Dose adjustment Flashcards
Where do recommended dose of drugs derive from?
Clinical trial data of patient population
What is pharmacogenetics?
It is the effect of genetic factors on reactions to drugs.
The genetic differences affect the pharmacokinetics of a drug in a particular patient. TRUE OR FALSE?
TRUE
What are the factors that can lead to a change in dose?
- Age
- Hepatic disease
- Renal impairment
In terms of age, how does absorption compare to children and the elderly?
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
Children can absorb drugs faster and more compared to adults. TRUE OR FALSE?
TRUE
If active transport is decreased, does this also decrease the bio-availability of the drug? TRUE OR FALSE?
TRUE
If pH is elevated the bioavailability of drug may increase. TRUE OR FALSE?
TRUE
Volume distribution does not increase with age. TRUE OR FALSE?
FALSE
Binding to plasma protein may be decreased in very young. TRUE OR FALSE?
TRUE
In the elderly, altered body composition may change distribution i.e change in adipose tissue, muscle mass. TRUE OR FALSE?
TRUE
Change in distribution of drug may affect how much of the drug is available in the systemic circulation. TRUE OR FALSE?
TRUE
What are the factors that can affect drug distribution in the elderly?
- Altered body composition
- Reduce cardiac output
- Increased peripheral resistance
- BBB permeability may increase
Drug metabolic ability increases from birth to 6 months . TRUE OR FALSE?
TRUE
P450 metabolism increases with age. TRUE OR FALSE?
FALSE, it decreases
In the elderly there is a increased hepatic blood flow. TRUE OR FALSE?
FALSE
GFR decreases with age but can be very variable, which can lead to higher exposure so increased chances of toxicity. TRUE OR FALSE?
TRUE
In hepatic disease is there an increase or decrease in metabolism of CYP450 for example?
There is a reduction in metabolism, but it is not inevitable and depends on the nature of liver disease
What is cirrhosis and viral hepatitis and their impacts on drug metabolism?
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
What is the major site where serum album is synthesised?
The liver
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?
TRUE
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?
TRUE
Reduced first pass effect may increase bioavailability. TRUE OR FALSE?
TRUE
How does protein binding affect drugs which are extensively bound to albumin?
Drugs which are extensively bound to albumin are more likely to be affected by hepatic disease
A decrease in albumin would cause an increase in drug unbound, what effects may this cause?
- Increase therapeutic effect
- Increased toxicity
- Change in distribution Vd which may cause unexpected toxicity
What is hepatic encephalopathy and which drugs are a major concern for this, give example?
This is impaired brain function which is particular concern with drugs known to have effect on the CNS
e.g sedatives, opioids
Which types of drugs cause fluid retention?
NSAIDS
What is hepatoxicity and which drugs are a major concern for this?
Liver toxicity is particular concern with drugs that are intrinsically hepatoxic (self perpetuating)
What are the consequences of having reduced renal function?
- decreased GFR
- Reduced clearance - higher plasma levels are possible
- Longer half life/ time to reach constant steady state is increased
Hoe can renal function be estimated?
By measuring creatine clearance as surrogate to estimate GFR
Where is creatinine produce?
In the muscles
How is Creatinine eliminated?
Eliminated largely by Glomerular Filtration
Creatinine clearance is aprox GFR. TRUE PR FALSE?
TRUE
Creatinine serum can be used to estimate GFR and results obtained is creatinine clearance. TRUE OR FALSE?
TRUE
Creatinine is not produced at a constant rate by muscles. TRUE OR FALSE?
FALSE
Which two equations can be used to estimate GFR?
- Cockroft gault equation
- MDRD method
Which of the equations is considered to be more accurate? Cockroft gault equation
-MDRD method
MDRD method - normalized to body surface area
What are the limitations to estimating GFR using these two equations/
- 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
Some creatinine is excreted by tubular secretion so creatinine clearance may be slightly greater than GFR . TRUE OR FALSE?
TRUE
What is a more accurate way of measuring creatinine clearance and give its disadvantages?
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
As patients get older renal function decreases, so creatinine clearance decreases and varies between men and women. TRUE OR FALSE?
TRUE
