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Obat-obat Nefrotoksik

Abraham Simatupang
Departemen Farmakologi &
Terapi
FK UKI

Tujuan Pembelajaran
Setelah mengikuti Kuliah ini
diharapkan mahasiswa:
1. Mengetahui obat-obat yang bersifat
nefrotoksik
2. Mengetahui beberapa mekanisme
obat nefrotoksik dan cara
pencegahannya

Ginja
l

Nefron

Ginjal salah satu organ penting


dalam eksresi dan menjaga stabilitas
homeostasis
Ginjal organ yang paling sering
terpapar dengan berbagai
zat/senyawa maupun metabolit

Toksisitas terhadap ginjal


Karena perubahan hemodinamik
Perlukaan langsung terhadap sel dan
jaringan
Perlukaan jaringan karena reaksi
inflamasi,
Dan/atau obstruksi ekskresi ginjal
(batu, kelainan anatomi, dll.)

Drugs Associated
Nephrotoxicity
Drug class/drug(s)
Pathophysiologic mecahnism
of renal injury
Analgesics
Acetaminophen, aspirin

Chronic interstitial nephritis,


altered intraglomerular
hemodynamics, chronic
interstitial nephritis,
glomerulonephritis

Antidepressant/mood stabilizers
Amitryptilin, doxepin, fluoxetine
(Prozac), Lithium

Antihistamines
Diphenhydramine (Benadryl),
doxylamine
Antimicrobials

Rhabdomiolysis
Chronic interstitial nephritis,
glomerulonephritis,
rhabdomiolysis
Rhabdomiolysis

Drug class/drug(s)

Pathophysiologic mechanism
of renal injury

Amphotericin B

Tubular cell toxicity

Beta lactams (penicillins,


cephalopsorins)

Acute interstitial nephritis,


glomerulonephritis (ampicillin,
penicillin)

Foscarnet (Foscavir)

Crystal nephropathy, Tubular cell


toxicity

Pganciclovir (Cytovene)

Crystal nephropathy

Pentamidine (Pentan)

Tubular cell toxicity

Quinolones

Acute interstitial nephritis, crystal


nephropathy (ciprofloxacin/Cipro)

Rifampin/Rifampisin

Acute interstitial nephritis

Sulfonamides

Acute interstitial nephritis, crystal


nephropathy

Vancomycin

Acute interstitial nephritis

Drug class/drug(s)
Antiretrovirals
Adefovir (Hepsera), cidofovir
(Vistide), tenofovir (Viread)

Pathophysiologic mecahnism
of renal injury
Tubular cell toxicity

Indinavir (Crixivan)

Acute interstitial nephritis, crystal


nephropathy

Benzodiazepines

Rhabdomyolysis

Calcineurin inhibitors
Cyclosporine (Neoral)

Altered intraglomerular
hemodynamics, chronic
interstitial nephritis, thrombotic
microangiopathy

Tacrolimus (Prograf)

Altered intraglomerular
hemodynamics

Cardiovascular agents
Angiotensin-converting enzyme
inhibitors, angiotensin receptor
blockers
Clopidogrel (Plavix), ticlopidine
(Ticlid)

Altered intraglomerular
hemodynamics
Thrombotic microangiopathy

Drug class/drug(s)
Chemotherapeutics
Carmustine (Gliadel), semustine
(investigational)

Pathophysiologic mecahnism
of renal injury
Chronic interstitial nephritis

Cisplatin (Platinol)

Chronic interstitial nephritis,


tubular cell toxicity

Interferon-alfa (Intron A)

Glomerulonephritis

Methotrexate

Crystal nephropathy

Mitomycin-C (Mutamycin)

Thrombotic microangiopathy

Contrast dye

Tubular cell toxicity

Diuretics
Loops, thiazides
Triamterene (Dyrenium)

Acute interstitial nephritis


Crystal nephropathy

Proton pump inhibitors


Lansoprazole (Prevacid),
omeprazole (Prilosec),
pantoprazole (Protonix)
Allopurinol

Acute interstitial nephritis

Acute interstitial nephritis

Patient-related risk factors


Absolute or effective intravascular
volume depletion
Age older than 60 years
Diabetes
Exposure to multiple nephrotoxins
Heart failure
Sepsis
Underlying renal insufficiency (glomerular
filtration rate < 60 mL per minute per 1.73
m2)

Prevention strategies
Drugs altering intraglomerular
hemodynamics
Medications

Risk-factors

Prevention strategies

ACE inhibitors, ARBs,


NSAIDs

Underlying renal
insufficiency;
intravascular volume
depletion; age older
than 60 years;
concomitant use of
ACE inhibitors, ARBs,
NSAIDs, cyclosporine
(Neoral), or
tacrolimus (Prograf

Use analgesics with


less prostaglandin
activity
(acetaminophen,
aspirin, sulindac
[Clinoril],
nabumetone [Relafen;
brand not available in
the United States])
Correct volume
depletion before
initiation of drug,
especially if used on a
chronic basis.
Monitor renal function
and vital signs

Drugs altering intraglomerular


hemodynamics
Cyclosporine,
tacrolimus

As above, plus:
Monitor serum drug
excessive dose,
concentrations and
concomitant use with renal function
other nephrotoxic
drugs or drugs that
inhibit cyclosporine
or tacrolimus
metabolism
Use lowest effective
dose

Drugs associated with tubular cell


toxicity
Aminoglycosides

Underlying renal
insufficiency,
duration of therapy
> 10 days, trough
concentrations > 2
mcg per mL,
concomitant liver
disease,
hypoalbuminemia

Use extended-interval
dosing Maintain trough
levels 1 mcg per mL

Drugs associated with chronic


interstitial nephropathy
Acetaminophen,
aspirin, NSAIDs

History of chronic
Avoid long-term use,
pain, age older than
particularly of more
60 years, female sex, than one analgesic
cumulative
consumption of
analgesic > 1 gram
per day for more than
two years
Use alternate agents
in patients with
chronic pain

Lithium

Elevated drug levels

Maintain drug levels


within the therapeutic
range
Avoid volume
depletion

Drugs associated with crystal


nephropathy
Acyclovir (Zovirax),

Volume depletion,

Discontinue or reduce

Ringkasan
Cukup banyak obat yang bersifat nefrotoksik
Dalam batas-batas tertentu toksisitas bersifat
sementara dan tubuh dapat mengkoreksinya
sendiri
Kerusakan yang timbul tergantung kondisi awal
ginjal dan sistem organ lainnya dan tingkat
nefrotoksisitas obat (mis. Aminoglikosida)
Perlu penyesuaian dosis obat pada keadaan
tertentu (gagal ginjal, gagal jantung, reaksi
alergi, dll.)