Chapter 4: Pharmacokinetics Flashcards
pharmacokinetics is derived from two Greek words:
pharmakon (drug or poison) and kinesis (motion).
Pharmacokinetics
is the study of drug movement throughout the body.
Pharmacokinetics also includes what
Pharmacokinetics also includes what happens to the drug as it makes this journey.
There are four basic pharmacokinetic processes:
- Absorption:
- Distribution:
- Metabolism:
- Excretion:
Absorption:
Absorption is the drug’s movement from its site of administration into the blood.
Distribution:
Distribution is the drug’s movement from the blood to the interstitial space of tissues and from there into cells
Metabolism:
Metabolism (biotransformation) is the enzymatically mediated alteration of drug structure.
Excretion:
Excretion is the movement of drugs and their metabolites out of the body.
Combo of metabolism + excretion=
elimination
The four pharmacokinetic processes, acting in concert, determine:
The four pharmacokinetic processes, acting in concert, determine the concentration of a drug at its sites of action.
Recall that the intensity of the response to a drug is directly related to:
Recall that the intensity of the response to a drug is directly related to the concentration of the drug at its site of action.
To move throughout the body, drugs must
cross membranes.
How do drugs enter the blood from their site of administration?
Drugs must cross membranes to enter the blood from their site of administration.
Once in the blood, how does blood leave?
Once in the blood, drugs must cross membranes to leave the vascular system and reach their sites of action.
Drugs must cross membranes to:
- enter blood from their site of administration
- drugs must cross membrane to leave vascular system and reach their sites of action
- drugs must cross membranes to undergo metabolism and excretion
The three most important ways by which drugs cross cell membranes are:
- Passage through channels or pores,
- Passage with the aid of a transport system, and
- Direct penetration of the membrane itself.
What is the most common way drugs cross membrane?
Of the three, direct penetration of the membrane is most common.
Why do very few drugs cross membranes via channels or pores?
The channels in membranes are extremely small and are specific for certain molecules.
Consequently, only the smallest of compounds (e.g., potassium or sodium) can pass through these channels
Transport Systems:
Transport systems are carriers that can move drugs from one side of the cell membrane to the other.
What determines whether a transporter will carry a particular drug
Whether a transporter will carry a particular drug depends on the drug’s structure.
P-Glycoprotein:PGP
PGP is a transmembrane protein that transports a wide variety of drugs out of cells.
What sites are PGP present?
This transporter is present in cells at many sites, including the liver, kidney, placenta, intestine, and capillaries of the brain.
What does PGP do in the liver?
In the liver, PGP transports drugs into the bile for elimination.
What does PGP do in the kidneys?
In the kidney, it pumps drugs into the urine for excretion.
What does PGP do in the brain capillaries?
In brain capillaries, it pumps drugs into the blood, thereby limiting drug access to the brain.
What does PGP do in the placenta?
In the placenta, it transports drugs back into the maternal blood, thereby reducing fetal drug exposure.
What does PGP do in intestines?
In the intestine, it transports drugs into the intestinal lumen and can thereby reduce drug absorption into the blood.
For most drugs, movement throughout the body is dependent on the ability to penetrate membranes directly. Why?
(1) most drugs are too large to pass through channels or pores, and
(2) most drugs lack transport systems to help them cross all of the membranes that separate them from their sites of action, metabolism, and excretion.
To directly penetrate membranes, drugs must
Membranes are composed primarily of lipids; therefore to directly penetrate membranes, a drug must be lipid soluble (lipophilic).
“like dissolves like”
Certain kinds of molecules cannot penetrate membranes. They are:
-not lipid soluble and therefore cannot penetrate membranes.
-This group consists of polar molecules and ions.
pH partitioning
The process whereby a drug accumulates on the side of a membrane where the pH most favors its ionization is referred to as ion trapping or pH partitioning.
Absorption
is defined as the movement of a drug from its site of administration into the blood.
What determines how soon effects will begin.
The rate of absorption determines how soon effects will begin.
What helps determine how intense effects will be?
The amount of absorption helps determine how intense effects will be.
Factors Affecting Drug Absorption:
- Rate of Dissolution:
- Surface Area
- Blood Flow
- Lipid Solubility
- pH partitioning
Drug Half-Life:
Drug half-life is defined as the time required for the amount of drug in the body to decrease by 50%.
What does half life tell us:
half-life tells us that, no matter what the amount of drug in the body may be, half (50%) will leave during a specified period of time (the half-life).
