Lecture 03 - Pharmacokinetics and Pharmacodynamics Flashcards
What can drug metabolites do
contribute significantly to therapeutic affects or adverse side effects
What are xenobiotics
organic compound that are foreign to the body
What are most pharmacologically active molecules
lipophilic and remain non-ionized or only partially ionized at physiological pH
What is drug metabolism
the means of converting these molecules into substances that are more easily excreted
What is biotransformation
the enzymatic transformation of molecules by functionalization reactions and/or conjugation reactions into molecules that are polar and water soluble
What are phase I reactions
introduction, exposure or modification of a specific chemical groups via oxidation-reduction reactions
What are phase II reactions
conjugation of small endogenous molecules
What do water soluble compounds of Phase I reactions require
conjugation
What do we need to dissolve xenobiotics in urine for efficient elimination
increased hydrophilicity
How can metabolism backfire
metabolites might be toxic
What is an example of a drug with toxic metabolites
Acetaminophen and its metabolite NAPQI
What does NAPQI do
destroys liver cells
What is used to conjugate NAPQI
glutathione
Where are the major enzymes for biotransformation
cytosolic or are anchored in the membrane of the endoplasmic reticulum
What is the main enzyme system for oxidation
cytochrome P450 (CYP)
What are the properties of benzodiazepines
anxiolytic, sedative, and anticonvulsant
How do secondary and tertiary amine tricyclics differ
their ability to block muscarinic, histaminergic and alpha-adrenergic receptors
Why is it important to monitor tricyclic antidepressants
their hydroxy metabolites cause cardiotoxicity
How do tertiary amines become secondary amines
demethylation
What do the metabolites of SSRIs do
selectively inhibit the reuptake of serotonin (same effect as precursor)
What are the CYP enzymes
heme-containing proteins that play a role in metabolizing
How many known drugs/xenobiotics do the CYP enzymes metabolize
over 400
What do we look for to indicate a redox reaction
Gain or lose elections, gain or lose oxygen, conversion between hydroxides aldehydes and carboxylic acids, movement of H+ between thiol functional groups, changes of the number of oxygens bound to a carbon atom
What are the components of the CYP enzyme system
hemoprotein, flavoprotein, heat stable lipid component
