Clinical Pharmacology in Renal Disease

Question 1

Nephrotoxic?

Answer 1

Drugs which can cause kidney damage

Question 2

What is therapeutic index?

Answer 2

Quantitative measurement of the relative safety of a drug

Question 3

Drugs are xenobiotics meaning the body recognises them as not being of self. How can the body deal with drugs?

Answer 3

-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

Question 4

In kinetics, what is the first mechanism for drugs by the body?

Answer 4

Absorption and distribution

Question 5

What follows absorption and distribution?

Answer 5

Excretion and then metabolism

Question 6

What is clearance?

Answer 6

Volume of plasma from which the drug would be totally removed per unit time

->babe even the lecturer said this was a weird definition

Question 7

If someone had low clearance, what would this mean in terms of systemic exposure?

Answer 7

Higher systemic exposure

->and vice versa e.g. high clearance = lower systemic exposure

Question 8

What is one risk of having low clearance?

Answer 8

Plasma concentration may be high enough to produce toxic effects

Question 9

Does clearance ability increase or decrease with age?

Answer 9

Decrease

Question 10

Clearance is a function of what three things happening at the kidney?

Answer 10

Glomerular filtration
Active tubule secretion
Tubular reabsorption

Question 11

Which part of the kidney is especially important in filtration?

Answer 11

Glomerulus

Question 12

Which two substances can be used to measure GFR as they undergo total renal clearance with no active secretion or reabsorption?

Answer 12

Creatinine and inulin

Question 13

In which part of the kidney does active renal secretion occur?

Answer 13

Proximal tubule

Question 14

What does reabsorption of a drug depend on?

Answer 14

Lipid solubility and concentration gradient in the tubule

Question 15

If kidneys are not healthy, what happens to plasma concentration and half life?

Answer 15

Both increase

Question 16

What is renal clearance proportional to?

Answer 16

GFR

->therefore, this means if we know a patient’s GFR, we can adjust the drug dose accordingly

Question 17

Where do drugs with a small volume of distribution tend to stay?

Answer 17

In the plasma

->while drugs with a large volume of distribution tend to leave the plasma

Question 18

Where does most of the metabolism and excretion of a drug happen?

Answer 18

Liver and kidney

Question 19

Do drugs with a higher volume of distribution tend to have a longer or shorter half life?

Answer 19

Longer half life

Question 20

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?

Answer 20

Despite the average curve being within the therapeutic range, the peaks and spikes of a drug being given may go into the toxic range

Question 21

Polypharmacy?

Answer 21

When someone is taking many forms of drugs

Question 22

Before prescribing drugs in someone with renal impairment, what needs to be considered?

Answer 22

Risks/benefits
Severity of toxicity and possible adverse effects
Availability of TDM (therapeutic drug monitoring)

Question 23

What should be done when prescribing drugs for someone with renal impairment?

Answer 23

Use drugs with a wide therapeutic range
Consider choosing a drug which isn’t renally excreted
Reduce drug dose
Reduce drug frequency

Question 24

What are the three types of acute kidney injury?

Answer 24

Pre-renal
Intra-renal
Post-renal

Question 25

What is meant by a pre-renal acute kidney injury?

Answer 25

Pre-renal factors that contribute to kidney injury e.g. anything that reduces perfusion, causes hypovolaemia or reduces cardiac output

Question 26

What is meant by intra-renal acute kidney injuries?

Answer 26

Direct toxic effects on the kidney

Question 27

What does post-renal damage usually arise as a result of?

Answer 27

Obstruction

Question 28

What is acute tubular necorisis?

Answer 28

A common acute kidney injury in which there is death of tubular epithelial cells

Question 29

Glomerulonephritis?

Answer 29

Umbrella term for a range of problems which arise as a result of inflammation of the kidney

Question 30

List the different ways drugs can cause renal damage.

Answer 30

1. Drugs may directly damage kidney tubular cells
2. Excessive exposure to drugs reduces GFR
3. Drugs may provoke immune effects
4. Drugs can form crystalline suspensions in the urine which can impair fluid flow
5. Drug accumulation
6. Drugs can react with proteins and cause excessive caste formation

Question 31

What is the most common intra-renal drug induced pathology?

Answer 31

Acute tubular necrosis

Question 32

Which drugs are associated with acute tubular necrosis?

Answer 32

Aminoglycoside antibiotics
Amphotericin B
Cisplatin
Statins/cyclosporins

Question 33

Which drugs are associated with interstitial nephritis?

Answer 33

Penicillin’s
Cephalosporins
Cocaine
Omeprazole
Herbal medicines

Question 34

Which biotherapeutics are associated with glomerulonephritis?

Answer 34

Thrombotic microangiopathy
Cyclosporin
Chemotherapeutic agents
19 oestrogen containing oral contraceptives

Question 35

List some drugs which can cause post-renal issues, often due to the formation of crystals which obstruct urine flow.

Answer 35

Methotrexate
Acyclovir, Indianvir
Sulfonamides
Triamterene
Vitamin C in large doses

Question 36

What is nephrotic syndrome due to?

Answer 36

Glomerular dysfunction

Question 37

What is nephrotic syndrome marked by?

Answer 37

Heavy proteinuria
Hypoalbuminaemia
Oedema

Question 38

List some drugs associated with nephrotic syndrome.

Answer 38

NSAIDs
Interferon
Captopril

Question 39

Which drugs are the main cause of acute kidney injury in primary care?

Answer 39

NSAIDs

Question 40

Which drugs are the main cause of acute kidney injury in secondary care?

Answer 40

Aminoglycosides