Prescribing in Special Populations: Hepatic and Renal Failure

Question 1

We we are considering drugs that are metabolised by the liver we need to assess liver function.
All of the following are measurement’s of liver function.
Which of the following is the WORST marker when assessing liver function?

1 - LFTs
2 - international normalised ratio (INR)
3 - prothrombin time
4 - albumin
5 - biliruben

Answer 1

1 - LFTs
- all of the others change acutely

Question 2

Does international normalised ratio (INR) and prothrombin time OR albumin become affected 1st by liver damage?

Answer 2

• international normalised ratio (INR) and prothrombin time
• in liver damage coagulant factors produced by the liver are reduced
• factors 2, 7, 9, 10, 11, 12

Question 3

What is pharmacokinetics?

1 - what the body does to a drug that is administered
2 - what the Drug does to the body once administered

Answer 3

1 - what the body does to a drug that is administered

Question 4

What is pharmacoDynamics?

1 - what the body does to a drug that is administered
2 - what the Drug does to the body once administered

Answer 4

2 - what the Drug does to the body once administered

Question 5

Which 2 of the following does acute liver affect?

1 - A = absorption
2 - D = distribution
3 - M = metabolism
4 - E = excretion

Answer 5

3 - M = metabolism
4 - E = excretion

Question 6

Which 2 of the following does chronic liver affect?

1 - A = absorption
2 - D = distribution
3 - M = metabolism
4 - E = excretion
5 - all of the above

Answer 6

5 - all of the above

Question 7

What is first pass metabolism?

1 - what the body does to a drug that is administered
2 - what the Drug does to the body once administered
3 - drug metabolism by liver that significantly reduces concentration of a drug
4 - all of the above

Answer 7

3 - drug metabolism by liver that significantly reduces concentration of a drug

• means a lower dose will reach the systemic circulation

Question 8

If a patient has significant liver damage, 1st pass metabolism will be affected. What does this do to bioavailability of a drug?

Answer 8

• increases bioavailability
• means we may need to give a lower dose of the drug to reduce toxic or adverse events

Question 9

If the liver is severely impaired and drugs cannot be absorbed, which of the following is an alternative route to deliver medication?

1 - IV
2 - IM
3 - oral
4 - suppository

Answer 9

1 - IV
2 - IM
4 - suppository

• if absorption is damaged, then the rate of absorption is impaired

Question 10

Which of the following is NOT one of the four compartments of the body that are taken into account in the four compartments model? (where drugs can move into)

1 - plasma
2 - intracellular fluid (inside cells)
3 - interstitial water (surrounding cells)
4 - parenchyme of tissue
5 - fat

Answer 10

4 - parenchyme of tissue

Question 11

Once a drug enters a different compartment in the four compartmental model approach does the drug remain free or does it bind to proteins within that cell?

Answer 11

• both
• some of the drug remains free
• some of the drug becomes bound in that space

Question 12

When looking at drug distribution of a drug in the four compartmental model, which of the following determines the distribution of a drug?

1 - solubility of the drug
2 - soluble in water and lipids
3 - molecular size of the drug
4 - all of the above

Answer 12

4 - all of the above

Question 13

Volume of distribution (Vd) is a measure of how widely a drug is distributed between various body fluids and tissues. If a drug has a low Vd like Warfarin, because it binds to plasma proteins, does that mean more is bound to proteins in the circulation or is bioavailable to have an affect on host tissue?

Answer 13

• more is bound to protein in plasma so it cannot freely move into tissues
• less is bioavailable and we therefore have a low volume of distribution

Question 14

If the liver is severely impaired, what affect can this have on volume distribution (Vd)?

1 - no effect as proteins are not produced in the liver
2 - increase Vd
3 - decrease Vd
4 - all of the above

Answer 14

2 - increase Vd
- damaged liver makes less protein
- less protein means nothing for drug to bind with in the plasma making it more bioavailable
- bioavailable drug is able to diffuse into different tissues

Question 15

In addition to the damaged liver reducing protein production and therefore less for drugs to bind with. What affect can hyperbilitubinaemia (high bilirubin) have on volume distribution (Vd)?

1 - increased Vd
2 - decreased Vd
3 - no change in Vd

Answer 15

1 - increased Vd
- bilirubin binds albumin
- less albumin for drug to bind with means Vd is increased as the blood can diffuse into tissues
- drug is highly bioavailable

Question 16

If a patient has ascites and/or oedema, why is it important to modify drugs like Gentamicin, which is water soluble with low lipid solubility?

1 - high Vd as drug remains in plasma
2 - high Vd as less protein to bind in plasma, so drug diffuse into tissues and interstitial fluid
3 - low Vd as drug remains in the plasma
4 - low Vd as drug leaves plasma and enters interstitial fluid and not cells

Answer 16

2 - high Vd as less protein to bind in plasma, so drug diffuse into tissues and interstitial fluid

• essentially means drug will end up in fluid in abdomen or oedema

Question 17

Which of the following are affected if the liver is significantly damaged?

1 - reduced enzymes to metabolise drugs
2 - reduced conversion of lipid soluble into water soluble compounds
3 - reduces excretion due to high level of lipid soluble drugs
4 - all of the above

Answer 17

4 - all of the above

• lipid soluble drugs are hard to excrete by the kidneys, so they need to be converted into water soluble drugs

Question 18

Severely damaged liver, such as in cirrhosis can cause hepatorenal syndrome. Does this increase or decrease renal excretion of drugs?

Answer 18

• decreases
• hepatorenal syndrome reduces renal blood flow, and thus excretion
• serum creatinine is often an unreliable method of assessing renal function as it is slow to respond to kidney damage

Question 19

Which of the following medications is able to disturb fluid/electrolyte balance?

1 - NSAIDS
2 - corticosteroids
3 - diuretics
4 - all of the above

Answer 19

4 - all of the above

Question 20

Which of the following medications may precipitate encephalopathy?

1 - diuretics
2 - sedatives
3 - opioids
4 - constipating medicines (opioids, 5 - antimuscarinic, sedating antihistamines)
5 - all of the above

Answer 20

5 - all of the above

Question 21

Which 2 of the following may have haematological effects, such as increasing the risk of bleeding?

1 - NSAIDS
2 - benzodiazepines
3 - warfarin
4 - ACE-I

Answer 21

1 - NSAIDS
3 - warfarin

Question 22

Which of the following medications is the most Nephrotoxic?

1 - NSAIDS
2 - benzodiazepines
3 - warfarin
4 - ACE-I

Answer 22

1 - NSAIDS

Question 23

Which 2 of the following are important in determining the presence of chronic kidney disease?

1 - eGFR
2 - albumin
3 - creatinine
4 - albumin:creatinine ratio

Answer 23

1 - eGFR
4 - albumin:creatinine ratio

Question 24

What is uraemia?

1 - increased urine output
2 - increased toxins and urea in the blood
3 - decreased urine output
4 - parasites present in urine

Answer 24

2 - increased toxins in the blood
- generally due to the kidneys not excreting the drugs

Question 25

Uraemia is the presence of increased toxins in the blood. This can affect pharmacodynamics, specifically distribution. What happens to the blood brain barrier in uraemia?

1 - increased permeability
2 - decreased permeability
3 - no change in permeability
4 - only lipid soluble drugs can pass

Answer 25

1 - increased permeability
- increases sensitivity to certain drugs such as benzodiazepines and anti-depressants
- drug dose may need to be altered

Question 26

Which of the following can chronic kidney disease cause?

1 - increased sensitivity to drugs acting on the CNS (benzodiazepines, antidepressants)
2 - increased risk of GI bleeding with irritant drugs (NSAIDs)
3 - Increased risk of hyperkalaemia (spirolactone)
4 - all of the above

Answer 26

4 - all of the above

Question 27

Patients with CKD typically have a lower gastric pH, due to higher levels of what?

1 - H+
2 - K+
3 - ammonia
4 - mucous

Answer 27

3 - ammonia

• CKD patients take lots of drugs to increase gastric pH

Question 28

In patients with CKD, they may have altered pharmacokinetics. Which of the following can affect absorption?

1 - altered gastric pH
2 - nausea, vomiting, diarrhoea
3- altered GI motility
4 - GIT oedema, uraemia
5 - decreased intestinal CYP450 activity
6 - all of the above

Answer 28

6 - all of the above

Question 29

Patients with CKD can have changes in pharmacokinetics, specifically distribution. Patients can become dehydrated or have ascites and/or oedema. What affect would dehydration have on volume distribution (Vd)?

1 - increased Vd
2 - decreased Vd
3 - no change in Vd

Answer 29

2 - decreased Vd

• less fluid means less potential for water soluble drugs to move into interstitial space

Question 30

Patients with CKD can have changes in pharmacokinetics, specifically distribution. Patients can become dehydrated or have ascites and/or oedema. What affect would ascites and/or oedema have on volume distribution (Vd)?

1 - increased Vd
2 - decreased Vd
3 - no change in Vd

Answer 30

1 - increased Vd

• more fluid means more potential for water soluble drugs to move into interstitial space
• can be due to low albumin lost in kidneys or osmotic effect as fluid and proteins collect in abdomen

Question 31

Patients with CKD can have changes in pharmacokinetics, specifically distribution. Patients can have altered protein binding. What affect can hypoalbuminaemia, due to loss of protein in urine, have on volume distribution (Vd)?

1 - increased Vd
2 - decreased Vd
3 - no change in Vd

Answer 31

1 - increased Vd

• drug unbound and can diffuse into tissues

Question 32

Patients with CKD can have changes in pharmacokinetics, specifically distribution. Patients can have altered protein binding. What affect can modified albumin structure have on volume distribution (Vd)?

1 - increased Vd
2 - decreased Vd
3 - no change in Vd

Answer 32

1 - increased Vd

• drug unbound and can diffuse into tissues

Question 33

Patients with CKD can have changes in pharmacokinetics, specifically distribution. What affect can uraemia have on volume distribution (Vd)?

1 - increased Vd
2 - decreased Vd
3 - no change in Vd

Answer 33

1 - increased Vd

• urea binds to albumin so drug cannot
• drug therefore diffuses into tissues

Question 34

Which 2 of the following medications are heavily dependent on protein binding, thus if the levels of the protein in plasma changes, increases the risk of toxicity?

1 - benzodiazepines
2 - NSAIDs
3 - warfarin
4 - phenytoin

Answer 34

3 - warfarin
4 - phenytoin

Question 35

Patients with CKD can have changes in pharmacokinetics, specifically metabolism. If there is significant damage to the liver this can then impact upon the kidneys. Which of the following can then be caused in the kidneys?

1 - reduced renal metabolism
2 - reduced insulin metabolism
3 - altered vitamin D metabolism
4 - all of the above

Answer 35

4 - all of the above

Question 36

Patients with CKD can have changes in pharmacokinetics, specifically excretion. Which of the following can occur in CKD, specifically related to excretion?

1 - reduced eGFR and drug excretion
2 - drug accumulates
3 - increased risk of toxicity and adverse events
4 - all of the above

Answer 36

4 - all of the above

Question 37

If a drug cannot be excreted from the body, what affect will this have on the drugs half life?

Answer 37

• increases half life

Question 38

What is drug half life (t½)?

1 - maximum concentration of drug in plasma
2 - lowest concentration of a drug in plasma
3 - time take for concentration of drug in blood to half
4 - overall drug exposure

Answer 38

3 - time take for concentration of drug in blood to half

• consume 40mg at 7am on day 1
• 20mg left in plasma at 7am on day 2
• so half life is 24 hours
• calculation is (Vd / clearance) x 0.7

Question 39

Which of the following is the correct calculation for calculating volume distribution?

1 - concentration consumed / concentration in urine
2 - concentration consumed / concentration in plasma
3 - (concentration consumed / 50%) /
concentration in urine

Answer 39

2 - concentration consumed / concentration in plasma

• 120mg consumed /20mg/L in plasma =
  120/20 = 6L = low Vd
• 120mg consumed /1mg/L in plasma =
  120/1 = 120L = high Vd

Question 40

Which of the following is the correct calculation for calculating clearance of a drug?

1 - concentration consumed / concentration in urine
2 - concentration consumed / concentration in plasma
3 - elimination rate / remaining drug concentration

Answer 40

3 - elimination rate / remaining drug concentration

• 120mg/hour (urine) / 20mg/mL (plasma) =
  120 / 20 = 6ml/hour = HIGH clearance
• 40mg/hour (urine) / 20mg/mL (plasma) =
  40 / 20 = 2ml/hour = LOW clearance