Lecture 6

Question 1

What is the main principle of pharmacokinetics?

Answer 1

a relationship exists between the effects of a drug and the concentration of drug in the body

Question 2

What does clinical pharmacokinetics try to provide?

Answer 2

1. a quantitative relationship between drug dose and effect

2. a framework to interpret measurements of drug concentrations in biological fluids to benefit patient drug therapy

Question 3

Where are drug concentrations usually measured?

Answer 3

in the plasma bc it is non-invasive and for most drugs there is a good correlation between plasma concentration and therapeutic and toxic drug effects

Question 4

Do we measure free or total plasma drug concentration?

Answer 4

We measure total plasma drug concentration ( even though free concentration would be ideal)

Question 5

Drug concentration time curve of oral administration

Answer 5

• oral drugs must be absorbed into blood so int he beginning the rate of drug absorption is greater than the rate of drug elimination & plasma drug concentrations increase
• then the rate of absorption equals the rate of elimination and there is a peak (called the cmax)
• after cmax, ROE > ROA so the concentration declines

Question 6

Characteristics of Plasma Concentration Time Curves

Answer 6

• Minimum effect concentration (MEC): minimum concentration required to have a therapeutic effect
• Duration: length of time the drug concentration is above the MEC (how long its effective for)
• Toxic concentration: levels in which if reached, toxicity occurs
• therapeutic range: drug concentrations above the MEC but below toxic concentrations

Question 7

What is the therapeutic range?

Answer 7

• an index for how safely a drug can be used
• narrow range: difficult to administer safely bc of narrow effective window, must undergo therapeutic monitoring
• wide range: generally safe, unlikely to get into toxic concentrations

Question 8

What is the Onset of Action of a drug?

Answer 8

• determines how soon a drugs effect will occur
• time lag varies between drugs (ex. oral drugs have larger time lag before they reach the MEC)
• rate and extent of absorption affect the onset of action

Question 9

What is continuous intravenous infusion and concentration curves?

Answer 9

• rate of drug entry into the body is constant, drug enters directly into systemic circulation without having to be absorbed
• plasma concentration rises until it the ROE = ROinfusion where it doesnt change overtime (called steady state)
• once infusion stops, concentrations rapidly decrease

Question 10

Concentration curve of IV Bolus

Answer 10

• here drug is rapidly injected directly into blood and then quickly distributes and is eliminated over time
• elimination usually follows first order kinetics i.e ROE dependent on drug concentration
• higher the blood conc. the greater the ROE

Question 11

What is repeated dosing?

Answer 11

• when patients receive repeated doses of a drug, accumulation occurs in the body until a steady state is reached
• repeat administrations result in high concentration levels (peaks) and low concentration levels (troughs)
• goal is to get these fluctuating levels at steady state where the peaks are constant at the same level and the troughs are constant at the same level

Question 12

When is therapeutic monitoring performed for repeated dosing of a drug with a narrow therapeutic range?

Answer 12

• taking a trough blood sample and measuring the drug concentration right before the next dosage

Question 13

what are 3 ways to reduce fluctuations in plasma drug concentrations?

Answer 13

• use continuous IV infusion (not usually feasible)
• use depot preparations (release drug at slow and constant rate)
• change the dosing interval (same total daily dose multiple times per day reduces size of peaks and troughs

Question 14

What is clearance (Cl)?

Answer 14

• describes the efficiency of irreversible drug elimination from the body
• is the volume of blood cleared per unit of time (ml/min or L/hr)
• can be discussed by route of elimination of total clearance (sum of all routes)

Question 15

Why is clearance important?

Answer 15

determines the dosage rate required to maintain a certain blood concentration of a drug

Question 16

What is the relationship between blood concentration and clearance?

Answer 16

dosing rate = plasma concentration * clearance

Question 17

What is the Half life of a drug (T1/2)?

Answer 17

• time it takes for the plasma drug concentration to decrease to 50%
• helps determine how long it takes to get to steady state and how long it takes for drug levels to decline
  T1/2= 0.693*Vd/Cl

Question 18

Relationship between clearance/Vd and half life

Answer 18

high clearance = small half life (inversely proportional)

high Vd = high half life (directly proportional)

Question 19

Time to steady state

Answer 19

when the same dose of a drug is administered repeatedly it takes about 5 half lives to get t steady state
- if dose of drug remains constant, the time to reach steady state is independent of the size of the dose (also steady state concentration will be higher for the higher dosed drug)

Question 20

Loading dose

Answer 20

• drugs with long half lives take a long time to reach steady state, so a large loading does may be given to get patients to steady state faster
• small maintenance doses then given to keep plasma drug concentrations at steady state
  loading dose = target drug plasma concentration * Vd

Question 21

Decline from steady state

Answer 21

• drug concentration decline depends on drugs half life and independent of the dose
• takes ~ 5 half lives for 97% of a drug to be eliminated and 9 half lives for every molecule to be gone (important for allergic rxns)