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URINARY > Clinical Pharmacology of Renal Disease > Flashcards

Clinical Pharmacology of Renal Disease Flashcards

1
Q

with regards to functions of the kidney, what is the most important in relation to clinical pharmacology

A

the excerpt of active drugs or their metabolites

also important are regulations extracellular volume and regulation of ionic concentration

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2
Q

what happens to levels of drugs if renal function is impaired

A

rapid build up of active drug, or toxic or active metabolites

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3
Q

what type of drugs are less likely to cause renal impairment

A

drugs that have a high therapeutic index or low toxicity e.g. benzylpenicillin

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4
Q

what type of drugs are more likely to cause renal impairment

A

drugs that have a narrow therapeutic index or high toxicity

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5
Q

give examples of 4 drugs that can cause toxicity and name the resulting complications

A

gentamicin - may cause renal or ototoxicity

digoxin -may cause arrhythmia, nausea or death

lithium - renal toxicity and death

tacrolimus - renal and CNS toxicity

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6
Q

name some factors that can interact to generate de novo renal impairment or worsen pre existing renal impairment/toxicity

A

sickness level (i.e. the more unwell a patient is the more likely they are to have complications)

volume depletion

hypotension

polypharmacy of potentially reno-toxic agents

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7
Q

what mechanism of renal excretion is most affected in renal impairment and what is the result

A

GLOMERULAR FILTRATION

  • passive tubular reabsorption
  • active tubular secretion

**changes in parameters due to disease, age or drug therapy will automatically change pharmacokinetics and pharmacodynamics

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8
Q

define pharmacokinetics

A

the bodies affect on the drug

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9
Q

define pharmacodynamics

A

the drugs affect on the body

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10
Q

how does renal impairment affect the half life of drugs

A

prolongs the half life of all drugs or their metabolites cleared by the glomerulus

**need to be extra careful when using drugs with a low therapeutic index

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11
Q

give some examples of normal drug half lives vs impaired half lives

A

benzylpen - 0.5hr - 8hr

gentamicin - 2.5 - 50

atenolol - 6 - 100

digoxin - 36 - 120

glibenclamide - 10 - 100

chlopropramide - 36 - 200

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12
Q

name two pharmacokinetic effects of renal impairment

A
  1. reduced GFR - leads to reduced clearance of drugs from the kidneys = ACCUMULATION
  2. reduced protein bindign - more active drug present in blood
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13
Q

what can be done to reduce the pharmacokinetic effects of renal impairment

A
  • REDUCE DOSE
  • increase dose interval
  • therapeutic drug monitoring (TDM) of blood levels for toxic drugs like gentamicin, lithium, digoxin, vancomycin
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14
Q

name three pharmacodynamic effects of renal impairment

A
  1. the blood brain barrier (and barrier to the testis and ovaries) becomes more permeable - e.g. brain becomes more sensitive to tranquillisers, sedatives and opiates
  2. circulatory volume may be reduced - patient more sensitive to antihypertensives, ACEIs or a-blockers
  3. increased tendency to bleed - beware warfarin or NSAIDs (ibuprofen, paracetamol, etc)
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15
Q

what can be said about the direct nephrotoxic actions drugs

A

SYNERGISTIC

  • gentamicin toxicity may be unmasked when used in conjunction with furosemide or lithium
    i. e. leads to increased sensitivity to the toxic effects of combined therapy
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16
Q

what are important things to know when prescribing drugs to a patient with renal impairment

A
  • which drugs can be used safely when eGFR decreased
  • which drugs have a low therapeutic index
  • risk/benefit ratio
  • severity of possible side effects
  • severity of toxicity
  • availability of TDM
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17
Q

what are important things that can reduce the possibility of renal impairment

A
  • reduce loading dose
  • reduce maintenance dose
  • increase down interval
  • importance of monitoring throughout course of treatment (TDM, renal function, blood pressure)
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18
Q

Ideally if a patient suffers from renal impairment what types of drug should be used

A
  • drugs with a high therapeutic index

- drugs that are metabolised by the liver to produce non-toxic metabolites

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19
Q

what is a common medical problem that can arise from renal damage

A

hypertension (HBP causes renal damage and vice versa)

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20
Q

normally what drugs would be used for a patient with hypertension

A

thiazide-type diuretics, CCBs, ACEIs

21
Q

why can’t hypertensive patients with renal damage have the usual HBP treatments

A

they have a low GFR - can lead to hyperuricaemia

they are also more sensitive to the hypotensive actions of antihypertensives

eg ACEIs commonly recommend but can produce severe acute renal dysfunction

eg direct vasodilators can produce profound hypotension and salt and water retention

eg thiazide diuretics may precipitate gout

22
Q

how can hypertensive really impaired patients be managed

A

use drugs which are totally metabolised by the liver or elsewhere in the body
- ACEIs (BUT monitor!)

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

23
Q

how does drug induced renal disease come about

A

any drug in the blood will eventually reach the kidney

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

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

24
Q

give an example how drug induced renal failure can go undetected

A

cardiac arrest

  • from acute hyperkalaemia
  • from acute renal dysfucntion
  • from drug toxicity
25
Q

why can bloods show “normal” renal function even though a patient may be really impaired

A

if looking at urea and creatinine levels - only show up as increased in blood when GFR <60% of normal

therefore patient have have some degree of renal impairment and reduced GFR but it not show up if not looking at correct things

26
Q

what are 4 types of disease that can occur from renal damage

A
  1. acute kidney injury
  2. acute tubular necrosis
  3. chronic kidney disease
  4. inflammatory disorders*

*eg cystitis - can be a drug induced inflammatory disorder o the bladder

27
Q

how can renal involvement in disease be identified

A

salt and water abnormalities - dehydration, oedema

acute renal failure
- from e.g. acute tubular necrosis, acute interstitial nephritis

chronic renal failure

28
Q

why is monitoring important when treating a patient with diuretics

A

to ensure renal function does not e impaired

29
Q

what are the four major syndromes associated with drug induced renal disease e

A
  1. acute renal failure
  2. nephrotic syndrome
  3. renal tubular dysfucntion with potassium wasting
  4. chronic renal failure
30
Q

define 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.

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

*also don’t have a thirst drive so don’t drink fluids

31
Q

what are the three types of acute renal failure

A

pre-renal
renal (intrinsic)
post-renal (obstructive)

32
Q

give examples of drugs that can induce pre-renal AKI (and how)

A

Water and electrolyte abnormalities:
diuretics, laxatives, lithium, NSAIDs

Increased catabolism:
Steroids, tertracyclines

Vascular occlusion:
Oestrogens/ OCP

33
Q

what are the three types of intrinsic acute renal failure

A
  1. Acute tubular necrosis (ATN)
  2. Acute interstitial nephritis
  3. Thrombotic microangiopathy.
34
Q

what drugs can cause acute tubular necrosis

A
  1. aminoglycoside, antibiotics
  2. amphotericin B
  3. cisplatin**, radiocontrast agents
  4. statins + immunosuppressives (eg cyclosporin

**always over hydrate patients before giving cisplatin

35
Q

when does acute interstitial nephritis present

A

Onset after drug exposure is 3-5 days with a second exposure, to as long as several weeks with a first exposure.

Latency period may be as short as 1 day with rifampicin, or as long as 18 months with an NSAID

36
Q

give some examples of drugs that can lead to acute interstitial nephritis

A

penicillins, cephalospirins, cocaine, NSAIDS*, omeprazole

chinese herbs

*could even be from e.g. ibuprofen used on a daily basis

37
Q

what is thrombotic microangiopathy

A

thrombi in the microvasculature of many organs - can use acute renal failure

include afferent arteriolar and glomerular thrombosis

38
Q

give some examples of drugs that can cause thrombotic microangipathy

A

cyclosporin, tacrolimus, OCP, cocain, quinine, clopidogrel

39
Q

how can drugs cause post renal/obstructive uropathy

A

drug associated obstruction of urine outflow:

  • within tubules or ureters (CRYSTAL FORMATION)
  • outside ureters due to retroperitoneal fibrosis (caused by e.g. methysergide)
40
Q

give some examples go drugs that can cause post renal damage

A

acyclovir, sulfonamides, methotrexate, vit C in alrge doses

41
Q

what drugs can lead to nephrotic syndrome

A

gold, NSAIDs, penicillamine, interferon

due to glomerular dysfunction and marked by heavy proteinuria

42
Q

give examples of some NSAID-induced renal syndromes

A

acute renal fiercer, hypertension, hyperkalemia, papillary necrosis*

*esp in women

**can be caused from even paracetamol

43
Q

what is the most common type of NSAID-induced acute renal failure

A

deceased synthesis of renal vasodilators prostaglandins - leads to reduced renal blood flow and reduced glomerular filtration

44
Q

which NSAIDs are related to NSAID-induced acute allergic interstitial nephritis

A

propionic acid derivatives - ibuprofen, naproxen, and fenoprofen

idiosyncratic reaction

associated with nephritic syndrome in 90% of cases

45
Q

what is amino glycoside-induced renal injury

A

proximal tubular injury leading to cell necrosis from nephrotoxicity of amino glycoside antibiotics used to treat severe gram eve sepsis

46
Q

SUMMARY: what should you be on the look out for in patients with renal damage

A

asymptomatic increase in urea and creatinine

fluid and electrolyte abnormalities

acute tubular necrosis

acute and chronic interstitial nephritis

47
Q

SUMMARY: what is the most common cause of acute renal failure

A

acute tubular necrosis due to aminoglycosides

48
Q

SUMMARY: what patients should you avoid nephrotoxic drugs in

A

volume deplete patients or
hypotensive patients with pre-existing renal disease

patents receives other nephrotoxic agents

**be aware of elderly, sick, polypharmacy patients too

URINARY (27 decks)

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