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BST2 > Mechanisms Of Drugs Induced Nephrotoxicity > Flashcards

Mechanisms Of Drugs Induced Nephrotoxicity Flashcards

1
Q

Renal impairment is often reversible or non-reversible

A

Reversible

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2
Q

What are the indicators of renal impairment?

A

a.Elevated BUN
b.Serum creatinine level

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3
Q

Name 3 types of AKI

A

Pre-renal, post renal, intrinsic

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4
Q

Pre-renal is caused by?

A

Transient renal hypoperfusion

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5
Q

Transient renal hypoperfusion is due to..

A

Hypotension, decreased CO, decreased effective arterial blood volume

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6
Q

Postrenal is due to…

A

Obstruction of urinary tract

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7
Q

State 6 Pathogenesis of Nephrotoxicity

A
  1. Altered intra-glomerular hemodynamics
  2. Tubular cell toxicity
  3. Inflammation
  4. Crystal nephropathy
  5. Rhabdomyolysis
  6. Thrombotic microangiopathy
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8
Q

What are drugs with anti-prostaglandin activity?

A

NSAIDs

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9
Q

What are drugs with antiangiotensin-
II activity

A

angiotensinconverting
enzyme (ACE) inhibitors,
angiotensin receptor blockers)

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10
Q

Other drugs which altered intra-glomerular hemodynamics

A

calcineurin inhibitors

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11
Q

Example of calcineurin inhibitors

A

cyclosporine, tacrolimus

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12
Q

MOA calcineurin inhibitors

A

cause dose dependent
vasoconstriction of the afferent
arterioles, leading to renal impairment in
at-risk patients

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13
Q

What are the roles of Renal tubular cells

A

concentrating
and reabsorbing glomerular filtrate

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14
Q

Site of renal tubule that more susceptible to high levels of circulating toxins?

A

PCT

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15
Q

How Drugs/toxins produce toxicity ?

A
  1. impairing mitochondrial function,
  2. interfering with tubular transport,
  3. increasing oxidative stress/forming free radicals.
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16
Q

Drug that can cause Tubular cell toxicity?

A
  1. aminoglycosides
  2. amphotericin B
  3. antiretrovirals (i.e. adenovir, cidofovir, tenofovir)
  4. cisplatin
  5. contrast dye
  6. foscarnet
  7. zoledronate.
17
Q

What is Glomerulonephritis

A

an inflammatory condition caused
primarily by immune mechanisms and is often associated
with proteinuria

18
Q

Drugs can cause inflammatory changes in the
glomerulus, renal tubular cells?

A

1.hydralazine,
2.interferon-alfa,
3.lithium,
4.NSAIDs,
5. propylthiouracil
6. pamidronate

19
Q

What are causative drugs of acute Interstitial Nephritis?

A
  1. allopurinol
  2. antibiotics (especially beta
    lactams, quinolones, rifampin, sulphonamides, and
    vancomycin
  3. antivirals (especially acyclovir and indinavir
  4. diuretics (loops, thiazides)
  5. NSAIDS
  6. phenytoin
  7. proton pump inhibitors (especially omeprazole,
    pantoprazole, and lansoprazole; and ranitidine).
20
Q

What are causative drugs of Chronic Interstitial Nephritis?

A
  1. calcineurin inhibitors (e.g., cyclosporine, tacrolimus)
  2. certain chemotherapy agents
  3. Chinese herbals containing aristocholic acid, and lithium
  4. Analgesics such as acetaminophen, aspirin, and NSAIDs when used chronically in high dosages
21
Q

What are commonly prescribed drugs associated with production
of crystals?

A
  1. antibiotics (e.g., ampicillin,
    ciprofloxacin, sulfonamides)
  2. antivirals (e.g., acyclovir,
    foscarnet, ganciclovir)
  3. indinavir
  4. methotrexate; and
    triamterene (Dyrenium) - potassium sparring
22
Q

What is Rhabdomyolysis?

A

a syndrome in which skeletal muscle injury leads to lysis of the myocyte, releasing intracellular
contents including myoglobin and creatine kinase into the plasma.

23
Q

How drugs may induce rhabdomyolysis?

A
  1. directly secondary to a toxic
    effect on myocyte function
  2. indirectly by predisposing the
    myocyte to injury
24
Q

What are the clinical manifestations of rhabdomyolysis?

A

weakness, myalgia, and tea-coloured urine.

25
Q

Causative factors of rhabdomyolysis?

A

Drugs and alcohol

26
Q

The most recognizable agents associated with
rhabdomyolysis is?

A

Statin

27
Q

Other factors that can cause rhabdomyolysis ?

A

Drugs of abuse, such as cocaine, heroin, ketamine, methadone, and methamphetamine

28
Q

What are drugs most often associated with Thrombotic microangiopathy?

A
  1. antiplatelet agents
    (e.g., clopidogrel, ticlopidine)
  2. cyclosporine
  3. mitomycin-C
  4. quinine.
29
Q

What are Patient-related Risk Factors for Drug-induced Nephrotoxicity ?

A
  1. Intravascular volume depletion (dehydrated)
  2. Age older than 60 years (elderly)
  3. Diabetes
  4. Exposure to multiple nephrotoxins
  5. Heart failure
  6. Sepsis
  7. Underlying renal insufficiency (GFR < 60 mL per minute per 1.73 m2)
30
Q

What are Drug-related Risk Factors for Drug-induced Nephrotoxicity ?

A
  1. The drugs inherently nephrotoxic i.e. aminoglycosides, cisplatin, contrast dye.
  2. Dose dependant or related to prolonged duration of treatment.
  3. Multiple drugs that synergistically nephrotoxic.
31
Q

Function MDRD?

A

To assess renal function and stage ckd

32
Q

Function Cockroft and Gault?

A

To adjust drug dosing for renal function in adult

33
Q

Function Schwartz ?

A

To adjust drug dosing for renal function in children

BST2 (10 decks)

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