Pharmacokinetics and Pharmacodynamics - Lecture 1

Toxicology

What is pharmacodynamics?

The therapeutic and/or toxic actions of the drug on the body

What is pharmacokinetics?

The effects of the body on the drug

What is pharmacogenetics?

The effect of how genetics shape metabolism of the drug

Why is pharmacokinetics useful?

Can predict drug effectiveness/toxicity

What are the 5 pharmacokinetic properties? (LADME)

Liberation

Absorption

Distribution

Metabolism

Excretion

Which two properties of LADME are involved in clearance?

Metabolism and Excretion

What is Liberation?

When the drug is released from their solid form to a soluble form

What are the 4 properties the rate of drug liberation depend on?

Formulation

Amount

Drug solubility

Environment pH

How can formulation of a drug affect liberation?

Outside layers can dissolve faster, difference in concentration, liquid version acts faster

What are the four factors that influence absorption?

Gastrointestinal factors

Physicochemical drug properties

Transporters

Route of adminstration

How does the gastrointestinal tract affect absorption?

Food can delay contact of drug, pH will affect charge, microflora can affect drug

What does Area Under the Curve (AUC) mean?

The best indicator of total exposure to a drug dosage

What is bioavailability?

The amount of drug dose that actually reaches the circulation

What can be used to estimate bioavalibility?

Ratio of AUC(route)/AUC(intravenous)

What is First Pass Metabolism?

When the drug gets metabolized by the liver and intestines before reaching circulation

Does First Pass Metabolism reduce bioavailability?

Yes since there is less drug reaching circulation

What is Bioavailability (F) Factor?

The fraction of active dose that makes it to circulation?

What is Chemical Form (S) Factor?

The fraction of the drug formulation in the active form

If F = 1 or F < 1, what do those values mean?

F=1 means complete absorption intravenously

F<1 means incomplete absorption through extravascular methods

What is Effective Dose?

The dose that reaches circulation

Effective dose = S x F x dose admin (mg)

What is Distribution?

Delivery of the drug via circulation to the fluids and tissue in body

Seen as a decreased in serum concentration graph

What do hydrophilic drugs follow?

The water

What do hydrophobic drugs folow?

The fat

What is Volume of Distribution (Vd) L/Kg

The amount required to contain total amount of drug in the body at the same concentration found in plasma

What is the formula for Vd?

Vd = total dose (mg) / [drug conc. (mg/L) x weight (kg]

What does a high Vd mean?

Most of the drug has distributed into the tissue (low conc. in plasma)

What does a low Vd mean?

Most of the drug has stayed in the plasma (high conc.)

What happens to Vd if the drug is more water soluble?

Vd would decrease as more would be present in the plasma

What happens to Vd if Plasma Protein Binding (albumin) is decreased?

Vd would increase since there is less albumin in the plasma for drug to bind to and it enters the tissue

Which form on the drug is active and can interact with receptors?

Free unbound drug

What is the loading dose?

The first dose given that has therapeutic affects

How can Vd be used to calculation loading dose?

LD = [Vd x Weight x Conc. plasma] / [S x F]