ADME

Question 1

Define purpose for TDM

Answer 1

CAICA

Check patient compliance

Assess inter-patient variability

Investigate therapeutic failure

Confirm safe + effective drug monitoring

Avoid/anticipate drug concentration resulting in adverse effects

Question 2

Outline factors that affect TDM

Answer 2

PPDSM

Pharmacokinetics

Pharmacodynamics

Dosage regimen

Sample type + timing

Testing methodology

Question 3

Specific indications for drug monitoring

Answer 3

NHTEC - not here to ear cloutchasers

These are drugs…

• wth a narrow therapeutic index
• which are HIGHLY protein bound
• whose TOXICITY is difficult to distinguish due to pts disease
• whose EFFICACY is difficult to establish clinically

+ including pts w/ IMPAIRED CLEARANCE w/ a narrow therapeutic index

Question 4

What are the pharmacokinetic parameters important in TDM?

Answer 4

• Bioavailability
• Clearance
• Half-life
• Volume of distribution + distribution phases
• Protein binding of drugs

Question 5

Drugs are given as repeated (ORAL / IV) doses

• Provide example of a repeated dose schedule
• What happens with the plasma drug concentration?
  *

Answer 5

Question 6

How is drug monitoring performed?

Types of samples used

Answer 6

By measuring plasma drug conc.

By its clinical effect e.g. lowering BP

By its biochemical effects e.g. glucose modulation by insuli

Types of samples incl.

• Blood plasma/serum
  
  • @ steady-state
  • convenient + standardised
• Other samples
  
  • blood
  • CSF, saliva, urine

Question 7

Give 7 major sources of pharmacokinetic variability

Answer 7

Patient compliance

Age

Disease

Physiology

Genetic influences

Environmental influences

Drug-drug interactions

Question 8

Importance of analytical methodology

Answer 8

Quantitative method with high throughput (results < 24hrs)

Distinguishes between compounds of similar structure

Detects low concentrations w/ high accuracy + precision

Simple enough to use as a routine assay

Not affected by other drugs administered simultaneously

Question 9

What are the analytical methodologies for TDM

Answer 9

hplc (high performache liquid chromatography)

gc (gas chromatography)

elisa (enzyme-immunosorbant assay)

radioimmunoassay (ria)

fluorescence polarisation immunoassay (fpia)

mass-spectometry-based methods (lc-ms, gc-ms)

Question 10

Advantages + Disadvantages of HPLC + GC

Answer 10

High precision, specificity + sensitivity

Reliable + automated

Rapid analysis of mixtures containg dozens of components

Widely used in pharmaceuticals, food + petrochemicals

Quantitative + qualitative analysis for purity checking of organic compounds

However,

Complex analytical procedures incl. sample prep.

Slow throughput

Time-consuming extraction

Question 11

HPLC colums

Answer 11

Question 12

HPLC detectors

Answer 12

Question 13

GC column + stationary phase

Answer 13

Question 14

Antibody-based Assays

Answer 14

Question 15

How does the ELISA test work?

Answer 15

Question 16

Radioimmunoassay

Answer 16

Question 17

Fluorescence polarization immunoassay (FPIA)

Answer 17

Question 18

Examples of drugs commonly monitored

Answer 18

BICAAAP

Question 19

Role of the pharmacist in TDM

Answer 19

• Advise other HCPs about correct use if TDM-sampling time + technique + interpretation of results
• Select initial drug dosage regimen dose, doing interval, route of admin, dosage form
• Revise + re-calculate dosage regimen depending upon TDM results + patient’s response
• Assess various reasons for unexpected results such as non-compliance, medication for laboratory errors
• Evaluate + adjust dosage dor pts on renal or haemodialysis
• Advise + manage acute drug interactions