The Use of Medicines in Hepatic and Renal Impairment Flashcards
Describe the relationship between drugs and the kidney.
- Reduced renal excretion of a drug and its metabolites may cause toxicity.
- Sensitivity to some drugs is increased even if eliination is unimpaired.
- Increased risk of ADRs.
- Some drugs are not effective when renal function is reduced.
What are the general prescribing considerations when prescribing medications to a patient with renal impairment?
- Degree of renal impairment.
- Whether acute or chronic kidney disease.
- Proportion of drug renally excreted.
- Does drug have a narrow or wide therapeutic window?
- Use eGFR or creatinine clearance?
- Is the drug potentially nephrotoxic?
- Is this patient established on renal replacement therapy?
What are the necessary adjustments when prescribing drugs with a high renal clearance and narrow therapeutic window?
Give examples.
- Require dose reductions or extended dosing intervals.
- Examples: vancomycin / gentamycin, digoxin, lithium.
What are the necessary adjustments when prescribing drugs with a high renal clearance and wide therapeutic window?
Give examples.
- This is unlikely to be problematic (except when high doses of intravenous).
- Examples: penicillins and cephalosporins.
What are the necessary adjustments when prescribing drugs with a low renal clearance and narrow therapeutic window?
Give examples.
- Dose and monitor in the same way as patients without renal impairment.
- Examples: theophylline, carbamazepine, phenytoin.
What are the drug-induced causes of pre-renal AKI?
- Blood flow to the kidney is restricted = renal underperfusion.
- E.g. NSAIDs
- Excessive water and electrolyte loss.
- E.g. diuretics
What are the drug-induced causes of intra-renal AKI?
- Tubular necrosis or interstitial nephritis or rhabdomyolysis.
- E.g. gentamycin, ciclosporin
What are the drug-induced causes of post-renal AKI?
- Obstructions of the renal tract.
- E.g. anticholinergics (amitriptyline), cytotoxic chemotherapy.
Which drugs should be closely monitored if you are worried about a patient’s kidney function?
- ACE-I, A2 blockers
- NSAIDs
- Lithium
- Metformin
- Contrasts (iodinated)
- Opioids
- Disease-modifying antirheumatic drugs (e.g. methotrexate)
- Anticoagulants
- Anticonvulsants
- Antivirals
- Digoxin
- Immunosuppressants
- Hypoglycaemics
- Aminoglycosides and vancomycin
Which drugs can cause / worsen kidney injury?
- Diuretics cause excessive water / electrolyte loss, increased catabolism, vascular occlusion, altered renal haemodynamics.
- NSAIDs inhibit prostaglandin synthesis leading to vasoconstriction, poor renal blood flow, reduced GFR and urine volume.
- Aminoglycosides (e.g. Gentamicin) causing intrinsic damage.
- Opioids - active metabolites can accumulate.
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Metformin
- Increased risk of metabolic acidosis (rise in lactate)
- Avoid if eGFR <30mL/min.
-
Nitrofurantoin
- Queries around efficacy due to inadequate urine concentration.
- Increased risk of ADRs - peripheral neuropathy, blood dyscrasias.
- If eGFR <30mL/min, use only if multi-resistant bugs, keep course short and only if benefits > risks.
What are the principles of prescribing in renal impairment?
- Check Us and Es, including eGFR and creatinine.
- Look at baseline and trends in renal function.
- Consider stopping or with-holding nephrotoxic drugs.
- Check resources.
- Choose non-nephrotoxic drugs if possible.
- Reduce size of dose, increase dosing interval, stop or with-hold.
- Use therapeutic drug monitoring to guide dose / frequency if appropriate.
- Continue to monitor U&Es, BP and clinical response.
What are the risk factors for AKI?
- DRUGS
- Age >65
- CKD
- Dehydration - hypovolaemia, fever
- Urinary blockage
- Sepsis
- Liver disease
- Diabetes
- Hypotension
- Heart failure
What if you needed to prescribe a drug and needed it to be at the therapeutic dose quickly? (Ie. there is no time to reduce drug and give it more slowly).
- Initial doses / loading doses often not reduced.
- Renal disease = prolongs half-lives of some drugs.
- Can take longer to get to steady state.
- Usual loading dose as per normal renal function to reach target therapeutic serum drug concentrations then reduce maintenance dose.
What is the difference in half-life of gentamicin and digoxin between normal and impaired kidneys?
What are the main components of CKD management?
- Detect early.
- Manage comorbid conditions - e.g. tight control of glucose, BP.
- Reno-protect - ACE-I and ARBs.
- Manage complications e.g. hyperkalaemia, anaemia, mineral / bone disorders, hyperphosphataemia.
What are the considerations of prescribing in patients on renal replacement therapy?
- What kind of dialysis are they on?
- What is the dialyser membrane, blood and dialysate flow rate?
- Some drugs are actively removed during dialysis.
- Information on how to deal with this is NOT in the BNF - must consult a renal colleague.
What are the basic principals of prescribing in hepatic impairment?
- What is causing the abnormal LFTs?
- Is the drug metabolism affected?
- Is there hyperproteinaemia?
- What are the clotting factors like?
- Are there signsof hepatic encephalopathy?
- What is the fluid balance like?
- Is the drug hepatotoxic?
- Be more cautious if the liver is decompensating.
-
Start low and go slow.
- Often lower the recommended dose by approximately 50%.
- Titrate to effect and monitor LFTs.
- Safety net patient - educate about ADRs.
What is hepatic shunting?
- A portosystemic shunt (PSS) is an abnormal connection between the portal vascular system and systemic circulation.
- Causes reduced first pass extraction through the liver.
- This causes high hepatic clearance of drugs (morphine, propanolol) and therefore increased bioavailability / plasma concentration, so increases the risk of adverse effects.
Which drugs might worsen the symptoms of liver disease?
- Constipating drugs.
- Medicines that cause GI ulceration.
- Sedating medicines.
- Anticoagulants, antiplatelets and other medicines that can cause bleeding.
- Medicines that can affect fluid-electrolyte balance.
- Medicines with a high sodium content.
- Medicines that are nephrotoxic.
What are the risk factors for drug-induced liver disease?
- Female
- Genetic predisposition
- Obesity
- Diabetes
- HIV
- Polypharmacy
What is the difference between intrinsic drug reactions and idiosyncratic drug reactions?
- Intrinsic drug reactions are predictable, dose-dependant, occur rapidly (e.g. paracetamol OD).
- Idiosyncratic drug reactions are not predictable or dose dependant, take longer to develop.
Give examples of drugs which can cause different types of liver damage.
- Acute liver failure - allopurinol, cyclophosphamide and NSAIDs.
- Fibrosis and cirrhosis - methotrexate.
- Hepatitis - phenytoin.
- Steatosis - amiodarone, corticosteroids, TPN.
- Vascular disorders - oral contraceptive pill, azathioprine.
- Cholestasis - warfarin, azathioprine, carbimazole, oral contraceptice pill and flucloxacillin.
If a patient has an adverse reaction, how do you work out if the drug is to blame?
- Consider:
- LFT trend
- Other potential causes of liver disease?
- Detailed medication history
- Onset of abnormalities
- Resolution of abnormalities if the drug is stopped
What routes of administration should be used in patients with liver disease?
- Oral route preferred.
- Avoid IM injections.
- Topical preparations.
- Rectal preparations.
SEE THIS LECTURE FOR A CASE STUDY ON RENAL IMPAIRMENT PRESCRIBING AND ONE ON HEPATIC IMPAIRMENT PRESCRIBING.
