Clinical Pharmacology in Renal Disease

Question 1

What happens to drugs in the body if renal function is impaired?

Answer 1

Rapid build up of active drugs or toxic/active metabolites from drugs

Question 2

Name a drug with a high theraputic index/low toxicity. What does this mean?

Answer 2

Benzylpenicillin

It means the drug build up would need to be very high to have an effect

Question 3

Name some drugs with a narrow therapeutic index. What does this mean?

Answer 3

Gentamicin
Digoxin
Lithium
Tacrolimus

Means build up can be VERY dangerous

Question 4

What can gentamicin do to the body?

Answer 4

Cause renal or oto-toxicity

Question 5

What can digoxin toxicity do?

Answer 5

Arrythmia’s
Nausea
death

Question 6

What does lithium toxicity cause?

Answer 6

Renal toxicity

Death

Question 7

What can tacrolimus toxicity do?

Answer 7

Renal and CNS toxicity

Question 8

Why is renal function important to drugs?

Answer 8

Renal function may have a effects on pharmacokinetics or pharmacodynamics

Question 9

Where are drugs/drug metabolites filtered?

Answer 9

Glomerulus

Question 10

What must you do regarding drug delivery if there is a reduction in GFR of a patient?

Answer 10

Reduce dosage
Increase dose interval
Monitor drugs levels in blood

Question 11

Is protein binding to drugs reduced if GFR is reduced? What does this mean?

Answer 11

Yes

Means more free drug will be available - this is why lower doses are given

Question 12

What are some effects of renal failure on pharmacodynamics?

Answer 12

BBB becomes more permeable making brain more sensitive to sedatives and opiates

Circulatory volume may be reduced making patient sensitive to anti-hypertensives

Increased risk of bleeding so beware of warfarin/NSAIDs -

Question 13

In patients with renal disease, the direct nephrotoxic actions of drugs are…this means…

Answer 13

Synergistic

Meaning there is increased sensitivity to toxic effects of combined therapy

Question 14

So, if a patient suffers from renal impairment, ideally we should use drugs which…

Answer 14

• have a high therapeutic index

- are metabolised by the liver with the production of non-toxic metabolites

Question 15

Why is hypertension and renal disease so closely linked?

Answer 15

Because HTN causes renal disease and renal disease causes HTN

Question 16

Why is anti-hypertensive therapy not the best idea for patients with renal impairment?

Answer 16

They have a low GFR = hyperuricaemia

Meaning they are more sensitive to the hypotensive actions of anti-hypertensives

Question 17

So how can we tackle the hypertension issue in renal disease?

Answer 17

1. Use drugs which are totally metabolised by the liver or else where in the body such as ACEI’s - but these are potentially nephrotoxic
   ACEIs
2. Use a reduced dose of the drug with longer dosing periods - atenolol 25mg/day or on alternative days

Question 18

Issues with direct vasodilators in renal impairment/HTN?

Answer 18

Can cause profound hypotension leading to salt/water retention

Question 19

Issues with thiazides?

Answer 19

Can precipitate gout

Question 20

Why do some drugs cause kidney damage?

Answer 20

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 21

What are the 4 major syndromes that drug induced renal toxicity can cause?

Answer 21

Acute renal failure/AKI
Chronic renal failure
Nephrotic syndrome
Renal tubular dysfunction with potassium wasting

Question 22

Briefly describe AKI.

Answer 22

Sudden deterioration in renal function = rapid creatinine rise
Drop of urine output

Can be prerenal, intrinsic or post-renal

Question 23

What sort of drugs cause pre-renal AKI?

Answer 23

Ones that cause water/electrolyte abnormalities - diuretics, laxatives, lithium, NSAIDs

Ones that increase catabolism - steroids, tetracyclines

Ones that cause vascular occlusion - oestrogens/the pill

Question 24

What are the 3 types of intrinsic acute renal failure?

Answer 24

Acute tubular necrosis
Acute interstitial nephritis
Thrombotic microangiopathy

Question 25

Name some drugs that can cause acute tubular necrosis.

Answer 25

Aminiglycoside antibiotics
Amphotericin B
Cisplatin/radiocontrast agents
Statins give with immunosuppresives (cyclosporin)

Question 26

Name some drugs that can cause Acute Interstitial Nephritis.

Answer 26

Penicillins
Cephalosporins
Cocaine
NSAIDs
Omeprazome
Chinese herbs (?)

Question 27

Thrombotic microangiopathy can cause…

Answer 27

Severe AKI
Thromobi in the microvasculature of many organs - (hallmark pathology of TM)
Afferent vessel and glomeruli thrombosis

Question 28

Thrombotic microangiopathy caused by…

Answer 28

Oestrogen containing oral contraceptive pills

Cocaine

Question 29

What is nephrotic syndrome?

Answer 29

High proteinuria
Oedema
Hyperlipidaemia

Question 30

Drugs that can cause nephrotic syndrome?

Answer 30

NSAIDs
Penicillamine
Gold

Question 31

Name some NSAID induced renal syndromes.

Answer 31

AKI
Nephrotic syndrome
HTN
Hyperkalaemia
Papillary necrosis

Question 32

What is the most common type of NSAID induced AKI?

Answer 32

Results from decreased synthesis of renal vasodilator prostaglandins = reduced blood flow to glomerulus = reduced GFR

Question 33

What is NSAID-induced acute allergic interstitial nephritis?

Answer 33

An idiosyncratic reaction to things like ibuprofen, naproxen and fenoprofen

Associated with nephrotic syndrome in 90% of cases

Question 34

What is AMINOGLYCOSIDE-INDUCED RENAL INJURY?

Answer 34

Aminoglycoside antibiotics, cause nephrotoxicity in ~20% of cases by causing proximal tubular injury leading to cell necrosis.

Question 35

When are aminoglycoside antibiotics used/

Answer 35

Severe gram-neg sepsis