The Use of Medicines in Hepatic and Renal Impairment Flashcards Preview

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Flashcards in The Use of Medicines in Hepatic and Renal Impairment Deck (25)
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1

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. 

2

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?

3

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. 

4

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. 

5

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. 

6

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

7

What are the drug-induced causes of intra-renal AKI?

  • Tubular necrosis or interstitial nephritis or rhabdomyolysis. 
    • E.g. gentamycin, ciclosporin

8

What are the drug-induced causes of post-renal AKI?

  • Obstructions of the renal tract.
    • E.g. anticholinergics (amitriptyline), cytotoxic chemotherapy. 

9

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

10

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. 
  • 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. 

11

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. 

12

What are the risk factors for AKI?

  • DRUGS
  • Age >65
  • CKD
  • Dehydration - hypovolaemia, fever
  • Urinary blockage
  • Sepsis
  • Liver disease
  • Diabetes
  • Hypotension
  • Heart failure

13

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. 

14

What is the difference in half-life of gentamicin and digoxin between normal and impaired kidneys?

15

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. 

16

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. 

17

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. 

18

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. 

19

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. 

20

What are the risk factors for drug-induced liver disease?

  • Female
  • Genetic predisposition
  • Obesity
  • Diabetes
  • HIV
  • Polypharmacy

21

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. 

22

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. 

23

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

24

What routes of administration should be used in patients with liver disease?

  • Oral route preferred. 
  • Avoid IM injections.
  • Topical preparations.
  • Rectal preparations. 

25

SEE THIS LECTURE FOR A CASE STUDY ON RENAL IMPAIRMENT PRESCRIBING AND ONE ON HEPATIC IMPAIRMENT PRESCRIBING.