2.B Flashcards
What is pharmacology?
the study of substances interacting with living systems through chemical processes
study of what drugs are, what drugs do, and how drugs work
What is pharmacotherapeutics?
study of the therapeutic uses and effects of drugs to relieve suffering or prevent disease
What is pharmacognosy?
study of medicine from natural sources
What is pharmacy?
the study of drug preparation, formulations, and patient counselling
What is toxicology?
the study of toxins
If ibuprofen and acetaminophen have the same purpose and same site of action, why do they have different dosage regimens?
PK!!!
they are absorbed, distributed, metabolized, and excreted differently
What is a logical explanation as to why THC gets you high but CBD doesnt?
they bind to different receptors
What are fundamental principles of drug action?
- there is an effective concentration at the site of action as explained by PHARMACOKINETICS
- there is a relationship between drug concentration and response from patients as explained by PHARMACODYNAMICS
- the binding of the drug to the receptor as explained by PHARMACOLOGY
What is a drug?
a chemical that interacts with macromolecules in the body to affect physiological function
they are promiscuous=bind to more than one receptor
What is a ligand?
anything that binds to a receptor
What are some examples of endogenous sources of drugs?
hormones
neurotransmitters
What are some examples of exogenous sources of drugs?
plants (phytochemicals)
marine life
micro-organisms
fungi
True or false: most of the drugs we prescribe are made from biological processes
false
most drugs synthetic
What is a receptor? What happens when a drug binds to a receptor?
the macromolecule to which a drug must bind to exert an effect
upon binding
the drug changes the receptor=biological function
What are some examples of receptors?
ligand-gated ion channel
G-protein coupled receptors
enzyme-linked receptors
intracellular receptors
Describe the characteristics of receptors.
they determine quantitative relationship between dose/concentration and effect
responsible for drug selectivity and mediate drug action
they are promiscuous (bind to more than one ligand)
What is an inert binding site? Example?
molecules to which drug bind but the binding does not cause any changes in the biological system
ex: albumin
Differentiate between agonist, partial agonist, and antagonist.
agonist: drugs that occupy receptors and activate them at full strength
partial agonist: drugs that occupy receptors and activate them but less than the full amount
antagonist: drugs that occupy receptors and do not activate them
Explain some characteristics of drug-receptor interaction.
drug and receptor must be close enough to interact
there is equilibrium in the biophase
the rate of K12 and K21 tells us the affinity
D-R interaction obeys the Law of Mass Action
What is signal transduction?
D-R binding can cause a cellular signal across a cell membrane that produces second messengers which contribute to the response
it allows for drug activity!
What are the four types of interactions?
covalent bond: drug and receptor share an electron pair
ionic bond: electrostatic forces between two ions of opposite chg
hydrogen bond: between a hydrogen atom linked to O/N and an electronegative atom
hydrophobic interactions: between non-polar functional groups
Which interaction is the strongest? Which is the weakest?
strongest=covalent bonds
weakest=hydrophobic interactions
Which interaction is irreversible? How do you terminate this effect?
covalent bonds
destroy the receptor, function recovers upon new receptor synthesis
Which interaction is most common and is the basis to many drug-receptor interactions?
hydrogen bonds
True or false: hydrophobic interactions are responsible for D-R interactions
false
they contribute but they are not responsible
What is the pharmacophore? Give an example.
the critical portion of the drug that participates in receptor binding and is therefore associated with pharmacological effect
ex: beta lactam ring in penicillins
Which macromolecule are receptors composed of? How are they divided?
most receptors are proteins
receptors: sensing elements of bodily systems
ion channels: allow the passage of specific ions (ligand-gated or voltage gated)
enzymes: drug can be a substrate or changes the enzymes activity
transporters: drugs interfere with the movement of other molecules
Describe ligand-gated ion channels.
found on cell membranes
channel opens upon binding of a ligand to the let the ion flow through
fastest channels
Describe G-protein coupled receptors.
found on plasma membrane
amplify signal transduction (one ligand can produce a significant response)
duration of activity depends on longevity of GTP binding
Describe kinase linked receptors.
cause changes in gene expression
the ligand binds and starts phosphorylation which changes gene transcription
3 groups: receptor tyrosine kinase, receptor serine-threonine kinases, cytokine kinases
Describe nuclear receptors.
ligand-gated transcription factors
changes gene transcription rates
drug must interact in nucleus or cytoplasm
lots of patient variability
take a long time to show a clinical response
What does the Law of Mass Action describe and state?
describes: the equilibrium between the concentration of reactants (D and R) and the concentration of drug-receptor complex
states: the rate of change of the reactant concentration is directly proportional to the concentrations of the reactants in both directions
-rate at which individual components associate depends on the drug and receptor concentrations individually
-rate at which complex dissociates depends on the concentration of the complex
Differentiate between K12 and K21.
K12: the rate at which individual components associate to make the DR complex
K21: the rate at which the DR complex dissociates to individual components
What is the main idea to grasp from the Law of Mass Action?
D binds reversibly to R at a rate proportional to the D and R concentrations, and the DR complex dissociates at a rate proportional to the DR complex concentration
Differentiate between Kd and Ka. Which is more useful and why?
Kd: how frequently dissociation occurs, dissociation constant
Ka: how frequently association occurs, association constant
Kd is more useful because it tells us about the strength of the reaction
What is affinity?
the ability of a drug to interact with a receptor
Will Kd be small or large for a high affinity? What about a low affinity?
high affinity: small Kd
low affinity: large Kd
If a drug has a high affinity for receptor, do we need we a high or low concentration of drug to produce a response?
lower concentration
higher the affinity, the lower the concentration needed to occupy receptor
If a drug has low affinity for receptor, do we need high or low concentration of drug to produce a response?
high concentration
the lower the affinity, the higher the concentration needed to occupy receptor
What is capacity? What is Rt?
the total number of receptors a drug can bind to
Rt=total concentration of receptors in the body that x drug can bind to, it is an index of capacity
What is the equation for Rt?
Rt=[R]+[D-R]
Describe Occupancy Theory.
it states that we have a finite number of receptors in the body and the response we get depends on how many receptors are occupied
magnitude of response is proportional to the number of receptors occupied at a particular time
What is the equation for [DR]?
[DR]=[Rt][D]/[D]+[Kd}
What is the general mathematical model describing all drug-receptor interactions?
Y=aX/(b+X)
non-linear (at some point you do not get a proportional increase in rate)
What defines the shape of the dose-response curve?
affinity and capacity
True or false: stimulating a receptor results in a new function
false
you either turn a receptor on or off
What can influence the functional capacity of receptors?
selectivity and specificity
occupancy theory
efficacy (instrinsic activity)
desensitization and tolerance
Differentiate between specificity and selectivity.
specificity: the ability of a drug to produce an action at a specific site, refers to relative potency of a drug between the receptors of two or more different endogenous binding sites
selectivity: relative potency of a drug for the receptor subtypes of the same endogenous site
What is intrinsic activity?
ability of a drug to elicit a response when it binds to the receptor
In terms of the 0-1 scale, what is the intrinsic activity of an agonist, partial agonist, and antagonist?
agonist=1
partial agonist=<1
antagonist=0
What is efficacy dependent on?
drug-receptor coupling
drug concentration
True or false: two different drugs can have the same level of affinity but different levels of efficacy and vice versa
true
What is competitive reversible antagonism?
one drug antagonizes the action of a second drug by competing for the same receptor site
drug with the highest affinity wins
How do we overcome competitive reversible antagonism?
increasing drug concentration
What is non-competitive reversible antagonism?
one drug antagonizes the action of another by binding to a different receptor site in a way that prevents the agonist action of the other
second drug is changing the intrinsic activity of the original drug
What is irreversible antagonism?
binds with receptor permanently
potential to change affinity and efficacy of the opposing drug
What is chemical antagonism?
one drug antagonizes the action of a second drug by binding to and inactivating the second drug
What is pharmacokinetic antagonism?
one drug antagonizes the action of another drug by reducing the concentration of drug at the site of action
affects ADME
What is physiological/functional antagonism?
one drug antagonizes the action of another drug by producing a response that opposes the other using DIFFERENT receptors
Differentiate between desensitization and tolerance.
desensitization: diminished effect occurs in minutes
tolerance: diminished effect occurs gradually
