Clinical pharmacology in renal disease Flashcards
What 2 things will there be a rapid build up of if renal function is impaired?
active drug
toxic or active metabolites
When is a rapid build up of drug not a problem? give an example
high therapeutic index or low toxicity
benzylpenicillin
What happens if there is a build up of a drug with low therapeutic index?
toxicity and death
Toxicity associated problems with
a) gentamicin
b) digoxin
c) lithium
d) Tacrolimus
a - renal or ototoxicity
b - arrhythmia, nausea, death
c - renal toxicity and death
d - tacrolimus
Pharmacokinetics
what they body does to the drug
Pharmacodynamics
What the drug does to the body
What factors increase likelihood to generate new renal failure or worsen pre-existing with some nephrotoxic medications?
old, volume deplete, multiple medications, hypotensive
What will renal impairment do to the half-life of a drug?
prolong it
Due to prolonging half life of drugs due to renal impairment what kind of therapeutic index drugs are we careful of?
low
Pharmacokinetic effects of renal failure
reduce GFR –> accumulation
decreased protein binding
3 things we need to do due to decreased protein binding in renal impairment
decrease dose
increase dose interval
TDM monitor blood levels for toxic drugs
How can renal disease alter the actions of drugs on the tissues?
Blood brain barrier more permeable - more sensitive to opioids, tranquilisers and sedatives
circulatory volume decreased - sensitive to anti-hypertensives
Increased tendency to bleed - beware warfarin or NSAIDs
Toxic effects of drugs are synergistic or antagonistic?
synergistic eg unmasked by each other - gentamicin +furosemide/lithium
What do we need to know in terms of drugs and renal impairment?
what drugs are safe to use in reduced eGFR
narrow therapeutic index
If a patient has renal failure suggest the 2 most important things when deciding on what drug to use
metabolised by liver –> non toxic metabolites
high therapeutic index
Is hypertension common in renal disease?
yes - they both cause eachother
Why are patients with renal disease more sensitive to hypertensive agents?
low GFR - uricaemia
volume deplete
Advantage and Problem with ACEI used for hypertension in renal disease
metabolised by liver
nephrotoxic
Problem with using vasodilators in hypertension in renal disease
profound hypotension - salt and water retention
Problem with using thiazide’s in hypertension in renal disease
precipitate gout - high urea
Problem with drugs metabolised solely by kidney in renal disease
concentrated as passed along tubule so exposing kidney to greater concentrations
How does salt and water abnormalities in renal disease present?
oedema and dehydration
List effects of drug induced renal disease
AKI, CKD, nephrotic syndrome, tubular dysfunction with potassium wasting
Describe AKI
sudden deterioration in renal function
rapid increase in creatinine and decrease in urine
dehydrated
3 prerenal causes of AKI and drugs which cause this
water and electrolyte abnormalities - diuretics, laxatives, lithium, NSAIDs increased catabolism - steroids vascular occlusion - OCP, oestrogen
3 causes of renal AKI
acute tubular necrosis
acute interstitial nephritis
thrombotic microangiopathy
Post renal causes of AKI
crystal formation in ureters or tubules
RPF
Drugs causing crystal formation
acyclovir
vitamin c in high doses
Drugs causing ATN
aminoglycoside antibiotics
radiocontrast
statin & immunosuppressant
Drugs causing AIN and why?
NSAIDS, omeprazole, penicillins, cocaine, Chinese herbs
long or short latency period of drugs used on a daily basis
3 things thrombotic microangiopathy can cause
severe AKI
thrombi in microvasculature of many organs
afferent arteriolar and glomerular thrombosis
Drugs causing thrombotic microangiopathy
oestrogen OCP, cocaine, tacrolimus, cyclosporine, clopidogrel
What is nephrotic syndrome due to?
glomerular dysfunction and heavy proteinuria
Drugs implicated in nephrotic syndrome
NSAIDS and gold injections
Renal syndromes caused by NSAIDs
AKI hyperkalaemia nephrotic syndrome hypertension papillary necrosis
Explain the cause of NSAID induced prerenal AKI
decreased prostaglandin synthesis which vasodilate
reduced blood flow and GFR
Why do aminoglycosides cause renal injury?
PCT injury and cell necrosis leading to AKI
When is aminoglycosides used?
severe gram negative sepsis
Main cause of acute allergic interstitial nephritis
propanionic derivatives eg ibuprofen
