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Urinary System > Clinical Pharmacology in Renal Disease > Flashcards

Clinical Pharmacology in Renal Disease Flashcards

1
Q

What are the functions of the kidney?

A 
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
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2
Q

How does renal disease affect clinical pharmacology?

A

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

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3
Q

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

A

Toxicity or death can occur

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4
Q

What is the basic mechanism of renal excretion?

A

Glomerular filtration
Passive tubular reabsorption
Active tubular secretion

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5
Q

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

A

Sick
Volume depleted
Hypotensive
Prescribed large numbers of potentially renotoxic agents

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6
Q

How will renal impairment affect glomerular filtration?

A

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

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7
Q

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

A

2.5h in normal vs 50h in impaired

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8
Q

What are the pharmacokinetic effects of renal impairment?

A

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

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9
Q

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

A

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

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10
Q

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

A

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

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11
Q

What are the pharmacodynamic effects of renal impairment?

A

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

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12
Q

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

A

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

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13
Q

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

A

synergistic

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14
Q

What can renal impairment lead to?

A

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

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15
Q

What alterations in pharmacokinetics might occur in renal disease?

A

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

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16
Q

What alterations in pharmacodynamics might occur in renal disease?

A

Increased sensitivity to pharmacological action

Increased sensitivity to toxicity and ADRs

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17
Q

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

A

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

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18
Q

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

A

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

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19
Q

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

A

Renal patients have a low GFR and hyperuricaemia

20
Q

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

A

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

21
Q

Adverse drug reactions affecting the kidneys are a common cause of

A

morbidity and mortality, especially in hospitalised patients

22
Q

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

A

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

23
Q

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

A

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

24
Q

Drug induced renal toxicity can produce what major syndromes?

A

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

25
Q

What is acute renal failure?

A

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

26
Q

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

A

40%

27
Q

What types of causes of acute renal failure are there?

A

Pre-renal
Renal
Post-renal

28
Q

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

A

Water and electrolyte abnormalities
Increased catabolism
Vascular occlusion

29
Q

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

A

Acute tubular necrosis
Acute interstitial nephritis
Thrombotic microangiopathy

30
Q

What are the drugs that cause acute tubular necrosis?

A

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

31
Q

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

A

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

32
Q

What drugs are implicated in acute interstitial nephritis?

A 
Penicillins 
Cephalosporins 
Cocaine 
NSAIDs
Omeprazole 
Sulphonamides 
Diuretics 
Lithium 
Amphotericin B 
(lots and lots of others)
33
Q

What can thrombotic microangiopathy cause in the kidneys?

A

Severe acute renal failure

34
Q

What is the pathological hallmark of thrombotic microangiopathy?

A

Thrombi in the microvasculature of many organs

35
Q

What drugs are implicated in the cause of thrombotic miroangiopathy?

A 
Cyclosporin 
Tacrolimus 
Chemotherapeutic agents 
Mitomycin C 
Bleomycin 
Cisplatin 
Ticlopidine 
Clopidogrel 
Oestrogen-containing oral contraceptives 
Quinine 
Cocaine
36
Q

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

A

Drug associated obstruction
Crystal formation
Retroperitoneal fibrosis

37
Q

What drugs are implicated in crystal formation?

A 
Acyclovir 
Indinavir 
Sulphonamides 
Triamterene 
Methotrexate 
Vitamin C in large doses 
Guaifenesin and ephedrine
38
Q

What is the marker of nephrotic syndrome?

A

Heavy proteinuria

39
Q

What drugs are implicated in nephrotic syndrome?

A 
Gold
NSAIDs
Penicillamine 
Interferon 
Captopril
40
Q

What are the NSAID-induced renal syndromes?

A 
Acute renal failure 
Nephrotic syndrome 
Hypertension 
Hyperkalaemia 
Papillary necrosis
41
Q

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

A

20%

42
Q

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

A

7% hospital patients

20-30% critically ill patients

43
Q

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

A

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

44
Q

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

A

Idiosyncratic

45
Q

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

A

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

46
Q

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

A

10-20%

47
Q

What is the mechanism of aminoglycoside-induced renal injury?

A

Proximal tubular injury leading to cell necrosis

Urinary System (22 decks)

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