Basics Flashcards
Pharmacokinetics
What the body does to the drug. Involves: Absorption Distribution Metabolism Elimination
What the body does to the drug.
Involves:
Absorption
Distribution
Metabolism
Elimination
Pharmacokinetics
Drugs doing their job at the receptor site. They bind to cellular reception sites. Drug-receptor binding is reversible, selective (affinity), and graded.
Mechanism of action
This means Drug-receptor binding is selective.
Affinity
Binds to a receptor site and produces a result
Agonist
Binds the receptor site and blocks an activity
Antagonist
Molecules can move from one side of a barrier to the other without using energy. Move down a concentration gradient from an area of high concentration to low concentration solubility of drug must match absorption site (lipophilic). Has better outcome if drug molecule is non-ionized and in same pH.
Passive diffusion
Requires energy. Protein membranes of the cell can act as carrier membranes. Works if the solubility doesn’t match. But must share molecular similarities.
Active transport
The fraction of the drug that reaches the systemic circulation.
Dependent on solubility, chemical structure, size, polarity, and presystemic biotransformation.
Bioavailability
When taken orally, some of it will pass through the hepatic circulation through the portal vein. Sometimes it is cleared by the liver before it ever reaches the systemic circulation. Have to give a higher PO dose than IV because it has a higher first-pass metabolism.
First pass metabolism
First step in pharmacokinetics. Getting into the body. Dependent on first-pass metabolism, food, surface area, and drug size.
Affected by solubility, chemical structure, polarity, route, site, bioavailability, peak blood flow,
Absorption
The 2nd step in pharmacokinetics. After absorption, it is transported to its site of action. Drugs bind to proteins (usually albumin) in the circulatory system. Highly bound drugs (to protein) are less available for action. Low binding drugs have higher distribution.
Less available protein, more free drug and higher chance for toxicity.
Barriers: blood-brain barrier and placental barrier
Distribution
Lack of enough Albumin. Albumin is the protein that most drugs bind to. If not enough protein, there are fewer binding sites, and there is more free drug, increasing toxicity.
Hypoalbuminemia
3rd step in pharmacokinetics. Drug is where it needs to be now needs to be transformed. This is the process of chemically changing a drug to a different compound called a metabolite. Want to increase water solubility and decrease lipid solubility.
Affected by age, genetics, gender, diet, disease states.
Metabolism/ Biotransformation
Found in the lipophilic ER membranes of the liver. They are involved in the biotransformation of drugs in the metabolism phase.
Enzyme Induction and Enzyme Inhibition
CYP450 enzymes
4th phase of pharmacokinetics. The excretion and their transport outside the body. A drug is removed from tissues and circulation.
Renal excretion most common. Needs to be water-soluble. Removes drug that is unbound and free in plasma. Glomelular in the filtration.
Biliary excretion- transported by liver cells from blood to bile then enter GI tract and excreted through feces.
Elimination
The amount of time over which the drug concentration in the plasma decreases to 1/2 of the original value. Ultimately determines how often a drug is administered. Takes 4-5 half-lives to reach steady state concentrations during continuous dosing of a drug.
Half-Life
Oral route of administration. Non-ionized drugs diffuse passively down a concentration gradient for the higher Concentration (GI tract) to a lower concentration (blood)
Enteral absorption
Most drugs undergo chemical alteration by various bodily systems to create compounds that are more easily excreted from the body. These chemical alterations occur primarily in the liver and are known as biotransformations.
Enzyme induction- some drugs can induce or stimulate production of the enzymes to increase metabolism (decrease amount of drug circulating in the body)
Enzyme inhibition drugs inhibit the production of CYP enzymes and decrease drug metabolism.
CYP450 enzymes- found in lipophilic ER of liver
Factors that affect it: age, genetics, gender, diet, environment, and disease state.
Biotransformation
Mechanism of action
In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targets to which the drug binds, such as an enzyme or receptor.
Drug-receptor binding is reversible, selective (affinity), and graded.
Affinity
A measure of how a drug binds to a receptor. Drug-receptor binding is selective.
Agonist
Binds to a receptor site and produces a result
Antagonist
Binds the receptor site and blocks an activity
Passive diffusion
Molecules can move from one side of a barrier to the other without using energy. Move down a concentration gradient from an area of high concentration to low concentration solubility of drug must match absorption site (lipophilic). Has better outcome if drug molecule is non-ionized and in same pH.
Active transport
Requires energy. Protein membranes of the cell can act as carrier membranes. Works if the solubility doesn’t match. But must share molecular similarities.
Bioavailability
The fraction of the drug that reaches the systemic circulation.
Dependent on solubility, chemical structure, size, polarity, and presystemic biotransformation.
First pass metabolism
How much of a drug is available after the first pass through absorption, usually in the liver.
When taken orally, some of it will pass through the hepatic circulation through the portal vein. Sometimes it is cleared by the liver before it ever reaches the systemic circulation.
Have to give a higher PO dose than IV because it has a higher first-pass metabolism.
Absorption
First step in pharmacokinetics. Getting into the body. Dependent on first-pass metabolism, food, surface area, and drug size.
Affected by solubility, chemical structure, polarity, route, site, bioavailability, peak blood flow,
Distribution
The 2nd step in pharmacokinetics. After absorption, it is transported to its site of action. Drugs bind to proteins (usually albumin) in the circulatory system. Highly bound drugs (to protein) are less available for action. Low binding drugs have higher distribution.
Less available protein, more free drug and higher chance for toxicity.
Barriers: blood-brain barrier and placental barrier
Hypoalbuminemia
Albumin is the protein that most drugs bind to. If not enough protein, there are fewer binding sites, and there is more free drug, increasing toxicity.
Metabolism/ Biotransformation
3rd step in pharmacokinetics. Drug is where it needs to be now needs to be transformed. This is the process of chemically changing a drug to a different compound called a metabolite. Want to increase water solubility and decrease lipid solubility.
Affected by age, genetics, gender, diet, disease states.
CYP450 enzymes
Found in the lipophilic ER membranes of the liver. They are involved in the biotransformation of drugs in the metabolism phase.
Enzyme Induction and Enzyme Inhibition
Elimination
4th phase of pharmacokinetics. The excretion and their transport outside the body. A drug is removed from tissues and circulation.
Renal excretion most common. Needs to be water-soluble. Removes drug that is unbound and free in plasma. Glomelular in the filtration.
Biliary excretion- transported by liver cells from blood to bike then enter GI tract and excreted through feces.
Half-Life
The amount of time over which the drug concentration in the plasma decreases to 1/2 of the original value. Ultimately determines how often a drug is administered. Takes 4-5 half-lives to reach steady state concentrations during continuous dosing of a drug.
Enteral absorption
Oral route of administration. Non-ionized drugs diffuse passively down a concentration gradient for the higher Concentration (GI tract) to a lower concentration (blood)
Biotransformation
Most drugs undergo chemical alteration by various bodily systems to create compounds that are more easily excreted from the body. These chemical alterations occur primarily in the liver and are known as biotransformations.
Enzyme induction- some drugs can induce or stimulate production of the enzymes to increase metabolism (decrease amount of drug circulating in the body)
Enzyme inhibition drugs inhibit the production of CYP enzymes and decrease drug metabolism.
CYP450 enzymes- found in lipophilic ER of liver
Factors that affect it: age, genetics, gender, diet, environment, and disease state.
