Clinical Pharmacology in Renal Disease Flashcards
If renal function is impaired, there is a rapid build up of what?
Active drug
Toxins or active metabolites
When is there not a problem of a drug or metabolites in renal impairment?
If the drug or metabolites have a high therapeutic index or low toxicity
Example of a drug which has a high therapeutic index / low toxicity
Benzylpenicillin
What toxicities can gentamicin cause?
Nephrotoxicity
Ototoxicity
What can a build up of digoxin cause?
Arrythmia
Nausea
Death
What can a build up of lithium cause?
Toxicity
Death
What can a build up of tacrolimus cause?
Renal toxicity
CNS toxicity
Mechanisms of renal excretion
Glomerular filtration
Passive tubular reabsorption
Active tubular secretion
Where are all drugs and their metabolites filtered?
At the glomerulus
What does a reduction in GFR lead to in respect to drugs?
Reduces clearance of drugs by the kidney resulting in accumulation
Protein binding also reduced
What must be done in respect to drugs when there is a reduction in GFR?
Reduce doseage
Increase dose interval
TDM monitor blood levels for toxic drugs like gentamicin, lithium, digoxin and vancomycin
What is the pharmacodynamic effect of renal disease on drugs?
Alters the actions of drugs on the tissues
How does renal disease alter the action of drugs on the tissues?
The BBB becomes more permeable and the brain becomes more sensitive to tranquilisers, sedatives and opitates
Circulatory volume may be reduced making the patient more sensitive to antihypertensive agents, ACEIS or ARBs
Increased tendency to bleed to beware of warfarin or NSAIDs
In renal disease, the direct nephrotoxic actions of drugs are synergistic. What does this mean?
For example gentamicin toxicity may be unmasked when used in conjunction with furosemide or lithium
Ideally, if a patient suffers from renal impairment, we should use drugs that what?
Have a high therapeutic index
Are metabolised by the liver with the production of non toxic metabolites
Are ACEIs potentially nephrotoxic?
Yes
What can ACEIs produce in the kidneys?
Severe acute renal dysfunction
What can direct vasodilators do to the kidneys?
Profound hypotenson
Salt and water retention
What may thiazides and thiazide type diuretics precipitate?
Gout
What are the common forms that renal involvement usually takes?
Salt and water abnormalities - dehydration - oedema Acute renal failure - acute tubular necrosis - acute intersitial nephritis Chronic renal failure
Drug induced renal toxicity can cause what four major syndromes?
Acute renal failure
Nephrotic syndrome
Renal tubular dysfunction with potassium wasting
Chronic renal failure
Definition of acute renal failure
A sudden deterioration in renal function which results in a rapid rise in creatinine
Types of acute renal failure
Prerenal
Renal / intrinsic
Post renal / obstructive
Who often gets acute renal failure?
Elderly patients who are sick, with a poor fluid intake, who are on multiple medications and who are not being monitored aggressively
What drugs cause drug induced pre-renal disease and how?
Water and electrolyte abnormalities - diuretics - laxatives - lithium - NSAIDs Increased catabolism - steroids - tetracyclines Vascular occlusion - oestrogens / OCP
What are the 3 types of intrinsic acute renal failure?
Acute tubular necrosis
Acute interstitial nephritis
Thrombotic microangiopathy
Drug causes of acute tubular necrosis
Aminoglycosides
Amphotericin B
Cisplatin / radiocontrast agents
Statins in combination with immunosuppresive agents e.g. cyclosporin
Drug causes of acute interstitial nephritis
Penicillins Cephalosporins Cocaine Sulfonamides NSAIDs diuretics Lithium Ranitidine Omeprazole Captopril Phenytoin Valproic acid Amphotericin B Streptokinase 5-aminosalicylates Allopurinol Rifampicin Chinese herbs
What can thrombotic microangiopathy cause?
Severe acute renal failure
- arteriolar and glomerular thrombosis
Drug causes of thrombotic microangiopathy
Cyclosporin Tacrolimus Chemotherapeutic agents Clopidogrel Ticlopidine 19-oestrogen containing oral contraceptives quinine Cocaine
Drugs implicated in crystal formation of obstructive renal failure
Acyclovir Sulfonamides Trimaterene Methotrexate Vit C in large doses Guaifenesin
What is nephrotic syndrome marked by?
Heavy proteinuria
Drugs causing nephrotic syndrome
Gold NSAIDs Penicillamine Interferon Captopril
What can NSAIDs result in in kidneys?
Acute renal failure Nephrotic syndrome HTN Hyperkalaemia Papillary necrosis
What % of hospital admissions are due to AKI that are drug related?
20%
What % of patients prescribed ibruprofen does acute renal failure occur in?
18%
What is the most common drug responsible for acquired renal insufficiency in the hospital?
Aminoglycosides
Mechanism of NSAID induced pre renal acute renal failure
Decreased synthesis of renal vasodilator prostaglandins
Leads to reduced renal blood flow and reduced GF
Mechanism of NSAID induced acute allergic interstitial nephritis
idiosyncratic reaction
Nephrotic syndrome in 90% cases
Mechanism of aminoglycoside induced renal injury
Proximal tubular injury leading to cell necrosis
How is the prevention of contrast induced nephropathy done?
IV 0.9% NaCl pre and post procedure
