lecture 2 LOs Flashcards
principles of different kinetics of drug clearance and different phases of drug metabolism
drugs are eliminated through bio-transformation (cytochrome P450), metabolites are excreted
first order kinetics: drug clearance is usually exponential (only a small fraction of clearance sites are occupied, so it is concentration dependent)
zero order kinetics: some drugs are eliminated at a constant rate regardless of concentration (occurs when supersaturation is present, aka when there are more molecules around than there are clearance sites)
phase 1: modification by oxidation, reduction, or hydrolysis (non synthetic). converts the molecule into less lipid soluble or less active forms for easy extraction. sometimes can convert into another active form
phase 2: conjugation (synthetic). attaching drugs to other small molecules. ionizes them and makes the inactive, some drugs are inactivated by phase 1 or 2, others need multiple phase 1 or 2 processes to inactivate.
define drug affinity
amount of attraction between ligan and receptor
higher affinity means more sticky to the receptor
affinity is not related to how well a ligand may activate a NT receptor
define efficacy
how well the ligand initiates a biological action upon binding to receptor
agonists: high efficacy and high affinity
antagonists: low efficacy and high affinity
define potency
absolute amount of ligand necessary to produce a specific effect, typically measured by the dose needed to produce 50% of maximal response (ED50)
define ligand/receptor reactions
ligand: molecule that binds to a receptor with some selectivity
receptor: all drugs bind to a receptor (proteins that are on/in a cell) that affects cell function/metabolism
define dose/response functions and their key points
describe the extent of effect produced by a given drug concentration
threshold dose: smallest dose that produces a measurable effect
maximum response: assumes all receptors are occupied
biphasic effect: lower dose has one effect, higher has no effect or opposite effect
temporary/probabilistic binding, regulation of receptors, selectivity
binding can be temporary or probabilistic
temporary: after the ligand separates the receptor is free to bind again
probabilistic: the likelihood of the ligand binding to receptor is influenced by multiple factors (increased dose means better chance of binding, higher affinity ligand is more likely to bind to receptor at lower dose)
upregulation of receptor: increase in number/sensitivity of receptors in response o absence of ligands
down regulation of receptor: reduced number of receptors or their sensitivity after chronic activation
selectivity: degree to which a drug binds to a particular receptor compared to other receptors
know how repeated drug exposure can lead to different types of tolerance
drug tolerance: diminished response to a drug after repeated exposure
cross tolerance: tolerance of one drug can diminish effectiveness of another drug
reversible when drug use stops
dependent on dose and frequency of drug use as well as drug taking environment
may occur rapidly, or after long periods of chronic use, or never
several different mechanisms can explain tolerance
metabolic (drug-dispositional) tolerance: repeated drug use that reduces the amount of drug available at the target tissue
functional (pharmacodynamic) tolerance: changes in cell function compensate for repeated drug exposure
behavioural tolerance: pavlovian conditioning can impact tolerance (brain makes associations between the drug effects and the context in which they occurred)
conditioned tolerance: tolerance is maximal when drug is given in environments similar to those where drug effects were previously experienced
understand the actions of different types of agonists (receptor agonist, partial agonist, inverse agonist, indirect agonist)
receptor agonists: best chemical fit and high efficacy, readily attaches to receptor and produces biological effect
partial agonists: bind to receptor and activate it, but less potent have intermediate efficacy (and prevents endogenous ligand from binding/activating receptor)
inverse agonists: initiate action opposite to that produced by agonists (ultimate effect is similar to antagonists but pharmacological action is different
indirect agonists: drugs can also act like agonists even though they may not interact directly with particular receptor (increase NT synthesis/release, increase binding of NT to receptor)
understand the actions of different types of antagonists
competitive antagonists: fit receptors but produce no cellular effect (low efficacy). ability to block effect of agonist depends on relative concentration/affinity of the 2 drugs (shift the dose response curve)
non-competitive antagonists: reduce agonist effect by binding to the receptor at a site other than the agonists binding site, interfering with cell processes initiated by the agonist, disturbing cell membrane supporting the receptor (change shape of dose response curve)
