SPR L9 Drugs and the Kidney Flashcards
Learning Outcomes
Impact of renal function on drug elimination
Nephro-toxic drugs
Principles of prescribing in renal failure
- 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
Revision of the Nephron
Outline the pharmacokinetics of penicillins
- Oral absorption variable
- widely distributed in body fluids
- Mainly renal excretion (tubular secretion)
- Short plasma half-life
Adjustment of Dose may be necessary
Give an example of a penicillin and adjustment
Tazocin (Piperacillin/tazobactam)
- Normal renal = 4.5g 8-hrly
- Renal impairment = 4.5g 12-hrly
- Give examples of some drugs that may be less effective in renal impairment
- Therefore, we need to use alternatives, give examples of these
- Thiazide diuretics
Nitrofurantoin (antibiotic)
- Loop diuretics (cautiously)
Trimethoprim
Some drugs may produce more adverse effects in renal impairment
- Give examples of a drug that will show increased effect
- Give examples of drugs that show increased toxicity
- Opioids / Sedatives
- Digoxin (arrhythmias / nausea)
K+ sparing diuretics (hyperkalaemia)
Nitrofurantoin (neuropathy)
Tetracyclines (increased protein breakdown)
Metformin (lactic acidosis)
Some drugs mauy produce more adverse effects in renal impairment
What effects can the following drugs have?
- Digoxin
- K+ sparing diuretics
- Nitrofurantoin
- Tetracyclines
- Metformin
- arrhythmias / nausea
- hyperkalaemia
- neuropathy
- increased protein breakdown
- lactic acidosis
Acute Kidney injury
Pre-renal impairment
- What is pre-renal impairment?
- What actions should be taken?
- Decreased renal perfusion / altered autoregulation
Especially if sudden changes in volume state e.g.:
–Vomiting / Diarrhoea
–Bleeding
–Cardiac failure
–Cirrhosis
- Should discontinue potentially nephrotoxic drugs if this is the case +/- support blood pressure
Which drugs are associated with pre-renal impairment?
- Diuretics
- Antihypertensives – especially:
- ACE inhibitors / ARBs
- Other vasodilators (CCBs, nitrates etc)
- NSAIDs
- Ciclosporin (DMARD)
- Radio contrast media
Acute Kidney injury
(Intrinsic) Renal impairment
Give examples of drugs
- 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
Acute Kidney injury
Post – renal impairment
Give examples of acute kidney injury, and associated drugs
- Crystals / stones (rare)
- Aciclovir
- Methotrexate
- Retroperitoneal fibrosis (rare)
- Ergot derivatives
- Methyldopa / Hydralazine / atenolol
What are the drugs that need to be specifically considered in renal impairment?
- NSAIDs
- ACE- I / ARBS
- Diuretics
- Lithium
- Digoxin
- Gentamicin
NSAIDs
- Which can cause nephrotoxicity?
- What can they cause?
- What must you ask about?
- ALL can cause nephrotoxicity
- Acute tubular necrosis, Interstitial nephritis, Glomerulonephritis, Renal papillary necrosis.
- Must ask about over-the-counter (OTC) use.
ACE inhibitors and ARBs
- What can these be used to control?
- What can they be associated with?
- When do they often need to be witheld?
- When are these contraindicated?
Complex relationship with renal impairment
- Can be used to control blood pressure and reduce intra-glomerular pressure, reducing proteinuria
- May be associated with deterioration of renal function
- often need to be witheld when patient is acutely unwell
- Renal Artery Stenosis
Diuretic drug interactions
- When is there risk of increased electrolyte disturbances?
- What is seen when they are combined with aminoglycoside antiobotics (loop)?
- When is there impaired diuresis?
- When can hypotension result?
- When is there likely to be lithium toxicity?
- when combined with other diuretics
- Increased oto and nephrotoxicity
- when combined with NSAIDs
- when combined with ACE inhibitors and other vasodilator drugs
- when co- prescribed (thiazides)
Lithium
- How is lithium excreted?
- When should it be avoided?
- When does the dose often need reduced?
- What can it block the effect of on the kidney?
- What can long-term use cause?
- When is risk of lithium toxicity increased?
- by the kidney
- in severe renal impairment
- during episodes of illness as Lithium renal excretion is reduced
- Can block the effect of ADH on the kidney – diabetes insipidus – Why is this a problem?
- tubulo-interstitial damage
- if co-prescribed with diuretics / ACE-i / ARBs
Digoxin
- How is it primarily excreted, describe it’s therapeutic range?
- What increases as renal function decreases?
- When is the risk of dig toxicity increased? What should there be caution with?
- by the kidney and has a narrow therapeutic range
- Half-life and therefore time to steady state
- by hypokalaemia so caution with diuretics (common co-prescription in heart failure)
Gentamicin
Aminoglycosides
- Why is this given IV?
- What is its penetration?
- What is it’s half-life?
- 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
- Highly polar molecules
- Variable penetration into body fluids
- Eliminated by kidney T1/2 2-3 hours - Elimination mirrors eGFR
- 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
Acute (drug-induced) kidney injury
Key points
- 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)
Outline the staging in Chronic Kidney Disease
Impact of renal impairment on drug elimination
- Why is no change in loading dose of a drug required?
- For patients with significant renal impairment, what actions should be taken?
- How can this be achieved?
- since the volume of distribution is unaltered.
- For drugs eliminated by the kidney the dose should be reduced
- by individual dose reduction or lengthening the dosage interval.
Dosage adjustment in renal impairment
- When is maintenance dose reduction required?
- How is adjustment of dosage usually achieved?
- for drugs which are primarily eliminated by the kidney and have a narrow therapeutic index
- using the eGFR or less accurately, the serum creatinine
Principles of prescribing in renal failure
- For which drugs is a simple scheme for dose reduction sufficient?
- What happens to the time taken to reach steady state?
- What drugs should be avoided?
- What should be adjusted, using what?
- For many drugs with only minor or no dose-related side-effects•Reduce the dose of drugs eliminated by the kidney
- will be increased
- nephro-toxic if possible
- Adjustment of the maintenance dose should be made using the GFR and where appropriate plasma drug levels
Revision of Other Renal Activities
Severe CKD
- 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
Dialysis
- What happens in dialysis?
- Which drugs are removed more readily, why?
- Clearance of drugs may necessitate supplementary doses of drug (drugs that you need are being removed) - give examples
- Solutes diffuse from blood into the dialysis fluid
- 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.
Dialysis
- When can dialysis be used?
- Give examples of the drugs implicated
- in certain acute poisoning, again dictated by how readily the drug molecule can diffuse across
–Aspirin
–Lithium
–Ethylene glycol
–Methanol
–Sodium Valproate
