Pharmacokinetics - Development of The Dosage Regimen

What is drug onset and what pharmacokinetic factors is it influenced by?

When the medication begins to exert it's therapeutic effects, impacted by drug absorption and distribution

What is drug intensity and what pharmacokinetic factors is it influenced by?

How "big" the drug's effect will be, impacted by drug absorption and distribution

What is drug duration and what pharmacokinetic factors is it influenced by?

How long the drugs effect will last, impacted by drug metabolism and elimination

What is the drug dosing interval and what pharmacokinetic factors is it influenced by?

How often a drug needs to be administered (once a day, BID, TID, etc.), impacted by drug metabolism and elimination

What is bioavailability?

The amount of an administered drug dose that reaches the plasma in an active form (not bound in plasma proteins)

What 4 factors impact the bioavailability of a drug?

Impacted by

1. First pass hepatic metabolism

2. Drug formulation + incomplete absorption

3. Plasma protein binding

4. Route of administration (oral, IV, etc.)

Why will the oral route always yield a bioavailability of less than 100%?

Drugs that are administered orally will always be impacted by the first-pass effect (first hepatic metabolism)

What is the volume of distribution of a drug?

The ratio of the amount of drug in the body to the concentration of drug in the plasma.

In other words, the amount of drug inside of the blood compared to the amount of drug outside of the blood (in the body's tissues)

What does a higher volume of distribution signify?

More drugs is spread throughout the body compared to being in the plasma

What does a longer volume of distribution signify?

More drugs is inside of the plasma compared to being spread throughout the body

Would a fat-soluble drug have a higher or lower volume of distribution?

Higher volume of distribution

What is the therapeutic concentration range of a drug?

The concentration range that a drug must fall within to exert it's therapeutic effects on the body (to do its thing)

What would occur if a drug is given in a dose that is below the therapeutic range of the drug?

The drug would be expected to produce little effect (the drug would not do its thing)

What would occur if a drug is given in a dose that is above the therapeutic range of the drug?

The drug would expected to cause adverse effects (an overdose)

What would occur if a drug is given within the therapeutic range of the drug?

The drug would be expected to produce a therapeutic response :)

What is a loading dose of a drug?

A larger initial dose that is given to quickly achieve a high therapeutic plasma concentration of a drug instantly. Especially used for treating acute conditions, since you want the effects to occur asap

Given that Wd = D0 X Vd, what would be the changes to a loading dose if a drug had a higher volume of distribution in a patient?

Loading dose would need to be increased

Given that Wd = D0 X Vd, what would be the changes to a loading dose if the drug had a higher therapeutic range?

Loading dose would need to be increased

Given that Wd = D0 X Vd, what would be the changes to a loading dose if a drug had a lower volume of distribution in a patient?

Loading dose would need to be decreased

Given that Wd = D0 X Vd, what would be the changes to a loading dose if the drug had a lower therapeutic range?

Loading dose would need to be decreased

How would a larger bioavailability affect the loading dose?

Loading dose would need to be decreased

How would a smaller bioavailability affect the loading dose?

Loading dose would need to be increased

What does a shorter half life of a drug signify?

The drug is metabolized and excreted more quickly, and will fall out of the therapeutic range more quickly as well

What does a longer half life of a drug signify?

The drug is metabolized and excreted more slowly, and will fall out of the therapeutic range more slowly as well

What is the plateau principle?

Once the dose of a drug is started, stopped, or changed, it will take approximately 4 half-lives before the drug will reach a steady state.

Therefore, a therapeutic effect of a drug may only be consistent until 4 half-lives have passed

How many half lives will it take for therapeutic effects to be observed once a drug dosage is initiated?

~approximately 4 half lives -> plateau principle

How many half lives will it take for a drug to be considered functionally eliminated?

~approximately 4 half lives -> plateau principle

What 3 factors influence a prescribed dosing interval (refer to dosing interval equation)?

1. The lower limit of the therapeutic range of a drug

2. The upper limit of the therapeutic range of a drug

3. The half life of the drug (elimination rate constant)

Given the dosing interval equation, what would be the changes to the dosing interval if the drug had a longer half life?

The drug would have a longer dosing interval

Given the dosing interval equation, what would be the changes to the dosing interval if the drug had a shorter half life?

The drug would have a shorter dosing interval

What does clearance rate measure?

The volume of plasma completely cleared of a drug per unit of time.

What 2 factors influence the clearance rate of a drug (refer to clearance rate equation)?

1. Half life of drug

2. Volume of distribution (apparent volume of distribution + weight of pt)

Given that C= k * Vd, what would occur to clearance rate if the drug had a larger volume of distribution in a patient?

Clearance rate would increase

Given that C= k * Vd, what would occur to clearance rate if the drug had a smaller volume of distribution in a patient?

Clearance rate would decrease

Given that C= k * Vd, what would occur to clearance rate if the drug had a longer half life?

Clearance rate would decrease

Given that C= k * Vd, what would occur to clearance rate if the drug had a shorter half life?

Clearance rate would increase

What is a maintenance dose?

Drug dose that is required to maintain plasma concentration of a drug within a certain therapeutic range

What 3 factors influence the maintenance dose of a drug (refer to maintenance dose equation)?

1. Middle of therapeutic range of drug

2. Dosing interval

3. Clearance rate of drug

Given the following:

Wd=Dpl T C -Maintenance dose

C = k * Vd - Clearance

What adjusts would need to be made to the maintenance dose if the patient had a higher clearance?

Maintenance dose would increase

Given the following:

Wd=Dpl T C -Maintenance dose

C = k * Vd - Clearance

What adjusts would need to be made to the maintenance dose if the patient had a lower clearance?

Maintenance dose would decrease

Given the following:

Wd=Dpl T C -Maintenance dose

C = k * Vd - Clearance

What adjusts would need to be made to the maintenance dose if the medication had a longer dosing interval?

Maintenance dose would increase

Given the following:

Wd=Dpl T C -Maintenance dose

C = k * Vd - Clearance

What adjusts would need to be made to the maintenance dose if the medication had a shorter dosing interval?

Maintenance dose would decrease

Given the following:

Wd=Dpl T C -Maintenance dose

C = k * Vd - Clearance

What adjusts would need to be made to the maintenance dose if the medication had a higher volume of distribution in a patient?

Maintenance dose would increase

Given the following:

Wd=Dpl T C -Maintenance dose

C = k * Vd - Clearance

What adjusts would need to be made to the maintenance dose if the medication had a lower volume of distribution in a patient

Maintenance dose would decrease