Dose adjustment

Question 1

Where do recommended dose of drugs derive from?

Answer 1

Clinical trial data of patient population

Question 2

What is pharmacogenetics?

Answer 2

It is the effect of genetic factors on reactions to drugs.

Question 3

The genetic differences affect the pharmacokinetics of a drug in a particular patient. TRUE OR FALSE?

Answer 3

TRUE

Question 4

What are the factors that can lead to a change in dose?

Answer 4

1. Age
2. Hepatic disease
3. Renal impairment

Question 5

In terms of age, how does absorption compare to children and the elderly?

Answer 5

Children

• Gastric emptying is slower
• Peristalsis is less regular (affects transit time)

Elderly

• Delayed gastric emptying
• Elevated gastric pH
• Reduced peristalsis
• Active transport may be decreased

Question 6

Children can absorb drugs faster and more compared to adults. TRUE OR FALSE?

Answer 6

TRUE

Question 7

If active transport is decreased, does this also decrease the bio-availability of the drug? TRUE OR FALSE?

Answer 7

TRUE

Question 8

If pH is elevated the bioavailability of drug may increase. TRUE OR FALSE?

Answer 8

TRUE

Question 9

Volume distribution does not increase with age. TRUE OR FALSE?

Answer 9

FALSE

Question 10

Binding to plasma protein may be decreased in very young. TRUE OR FALSE?

Answer 10

TRUE

Question 11

In the elderly, altered body composition may change distribution i.e change in adipose tissue, muscle mass. TRUE OR FALSE?

Answer 11

TRUE

Question 12

Change in distribution of drug may affect how much of the drug is available in the systemic circulation. TRUE OR FALSE?

Answer 12

TRUE

Question 13

What are the factors that can affect drug distribution in the elderly?

Answer 13

• Altered body composition
• Reduce cardiac output
• Increased peripheral resistance
• BBB permeability may increase

Question 14

Drug metabolic ability increases from birth to 6 months . TRUE OR FALSE?

Answer 14

TRUE

Question 15

P450 metabolism increases with age. TRUE OR FALSE?

Answer 15

FALSE, it decreases

Question 16

In the elderly there is a increased hepatic blood flow. TRUE OR FALSE?

Answer 16

FALSE

Question 17

GFR decreases with age but can be very variable, which can lead to higher exposure so increased chances of toxicity. TRUE OR FALSE?

Answer 17

TRUE

Question 18

In hepatic disease is there an increase or decrease in metabolism of CYP450 for example?

Answer 18

There is a reduction in metabolism, but it is not inevitable and depends on the nature of liver disease

Question 19

What is cirrhosis and viral hepatitis and their impacts on drug metabolism?

Answer 19

Cirrhosis - Part of the liver tissue is replaced by scar tissue, it is possible that metabolism may be reduced due to scar tissue

Viral hepatitis - Inflammation of the liver, with this it is less likely that metabolism will be reduced

Question 20

What is the major site where serum album is synthesised?

Answer 20

The liver

Question 21

Some drugs do not undergo extensive hepatic metabolism, so giving a patient with hepatic disease drugs that do not under go extensive hepatic metabolism should not really impact the therapeutic effect of the drug. TRUE PR FALSE?

Answer 21

TRUE

Question 22

In terms of hepatic disease; Half life may not decrease due to decreased albumin, which leads to an increase in volume distribution. TRUE OR FALSE?

Answer 22

TRUE

Question 23

Reduced first pass effect may increase bioavailability. TRUE OR FALSE?

Answer 23

TRUE

Question 24

How does protein binding affect drugs which are extensively bound to albumin?

Answer 24

Drugs which are extensively bound to albumin are more likely to be affected by hepatic disease

Question 25

A decrease in albumin would cause an increase in drug unbound, what effects may this cause?

Answer 25

- Increase therapeutic effect - Increased toxicity - Change in distribution Vd which may cause unexpected toxicity

Question 26

What is hepatic encephalopathy and which drugs are a major concern for this, give example?

Answer 26

This is impaired brain function which is particular concern with drugs known to have effect on the CNS e.g sedatives, opioids

Question 27

Which types of drugs cause fluid retention?

Answer 27

NSAIDS

Question 28

What is hepatoxicity and which drugs are a major concern for this?

Answer 28

Liver toxicity is particular concern with drugs that are intrinsically hepatoxic (self perpetuating)

Question 29

What are the consequences of having reduced renal function?

Answer 29

- decreased GFR - Reduced clearance - higher plasma levels are possible - Longer half life/ time to reach constant steady state is increased

Question 30

Hoe can renal function be estimated?

Answer 30

By measuring creatine clearance as surrogate to estimate GFR

Question 31

Where is creatinine produce?

Answer 31

In the muscles

Question 32

How is Creatinine eliminated?

Answer 32

Eliminated largely by Glomerular Filtration

Question 33

Creatinine clearance is aprox GFR. TRUE PR FALSE?

Answer 33

TRUE

Question 34

Creatinine serum can be used to estimate GFR and results obtained is creatinine clearance. TRUE OR FALSE?

Answer 34

TRUE

Question 35

Creatinine is not produced at a constant rate by muscles. TRUE OR FALSE?

Answer 35

FALSE

Question 36

Which two equations can be used to estimate GFR?

Answer 36

- Cockroft gault equation | - MDRD method

Question 37

Which of the equations is considered to be more accurate? Cockroft gault equation -MDRD method

Answer 37

MDRD method - normalized to body surface area

Question 38

What are the limitations to estimating GFR using these two equations/

Answer 38

- Average muscle mass appropriate to patient's age, height and age - May be inaccurate if poor nutrional state, highly muscular, obese and extremes i.e GFR too high or too low, limb amputation, extremes of age

Question 39

Some creatinine is excreted by tubular secretion so creatinine clearance may be slightly greater than GFR . TRUE OR FALSE?

Answer 39

TRUE

Question 40

What is a more accurate way of measuring creatinine clearance and give its disadvantages?

Answer 40

By measuring creatinine excreted in urine over 24hr Disds: -more accurate than inconvenient -need to collect urine over 24hr and measure volume -Incomplete collection -need to measure creatinine in serum and urine

Question 41

As patients get older renal function decreases, so creatinine clearance decreases and varies between men and women. TRUE OR FALSE?

Answer 41

TRUE