Therapeutic Drug Monitoring Flashcards
What is pharmacokinetics? What is pharmacodynamics?
pharmacokinetics
- Focuses on measurement of the time course of drug concentrations in serum and tissues
- ’What the body does to the drug’
= ADME
pharmacodynamics
- Focuses on the measurement of microbial exposure to drugs in serum and tissues at a cellular level and the consequence to microbial viability
- ‘What the drug does to the body’
What is the difference between concentration dependent and time dependent antimicrobials?
concentration dependent
- the higher the drug concentration relative to MIC, the greater the rate and extent of antimicrobial activity
time dependent
- the longer the duration pathogens are exposed to antibiotics/antimicrobials, the greater the rate and extent of antimicrobial activity
What are examples of concentration and time dependent antibiotics?
concentration dependent
- aminoglycosides = streptomycin, gentamicin
- metronidazole
- quinolones = ciprofloxacin, ofloxacin
time dependent
- vancomycin
- beta lactams = penicillins, cephalosporin
What is therapeutic drug monitoring?
TDM is measuring the concentration of drug in the blood
- mainly for drugs with a narrow therapeutic drug window
monitoring drug levels helps us to adjust the dose of drugs to maximise efficacy and reduce toxic effects
What are indications for TDM?
drugs with narrow therapeutic index
unpredictable/variable PK
ensure adequate levels for treatment:
- efficacy
reduce/avoid toxicity
- always needed for aminoglycosides, itraconazole
may be required in certain circumstances e.g:
- TB meds if GI absorption is impaired
- ARVs = interactions, poor compliance, lack of VL suppression
- severe infections with renal impairment e.g. daptomycin
What is the ADME of gentamicin?
is concentration dependent
- amino glycoside
absorption - no GI absorption so must be given via i.m or i.v
distribution - is water soluble
metabolism - 90% is excreted unchanged
excretion - via the kidneys
What is the toxicity associated with gentamicin? What are the contraindications?
Ototoxicity – usually irreversible (0.5-3.0%)
= vestibular and auditory effects
Nephrotoxicity – usually reversible (5-10%)
= non-oliguric (increased urine output), acute tubular necrosis (ATN, damage of kidney cells)
CI in myasthenia gravis – impaired neuromuscular transmission
Others - rash, nausea, blood dyscrasias etc.
What is the difference between single dose and multiple dose regimen for gentamicin?
single dose
- must be given after/during trough which is 18-24hrs after the initial dose is given, levels must be <1mg/L
- peak levels are NOT required
multiple dose
- must achieve steady state before sampling
- peak levels must be taken 60 mins after dose is given, aim is 3-5 or 5-10mg/L
- trough levels must be taken before the next dose, aim is <1mg/L or <2mg/L
single dosing is not superior or inferior to multiple dosing
What is vancomycin? How does it act? What does it treat?
time dependent antibiotics (time spent above MIC)
- has narrow spectrum activity
- acts on gram positive bacteria
= staph, strep, clostridium difficile and enterococcus species
treats infections including
- MRSA
- infective endocarditis
- pneumonia
- bone/joint
requires a loading dose
What is the ADME?
absorption - poor oral absorption
distribution - water soluble
metabolism - 80-100% excreted unchanged
excretion - via the kidneys
What toxicities and side effects of vancomycin?
toxicity
- ototoxicity and nephrotoxicity is unconfirmed
red man syndrome
blood disorders
rash
nausea
How should vancomycin be given?
trough levels (0-60 minutes pre-dose) must be taken at steady state
peak levels not required
do not wait for levels to come back before giving dose unless dialysis pt/severe renal impairment
only need to check levels twice weekly if renal function stable
