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*Urinary System > Clinical Pharmacology in Renal Disease > Flashcards

Clinical Pharmacology in Renal Disease Flashcards

1
Q

If renal function is impaired then in terms of clinical pharmacology what will there be a buildup of?

A
  • Active drug
  • Toxic or active metabolites
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2
Q

What 2 features would a drug have for there to be no problem between impaired renal function and pharmacology?

A

High therapeutic index

Low toxicity

(e.g. benzylpenicillin)

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3
Q

Certain drugs have a narrow therapeutic index which can lead to toxicity and death; what are the specific possible effects of these drugs: gentamicin, digoxin, lithium, tacrolimus

A

Gentamicin = may cause renal or ototoxicity

Digoxin = may cause arrythmia, nausea or death

Lithium = renal toxicity and death

Tacrolimus = renal and CNS toxicity

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4
Q

What factors found in hospital patients will interact to generate de novo renal impairment or worsen pre-existing renal impairment/toxicity?

A

Patients are:

    • Sick*
    • Volume depleted*
    • Hypotensive*
    • Prescribed a large number of potentially reno-toxic agents*
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5
Q

Mechanism of renal excretion; changes in what parameters of kidney physiology (due to disease, age or drug therapy) will automatically change drug pharmacokinetics and pharmacodynamics?

A
  • Glomerular filtration
  • Passive tubular reabsorption
  • Active tubular secretion
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6
Q

All drugs and their metabolites are filtered at the glomerulus, renal impairment will do what to drugs cleared by this route?

A

Prolong their half-life

(reduction in GFR reduces clearance of drugs by the kidney resulting in accumulation; protein binding is also reduced)

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7
Q

What 3 things must be done with drugs when they have effects with renal impairment?

A
  • REDUCE DOSAGE
  • Increase dose interval
  • TDM monitor blood levels for toxic drugs like gentamicin, lithium, digoxin, vancomycin
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8
Q

How does renal disease alter the actions of drugs on tissues in terms of: blood brain barrier, circulatory volume, tendency to bleed

A
  • BBB becomes more permeable + brain becomes more sensitive to tranquilisers, sedative and opiates
  • Circulatory vol may be reduced making the patient sensitive to antihypertensive agents ACEIs or alpha-blockers
  • Increased tendency to bleed (beware warfarin or NSAIDs)
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9
Q

In patients with renal disease how do the direct nephrotoxic actions of drugs work?

A

Synergistically (e.g. gentamicin toxicity may be unmasked when used in conjunction with furosemide or lithium)

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10
Q

Renal impairment may lead to: dramatic alterations in pharmacokinetics; alteration in pharmacodynamics; increased sensitivity to the toxic effects of combined therapy - here is a more detailed summary:

A
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11
Q

When prescribing in patients with impaired renal function, what 4 things should be considered? What should be done?

A

Consider:

- risk/benefit ratio

- severity of possible side effects

- severity of toxicity

- availability of TDM

Do: reduce dose, change dose freq, change the drugs

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12
Q

Ideally if a patient suffers from renal impairment, we should should use drugs which have which 2 features?

A
  1. Have a high therapeutic index
  2. Are metabolised by the liver with the production of non-toxic metabolites
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13
Q

What is the relationship between hypertension and renal disease?

A

Hypertension causes renal damage

Renal damage causes hypertension

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14
Q

What is the dilema associated with treating hypertension in patients with renal disease?

A

–Normally use thiazide-type diuretics, CCBs, ACEIs

–However patients with renal impairment have a low GFR, hyperuricaemia,

–More sensitive to the hypotensive actions of antihypertensive agents.

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15
Q

What are the 2 ways we can tackle to problem of treating hypertension in renally impaired patients?

A
  • Use drugs which are totally metabolised by the liver or elsewhere in the body (e.g. ACEI (but can be nephrotoxic))
  • Use reduced dose of the drugs with longer dosing periods i.e. atenolol 25mg/day or on alternate days
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16
Q

What is the problem with using direct vasodilators for hypertension?

A

Can produce profound hypotension and salt + water retention

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17
Q

What is a possible problem with using thiazide/thiazide-type diuretics to treat hypertension?

A

May precipitate gout

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18
Q

If a drug is primarily cleared by the kidney, what will happen to it as it moves from the glomerulus along the renal tubules?

A

It will become increasingly concentrated

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

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19
Q

What are the outcomes of renal damage?

A
  • Acute kidney injury
  • Acute tubular necrosis
  • Chronic kidney disease
  • Inflammatory disorders
  • Salt and water abnormalities - dehydration, oedema
  • Acute renal failure - acute tubular necrosis, acute interstitial nephritis
  • Chronic renal failure
20
Q

What are the 4 major syndromes which drug-induced toxicity can cause?

A

Acute renal failure

Nephrotic syndrome

Renal tubular dysfunction with potassium wasting

Chronic renal failure

21
Q

What is acute renal failure?

A

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

Urine volume falls to <400ml/day in 40% of patients

22
Q

What patients does acute renal failure usually occur in?

A

Often elderly patients who are sick, have a poor fluid intake, who are on multiple medications and who are not being monitored aggressively

23
Q

Give 3 pre-renal causes of drug induced renal disease

A
  • Water and electrolyte abnormalities (diuretics, laxatives, lithium, NSAIDs)
  • Increased catabolism (steroids, tetracyclines)
  • Vascular occlusion (oestrogens/OCP)
24
Q

What are the 3 types of intrinsic acute renal failure?

A
  • Acute tubular necrosis (ATN)*
  • Acute interstitial nephritis*
  • Thrombotic microangiopathy*
25
Q

What 4 drugs can cause acute tubular necrosis (intrinsic acute renal failure)?

A

Aminoglycoside abx

Amphotericin B

Cisplatin (up to 25% patients), radiocontrast agents

Statin drugs in combo with immunosuppressive agents e.g. cyclosporin (i.e. transplant patients - highly susceptible to atherosclerosis)

26
Q

In acute interstitial nephritis (intrinsic acute renal failure), give 2 drugs which cause it and the difference in their latency period

A

Rifampicin - can be as short as 1 day

NSAID - can be as long as 18 months

27
Q

Give more examples of drugs possible implicated in acute interstitial nephritis

A
  • Penicillins, cephalosporins, cocaine,

sulfonamides, NSAIDs, diuretics,

lithium, ranitidine, omeprazole,

captopril, lithium, phenytoin, valproic acid,

amphotericin B, streptokinase, 5-aminosalicylates,

allopurinol, rifampin

  • Chinese herbs
28
Q

What can thrombotic microangiopathy (intrinsic acute renal failure) cause?

A
  • Severe acute renal failure
  • Thrombi in the microvasculature of many organs - pathological hallmark !
  • Changes in kidney - inc afferent arteriolar and glomerular thrombosis
29
Q

What drugs can cause thrombotic microangiopathy?

A

Cyclosporin, tacrolimus

Chemotherapeutic agents mitocyin C, bleomycin, cisplatin

Ticipidine, clopidogrel

19 eostrogen-containing oral contraceptives

Quinine (used in malaria, leg cramps, restless leg syndrome)

Cocaine

30
Q

Drug associated obstruction of urine outflow (post-renal/obstructive uropathy causes of intinsice acute renal failure) - how does it occur in the tubules or ureters?

A

Due to crystal formation

31
Q

How does drug associated obsruction of urine outflow occur outside the ureters?

A

Due to retroperitoneal fibrosis by agents such as methysergide (prophylaxis for migraine/cluster headaches)

32
Q

Name some drugs implicated in crystal formation

A
  • Acyclovir, indinavir
  • Sulfonamides
  • Triamterene
  • Methotrexate
  • Vit C in large doses (due to oxalate crystals)
  • Guaifenesin and ephidrine can also cause stones to form in kidneys (found in weight loss preparations)
33
Q

What is nephrotic syndrome due to (pathophysiologically)?

What is it marked by?

A

Glimerular dysfunction

Marked by heavy proteinuria

34
Q

Name some dugs implicated in nephrotic syndrome

A

Gold

NSAIDs

Penicillamine

Interferon

Captopril

35
Q

Give some recognisde adverse renal effects of non-selective NSAIDs

A

Acute renal failure

Nephrotic syndrome

Hypertension

Hyperkalaemia

Papillary necrosis (females>males)

(NSAIDs = one of biggest causes of ADRs and mortality)

36
Q

Mechanisms of nephrotoxicity

A
37
Q

What drugs are most commonly responsible for HOSPITAL ACQUIRED renal insufficiency (not inc primary care)

A

Aminoglycosides

NSAIDs

Piperacillin/tazobactam

Amphotericin B

Trimethoprin/sulfa

(also cyclosporin, ACEI, multiple nephrotoxins, ciprofloxacin, cis-platinum, acyclovir, ceftazidine - to a lesser extent)

38
Q

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

A

Decreases synthesis of renal vasodilator prostaglandins, which can lead to reduced BF and reduced GFR

39
Q

Which patients become more susceptible to acute renal failure?

A

Patients who’s renal blood flow is already reduced

40
Q

What type of reaction is NSAID-induced acute allergic intestitial nephritis? What drugs is it particularly a reaction to?

A

Idiosyncratic reaction (rare and unpredictable)

Propionic acid derivatives - ibruprofen, naproxen, fenoprofen

41
Q
A
42
Q

What is NSAID-induced acute allergic interstitial nephritis associated with in about 90% of cases?

A

Nephrotic syndrome

43
Q

What are aminoglycosde abx used in?

A

Severe gram-negative sepsis

44
Q

In how many therapeutic courses does aminoglycoside abx cause nephrotoxicity?

A

10-20%

45
Q

What is the mechanism of aminoglycoside-induced renal injury? (basic)

A

Proximal tubular injury leading to cell necrosis

46
Q

Summary 1

A
47
Q

Summary 2

A

*Urinary System (26 decks)

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