WEEK 6 - Specialist and Therapeutic Drug Monitoring Flashcards
(10 cards)
What is Therapeutic Drug Monitoring (TDM)
- Measuring drug at designated intervals to maintain constant conc. in pt bloodstream
- required for drugs narrow therapeutic index = ↑ risk of tipping into toxicity
What is the importance of TDM in clinical practice
- Optimise dosage regimens / therapuetic efficacy
- make dose adjustments
- adjust frequency of montioring based off pt response - Improved disease control
- Get + maintain steady state conc.
- Balance efficacy and toxicity risk
- avoid ADRs, toxicity, SE
- manage DDIs (↑ risk)
- monitor therapeutic range - Personalised dosing
- consider pt characteristics, genome - Manage consequences of changing health status
- e.g. renal impairment, pregnancy - Interpreting results
What 4 factors need to be considered
- Inter-patient Variability:
- ADME responses
- renal / hepatic function - Compliance Issues:
- impact of poor pt adherence - Drug Interactions:
- adds complexity - Analytical Variability:
- factors influencing reliability of test results
Example of drugs that require TDM
Warfarin (in AF)
5FU
Anti-epileptics in pregnancy
NSAIDs and methotrexate
Narrow index
- Digoxin (in HF)
- Phenytoin
- Theophyline
- Vancomycin
- Lithium
- Clozapine
- pt needs to have green result prior week before able to commence
- if amber need to re-test, after 2 green can commence
- if red = can’t give next dose
Explain the relationship between:
1. Therapeutic window
2. Narrow therapeutic index
3. Target concentration strategies
- Range between minimum effective conc. and minimum toxic conc.
- TDM ensures we keep within this - Drugs with small therapeutic window
- How TDM helps achieve target drug levels
When is TDM clinically indicated and how do we do sampling
Indications:
- Have drug with narrow therapeutic index
- Pt has acute or chronic conditions
- Variability in drug response
- Known ADRs / DDIs
How is TDM performed (sampling)
Occurs at diff. time points and the peaks / troughs inform us about what pt dose will be
Examples:
- HPLC (chromatography)
- Immunoassays
- Mass spectrometry
Explain TDM principles
5 Principles
- Conditions
- e.g. PK variability, adverse and therapeutic effects, narrow index, undefined conc. range
- Drugs requiring monitoring
- e.g. antibiotics, cardiac, psychotics, anti-epileptics, immunosuppresants, anti-cancer
- Advantage
- indivualised therapy, avoid toxicity, monitor + detect drugs
- Matrix
- i.e. plasma, blood, urine, serum
- Technical / Sampling
- i.e. HPLC, immunoassays, biosensores
Explain TDM with IV antibitoics
Vancomycin and Gentamicin
Vancomycin:
- Treats gram +ive bacteria
- Large proprtion is not metabolised
- 90% eliminated in urine
- Eliminaion half life increases in pt with renal impairment
- Large doses can restrict mobility
- 2 Types of Doseing: Intermittent (pulse to keep within window) or Continuous (↓ peaks / troughs)
AIM:
- target trough level < 15mg/L
- Trough = 1hr before dose administration
- peak = 40mg/L
- Peak = 1hr after administration
- Therapeutic range = 10-20mg/L
Gentamicin:
- Has broad spectrum of activity
- Highly bound to plasma albumin
- 90% excreted unchanged in urine
- Half life increases in pt with renal impairmenr
- Can cause nephrotoxicity and ototoxicity
- 2 Types of Dosing: OD (for systemically unwell pts) or Intermittent (for pt unsuitable for OD)
AIM:
- Target target trough level <2mg/L
- Peak 5-10mg
Summary of the emerging trends /technologies and their affects in personalised medicine
- Growth of personalised medicine
- e.g. pharmacogenomics
- Point of Care Testing
- Have portable devices
- Have PCR (rapid testing)
- Have phone diagnostics
- Facilitate quicker + effective clinical decisions as some tests can be done at bedside ( dont require lab)
- Use of AI
- PK computational modelling
- Virtual trials / simulations
- DDI predicitions, toxicity
- Investigate pharmacovigilanc e (pt groups we know little about)
