Mechanisms Of Drugs Induced Nephrotoxicity Flashcards
Renal impairment is often reversible or non-reversible
Reversible
What are the indicators of renal impairment?
a.Elevated BUN
b.Serum creatinine level
Name 3 types of AKI
Pre-renal, post renal, intrinsic
Pre-renal is caused by?
Transient renal hypoperfusion
Transient renal hypoperfusion is due to..
Hypotension, decreased CO, decreased effective arterial blood volume
Postrenal is due to…
Obstruction of urinary tract
State 6 Pathogenesis of Nephrotoxicity
- Altered intra-glomerular hemodynamics
- Tubular cell toxicity
- Inflammation
- Crystal nephropathy
- Rhabdomyolysis
- Thrombotic microangiopathy
What are drugs with anti-prostaglandin activity?
NSAIDs
What are drugs with antiangiotensin-
II activity
angiotensinconverting
enzyme (ACE) inhibitors,
angiotensin receptor blockers)
Other drugs which altered intra-glomerular hemodynamics
calcineurin inhibitors
Example of calcineurin inhibitors
cyclosporine, tacrolimus
MOA calcineurin inhibitors
cause dose dependent
vasoconstriction of the afferent
arterioles, leading to renal impairment in
at-risk patients
What are the roles of Renal tubular cells
concentrating
and reabsorbing glomerular filtrate
Site of renal tubule that more susceptible to high levels of circulating toxins?
PCT
How Drugs/toxins produce toxicity ?
- impairing mitochondrial function,
- interfering with tubular transport,
- increasing oxidative stress/forming free radicals.
Drug that can cause Tubular cell toxicity?
- aminoglycosides
- amphotericin B
- antiretrovirals (i.e. adenovir, cidofovir, tenofovir)
- cisplatin
- contrast dye
- foscarnet
- zoledronate.
What is Glomerulonephritis
an inflammatory condition caused
primarily by immune mechanisms and is often associated
with proteinuria
Drugs can cause inflammatory changes in the
glomerulus, renal tubular cells?
1.hydralazine,
2.interferon-alfa,
3.lithium,
4.NSAIDs,
5. propylthiouracil
6. pamidronate
What are causative drugs of acute Interstitial Nephritis?
- allopurinol
- antibiotics (especially beta
lactams, quinolones, rifampin, sulphonamides, and
vancomycin - antivirals (especially acyclovir and indinavir
- diuretics (loops, thiazides)
- NSAIDS
- phenytoin
- proton pump inhibitors (especially omeprazole,
pantoprazole, and lansoprazole; and ranitidine).
What are causative drugs of Chronic Interstitial Nephritis?
- calcineurin inhibitors (e.g., cyclosporine, tacrolimus)
- certain chemotherapy agents
- Chinese herbals containing aristocholic acid, and lithium
- Analgesics such as acetaminophen, aspirin, and NSAIDs when used chronically in high dosages
What are commonly prescribed drugs associated with production
of crystals?
- antibiotics (e.g., ampicillin,
ciprofloxacin, sulfonamides) - antivirals (e.g., acyclovir,
foscarnet, ganciclovir) - indinavir
- methotrexate; and
triamterene (Dyrenium) - potassium sparring
What is Rhabdomyolysis?
a syndrome in which skeletal muscle injury leads to lysis of the myocyte, releasing intracellular
contents including myoglobin and creatine kinase into the plasma.
How drugs may induce rhabdomyolysis?
- directly secondary to a toxic
effect on myocyte function - indirectly by predisposing the
myocyte to injury
What are the clinical manifestations of rhabdomyolysis?
weakness, myalgia, and tea-coloured urine.
Causative factors of rhabdomyolysis?
Drugs and alcohol
The most recognizable agents associated with
rhabdomyolysis is?
Statin
Other factors that can cause rhabdomyolysis ?
Drugs of abuse, such as cocaine, heroin, ketamine, methadone, and methamphetamine
What are drugs most often associated with Thrombotic microangiopathy?
- antiplatelet agents
(e.g., clopidogrel, ticlopidine) - cyclosporine
- mitomycin-C
- quinine.
What are Patient-related Risk Factors for Drug-induced Nephrotoxicity ?
- Intravascular volume depletion (dehydrated)
- Age older than 60 years (elderly)
- Diabetes
- Exposure to multiple nephrotoxins
- Heart failure
- Sepsis
- Underlying renal insufficiency (GFR < 60 mL per minute per 1.73 m2)
What are Drug-related Risk Factors for Drug-induced Nephrotoxicity ?
- The drugs inherently nephrotoxic i.e. aminoglycosides, cisplatin, contrast dye.
- Dose dependant or related to prolonged duration of treatment.
- Multiple drugs that synergistically nephrotoxic.
Function MDRD?
To assess renal function and stage ckd
Function Cockroft and Gault?
To adjust drug dosing for renal function in adult
Function Schwartz ?
To adjust drug dosing for renal function in children
