Clinical Pharmacology in Renal Disease

Question 1

What are the functions of the kidney?

Answer 1

Excretion of metabolic waste products 
Regulation of extracellular volume 
Regulation of ionic concentration 
Regulation of physiological pH 
Metabolism of a small number of drugs 
Excretion of active drugs or their metabolites

Question 2

How does renal disease affect clinical pharmacology?

Answer 2

If renal function is impaired there will be a rapid build-up of the active drug or its metabolites

Question 3

What happens if drugs have a narrow therapeutic index or high toxicity and are used in a patient with renal disease?

Answer 3

Toxicity or death can occur

Question 4

What is the basic mechanism of renal excretion?

Answer 4

Glomerular filtration
Passive tubular reabsorption
Active tubular secretion

Question 5

What features of patients in hospital make them more predisposed to kidney disease?

Answer 5

Sick
Volume depleted
Hypotensive
Prescribed large numbers of potentially renotoxic agents

Question 6

How will renal impairment affect glomerular filtration?

Answer 6

Renal impairment will prolong the half-life of drugs or their metabolites cleared by glomerular filtration

Question 7

What is the T1/2 of gentamicin in a normal individual compared with the T1/2 of gentamicin in renal impairment?

Answer 7

2.5h in normal vs 50h in impaired

Question 8

What are the pharmacokinetic effects of renal impairment?

Answer 8

Reduced GFR
Reduced clearance of drugs by the kidney
Reduced protein binding

Question 9

What must be done when prescribing drugs to patients with renal impairment?

Answer 9

Lower dosage
Increase dose interval
Therapeutic drug monitoring (TDM) - monitor blood levels of toxic drugs

Question 10

How are the blood-brain-barrier and the brain affected by renal impairment?

Answer 10

The blood-brain-barrier becomes more permeable and the brain becomes more sensitive to tranquillisers, sedatives and opiates

Question 11

What are the pharmacodynamic effects of renal impairment?

Answer 11

Blood-brain-barrier more permeable
Brain more sensitive to some drugs
Circulatory volume reduced
Increased tendency to bleed

Question 12

What is the effect of a reduced circulatory volume on the patient?

Answer 12

Reduced circulatory volume can make the patient more sensitive to antihypertensive agents e.g. ACEIs and alpha blockers

Question 13

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

Answer 13

synergistic

Question 14

What can renal impairment lead to?

Answer 14

Dramatic alterations in pharmacokinetics
Alterations in pharmacodynamics
Increased sensitivity to toxic effects of combined therapy

Question 15

What alterations in pharmacokinetics might occur in renal disease?

Answer 15

Increased half life
Build up of drug or metabolites
Decrease in protein binding so more free drug available

Question 16

What alterations in pharmacodynamics might occur in renal disease?

Answer 16

Increased sensitivity to pharmacological action

Increased sensitivity to toxicity and ADRs

Question 17

What should be considered when prescribing for patients with impaired renal function?

Answer 17

Risk/benefit ratio
Severity of possible side effects
Severity of toxicity
Availability of TDM

Question 18

What drugs should be used (ideally) in patients who suffer from renal impairment?

Answer 18

Drugs which have a high therapeutic index and are metabolised by the liver with the production of non-toxic metabolites

Question 19

Why are renal patients more sensitive to the hypotensive actions of antihypertensives?

Answer 19

Renal patients have a low GFR and hyperuricaemia

Question 20

What effects can ACEIs, direct vasodilators and thiazides/thiazide-like diuretics have on patients with renal impairment?

Answer 20

ACEIs - can produce severe acute renal dysfunction
Direct vasodilators can produce profound hypotension and salt and water retention
Thiazides/Thiazide-like diuretics can precipitate gout

Question 21

Adverse drug reactions affecting the kidneys are a common cause of

Answer 21

morbidity and mortality, especially in hospitalised patients

Question 22

What will happen to a drug which is primarily cleared by the kidney in patients with renal impairment?

Answer 22

Drug will become increasingly concentrated as it is moved from the glomerulus and along the renal tubules, the concentrated drug exposes the kidney tissue to far greater drug concentration per surface area

Question 23

What forms does renal involvement in adverse drug reactions commonly take?

Answer 23

Salt and water abnormalities e.g. dehydration, oedema
Acute renal failure
Chronic renal failure

Question 24

Drug induced renal toxicity can produce what major syndromes?

Answer 24

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

Question 25

What is acute renal failure?

Answer 25

A sudden deterioration in renal function which results in a rapid rise in creatinine

Question 26

In what percentage of people with renal failure does urine output fall to < 400ml/day?

Answer 26

40%

Question 27

What types of causes of acute renal failure are there?

Answer 27

Pre-renal Renal Post-renal

Question 28

What are the pre-renal causes of acute renal failure?

Answer 28

Water and electrolyte abnormalities Increased catabolism Vascular occlusion

Question 29

What are the renal/intrinsic causes of acute renal failure?

Answer 29

Acute tubular necrosis Acute interstitial nephritis Thrombotic microangiopathy

Question 30

What are the drugs that cause acute tubular necrosis?

Answer 30

Aminoglycoside antibiotics Amphotericin B Cisplatin Statin drugs given in combination with immunosuppressive agents e.g. cisplatin

Question 31

What is the onset of acute interstitial nephritis after drug exposure?

Answer 31

Ranges from 3-5 days with a second exposure, to several weeks with a first exposure

Question 32

What drugs are implicated in acute interstitial nephritis?

Answer 32

``` Penicillins Cephalosporins Cocaine NSAIDs Omeprazole ``` ``` Sulphonamides Diuretics Lithium Amphotericin B (lots and lots of others) ```

Question 33

What can thrombotic microangiopathy cause in the kidneys?

Answer 33

Severe acute renal failure

Question 34

What is the pathological hallmark of thrombotic microangiopathy?

Answer 34

Thrombi in the microvasculature of many organs

Question 35

What drugs are implicated in the cause of thrombotic miroangiopathy?

Answer 35

``` Cyclosporin Tacrolimus Chemotherapeutic agents Mitomycin C Bleomycin Cisplatin Ticlopidine Clopidogrel Oestrogen-containing oral contraceptives Quinine Cocaine ```

Question 36

What are the post-renal causes of acute renal failure?

Answer 36

Drug associated obstruction Crystal formation Retroperitoneal fibrosis

Question 37

What drugs are implicated in crystal formation?

Answer 37

``` Acyclovir Indinavir Sulphonamides Triamterene Methotrexate Vitamin C in large doses Guaifenesin and ephedrine ```

Question 38

What is the marker of nephrotic syndrome?

Answer 38

Heavy proteinuria

Question 39

What drugs are implicated in nephrotic syndrome?

Answer 39

``` Gold NSAIDs Penicillamine Interferon Captopril ```

Question 40

What are the NSAID-induced renal syndromes?

Answer 40

``` Acute renal failure Nephrotic syndrome Hypertension Hyperkalaemia Papillary necrosis ```

Question 41

What percentage of hospital admissions due to AKI are drug related?

Answer 41

20%

Question 42

How many hospital patients and critically ill patients does AKI affect?

Answer 42

7% hospital patients | 20-30% critically ill patients

Question 43

What does the most common type of NSAID-induced acute renal failure result from?

Answer 43

Decreased synthesis of renal vasodilator prostaglandins which can lead to reduced renal blood flow and reduced glomerular filtration

Question 44

What kind of reaction is NSAID-induced acute allergic interstitial nephritis?

Answer 44

Idiosyncratic

Question 45

NSAID-induced acute allergic interstitial nephritis is a reaction that occurs particularly to what group of drugs?

Answer 45

Propionic acid derivatives e.g. ibuprofen, naproxen, fenoprofen

Question 46

In what percentage of therapeutic courses do amino glycoside antibiotics cause nephrotoxicity?

Answer 46

10-20%

Question 47

What is the mechanism of aminoglycoside-induced renal injury?

Answer 47

Proximal tubular injury leading to cell necrosis