click below
click below
Normal Size Small Size show me how
Toxicology & TDM
Therapeutic Drug Monitoring
Question | Answer |
---|---|
TDM: -Define | analysis, assessment & evaluation of circulating concentrations of drugs in serum, plasma or whole blood |
TDM: -Purpose | ensure that a given drug dosage produces maximal therapeutic benefit & minimal toxic adverse effects |
TDM: -Used when | safe dosage regiments have not been established and a trial & error approach is not appropriate |
TDM: -Involves ____evaluation of circulating drug concentrations | quantitative |
TDM: -4 key factors | 1. route of administration 2. rate of absorption 3. distribution of drug w/in body 4. rate of elimination |
The Role of MLS in TDM: -x3 things MLS is responsible for | 1. assuring the sample is collected at requested time 2. processing STATs in timely manner 3. assuring accuracy of results by maintaining instruments and performing operations correctly |
The Role of the Dr in TDM: -Interpret drug concentrations in the context of the | clinical status of the PT |
Ind. PT drug utilization & pharmacokinetic patterns are a direct consequences of the interaction of numerous factors including...[x6] | 1. genetic makeup--pharmacoenomics 2. age 3. sex 4. physiological status 5. presence of concurrent disease 6. multiple drug therapy |
Pharmacogenomics -Responders | PTs benefiting from therapeutic & desired effects of drugs |
Pharmacogenomics -Non-Responders | PTs not benefiting from therapeutic & desired effects of drugs |
Name a gene group family that affects drug metabolism? (FYI) | Cytochrome P450 |
Indications for using TDM [1-4/8] | 1. drug has narrow-therapeutic range 2. PT noncompliance is suspected 3. Drug exhibits marked pharmacokinetic variations from Pt to Pt 4. PT metabolic state is unpredictable |
Indications for using TDM [4-8/8]5 | 5. possible drug-drug interactions 6. PT is exhibiting unexplained toxic effects 7. a medicolegal need to verify treatment exists 8. a loading dose regimen is being used |
Criteria for TDM -Blood concentrations of the drug _______ w/ therapeutic | correlate |
Criteria for TDM -The drug has a ____ therapeutic index (TI) | Low |
Low Therapeutic Index means that the dose providing the therapeutic effect is | very close to the dose that causes toxicity |
Criteria for TDM -The drug is being used to treat an intermittent condition--the resulting pharmacodynamic effect of the drug is.... | hard to measure |
Criteria for TDM -Evaluate the PT on chronic drug treatment so the dosage regimen can be adjusted in re: to.... | physical changes |
PT Info needed to TDM [1-4/8] | 1. Time of last dose 2. Amt of last dose 3. Dose regimen 4. Dose route |
PT Info needed to TDM [5-8/8] | 5. time of dosing regimen 6. time of phlebotomy 7. PT age, weight & sex 8. Other concurrent meds |
Elimination Half-Life -Defined as: the time it takes for the plasma concentration or | amt of drug in the body to be reduced by 50% |
Elimination Half-Life - how many half lives are required for steady state using oral dosing -how can it be achieved more rapidly? | 5-7 half lives are required for stead stead --may be achieved more rapidly in IM or IV dosing |
Half-Life (T1/2) -The rate at which a drug removed is called the E_____, D___, or C____time | Elimination, Disappearance or clearance time |
Half-Life (T1/2) - the term half-life is used to | express the rate or time of elimination |
Half-Life (T1/2) -i.e: if no more drug is given, it takes approx. how many half lifes to completely remove the drug from the blood? | 5-7 |
Half-Life (T1/2) -a dosing interval SIGNIFICANTLY longer than the T1/2 results in ____fluctuations | dosing interval SIGNIFICANTLY longer than T1/2 results in WIDE fluctuations b/t peak & trough levels |
Half-Life (T1/2): dosing interval SIGNIFICANT Y longer -Trough level may be ____ than the lower therapeutic limit -how does this affect disease states? | Trough may be lower than thera.limit --disease state may not be properly controlled |
Half-Life (T1/2): dosing interval SIGNIFICANTLY shorter than the T1/2 -Peak levels compared to therapeutic range | Significantly shorter --> peak levels might exceed the upper limit of thera. range & become toxic |
Half-Life (T1/2: dosing interval SLIGHTLY shorter than the T1/2 -what should happen to the therapeutic range? | Should maintain therapeutic range once the steady-state condition is achieved |
Steady State -Defined as the time required for an amt of drug in the blood to... | decline to one-half its measured values |
Steady State -dependent on the D____ R____ & C_____ | Dosing Rate & Clearance |
Steady State -what happens to blood concentration when multiple doses of the drug are taken? | Blood concentration levels continue to rise until a steady-state is reached |
Steady State -how is drug intake balanced | by the clearance of the drug from the body |
Steady State -in order to maintain, it is important to | not miss, add, or change any doses |
Following the first administration of a drug, the serum concentration of the drug reaches a.... | Peak or maximum level |
The time b/t the first dose & reaching peak level in the blood is dependent on.... | the route of administration |
When a drug is administered intravenously, when is the peak level attained? | 30-60 min |
When a drug is administered orally, when is the peak level attained? | 1-2 hrs due to intestinal absorption |
A S____ R_____ oral medication takes (longer or shorter) to achieve peak serum levels | Sustained-Release oral med takes longer to achieve serum peak levels |
the absorption of a drug administered _______ is usually erratic, causing the time to reach peak levels to be unpredictable | Intramuscularly |
The serum level drops from peak concentration to zero within ____ half lives unless.... | w/in 5 half-lives unless a second dose is given soon after the first |
The Trough or Valley level is the blood drug level.... | just before the dose is administered |
Pharmacokinetics -Mathematic modeling of... | drug concentration in circulation |
Pharmacokinetics -Assists in... | establishing/modifying a dosage regimen |
Pharmacokinetics-Sample Collection -Timing -Specimen type | -Timing is critical; trough concentrations--right before next dose, peak concentrations--1 hr after dose -Serum or plasma specimens |
Loading Dose Regimen -how do you reach therapeutic levels w/out waiting for 5 half lives? | larger or more frequently administered dose |
Loading Dose Regimen--troubleshooting -Serum drawn before the admin of loading dose | Indicates existing blood levels--Dr wont adjust length of admin and/or concentration correctly |
Loading Dose Regimen--troubleshooting -Serum drawn during the admin of loading dose | indicates possible toxic levels |
Loading Dose Regimen--troubleshooting -Effects of antibiotics | some drugs, including antibiotics are not effective until a min. level is attained |