
pharmacokinetic calculation, TW luas terapkan
general dosing recommendation
Basis Dosage Adjustment

 Loading dose uremic=LD normal krn

apparent Vd tidak berubah
 Maintenance dose tergantung klirens obat
 Fungsi renal yg normal diprediksi dari CrCl
 Non-renal klirens diasumsikan tetap
 Penyesuaian dosis: kurangi dosis atau
perpanjang interval
METODE PENYESUAIAN DOSIS

 1. NORMOGRAM
 2. GIUSTI-HAYTON
 3. General Clearanace
 4. Wagner
 METODE NORMOGRAM
 Asumsi: non-renal eliminasi tdk terpengaruh
 ku = k nr + CrCl
 Uremic dose = ku x normal dose
 kN

 Interval uremic ( u) = kN x N
 ku