Clinical Pharmacology in Renal Disease

Question 1

What will happen to a patient who is taking medications when their renal function is impaired?

Answer 1

Rapid build up of active drug and toxic / active metabolites

Question 2

What are some drugs with a narrow therapeutic index that can be risky in renal impairment?

Answer 2

gentamicin may cause renal or ototoxicity

digoxin may cause arrhythmia, nausea or death

lithium: renal toxicity and death
tacrolimus: renal and CNS toxicity

Question 3

How does renal impairment affect drug activity in the body?

Answer 3

• Prolongs the half life of drugs & their metabolites, longer period of activity

Question 4

What is often the necessary intervention when managing the pharmaceuticals of a patient with renal impairment?

Answer 4

• Reduce dosage of drugs (change drugs?)

- Increase dosing interval

Question 5

What are some possible pharmacodynamic effects in the body that may be caused by renal impairment?

Answer 5

• Higher permeability at BBB, brain more sensitive to tranquilizers, sedatives and opiates
• May have a reduction in plasma volume, higher sensitivity to ACE inhibitors / anti-hypertensives
• May be an increased tendency to bleed, beware of warfarin / NSAIDs
• Decrease in protein binding of drugs

Question 6

What characteristics make a drug more suitable to be used in renal impairment?

Answer 6

• High therapeutic index

- Drug is metabolized by the liver with the production of non-toxic metabolites

Question 7

Why are the kidneys particularly vulnerable to drug induced damage?

Answer 7

If the drug is primarily cleared by the kidney, it will be increasingly concentrated as it is moves from the glomerulus and along the renal tubules

The concentrated drug exposes the kidney tissue to far greater drug concentration per surface area

Question 8

What major syndromes are most commonly caused by drug induced renal disease?

Answer 8

Acute renal failure

Nephrotic syndrome

Renal tubular dysfunction with potassium wasting

Chronic renal failure

Question 9

What are the three types of Intrinsic acute renal failure that may be caused by drug effects?

Answer 9

• Acute tubular necrosis (ATN)
• Acute interstitial nephritis
• Thrombotic microangiopathy.

Question 10

Where does drug induced obstructive uropathy tend to occur?

Answer 10

within the tubules or the ureters (due to crystal formation),

Outside the ureters due to retroperitoneal fibrosis

Question 11

What are some drugs that are heavily indicated in causing nephrotic syndrome?

Answer 11

NSAIDs,

penicillamine,

interferon,

captopril.

Question 12

What are some common renal syndromes that can be caused by the inappropriate usage of NSAIDs?

Answer 12

acute renal failure,
nephrotic syndrome, 
hypertension, 
hyperkalemia,
papillary necrosis

Question 13

What drugs are most commonly responsible for hospital acquired renal insufficiency?

Answer 13

1. Aminoglycosides (broad-spectrum, bactericidal antibiotics)
2. NSAIDs
3. Piperacillin
4. Amphoterecin B

Question 14

How do NSAIDs tend to cause renal failure?

Answer 14

Causes a decrease in synthesis of renal vasodilator prostaglandins

• which can lead to reduced renal blood flow and reduced glomerular filtration

Question 15

How do aminoglycosides tend to cause renal insufficiency?

Answer 15

Mechanism is proximal tubular injury leading to cell necrosis

Question 16

What is the most common drug induced renal insufficiency? which drugs cause it?

Answer 16

Acute renal failure due to Acute Tubular Necrosis is the most common and is due to aminoglycosides

Question 17

What drugs are used to treat hypertension in patients suffering from renal impairment?

Answer 17

Use drugs which are totally metabolised by the liver or else where in the body:
ACE inhibitors

Use reduced dose of the drug with longer dosing periods. i.e. atenolol 25mg/day or on alternate days.