ADME

Question 1

What is the Purpose of TDM

Answer 1

TDM is Therapeutic drug monitoring, with the aim to keep the dose of a drug within a therapeutic range. It is based on recognition that certain drug have narrow therapeutic windows with the exceeding of upper levels resulting in toxicity and being below the lower Limit leading to the drug being ineffective

TDM is a measurement of a chemical parameter that will directly incluence drug dosing procedures and by doing so we are confirming that the patient is maintaing a safe and effectice drug concentration.

It can also be done to investigate therpeutic failure and check patient compliance. Through TDM we can avoid or anticipate drug concenrations which may result in adverse effects.

We can also assess inter-patient variabilaity

Question 2

What are specific indications for when TDM is requred

Answer 2

TDM is especially indicated for Narrow therapeutic index

Drugs which are highly protein-bound or may have an indication in the removal or elimination of the drug

Patients who have impaired clearence of a drug with a narrow therapeutic index whcih may result in toxicity due to accumulation of drug.

If symptoms of drug toxicty are similar to the disease they are treating, for example Theophyline

Question 3

What factors affect TDM measurements(Clinical, Genetic, and environmental factors)

Answer 3

• Alcohol intake, Age, Sex, Diseaes, Occupational exposure to certain chemicals, Renal function
• Generic polymorphisms may effect TDM measurements. Polymorphisms I genes coding for metabolising enzymes and drug transporters

Question 4

How is drug monitoring in TDM performed analyically

Answer 4

TDM is performed by measuring the plasma concentration of the blood.

We could look at the clincal effect of the drug at concentrations e.g How much blood pressure is lowered

We could also look at its biocemical effect for examaple glucose modulaion by insulin

Question 5

How are the analytical methods used for TDM

Answer 5

• Quantitative methods with high throughput results. We need quick results preferably under 24 hours
• Distinguishes between compounds of similar structure - drug/metabolite
• Detects low concentrations of drugs with high accuracy and precision
• Simple enough to use as a routine assay
• Not affected by other drugs administered simultaneously
• A compromise between specificity and cost
• Some of the methods used are:
  
  • High-performance liquid chromatography
  • Gas chromatography
  • Enzyme-linked immunosorbent assay
  • Radioimmunoassay
  • Mass spectrometry-based methods
  • Fluorescence polarisation immunoassay

Question 6

How does HPLC work

Answer 6

It is used for separating mixtures, as wel as find relaive amounts of different components in a mixture

The stationaty phase is a solid packed into a column, in paper chromatography, the liquid is forced through the pressure by high pressure pumps

A solvent is injeted into the injection port

Two solvents can be mixed to give a liquid phase which should be of a suitable polarity for separation to occur

The solvent which emerges from the column carrying the separated components of the mixture passess into the detector where a beam of UV light passess through it to detect the seperate subtstances