Therapeutic Drug Monitoring

Question 1

Therapeutic drug monitoring (TDM)

Answer 1

The measurement of drugs and/or their metabolites in body fluids (usually blood) to maintain therapeutic benefits.

Question 2

Therapeutic range (TR)

Answer 2

Dose/concentration range of a drug. The drug produces the desired effect within that range

Question 3

True/False
Most drugs don’t require monitoring to achieve therapeutic levels

Answer 3

So true, my friend

Question 4

When is TDM used?

Answer 4

When a drug has:
- Narrow TR
- Marked pharmacokinetic variabilities
- Critical adverse effects

Question 5

Main purposes of TDM

Answer 5

• Ensure correct drug dosages for TR
• ID drug-drug interactions if multiple drugs are taken together

Question 6

Factors influencing drug concentrations and efficacy

Answer 6

• Age
• Gender
• Genetics
• Diet
• Co-administered drugs
• Naturopathic agents (natural)

Question 7

Pharmacokinetics

Answer 7

Study of the movement of drugs in the body

Question 8

Pharmacokinetics provides a time-course of drug concentrations in the body as a function of _____

Answer 8

1. Absorption
2. Distribution
3. Metabolism
4. Excretion

Question 9

Routes of administration

Answer 9

• Oral (most common/least invasive)
• IV (most direct/effective)
• IM
• Subcutaneous
• Aerosol
• Transdermal patch
• Rectal

Question 10

Bioavailability

Answer 10

The fraction (%) of an administered drug that reaches the systemic circulation.

Question 11

Oral drug absorption depends on these 3 factors

Answer 11

Efficiency of absorption from GI depends on 1) Dissociation from its administered form, 2) Solubility in GI fluids, and 3) Diffusion across GI membranes

Question 12

Drugs most passively diffused from GI to bloodstream require what?

Answer 12

• Drug must be hydrophobic (nonionized)
• Gastric acidity (weak acids best absorbed by stomach; weak bases best absorbed by intestine)

Question 13

What affects drug absorption?

Answer 13

• Affected by changes in intestinal motility, pH, and inflammation
• Administration with other substances (antacids, fiber, kaolin, sucralfate, cholestyramine, antiulcer medications)

Question 14

Ability of drug to leave circulation depends on ____ of the drug.

Answer 14

Lipid solubility
- Highly hydrophobic can easily cross cell membranes or lipid compartments
- Polar/non-ionic can cross membranes but don’t enter lipid compartments
- Ionized diffuse out of vasculature but at a slow rate

Question 15

Volume of distribution equation

Answer 15

Volume of distribution = Dose of drug/Concentration of drug

Question 16

Drug with large and small Vd: lipid properties

Answer 16

• Large Vd = Hydrophobic
• Small Vd = Ionizable/protein-bound

Question 17

True/False: Only bound drug fractions can interact with site of action and result in biological response (active fraction)

Answer 17

False
Only the free/unbound fractions are the biologically active fractions

Question 18

Major transporter of drugs and how it affects free vs bound drug concentrations

Answer 18

Albumin. Its concentration affects free vs bound drug

Question 19

First pass effect

Answer 19

Phenomenon in which a drug is metabolized before reaching the circulatory system, which decreases its concentration before entering circulation

Question 20

Biotransformation

Answer 20

Where a drug gets metabolized into a therapeutically active metabolite (usually in the liver)

Question 21

Biochemical pathway responsible for large portion of drug metabolism. Basic function of pathway?

Answer 21

• Hepatic mixed-function oxidase (MFO) systems.
• Function: converting hydrophobic substances to water-soluble products, which are then transported into bile or released into circulation for elimination by renal filtration

Question 22

Phase 1 reactions in MFO system

Answer 22

Produce reactive intermediates

Question 23

Phase 2 reactions in MFO system

Answer 23

Conjugate functional groups to reactive sites in water-soluble products

Question 24

Specificity of MFO system

Answer 24

Non-specific. Allows many endo/exogenous substances to go through this pathway. E.g., grapefruit, alcohol, or caffeine

Question 25

How do hepatic diseases affect clearance and half-life?

Answer 25

Slow clearance and increase half-life, such as cirrhosis

Question 26

How are free drug fractions eliminated? Kinetics?

Answer 26

• Glomerular filtration, renal secretion, or both, also bile
• First-order kinetics (exponential)

Question 27

How many doses are typically needed before steady-state oscillation is achieved?

Answer 27

5-7 doses

Question 28

Pharmacodynamics

Answer 28

Study of the biochemical and physiological effects of drugs and their mechanisms of action. It describes the relationship between a drug’s concentration at its site of action and its responses

Question 29

Tolerance

Answer 29

Constant exposure of receptors to drugs leads to reduced response to drug

Question 30

Specimen collection

Answer 30

• Trough drawn right before next dose
• Peak drawn 1 hr post oral dose
• Peak drawn 90 min post IV aminoglycosides
• Royal blue normally
• Gray top for lead testing

Question 31

When does drug peak?

Answer 31

Only after steady state

Question 32

Which tube can you NOT use for specimen collection in TDM and why?

Answer 32

Gold top because gel causes false decreases. It interferes

Question 33

When is EDTA whole blood used?

Answer 33

For immunosuppressive drugs

Question 34

Pharmacogenomics

Answer 34

The science of studying variations and developing drug therapies to compensate for the genetic differences impacting therapy regiments

Question 35

CYP450

Answer 35

Prominent gene affecting drug metabolism which encodes cytochrome P450. Has 3 variations. Can use this info to personalize drug doses

Question 36

List the drug classes that we cover in class

Answer 36

1. Cardioactive
2. Antibiotics
3. Anti-epileptic
4. Psychoactive
5. Immunosuppressive
6. Anti-neoplastics
7. Bronchodilators