Renal Therapeutics 5: Renal Impact on Drug Therapy

Question 1

How can the renal system impact on drugs taken by the patient for therapy?

Answer 1

1. Reduced clearance of hydrophilic drugs with lower GFR - creates a potential for toxic accumulation
2. Azotaemia impairs the plasma binding proteins which leads to proteinuria (low levels of protein)
   - protein bound drugs end up free
3. Fluid retention may increase distribution (oedema)
4. Hepatic drug metabolism is depressed
5. Reduced renal reserve
6. Action of some drugs that rely on the renal mechanisms can be impaired

Question 2

How can the renal system impact on absorption of drugs

Answer 2

1. Kidney function can alter the absorption of compounds in the gut
2. Example: Can lead to reduced renal function leading to oedema in the bowel wall

Question 3

How can the renal system impact metabolism of drugs?

Answer 3

1. Drugs which are metabolised by the kidneys (insulin) are impacted by renal function
2. Uraemia can have a knock out effect on liver function- altering metabolism of drugs

Question 4

How can the renal system impact the distribution of drugs?

Answer 4

1. The degree of hydration can alter the distribution
2. Oedema increases volume of distribution and dehydration decreases it (small Vd)
3. Serum protein binding can be reduced to protein loss or alteration in binding caused by uraemia
   - level of free drug higher can cause toxicity
4. Renal replacement therapy can alter the rate of elimination of the drug

Question 5

How can the renal system impact the excretion of drugs?

Answer 5

1. Alterations in renal clearance means an adjustment of drug dose is necessary
2. GFR is a good estimation of how well nephrons are functioning
3. The guidelines to work out renal impairment is in the BNF

Question 6

How can the renal system impact the nephrotoxicity of drugs?

Answer 6

1. Interstitial nephritis (spaces between kidneys get swollen) and glomerulonephritis (cells attack each other) can be caused by hypersensitivity to drugs
2. Direct nephrotoxic drugs can cause acute tubular necrosis (ATN)
3. This can damage the nephron and renal function easily

Question 7

What effect can ACE/angiotensin II inhibitors have in drug therapy and what are they used for?

Answer 7

1. Treatment of hypertension, cardiac failure and possibly proteinuric renal disease
2. Influences renal blood flow through the glomerulus and the amount of liquid/solute filtered depends on bowman’s capsule
3. Nephrotoxicity can be reversible if discontinued

Question 8

What effect can Aminoglycosides and Antibiotics have in drug therapy?

Answer 8

1. Excreted unchanged, freely filtered and reabsorbed by proximal tube cells (binding)
2. Leads to structural changes in cells and acute tubular necrosis
3. Vancomycin can cause nephrotoxicity

Question 9

What effect can Radiocontrast agents have in drug therapy?

Answer 9

1. These agents are nephrotoxic with pre-existing renal diseases, diabetes mellitus, cardiac failure and hypotension
2. lead to altered haemodynamics, increased blood viscosity and increased tubular oxygen consumption
3. Minimum volume, reduced frequency and pre hydration

Question 10

What effect can anti-cancer agents in have drug therapy?

Answer 10

Reduced GFR, hypophosphataemia, Ifosphamide (alkylating agent) (toxic in kidney)

Question 11

What effect can Lithium have in drug therapy?

Answer 11

1. Freely filtered and 2/3 are reabsorbed in proximal tubule
2. Can lead to diabetes insipidus or renal tubular acidosis

Question 12

What effect can drugs of misuse have such as cocaine and heroin?

Answer 12

1. Cocaine (powerful vasoconstrictor)

2. Heroin (large amounts of adulterans which are nephrotoxic)