Clinical Pharmacology in Renal Disease Flashcards
(40 cards)
How does renal disease affect clinical pharmacology?
•If renal function is impaired then there will be a rapid build up of:
– active drug
– toxic or active metabolites
Reduced GFR means reduced clearance of drugs
Protein binding is also reduced
Renal impairment will prolong the half life of all drugs or their metabolites cleared by the glomerulus
What drugs are still okay to use in renal impairment?
If the drug or metabolites have a high therapeutic index or low toxicity
Which classifications of drugs are particularly dangerous when there is renal impairment?
When the drugs or metabolites have a narrow therapeutic index - causes toxicity or death
What is the effect of toxicity of the following drugs?
Gentamicin
Digoxin
Lithium
Tacrolimus
Gentamicin - may cause renal or otoxicity
Digoxin - may cause arrhythmia, nausea or death
Lithium - renal toxicity and death
Tacrolimus - renal and CNS toxicity
What factors interact to generate new renal impairment / worsen pre-existing renal impairment / toxicity?
Sick
Volume depleted
Hypotensive
Prescribed a large number or potentially reno-toxic agents
Changes in what parts of kidney function will alter the pharmacokinetics and pharmacodynamics?
Glomerular filtration
Passive tubular reabsorption
Active tubular reabsorption
How must you respond the the new pharmacokinetic effects of drugs when there is renal impairment?
You must reduce the dosage (loading dose and maintenance dose)
Increase the dose interval
TDM (therapeutic drug monitoring) - monitor blood levels for toxic drugs like gentamicin, lithium, digoxin, vancomycin
Monitor renal function and blood pressure during the course of the treatment
How does renal disease alter the actions of drugs on the tissues?
–The blood brain barrier becomes more permeable and the brain becomes more sensitive to tranquillisers, sedatives and opiates
–Circulatory volume may be reduced making the patient sensitive to antihypertensive agents ACEIs or a-blockers
–There may be an increased tendency to bleed beware warfarin or NSAIDs
Describe the toxic effects of drugs when used in conjunction with one another - (when there is renal failure)
The direct nephrotoxic actions of drugs are synergistic
–gentamicin toxicity may be unmasked when used in conjunction with furosemide or lithium.
Here is a summary of the effects of pharmacokinetics and pharmacodynamics
What type of drugs are best for patients with renal impairment?
–have a high therapeutic index and
–are metabolised by the liver with the production of non-toxic metabolites
What is the relationship between hypertension and renal disease?
–A common problem in patients with renal disease
–Hypertension causes renal damage,
–Renal damage causes hypertension.
What is the dilema associated with treating hypertension in patients with renal disease?
–Normally use thiazide-type diuretics, CCBs, ACEIs
–However patients with renal impairment have a low GFR, hyperuricaemia,
–More sensitive to the hypotensive actions of antihypertensive agents.
How do we treat hypertension in kidney disease?
Use drugs which are totally metabolised by the liver or elsewhere in the body
(ACEi - these are commonly recommended however they produce severe acute renal dysfunction)
Use reduced dose of the drug with longer dosing periods
or use on alternative days
What is the issue with vasodilators?
Can produce profound hypotension and salt and water retention
What is the issue associated with thiazide - type diuretics in the treatment of high blood pressure?
Thiazides/thiazide - type diuretics may precipitate gout
•Adverse drug reactions affecting the kidneys are a common cause of morbidity and mortality especially in hospitalised patients
How does the drug concentration change as it is processed by the kidney?
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 outcomes of renal damage?
Acute kidney injury
Acute tubular necrosis
Chronic kidney disease
Inflammatory disorders
Salt and water abnormalities - dehydration, oedema
Acute renal failure - acute tubular necrosis, acute interstitial nephritis
Chronic renal failure
What part of the urinary system does drug induced renal disease damage?
Can affect any part of the urinary system from the kidney to the bladder and genitalia
What are the 4 major syndromes caused by drug induced renal disease?
–Acute renal failure
–Nephrotic syndrome
–Renal tubular dysfunction with potassium wasting
–Chronic renal failure
What is the definition of acture renal failure?
- A sudden deterioration in renal function which results in a rapid rise in creatinine
- Urine volume falls to < 400ml/day in 40% of patients.
What are the pre-renal causes of drug induced renal disease?
Water and electrolyte abnormalities
(diuretics, laxitives, lithium and NSAIDs)
Increased Catabolism
Steroids, tetracyline
Vascular Occlusion
Oestrogens/ OCP
What are the three types of intrinsic acute renal failure?
Acute tubular necrosis (ATN)
- Acute interstitial nephritis
- Thrombotic microangiopathy.
