1. TDM Therapeutic Drug Monitoring
Goal of TDM is to use appropriate concentrations of difficult to manage medications to optimize clinical outcomes in patients in various clinical situations

2. TDM
Clinical practice of measuring specific drugs at designated intervals to maintain a constant concentration in a patient’s blood stream
Used for Drugs that have narrow therapeutic ranges, marked pharmacokinetic variability and have adverse effects.

3. Pharmacokinetics Relationship between drug dose and blood drug level
Mathematical formula that takes into consideration the
Absorption
Distribution
Metabolism
Excretion

4. Absorption
Route of Drug administration such as Enteral (by mouth), Parenteral (by Injection), or Pulmonary, Rectal or Topical.
First-Pass Effect Drugs given by mouth must first go to the stomach and then intestine. They then go to the LIVER where metabolism or biliary excretion may occur before going to the general circulation.

5. Absorption Rate at which a drug leaves its site of absorption
Rate is affected by area of absorbing capillary membranes and solubility in interstitial fluid pH
Physical Factors such as Blood Flow or total surface area available

6. Distribution
Blood Flow Drugs first go to the well perfused organs such as liver, kidney and brain and then to muscles, skin, fat and viscera
Capillary permeability
Tissue Volume
Binding of drugs to Proteins
Note We typically measure total drug present but what counts is the total unbound drug. Patients with low Albumin levels will have more unbound drug available
Unbound = Free= Pharmacological Effect

7. Metabolism Biotransformation
Biotransformation reactions generate more polar inactive metabolites which are readily excreted from the body and usually involve enzymes
Liver is a major site of drug biotransformation
Cytochrome P450 major enzyme system involved

8. Excretion
Once drugs are in water soluble form they are excreted by KIDNEYS in URINE
Also excreted in feces, bile, and Breast milk

9. Elimination Half Life
The time it takes for an amount of drug in blood to decline to one-half its measured value
The following conditions may increase half life of a drug
Decreased renal blood flow (heart disease, shock)
Addition of second drug which displaces it from its carrier protein
Decreased metabolism (hepatic insufficiency)

10. Steady State
In pharmacokinetics, steady state refers to the situation where the overall intake of a drug is fairly in dynamic equilibrium with its elimination. In practice, it is generally considered that steady state is reached when a time of 4 to 7 times the half-life for a drug after regular dosing is started.

11. Steady State

12. Specimen and Collection Tubes
Serum is specimen of choice for most drugs
Plasma is OK for some drugs
Whole Blood may be used for some
example cyclosporin A
Whole blood specimens may require preanalytical treatment which increases turn around time and may introduce error

13. Peak and Trough
Peak levels need to be drawn when the drug is at its highest concentration Will vary by drug
Trough levels are drawn immediately before the next dose and is the lowest concentration
*Documentation of dosage and sample draw times are critical
Antibiotic medication such as aminoglycosides are monitored for trough levels

14. Drug groups Group What they do Examples Comment Antibiotics
Prevent growth of microorganisms
Amikacin, gentamicin, tobramycin, vancomycin
Toxic to Ear and Kidney
Creatinine and BUN
Antiepileptic
Control seizures
Phenobarbitol, Dilantin, Valproic acid, Carbamazepine(Tegretol)
Antihypertensives
Lower blood pressure
Sodium Nitroprusside
Metabolite is thiocyanate which should be regularly monitored

15. Drug groups continued Group Antineoplastic Reduce tumor growth
Methotrexate
Toxic to bone marrow and intestine Rescue drugs administered
Narrow therapeutic range and many side effects
Antipsychotic
Mania and depression in bipolar disorders
Lithium
Make sure collection tube does not contain Lithium
Levels above 1.5 mmol/L are considered toxic
Bronchodilators
Asthma
Theophylline
Cardioactive Drugs
Heart Failure
Digoxin, Procainamide, Quinidine, Lidocaine
Procainamide
Lidocaine also anesthetic
Immunosuppressive
Transplante
Cyclosporine, Tacrolimus

16. Analytic Techniques Earliest methods were RIA and chromatography
EMIT introduced in the 1970’s
Immunoassay is now used on most major automated instruments