Therapeutic Drug Monitoring Flashcards
Definition of TDM
Evaluation of circulating concentration of drugs in the blood to ensure adequacy of therapeutic effect and minimize toxic effects
2 ways pharmacological effect can be elicited
Direct interaction of drugs with receptors controlling specific function
Drug mediated alteration of normal physiological response, regulating the function
Definitions of T. Index, T.Range, Steady state and Half life
Therapeutic Index- ratio between the plasma conc of the drug yielding desired and undesired effects
Therapeutic Range- Range of values between the minimum effective concentration and minimum toxic concentration of a drug in circulation
Steady state- point at which the plasma conc of the drug is in equilibrium with the dose administered and elimination rate( occurs after about 3-5 half lives)
Half life/elimination half life- time taken for the plasma conc of a drug to reduce to half its original value
Determinants of Drug plasma concentration
- absorption and distribution
- Metabolism and elimination
- Timing of sample
- Patient compliance
- Patient variation
10 routes of drug administration
Inhalational Rectal Sublingual Intra lesion Intrathecal Transcutaneous Subcutaneous Intramuscular Intravenous Oral
ADME
Absorption- Depends on dose form, fraction of drug absorbed into system determines bioavailability
Distribution- affected by binding proteins and drug drug interactions and also first pass metabolism
Metabolism- majority is by hepatic MFO system( Mixed Function Oxidase). Converts hydrophobic drugs to water soluble. Also affected by drug drug interactions, age, genetics and nutrition
Drug drug interactions including:
Enzyme inducers: phenobarbital, alcohol, theophylline, rifampicin
Enzyme inhibitors: anti retroviral drugs, cimetidine, erythromycin, grapefruit juice
Elimination: could follow first order kinetics or zero order kinetics
First order kinetics: rate of decline of drug plasma conc overtime varies with concentration of the drug
Zero order kinetics: rate of elimination not proportional to concentration of drug e.g alcohol
Requirements of therapeutic drug monitoring
- Timing of sample
- Dosage regimen
- Patients demographics ( age sex ethnicity)
- Co medications
- Indications for monitoring
- Therapeutic range of drug
Sampling Time
The most important factor in TDM. TDM commenced only after steady state has been achieved( sampling time is the time the sample of drug is take)
Trough concentration: conc of the drug just before the next dose is administered ( not necessarily the lowest conc of the drug during dosing interval) commonly used for anticonvulsants, Sample is obtained just prior to the next dose at steady state
Peak concentration: useful for antibiotics
Peak conc is attained 0.5hr after IV, 1hr after IM and SC and 2-4hrs after oral administration
Random sampling: drugs with no significant difference in trough and peak whose half lives are much longer than dosing intervals e.g phenobarbitone
Indications for TDM
1 Drugs with narrow therapeutic range
- Plasma drug conc not predictable from dosage alone
- To check non compliance
- Alteration of drug utilization due to disease
- Inter individual variability
- Drug interactions
- Medicolegal verification of treatment
Non indications of TDM
Toxicity is not a concern( wide therapeutic range)
Effects can be measured using functional lab tests
Plasma conc not predictably related to effect( anticoagulant)
Drugs have surrogate marker e.g Blood pressure, blood glucose
Uses of TDM
Maximizes Efficacy
Avoids toxicity
Identify therapeutic failure
Facilitate dosage adjustment
Identify poisoning and drug abuse
Hindrances to TDM
Hospital personnel not aware Physicians don’t understand principles benefits and limitations Inappropriate sampling times Not stating the indications for TDM Insufficient patient history and data No consultation when problem arises
Drugs for TDM
Anti epileptics Anti arrythmics Antibiotics Bronchodilators Immunosuppressive Antidepressants
Lab techniques
Mass spectrometry
Chromatographic techniques
Immunoassays
Flame photometry
Therapeutic range of TDM drugs
Digoxin- 0.8- 2 u/l Theophylline- 10-20 mg/l Gentamicin: 2-12 mg/l Lithium- 0.8-1.2 mmol/l Phenytoin- 10-20 mg/l Carbamazepine 4-12 mg/l Cyclosporine: 100-200 mg/l
