FARMAKOTERAPI TERAPAN

PROGRAM PENDIDIKAN PROFESI APOTEKER

MEDAN
2011
Dosen Prof. Dr. Urip Harahap, Apt.
21 Oktober 2011
KELOMPOK 4
PSP APOTEKER 2011

Rogabe
Roma Anita
Rosfianita
Santaria
Sri Dewi
Sri Kurniasih
Sri Rahmadani
Sri Dewi Handayani
T. Azma Ulya
Tonny Setiawan


Wahyuni
Widya Akarina
Wilson
Yuliana
Zulkifli
Zulhamidah
Layani Pransiska N
Yustina Samosir
Yensi Zahara
Tamba T. Pasaribu

Identify ARF earlier and eliminate the cause to
avoid the spread of damage
Prevention is the key!!
In developed ARF, patients should receive
therapy to prevent occurrence and reduce its
severity
Avoid nephrotoxins as much as possible
Once the cause of ARF is identified and
eliminated, supportive therapy is the only
remaining option, as we can hasten the
recovery of developed ARF

RENAL BLOOD FLOW
Effective Circulating Volume
Normal
RBF/RPF
Intrarenal Autoregulation
GFR, FF
Renal
Perfusion
Pressure
Cardiac
out put
Mean
Arterial
Pressure
Autoregulation is the maintenance
of a near normal intrarenal
hemodynamic environment (RBF,
RPF, FF and GFR) despite large
changes in the systemic blood
pressure
RBF - blood perfusing the kidneys each minute
(1200 ml/min)
Renal Plasma Flow (RPF) - plasma flowing to
kidneys each minute (670 ml/min or 55-60% of
RBF)
GFR - amount of plasma filtered each minute
by the glomeruli. (Normal GFR -125 ml /min for
men and 100 ml/min for women)
Filtration Fraction (FF) - the ratio of GFR to
RPF (Normal - .18 - .22)

F = P
R


RAP
RBF
R
aff
+ R
eff
~
F = Flow
P = Pressure Changes
R = Resistance
RBF = Renal blood flow
Raff = Afferent arteriolar resistance
RAP = Renal arterial pressure
Reff = Efferent arteriolar resistance
Major sites of renal vascular
resistance -> Glomerular afferent
(R
aff
)

and efferent (R
eff
) arterioles

Changes in R
aff
and R
eff
affect RBF
Vasoconstrictors
Renin
Angiotensin II
Endothelin
ADH
Vasodilators
PGs
Kinins
NO
ANP
RBF
GFR
Figure : RBF / GFR is maintained by a balance between vasodilators and
vasoconstrictors of Afferent and Efferent arterioles
Afferent
Arteriole
PGC
GFR.
Glomerulus
Efferent
Arteriole
Tubule
Figure - shows normal conditions normal renal perfusion
pressure and a normal GFR.
RBF
Reff / Raff ratio
=N
N Engl J Med 357;8 August 23, 2007
RBF
Afferent
Arteriole
PGC
GFR.
Efferent
Arteriole
PGE
Ang II
Figure: shows reduced perfusion pressure within the autoregulatory range.
Normal glomerular capillary pressure is maintained by afferent
vasodilatation and efferent vasoconstriction.
MAP
Reff / Raff ratio =
N Engl J Med 357;8 August 23, 2007
Reff / Raff ratio
Figure: Loss of vasodilatory PGs increases afferent resistance causing drop in the
glomerular capillary pressure below normal values and the fall in GFR
RBF
PGC
GFR.
Ang II
Afferent
Arteriole
Efferent
Arteriole
PGE
NSAID

Reduced perfusion pressure with a NSAID.
N Engl J Med 357;8 August 23, 2007
PGC
GFR.
Ang II
Afferent
Arteriole
Efferent
Arteriole
PGE
ACEIs /ARB

Figure: Loss of angiotensin II action reduces efferent resistance;
this causes the glomerular capillary pressure to drop below normal values
and the GFR to decrease.
Reff / Raff ratio
RBF
N Engl J Med 357;8 August 23, 2007
Sudden and sustained decrease in GFR which
is occuring over hours to days, sometimes
over weeks, that associated with an
accumulation of waste products, including
urea and creatinine (Cr).

Acute renal failure is an acute loss of kidney
function that occurs over days to weeks and
results in an inability to appropriately excrete
nitrogenous wastes and creatinine.




ARF is a common condition in the general
population, with an annual incidence of
approximately 200 cases per million
population per year.
The incidence rate is higher in hospitalized
patients (1-5%).
The highest incidence of ARF is in
hospitalized patients in the intensive care
unit (15-20%), reported mortality rates range
from 50-70%.
Am Fam Physician 2005;72:1739-46. Copyright 2005
American Academy of Family Physicians
Infection and cardiorespiratory complications
are the most common causes of death in
patients with acute renal failure.
Am Fam Physician 2005;72:1739-46. Copyright 2005
American Academy of Family Physicians
Based on Severity (RIFLE classification).

RIFLE : Risk, Injury, Failure, Loss, and
End-stage Kidney Disease
STAGE I



RISK
(R)
STAGE II


INJURY
(I)

STAGE V
ESRD
(E)
STAGE III

FAILURE
(F)
STAGE IV
LOSS
(L)
Severity
Outcome
increasing in the serum creatinine level of 0.5 mg
per dL (44.2 mol per L) or a 50 percent increase
in the creatinine level above the baseline value,
a 50 percent decrease in the baseline-calculated
glomerular filtration rate (GFR), or the need for
acute kidney replacement therapy.
Oliguria : a urine output of less than 400 mL in
24 hours.
Anuria : a urine output of less than 100 mL in 24
hours.

Catt : Nilai Normal GFR = 120-125 ml/menit
Am Fam Physician 2005;72:1739-46. Copyright 2005
American Academy of Family Physicians

CAUSES OF ARF
Generalized or localized
reduction in RBF
Hypovolaemia
Haemorrhage
Volume depletion
( vomiting,
diarrhoea,
inappropriate
diuresis, burns)

Hypotension
Cardiogenicshock
Distributive shock
(sepsis,
anaphylaxis)
Oedema
states
Cardiac failure
Hepatic cirrhosis
Nephrotic syndrome
Renal
Hypoperfusion
NSAIDs
ACEI / ARBs
AAA
RAS /occlusion
Hepatorenal
syndrome
Reduced GFR
PRE-RENAL (Hemodynamic)
PRERENAL
RENAL
TUBULAR
Ischemia, Nefrotoxins (Table 2)
tubular cells begin to die ATN (Acute
Tubular Necrosis)

GLOMERULAR
Glomerulonefritis : fever, rash, and
arthritis, urine findings include red
blood cell casts, hematuria, and
proteinuria.

Red blood cell cast
MARKER OF GLOMERULAR INJURY
Granular cast
Am Fam Physician 2005;72:1739-46. Copyright
2005 American Academy of Family Physicians
INTERSTITIAL
Acute Interstitial Nephritis
results from an allergic reaction to a drug
(Table 3)
Sign : fever, rash, serum and urine eosinophil
counts may be elevated.

VASCULAR
microvascular
macrovascular



Am Fam Physician 2005;72:1739-46. Copyright 2005
American Academy of Family Physicians
MARKER OF ACUTE INTERSTITIAL NEPHRITIS
POST RENAL
Obstruction of the outflow tracts of the
kidneys
Prostatic hypertrophy,
Catheters,
Tumors, Strictures, Crystals
Neurogenic bladder obstruction
The following symptoms may occur with acute Renal
failure. Some people have no symptoms, at least in
the early stages. The symptoms may be very subtle.
Hyperkalemia
Nausea/Vomiting
Pulmonary edema
Oliguria or non oliguria
Swelling, especially of the legs and feet
Ascites
Asterixis
Encephalopathy
Decrease urine output
Mental changes
Heart failure
Pruritus
Anemia
Tachypenic
Pale and moist skin

Identify and correct pre-renal, renal and post-
renal factors
Optimise cardiac output and RBF
Review drugs:
Stop ACEIs, NSAIDs
Adjust doses / monitor drug concentrations
Avoid aminoglicoside
Maintaining adequate intravascular volume and
mean arterial pressure

Discontinuing all nephrotoxic drugs
Eliminating exposure to any other nephrotoxins
Accurately monitor fluid balance and daily body
weight
Identify and treat acute complications
Hyperkalaemia
Acidosis
Oedema
Optimise nutritional support


Prinsip Terapi
Pengetahuan dan perjalanan klinik dari tahap-
tahap GGA, dengan cairan:

1. Terapi Konservatif
a. Preventif
b. Suportif
c. Substitusi

2. Terapi ginjal pengganti/dialisa
Dilakukan apabila terapi konservatif gagal

Mencegah faktor risiko yg ada baik akibat
tindakan di dalam Rumah sakit maupun yang
memang sudah ada sebelumnya

Memperingan keadaan GGA dan mengusahakan
agar perfusi renal seoptimal mungkin (oliguri
menjadi non-oliguri).

Volume efektif tubuh diusahakan normal, bila
hipovolemi ditambah, bila hipervolemi harus
dikurangi.

Catt : Volume urine normal = 600-1800 mL


1. Perdarahan, diberi transfusi
2. Plasma expander bila ada luka peritonitis
3. Air dan elektrolit yang sesuai
a. Muntah-muntah : NaCl 0,45% + Kalium 10-20
mmol/l
b. Kehilangan cairan/gangguan pankreatitis : NaCl
0,9 % + HCO3
c. Diare : D5% ditambah HCO3 + Kalium
4. Bila masih terjadi oliguri, diberi diuresis
osmotik berupa:

a. Mannitol 12,5 g iv/5 menit diulang 30 menit
kemudian bila produksi urin <20cc/jam. Bila
produksi urin >20cc/jam teruskan Mannitol 100
grdalam D5% liter/24 jam.
b. Furosemid 40-80 mg iv. Bila dalam 1-2jam
diuresis tidak timbul, dilakukan diuresis paksa
dengan dosis 250-500 mg drip dalam 150cc
D5%/jam.
5. Bila tetap oliguri, berikan vasoaktif untuk
memperbaiki perfusi ginjal yaitu: dopamin
dosis rendah 2-5mg per kg/menit dalam 12
jam.
6. Bila semua tindakan 1-5 gagal, diperlukan
terapi aktif/dialisa agar tidak terjadi oliguri
menetap.

Fase gawat dalam GGA

Biasanya disertai komplikasi : Hiperkalemia,
infeksi/sepsis, koma, kardiovaskuler,
gastrointestinal, respirasi, dan asidosis
metabolik.

Tujuan : untuk menjaga agar pasien tetap dpt
bertahan hidup sehingga ada kesempatan ginjal
pulih.

Terapi suportif adalah dengan mengatasi
gangguan keseimbangan.
1. Cairan
a. Bila ada overhidrasi, berikan furosemid 40-80 mg/iv.
Dapat dilakukan diuresis paksa dosis 250 mg dalam
600cc D5%. Bila gagal lakukan dialisa.
b. Pemberian cairan dibatasi 500 cc
c. Bila penderita panas dpt ditambah 10cc/jam tiap
kenaikan 1derajat C.

Catt : pedoman kebutuhan cairan dipantau dari kadar
Na, bila turun, berarti terjadi overhidrasi, sehingga
asupan cairan lebih dibatasi.

2. Elektrolit Asam Basa
a. Hiperkalemi
Penyebab kematian yang paling sering
pada GGA.
Bila <6 mg/L, hiperkalemi ringan, berikan
resin exchange 25-50 gr/3-4 hari
Bila >6mg/L, hiperkalemi sedang + berat,
dapat dilakukan pilihan pengobatan
hiperkalemia sbb :


2. Hiponatremia
Sering terjadi karena hidrasi berlebihan akibat
pemberian cairan yg sangat banyak
Terapi : pembatasan cairan atau pemberian 2g NaCl
0,9% atau 34 mEq.
3. Hipokalsemia
Akibat kegagalan absorbsi di GI, asidosis, dan
rhabdomiolisis
Terapi : pemberian Ca Gkukonat 10-30 cc/hari
4. Hipermagnesia
Sering berupa gejala paralisis otot, depresi
pernapasan, hipotensi bahkan koma
Terapi : preparat Kalsium, insulin + D5%.


5. Asidosis metabolik
Terjadi pernapasan Kussmaul, kadar bikarbobat
sering 15mg/l
Jumlah bikarbonat = 0,5 x BB x 15 serum HCO3
6. Nutrisi
1. Kalori : diberikan kalori 35-50 kal/kg BB
2. Protein : ditentukan oleh hiperkatabolisme pasien,
sebaiknya 0,5 gr/kgBB/hari
3. Lemak : jumlah kecil (maksimal 1/3 jumlah kalori)
7. Pemakaian obat-obatan
Hindari pemakaian obat-obatan yang nefrotoksik
Jika memang sangat dibutuhkan, atur lama dan
interval dosis
Perlu diperhatikan adanya poliuri (4000-5000
cc/hari) yang mungkin berakibat dehidrasi,
asidosis, bahkan hipokalemi.

Terapi substitusi cairan, garam, bikarbonat,
kalium, dicoba per oral, bila tidak mungkin
dapat secara parenteral 3-5 hari.

Indikasi dilakukan dialisa pada GGA :
1. Secara Klinis
overload cairan, perdarahan hebat, sindrom
ureum, asidosis metabolik, koma yang tidak
teratasi dengan terapi konservatif

2. Secara Laboratoris
HCO3 < 12 mEq , K > 6,0 mEq , Na < 120 mEq
, BUN > 100 mg/dl

ARF is common worldwide

Occurs in all clinical & community settings

It carries a high morbidity and mortality risks,
involves high cost of management.

ARF is increasingly common, particularly among
hospital inpatients, elderly people, and critically ill
patients.

It carries a high mortality

Patients at risk are - elderly people; patients with
diabetes, hypertension, or vascular disease; and
those with pre -existing renal impairment


ARF is often preventable.

Rapid recognition of incipient ARF and early
treatment of established ARF may prevent
irreversible loss of nephrons.

No drug treatment has been shown to limit the
progression of, or speed up recovery from, ARF.

Advice from a nephrologist should be sought for all
cases of ARF.