Clinical Pharmacology in Renal Disease Flashcards
What happens to drugs in the body if renal function is impaired?
Rapid build up of active drugs or toxic/active metabolites from drugs
Name a drug with a high theraputic index/low toxicity. What does this mean?
Benzylpenicillin
It means the drug build up would need to be very high to have an effect
Name some drugs with a narrow therapeutic index. What does this mean?
Gentamicin
Digoxin
Lithium
Tacrolimus
Means build up can be VERY dangerous
What can gentamicin do to the body?
Cause renal or oto-toxicity
What can digoxin toxicity do?
Arrythmia’s
Nausea
death
What does lithium toxicity cause?
Renal toxicity
Death
What can tacrolimus toxicity do?
Renal and CNS toxicity
Why is renal function important to drugs?
Renal function may have a effects on pharmacokinetics or pharmacodynamics
Where are drugs/drug metabolites filtered?
Glomerulus
What must you do regarding drug delivery if there is a reduction in GFR of a patient?
Reduce dosage
Increase dose interval
Monitor drugs levels in blood
Is protein binding to drugs reduced if GFR is reduced? What does this mean?
Yes
Means more free drug will be available - this is why lower doses are given
What are some effects of renal failure on pharmacodynamics?
BBB becomes more permeable making brain more sensitive to sedatives and opiates
Circulatory volume may be reduced making patient sensitive to anti-hypertensives
Increased risk of bleeding so beware of warfarin/NSAIDs -
In patients with renal disease, the direct nephrotoxic actions of drugs are…this means…
Synergistic
Meaning there is increased sensitivity to toxic effects of combined therapy
So, if a patient suffers from renal impairment, ideally we should use drugs which…
- have a high therapeutic index
- are metabolised by the liver with the production of non-toxic metabolites
Why is hypertension and renal disease so closely linked?
Because HTN causes renal disease and renal disease causes HTN
Why is anti-hypertensive therapy not the best idea for patients with renal impairment?
They have a low GFR = hyperuricaemia
Meaning they are more sensitive to the hypotensive actions of anti-hypertensives
So how can we tackle the hypertension issue in renal disease?
- Use drugs which are totally metabolised by the liver or else where in the body such as ACEI’s - but these are potentially nephrotoxic
ACEIs - Use a reduced dose of the drug with longer dosing periods - atenolol 25mg/day or on alternative days
Issues with direct vasodilators in renal impairment/HTN?
Can cause profound hypotension leading to salt/water retention
Issues with thiazides?
Can precipitate gout
Why do some drugs cause kidney damage?
If the drug is primarily cleared by the kidney, it will be increasingly concentrated as it is moves from the glomerulus and along the renal tubules
The concentrated drug exposes the kidney tissue to far greater drug concentration per surface area
What are the 4 major syndromes that drug induced renal toxicity can cause?
Acute renal failure/AKI
Chronic renal failure
Nephrotic syndrome
Renal tubular dysfunction with potassium wasting
Briefly describe AKI.
Sudden deterioration in renal function = rapid creatinine rise
Drop of urine output
Can be prerenal, intrinsic or post-renal
What sort of drugs cause pre-renal AKI?
Ones that cause water/electrolyte abnormalities - diuretics, laxatives, lithium, NSAIDs
Ones that increase catabolism - steroids, tetracyclines
Ones that cause vascular occlusion - oestrogens/the pill
What are the 3 types of intrinsic acute renal failure?
Acute tubular necrosis
Acute interstitial nephritis
Thrombotic microangiopathy
Name some drugs that can cause acute tubular necrosis.
Aminiglycoside antibiotics
Amphotericin B
Cisplatin/radiocontrast agents
Statins give with immunosuppresives (cyclosporin)
Name some drugs that can cause Acute Interstitial Nephritis.
Penicillins Cephalosporins Cocaine NSAIDs Omeprazome Chinese herbs (?)
Thrombotic microangiopathy can cause…
Severe AKI
Thromobi in the microvasculature of many organs - (hallmark pathology of TM)
Afferent vessel and glomeruli thrombosis
Thrombotic microangiopathy caused by…
Oestrogen containing oral contraceptive pills
Cocaine
What is nephrotic syndrome?
High proteinuria
Oedema
Hyperlipidaemia
Drugs that can cause nephrotic syndrome?
NSAIDs
Penicillamine
Gold
Name some NSAID induced renal syndromes.
AKI Nephrotic syndrome HTN Hyperkalaemia Papillary necrosis
What is the most common type of NSAID induced AKI?
Results from decreased synthesis of renal vasodilator prostaglandins = reduced blood flow to glomerulus = reduced GFR
What is NSAID-induced acute allergic interstitial nephritis?
An idiosyncratic reaction to things like ibuprofen, naproxen and fenoprofen
Associated with nephrotic syndrome in 90% of cases
What is AMINOGLYCOSIDE-INDUCED RENAL INJURY?
Aminoglycoside antibiotics, cause nephrotoxicity in ~20% of cases by causing proximal tubular injury leading to cell necrosis.
When are aminoglycoside antibiotics used/
Severe gram-neg sepsis
