Week 3 - TDM content Flashcards
Finish the sentence:
“Therapeutic Drug Monitoring (TDM) involves measuring drug concentration in…”
…plasma, serum or blood”
What is the information gathered from Therapeutic Drug Monitoring (TDM) used for?
to individualise dosage so that drug concentrations can be maintained within a target range
Drug concentration range is associated with a _______ likelihood of treatment success and an __________ ______ of drug-related harm in the majority of patients.
Drug concentration range is associated with a HIGH likelihood of treatment success and an ACCEPTABLE RISK of drug-related harm in the majority of patients
What is the ‘therapeutic window’?
The range or window of time between the ‘desired response’ and the ‘adverse response or side effect’
Name some of the clinical needs for TDM.
-Confirming and managing suspected drug-related toxicity
-Individualised dosing
-Assessing treatment failure (e.g. distinguishing between non-adherence/poor bioavailability and ineffective drug treatment)
Identify 3 times we use TDM for the clinical need of ‘individualised dosing.’
- After a loading dose (or dose regimen) has been administered, or at steady state
- When a potentially interacting drug is added or removed
- After a significant change in health status such as renal or liver function
What is the simplified way of defining Pharmacokinetics?
What the body does to the drug
What is the simplified way of defining PharmacoDynamics?
What the Drug does to the body
What does the ‘Therapeutic Index’ reflect?
The relationship between the therapeutic and toxic dose of a drug
What is ED50 concerning the Therapeutic Index?
The dose required to produce a THERAPEUTIC effect in 50% of the population
(memory cue - think E from ED50 for ‘Emergency’ services providing ‘therapeutic’ help)
What is TD50 concerning the Therapeutic Index?
The dose required to produce a TOXIC effect in 50% of the population
(memory cue - think T from TD50 for ‘Toxic’)
TRUE OR FALSE?
SMALLER the Therapeutic Interval (TI) = closer to toxic effects and GREATER need for close monitoring
TRUE
What does the acronym ‘LADME’ stand for, and what does the L refer to?
Liberation
Absorption
Metabolism
Distribution
Excretion.
Liberation refers to the release of the drug from its dosage form.
What are the units of Vd (Volume of Distribution)
L or L/kg
What are some things that can impact the Vd?
Pregnancy
Weight
Age
Gender
What does Cp stand for?
Concentration in Plasma
TRUE OR FALSE
Clearance (Cl) IS NOT an important factor in determining the maintenance dose required to reach the target average Cp.
False
The average steady-state concentration associated with optimal drug effects is referred to as ____________ ______ ______?
“Css” or “Concentration Steady State”
What is a plasma half-life (t1/2)?
The time interval during which the drug concentration is reduced by one half
List 4 situations where onset and duration of clinical effect of drugs are NOT related to the drug’s t1/2.
- Drugs act via an IRREVERSIBLE mechanism (e.g. aspirin)
- Drugs act via an INDIRECT mechanism (e.g. warfarin)
- Drug is PRODRUG (e.g. codeine)
- Drug is converted to an active metabolite that has a longer t1/2 (e.g. allopurinol-oxypurinol)
Select the correct option:
a) at steady-state, the rate of drug administration is HIGHER than the rate of drug elimination & plasma drug concentration is relatively CONSTANT
b) at steady-state, the rate of drug administration is EQUAL to the rate of drug elimination & plasma drug concentration FLUCTUATES
c) at steady-state, the rate of drug administration is EQUAL to the rate of drug elimination & plasma drug concentration is relatively CONSTANT
c) at steady-state, the rate of drug administration is EQUAL to the rate of drug elimination & plasma drug concentration is relatively CONSTANT
Most drugs reach steady-state (SS) after how many half lives?
4-5 half lives
In relation to plasma protein binding- is only bound or unbound drug active?
- only unbound drug is active.
-SIDE NOTE: If bound, drug is unable to go through metabolism or excretion and exert it’s pharmacological effects
What can occur is someone has a drug concentration that exceeds the number of plasma proteins they have for binding?
Means an increased concentration of free drug in systemic circulation- and hence increased risk for toxicity.
TRUE OR FALSE
Most commonly used medicines have a wide TI (wide safety margin)
TRUE
TDM drugs have>1 of several of notable characteristics. Identify 3 notable characteristics of TDM drugs.
- Defined, measurable target concentration range
- Narrow Therapeutic Index
- No active Metabolite (unless the metabolite can be measured)
Which of the following are NOT considered TDM?
a) monitoring INR for a patient with AF on warfarin Target INR range = 2-3
b) monitoring vancomycin level for a patient with MRSA infection. Target Range = 0.5-1mcg/L
c) Monitoring digoxin level in a patient with heart failure. Target range 0.5-1mcg/L
Therapeutic Drug Monitoring applies to the direct monitoring of DRUGS
A is NOT measuring a drug; therefore is not considered TDM
When is the least variable time for sampling requirements?
Just before the next dose is due “pre-dose” or “trough concentration”
What type of drug is Digoxin, what is it’s time to SS, and when can TDM be undertaken?
-Digoxin is an Antiarrhythmic
-Time to SS 6-10 days (longer in renal failure patients)
-TDM pre-dose or >6hrs post-dose
What type of drug is Theophylline, what is its time to SS and it’s half life
-Theophylline is used for severe asthma or COPD.
-time to SS 1-3 days
- half lif is 3-12 hrs.
Note: shorter steady state = shorter half-life
What type of drug is Amidarone, what is its time to SS, and when can TDM be undertaken?
-Amiodarone is an Antiarrhythmic
-26-107 days to SS
- TDM ~3 months AFTER dose
What type of drug is Perhexilline, what is it’s time to SS, and when can TDM be undertaken?
-Perhexiline is a last-line treatment (due to narrow therapeutic window) for Angina
- 2-4 weeks to SS in fast metabolisers, longer in poor metabolisers
-TDM in 3-5 days to identify poor metabolism
Which of these 4 medications have the ADR of “potential to worsen arrhythmia”?
a) Digoxin
b) Amiodarone
c) Theophylline
d) Perhexilline
a) & b)
What is a potential lifestyle consideration that can impact Theophylline levels, and how?
Smoking. It can induce theophylline enzymes CYP1A (metabolism) leading to increased drug clearance (excretion). People who smoke require higher dosages of theophylline.
How is PERHEXILLINE an example of how poor metabolism can impact drug dosing regimes?
6-10% of Caucasians and 1-2% of Asians are poor metabolisers (PMs) and require very low doses of perhexaline to avoid toxicity.
What is a potentially harmful concentration of antiarrhythmic Digoxin?
> 2microg/L
Note: reference ranges for Digoxin differ for those with AF from HF.
0.5-2microg/L (AF)
0.5-1microg/L (HF)
What is a potentially harmful concentration of bronchodilator Theophylline?
> 20mg/L
What is a potentially harmful concentration of antiarrhythmic Amiodarone?
> 2.5mg/L
What is a potentially harmful concentration of antianginal perhexiline?
> 0.6mg/L
