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Pharmacology > SPR L9 Drugs and the Kidney > Flashcards

SPR L9 Drugs and the Kidney Flashcards

1
Q

Learning Outcomes

Impact of renal function on drug elimination

Nephro-toxic drugs

Principles of prescribing in renal failure

A
  • Describe the impact of renal and liver disease on drug pharmacokinetics and pharmacodynamics
  • List safety precautions that should be taken when prescribing in renal and liver disease
  • Give examples of common drugs that must be used with caution or contra-indicated in renal and liver disease
  • Discuss the drugs that are used to treat liver failure
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2
Q

Revision of the Nephron

A
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3
Q

Outline the pharmacokinetics of penicillins

A
  • Oral absorption variable
  • widely distributed in body fluids
  • Mainly renal excretion (tubular secretion)
  • Short plasma half-life
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4
Q

Adjustment of Dose may be necessary

Give an example of a penicillin and adjustment

A

Tazocin (Piperacillin/tazobactam)

  • Normal renal = 4.5g 8-hrly
  • Renal impairment = 4.5g 12-hrly
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5
Q
  1. Give examples of some drugs that may be less effective in renal impairment
  2. Therefore, we need to use alternatives, give examples of these
A
  1. Thiazide diuretics

Nitrofurantoin (antibiotic)

  1. Loop diuretics (cautiously)

Trimethoprim

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6
Q

Some drugs may produce more adverse effects in renal impairment

  1. Give examples of a drug that will show increased effect
  2. Give examples of drugs that show increased toxicity
A
  1. Opioids / Sedatives
  2. Digoxin (arrhythmias / nausea)

K+ sparing diuretics (hyperkalaemia)

Nitrofurantoin (neuropathy)

Tetracyclines (increased protein breakdown)

Metformin (lactic acidosis)

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7
Q

Some drugs mauy produce more adverse effects in renal impairment

What effects can the following drugs have?

  1. Digoxin
  2. K+ sparing diuretics
  3. Nitrofurantoin
  4. Tetracyclines
  5. Metformin
A
  1. arrhythmias / nausea
  2. hyperkalaemia
  3. neuropathy
  4. increased protein breakdown
  5. lactic acidosis
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8
Q

Acute Kidney injury
Pre-renal impairment

  1. What is pre-renal impairment?
  2. What actions should be taken?
A
  1. Decreased renal perfusion / altered autoregulation

Especially if sudden changes in volume state e.g.:

–Vomiting / Diarrhoea

–Bleeding

–Cardiac failure

–Cirrhosis

  1. Should discontinue potentially nephrotoxic drugs if this is the case +/- support blood pressure
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9
Q

Which drugs are associated with pre-renal impairment?

A
  • Diuretics
  • Antihypertensives – especially:
    • ACE inhibitors / ARBs
    • Other vasodilators (CCBs, nitrates etc)
  • NSAIDs
  • Ciclosporin (DMARD)
  • Radio contrast media
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10
Q

Acute Kidney injury
(Intrinsic) Renal impairment

Give examples of drugs

A
  • Aminoglycosides (gentamicin)
  • Amphotericin B
  • Other antimicrobials (Quinolones, macrolides)
  • Anti-platelets (clopidogrel)
  • Anti-convulsants (Phenytoin / carbamazepine)
  • DMARDs (ciclosporin, gold, penicillamine)
  • Lithium
  • NSAIDs / COX-2 inhibitors
  • Radio contrast media
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11
Q

Acute Kidney injury
Post – renal impairment

Give examples of acute kidney injury, and associated drugs

A
  • Crystals / stones (rare)
    • Aciclovir
    • Methotrexate
  • Retroperitoneal fibrosis (rare)
    • Ergot derivatives
    • Methyldopa / Hydralazine / atenolol
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12
Q

What are the drugs that need to be specifically considered in renal impairment?

A
  • NSAIDs
  • ACE- I / ARBS
  • Diuretics
  • Lithium
  • Digoxin
  • Gentamicin
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13
Q

NSAIDs

  1. Which can cause nephrotoxicity?
  2. What can they cause?
  3. What must you ask about?
A
  1. ALL can cause nephrotoxicity
  2. Acute tubular necrosis, Interstitial nephritis, Glomerulonephritis, Renal papillary necrosis.
  3. Must ask about over-the-counter (OTC) use.
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14
Q

ACE inhibitors and ARBs

  1. What can these be used to control?
  2. What can they be associated with?
  3. When do they often need to be witheld?
  4. When are these contraindicated?
A

Complex relationship with renal impairment

  1. Can be used to control blood pressure and reduce intra-glomerular pressure, reducing proteinuria
  2. May be associated with deterioration of renal function
  3. often need to be witheld when patient is acutely unwell
  4. Renal Artery Stenosis
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15
Q

Diuretic drug interactions

  1. When is there risk of increased electrolyte disturbances?
  2. What is seen when they are combined with aminoglycoside antiobotics (loop)?
  3. When is there impaired diuresis?
  4. When can hypotension result?
  5. When is there likely to be lithium toxicity?
A
  1. when combined with other diuretics
  2. Increased oto and nephrotoxicity
  3. when combined with NSAIDs
  4. when combined with ACE inhibitors and other vasodilator drugs
  5. when co- prescribed (thiazides)
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16
Q

Lithium

  1. How is lithium excreted?
  2. When should it be avoided?
  3. When does the dose often need reduced?
  4. What can it block the effect of on the kidney?
  5. What can long-term use cause?
  6. When is risk of lithium toxicity increased?
A
  1. by the kidney
  2. in severe renal impairment
  3. during episodes of illness as Lithium renal excretion is reduced
  4. Can block the effect of ADH on the kidney – diabetes insipidus – Why is this a problem?
  5. tubulo-interstitial damage
  6. if co-prescribed with diuretics / ACE-i / ARBs
17
Q

Digoxin

  1. How is it primarily excreted, describe it’s therapeutic range?
  2. What increases as renal function decreases?
  3. When is the risk of dig toxicity increased? What should there be caution with?
A
  1. by the kidney and has a narrow therapeutic range
  2. Half-life and therefore time to steady state
  3. by hypokalaemia so caution with diuretics (common co-prescription in heart failure)
18
Q

Gentamicin
Aminoglycosides

  1. Why is this given IV?
  2. What is its penetration?
  3. What is it’s half-life?
  4. Why MUST dose and frequency be reduced in renal impairment?

Adjustment of regimen will be necessary

Give a worked example of how this is carried out

A
  1. Highly polar molecules
  2. Variable penetration into body fluids
  3. Eliminated by kidney T1/2 2-3 hours - Elimination mirrors eGFR
  4. to prevent dose dependent side effects

E.g. Gentamicin in a 60 kg man

Normal renal = 5 mg/kg = 300mg daily

Renal impairment = 300mg 36-hrly or 240mg 24-36hrly

Will need to measure ‘trough’ levels and U+E more often

19
Q

Acute (drug-induced) kidney injury
Key points

A
  • Injury is usually reversible if detected early
  • Looking at the serum creatinine and eGFR (estimated glomerular filtration rate) along with urinary sediment enables this detection
  • Stop potentially nephrotoxic drugs
  • Ensure appropriate supportive treatment (e.g. IV fluids)
20
Q

Outline the staging in Chronic Kidney Disease

A
21
Q

Impact of renal impairment on drug elimination

  1. Why is no change in loading dose of a drug required?
  2. For patients with significant renal impairment, what actions should be taken?
    1. How can this be achieved?
A
  1. since the volume of distribution is unaltered.
  2. For drugs eliminated by the kidney the dose should be reduced
    1. by individual dose reduction or lengthening the dosage interval.
22
Q

Dosage adjustment in renal impairment

  1. When is maintenance dose reduction required?
  2. How is adjustment of dosage usually achieved?
A
  1. for drugs which are primarily eliminated by the kidney and have a narrow therapeutic index
  2. using the eGFR or less accurately, the serum creatinine
23
Q

Principles of prescribing in renal failure

  1. For which drugs is a simple scheme for dose reduction sufficient?
  2. What happens to the time taken to reach steady state?
  3. What drugs should be avoided?
  4. What should be adjusted, using what?
A
  1. For many drugs with only minor or no dose-related side-effects•Reduce the dose of drugs eliminated by the kidney
  2. will be increased
  3. nephro-toxic if possible
  4. Adjustment of the maintenance dose should be made using the GFR and where appropriate plasma drug levels
24
Q

Revision of Other Renal Activities

A
25
Q

Severe CKD

A
  • Phosphate binding agents – Calcium carbonate taken with meals
  • Secondary HyperPTH / renal osteodystrophy – 1,25-OH vitamin D (calcitriol) daily tablet
  • If symptomatic anaemia – specialist may use erythropoetins
  • Dialysis / renal replacement therapy
26
Q

Dialysis

  1. What happens in dialysis?
  2. Which drugs are removed more readily, why?
  3. Clearance of drugs may necessitate supplementary doses of drug (drugs that you need are being removed) - give examples
A
  1. Solutes diffuse from blood into the dialysis fluid
  2. Drugs that are small molecules with low protein binding will be removed more readily

–Theophylline

–Metronidazole

–Gentamicin/ Tobramicin

–Anti-virals

Dialysis doesn’t only remove urea, but also small diffusible drugs in the pts bloodstream.

27
Q

Dialysis

  1. When can dialysis be used?
    1. Give examples of the drugs implicated
A
  1. in certain acute poisoning, again dictated by how readily the drug molecule can diffuse across

–Aspirin

–Lithium

–Ethylene glycol

–Methanol

–Sodium Valproate

Pharmacology (26 decks)

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