Toxicology/Therapeutic Drug Monitoring Flashcards Preview

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Flashcards in Toxicology/Therapeutic Drug Monitoring Deck (87)
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1

Testing Methodology

  • Immunoassay
  • Thin-Layer Chromotography
  • HPLC
  • Gas Chromotography-Mass Spectrophotometry

2

Specimen Collection in Therapeutic Drug Monitoring

Steady State must be reached before monitoring can begin, which takes around 5 1/2 half lives

Usually drawn during a trough state

3

Therapeutic Drug Monitoring Testing Methods

Immunoassays, HPLC and GC (measure parent drug and metabolites)

4

Therapeutic Drug Metabolism

Most metabolized in Liver and excreted in urine, meaning kidney and liver diseases affect drug levels

5

Aminoglycosides

  • Inhibit protein synthesis, treat severe gram-neg bacterial infections
  • Need to be monitored because they can cause kidney and hearing damage
  • Administered via IV/IM due to poor GI absorption
  • Poor tissue distribution

6

Antiarrhythmias/Cardioactive Drugs

  • Digoxin
  • Quinidine
  • Procainamide
  • Disopyramide
  • Lidocaine

7

Digoxin

  • When K+ is low or Mg+ is high, therapeutic levels can be toxic; overdoses can be treated with Digibind (antibody)
  • Cardioactive inotropic for Congestive Heart Failure acts by inhibiting Na/K ATPase pump, decreasing intracellular K and increasing intracellular Ca giving improved Cardiac Contractions
  • Metabolism: Need monitoring because absorption varies
  • Measure Cp 8 hr after dose, due to slow tissue absorption
  • Range: 0.8-20ng/mL 

8

Quinidine

If the patient is already taking digoxin, the levels with this drug will increase

9

Procainamide

  • Antiarrhythmic
  • Block K outflow
  • Major Active Metabolite, NAPA
  • Slow and Fast Acetylators

10

Why do we monitor Drug Concentrations?

  • Patient Compliance
  • Dosage Adjustment
  • Toxicity from Drug interactions
  • Optimize Single Drug Therapy prior to introducing Multi-drug Therapy
  • Confirm steady concentration while other drugs are added

11

Drug Concentration Dynamics depend on:

  • Administration method
  • Metabolic pathways
  • Drug half-life
  • Patient age/health

12

Drug administration routes

  • IV
  • IM
  • Ointments/Topical
  • Orally
  • Buccal
  • Sublingual
  • Subcutaneous
  • Inhaled
  • Transdermal
  • Intrathecal
  • Enteral
  • Parenteral
  • Rectally

13

Buccal

Cheek, mouth

14

Intrathecal

Within spinal cord

15

Enteral

Through intestines

16

Parenteral

Any route other than enteral

17

Absorption

Usually through GI at steady rate

Liquids are absorbed more rapidly

18

Absorption in Circulation

Oscillate between maximum and minimum levels in blood, as the drug is distributed, absorbed, and eliminated.

Dependent on drugs pKa and pH

19

Free vs Bound Drugs

Free drugs interact with target sites and produce a response, and are best monitored by therapeutic and toxic effect

Other drugs or endogenous substances can compete for binding sites

20

Drug Metabolism

Biotransformation of parent drug to metabolite

21

Prodrugs

Parent compounds that must be metabolized to active form

22

Active Metabolites

Formed from parent drug and required measurement of prodrug and metabolite

23

First Pass Metabolism

90% of oral drugs absorbed in GI must go through Liver before entering circulation

24

Drug binding to protein

Most drugs circulate bound to plasma proteins

  • Acidic drugs, bind to albumin
  • Basic drugs, bind to alpha1-acid glycoprotein (AAG)
  • Some can bind to both

Only free drug may interact with target sites and produce a response

25

Drug Metabolism in Body

Primarily in Liver and Kidney

Liver damage will slow metabolization

Kidney damage will excrete drugs more slowly

26

Drug metabolite activity in the body

Usually more water-soluble to be excreted by Kidney

Less active/toxic than parent compounds

27

Drug distribution in body

After travelling in blood, it can stay within bloodstream and enter extravascular fluids or migrate into tissues/organs

Two-compartment distribution may be between

  1. Plasma and Liver
  2. Plasma and Bone
  3. Plasma and Muscle

28

Drug Equilibrium Post-distribution

Plasma and Active metabolites are measured by total drug concen.

Total may differ between central and peripheral areas

Free drugs will have the same concentration whether at action site or another location

29

Elimination

Half-life, time required to reduce blood level by half

Mainly eliminated via:

  • Hepatic: altered to metabolites and make them water-soluble
  • Renal filtration: conjugated drugs excreted in urine or bile

30

Factors affecting drug function

  • Lipemia
  • Low albumin
  • Uremia
  • Other hydrophobic drugs
  • CHF
  • Liver Disease
  • Kidney Disease
  • GI malabsorption
  • Age