What does TMD stand for?

Therapeutic Drug Monitoring

What are the criteria for TDM?

1. Drug has to have a narrow therapeutic range

2. Drug has to have wide variability between patients

3. The drug's variability has to exceed the therapeutic range

4. There has to be a linear concentration to effect

(1st Order)

SDCs need to correlate with pharmalogical effect

Increasing the drug concentration leads to a larger response (more efficacy or more toxicity)

What is meant by 1st order elimination of a drug? 

The rate of elimination in a 1st order drug is proportional? and dependent on the amount of the drug given

What is meant by zero order elimination of a drug?

The rate of elimination of a zero order drug is independent of the amount of the drug in the system 

How many doses does it take for a drug to reach steady-state?

About 5 cycles of peak and trough

What is meant by peak?

Peak is the maximum plasma/serum? concentration that a drug will reach

What is meant by trough?

A trough is where the drug has been eliminated from the body to a point where another dose is needed

What are three drugs that require TDM?

Antibiotics : vancomycin, dioxyn

Anticoagulants: warfarin

Phenytoin Drug Levels ...

Show variability

Pharmatokinetics (a subdivision of pharmacology) is concerned with...

1. The absorption, distribution, and elimination of drugs

2. Seeking to mathematically describe and predict the time-course of drugs in the body

(describe what the body does to a drug)

What three things happen to a drug once it enters a body?

1. Absorption

2. Distribution

3. Elimination

What happens to a tablet as it passes through absorption?

1. The tablet disintegrates

2. Dissolves into solution

3. Diffuses through the intestinal membrane

4. Enters the portal vein of the liver

5. The tablet enters hepatic metabolism "1st pass effect"

6. Tablet enters systemic circulation

What happens to a drug as it is distributed?

The drug moves from the vasculature into body tissues and other fluids

What does V (or Vd) measure?

The volume of distribution measures the extent of drug tissue distribution

In aminoglycoside antibiotics Vd is...

Small as the drug is concentrated intravascularly

In a tricyclic antidepressant Vd is...

Large as it is concentrated in tissues

In first order elimination...

1. Elimination patterns apply to _____

2. The rate of elimination is ____________

3. There is a ______ between dose and concentration

1. Most medications

2. Proportional to concentration

3. Linear relationship

What are the six parameters of pharmacokinetic terminology?

1. Peak

2. Trough

3. Half-life

4. Steady-State

5. Clearance

6. Volume of distribution

What is the peak?

How is it useful?

The maximum drug concentraion in the plasma

It reflects dose size

What is the trough?

How is it useful?

Lowest concentration in plasma

Reflects drug clearance

What is the half-life?

How is it useful?

The time period for drug concentrations to fall by 50%

Determines the time to steady-state

What is steady-state?

How is it useful?

Rate of drug administration equals the rate of drug elimination

Serum concentrations should be drawn at steady-state

What is clearance?

How is it useful?

Reflects the capacity of the organ to metabolize or excrete a drug

Determines the frequency of drug administration

What is the volume of distribution?

How is it useful?

Measures the extent of drug tissue distribution

Determines the size of the dose

if gentamicin 80 mg is given by 30 minute infusion every 8 hours, what two stages does it go through?

Accumulation

Steady-State

Name four antimicrobials

Vancomycin

-and- 

Aminoglycosides are:

Gentamicin

Tobramycin

Amikacin

Name four anti-epileptic drugs

Phenytoin (Dilantin)

Phenobarbital

Valproic Acid

Carbamazepine

Describe the pharmacokinetics of Phenytoin (Dilantin)

Zero order elimination via hepatic metabolism

What is the elimination mechanism for phenobarbital?

Hepatic 

Renal (20-40%?)

What is the elimination mechanism for Valproic acid?

Hepatic

What is the elimination mechanism for carbamazepine?

Hepatic

What are the adverse effects of phenobarbital?

Sedation

What are the adverse effects of valproic acid?

GI, weight gain

What are the adverse effects of carbamazepine?

GI, sedation, leukopenia

What is the best sampling time for phenobarbital?

Trough

What is the best sampling time for valproic acid?

Morning

-and-

Trough

What is the best sampling time for carbamazepine?

Trough

What are some unique properties for phenobarbital?

None listed

What are some unique properties for valproic acid?

Diurnal variation in concentrations

What are some unique properties for carbamazepine?

Induces its own metabolism

Name four tricyclic anti-depressants

Their mode of elimination, adverse effects and best sampling time

1. Amitriptyline

2. Imipramine

3. Desipramine

4. Nortriptyline

Elimination : Hepatic

Adverse Effects: Dry mouth, Weight gain

Sampling time: Trough 

What is the active metabolite of amitriptyline?

Nortriptyline

What is the active metabolite for imipramine?

Desipramine

What is a unique property of Nortriptyline

The theraputic window has a linear curve???

Name a cardiac glycoside

Digoxin

What does digoxin treat?

Atrial arrhythmias and congestive heart failure

Name two anti-coagulants

Warfarin and Heparin

Name a respiratory drug

Theophylline

What does theophylline do?

It is a bronchial smooth muscle relaxant that treats asthma and other respiratory diseases

(Its use has decreased over the past 20 years)