Clinical Pharmacology in Renal Disease Flashcards
Nephrotoxic?
Drugs which can cause kidney damage
What is therapeutic index?
Quantitative measurement of the relative safety of a drug
Drugs are xenobiotics meaning the body recognises them as not being of self. How can the body deal with drugs?
-Body can prevent the drug from entering the bloodstream e.g. bloodbrain barrier
-Body can physically remove the drug
-Body can adapt drugs so that they can be removed from the body more quickly
In kinetics, what is the first mechanism for drugs by the body?
Absorption and distribution
What follows absorption and distribution?
Excretion and then metabolism
What is clearance?
Volume of plasma from which the drug would be totally removed per unit time
->babe even the lecturer said this was a weird definition
If someone had low clearance, what would this mean in terms of systemic exposure?
Higher systemic exposure
->and vice versa e.g. high clearance = lower systemic exposure
What is one risk of having low clearance?
Plasma concentration may be high enough to produce toxic effects
Does clearance ability increase or decrease with age?
Decrease
Clearance is a function of what three things happening at the kidney?
Glomerular filtration
Active tubule secretion
Tubular reabsorption
Which part of the kidney is especially important in filtration?
Glomerulus
Which two substances can be used to measure GFR as they undergo total renal clearance with no active secretion or reabsorption?
Creatinine and inulin
In which part of the kidney does active renal secretion occur?
Proximal tubule
What does reabsorption of a drug depend on?
Lipid solubility and concentration gradient in the tubule
If kidneys are not healthy, what happens to plasma concentration and half life?
Both increase
What is renal clearance proportional to?
GFR
->therefore, this means if we know a patient’s GFR, we can adjust the drug dose accordingly
Where do drugs with a small volume of distribution tend to stay?
In the plasma
->while drugs with a large volume of distribution tend to leave the plasma
Where does most of the metabolism and excretion of a drug happen?
Liver and kidney
Do drugs with a higher volume of distribution tend to have a longer or shorter half life?
Longer half life
As most drugs are given in multiple doses, there can be ups and downs if looking at a graph at drug concentrations (think waves).
What is important to bear in mind regarding the therapeutic range?
Despite the average curve being within the therapeutic range, the peaks and spikes of a drug being given may go into the toxic range
Polypharmacy?
When someone is taking many forms of drugs
Before prescribing drugs in someone with renal impairment, what needs to be considered?
Risks/benefits
Severity of toxicity and possible adverse effects
Availability of TDM (therapeutic drug monitoring)
What should be done when prescribing drugs for someone with renal impairment?
Use drugs with a wide therapeutic range
Consider choosing a drug which isn’t renally excreted
Reduce drug dose
Reduce drug frequency
What are the three types of acute kidney injury?
Pre-renal
Intra-renal
Post-renal
What is meant by a pre-renal acute kidney injury?
Pre-renal factors that contribute to kidney injury e.g. anything that reduces perfusion, causes hypovolaemia or reduces cardiac output
What is meant by intra-renal acute kidney injuries?
Direct toxic effects on the kidney
What does post-renal damage usually arise as a result of?
Obstruction
What is acute tubular necorisis?
A common acute kidney injury in which there is death of tubular epithelial cells
Glomerulonephritis?
Umbrella term for a range of problems which arise as a result of inflammation of the kidney
List the different ways drugs can cause renal damage.
- Drugs may directly damage kidney tubular cells
- Excessive exposure to drugs reduces GFR
- Drugs may provoke immune effects
- Drugs can form crystalline suspensions in the urine which can impair fluid flow
- Drug accumulation
- Drugs can react with proteins and cause excessive caste formation
What is the most common intra-renal drug induced pathology?
Acute tubular necrosis
Which drugs are associated with acute tubular necrosis?
Aminoglycoside antibiotics
Amphotericin B
Cisplatin
Statins/cyclosporins
Which drugs are associated with interstitial nephritis?
Penicillin’s
Cephalosporins
Cocaine
Omeprazole
Herbal medicines
Which biotherapeutics are associated with glomerulonephritis?
Thrombotic microangiopathy
Cyclosporin
Chemotherapeutic agents
19 oestrogen containing oral contraceptives
List some drugs which can cause post-renal issues, often due to the formation of crystals which obstruct urine flow.
Methotrexate
Acyclovir, Indianvir
Sulfonamides
Triamterene
Vitamin C in large doses
What is nephrotic syndrome due to?
Glomerular dysfunction
What is nephrotic syndrome marked by?
Heavy proteinuria
Hypoalbuminaemia
Oedema
List some drugs associated with nephrotic syndrome.
NSAIDs
Interferon
Captopril
Which drugs are the main cause of acute kidney injury in primary care?
NSAIDs
Which drugs are the main cause of acute kidney injury in secondary care?
Aminoglycosides
