Therapeutic Drug Monitoring

Question 1

In what circumstances is therapeutic drug monitoring useful? Illustrate
your answer with several examples.

Answer 1

• when clinical/toxic response not easily recognised
• Drugs w/ narrow TI (e.g. Digoxin, Li, Phenytoin)
• varying TI in individuals
• possiblilty of drug-drug interactions
• pathological conditions (e.g. renal failure, liver disease) influencing drug disposition

Question 2

Why is it important that samples taken for measurement of digoxin are
taken at least 8 hours after the last dose

Answer 2

bc conc. of dose match the dose in tissues
(trough levels not measured)

Question 3

Digoxin is considered to have a narrow therapeutic index. What does that mean

Answer 3

therapeutic & toxic effect is narrow/close to each other

Question 4

In context of TDM, what are trough and peak levels

Answer 4

Trough: Time before next dosage (bc conc dropped) *less important to measure
peak: given dosage

Question 5

definition of TDM & when is it useful (Criteria of TDM)

Answer 5

• measure efficacy of drug (the desired effect)
• for individualised dosing regimens
• produce maximal therapeutic benefit & minimise toxic side effects

Question 6

explain the term ADME (pharmacokinetics)

Answer 6

Pharmacokinetics determines ADME:
A: Adsorption
D: Distribution
M: Metabolism
E: Excretion

Question 7

Achieving steady-state drug levels using blood level/time curve to determine…

Answer 7

dose required to achieve desired steady state conc. Measure dosage at particular time

Question 8

4 precautions in TDM

Answer 8

• assays used measure the active form of the drug
• some drugs are intrinsically active (active in administered form)
• other drugs need to be converted in their active form
• Multiple drug regimens can interfere in protein binding (e.g. serum proteins), competition for metabolic pathways, production? of drug metabolising enzymes

Question 9

difference b/w pharmacokinetics and pharmacodynamics

Answer 9

-kinetics: the way drugs acted on by body (e.g. excretion/metabolism)
-dynamics: influence of drugs on body (pharmacological effect in target tissue)

Question 10

Factors influencing ADME

Answer 10

• Age, gender, race, weight
• disease state
• liver, kidney, thyroid, GIT
• Diet
• other drugs (drug-drug interactions)

Question 11

What does the blood level time curve display

Answer 11

• concentration of drug circ. in blood over time
• dec. overtime as gets metabolised

Question 12

What does the therapeutic window display

Answer 12

• Response (y) vs dosage (x)
• Therapeutic efficacy & toxicity graph & determines the distance in b/w graphs (=therapetutic window)

Question 13

What’s the equation for therapeutic index (TI) & interpretation

Answer 13

TI = toxic dose/ therapeutic dose
Low TI = bad bc difference b/w therapeutic & toxic effect is narrow/close to each other
Hi TI = good

Question 14

Describe the principle Micro-particle Enhanced Immunoassay (MEI)

Answer 14

• immunochemical assay
• competitive assay: free sample Ag competes w/ microparticle coupled w/ Ag/drug for ALP labelled anti-drug Aby
• heterogenous: rxn is filtered = drug-microparticle unfiltered & reacted against umbelliferone phosphate (substrate for ALP)

Question 15

Describe the principle Kinetic Micro-particle Immunoassay (KIM)

Answer 15

• immunochemical
• competitive: free sample Ag competes w/ drug-microparticle conjugate for anti-drug Aby
• heterogenous
• measure immunoturbidimetry: less free sample = more X-linking = Hi light scatter
  vs more free sample = less X-linking = less scatter

Question 16

Describe the principle Fluorescence polarization immunoassay (FPIA)
*can’t do on general chem analyser

Answer 16

• immunochemical
• Homogenous
• competitive: fluorescent labelled drug compete w/ sample drug for binding Aby => each form Ag-Aby complex
• use fluorimeter illuminates rxn w/ polarised light
• more sample Ag = rapid rotation = low polarisation bc binds less to labelled Ag.
  Vs less sample Ag = slow rotation = high polarisation

Question 17

Describe the principle Enzyme Immunoassay (EIA) eg EMIT

Answer 17

• immunoassay
• homogenous
• competitive: Enz labelled Ag competes w/ sample Ag for Aby => will inactivate enz
  *PROPORTIONAL curve: bc enzyme activity = [Ag]
  i.e. Hi sample Ag = Aby bind less to Ag-Enz = Enz remain active
  VS lo sample Ag = Aby binds more to Ag-Enz = inactivating Enz

Question 18

PETTINA principle is similar to which assay:
EMIT / KIMS / Fluorescent polarisation immunoassay / MEI, & briefly describe assay

Answer 18

• similar to KIMS
• Aby binds to drug-latex = aggregates = inc turbidimetry
• Free drug competes w/ drug-latex = dec aggregation

Question 19

2 factors that have low Sn to digoxin (adsobed less)

Answer 19

Hyperthyroid, GIT disease/ motility

Question 20

What is digoxin used for & which organ does it cause toxicity (hence requirement of TDM)

Answer 20

• cardiac failure (anything heart related)
• Renal function

Question 21

What is phenytoin (dilantin, diphenylhydantoin)?
And the effect of Valproate (drug) to it

Answer 21

• anti-convulsant: control seizures for epilepsy
• Valproate displaces phenytoin from Alb = free form = toxic

Question 22

Methodological considerations for Tri-cyclic Antidepressants like Imipramine, amitryptyline, doxepin. (2)

Answer 22

• must measure parent drug + active metabolites
• free from interferance of similarly structured compounds

Question 23

3 Factors that are more Sn to digoxin (adsorbed more)

Answer 23

Hypothyroidism, Hypercalcemia, hypokalemia,

Question 24

What is Li used for & toxic side effects. does it bind to protein?

Answer 24

• Manica-depressive (bi-polar disorder)
• Schizophrenia
• side effect: coma
  *doen’t bind to protein