module 7 Flashcards
what is the definition of pharmicodynamics
-study of what the drug does to the body
-study the biochemical and physiological effects of drug and physiological effects of drugs and the mechanisms by which drugs produce effects
what is a dose-response curve
-monotonic (meaning response increases as dose increases)
-NOT linear (semi logarithmic)
what occurs during phase 1 of the semi-logarithmic dose-response curve?
doses are too low to elicit a clinically relevant response
what occurs during phase 2 of the semi-logarithmic dose-response curve?
the response is graded and nearly linear
what occurs during phase 3 of the semi-logarithmic dose-response curve?
-larger doses do not lead to greater response
-larger doses may cause toxicity
what is efficacy?
is the measure of how effective a drug is at a given dose
what is maximal efficacy?
-represents the maximal effect that a drug is capable of producing
-maximum height on dose-response curve
do we always choose the drug with the highest efficacy to treat patients?
NO
we choose the drug that are therapeutically effective with the fewest side effects
how do hcp slowly change the efficacy of a drug?
-titrate the dose
-start with low dose and slowly increase while monitoring pt response
what is potentcy?
the amount of drug required to elicit a pharmacological response
what is the relationship between therapeutic effectiveness and potency
high potency does NOT mean it is more therapeutically effective
how is potency compared between drugs?
- to compare - drugs must produce the same therapeutic effect
-determined by comparing the dose required to produce half-maximal response (ED50)
is a higher or lower ED50 said to be more potent
lower
FILL IN THE BLANK:
a more potent drug will require a _____ dose to achieve to achieve the desired effect than a less potent drug
smaller
how do drugs produce effects?
most drugs act on cellular macromolecules
receptors, enzymes
involves binding of the drug to the macromolecule target - the complex is then able to produce a biological effect
what are drug targets?
-receptors
-ion channels
-transport proteins
do drugs act on all cellular targets?
NO
most drugs do act on cellular targets but some don’t
example:
antiacid neutralizes stomach acid & this does NOT bind to any cellular target
what is a drug receptor?
-is a protein that a drug binds to and produces a measurable response
-majority of receptors are able to translate extracellular signals into a biological response
4 most important types of receptors
- ligand gated ion channel
- g protein coupled receptors
- enzyme linked receptors
- intracellular receptors
what are some characteristics of ligand-gated ion channels?
-ligands (drugs or endogenous molecules) control the opening and closing of ion channels
-many neurotransmitters bind to these receptors
what is a GABA receptor?
-important ligand-gated ion channel
-when GABA binds to the GABA receptor, it causes opening of channel and Cl flows into cell
-benzos bind to GABA and allow Cl to enter the cell
-activation of the GABA receptor causes sedation and muscle relaxation mediated by increased intracellular chloride
-responses to activation of these receptors are VERY rapid, occurring in milliseconds
what percent of marketed drugs mediate their effects through actions on G Protein Coupled Receptors?
50%
what are the three components of GPCRs
- a seven-transmembrane spanning protein receptor
- an effector molecule (an enzyme)
- a G-protein which has 3 subunits
how do G protein-coupled receptors work?
-binding of ligand to GPCR causes activation of G protein
- the g protein then dissociates from the receptor and activates the effector
-activation of GPCR results in a response that lasts from seconds to minutes in duration
what endogenous neurotransmitters use the GPCR?
norepinephrine, serotonin, and histamine mediate their effects by binding to GPCRs
how do enzyme-linked receptors
-enzyme-linked receptors span the cell membrane with the ligand binding domain on the outside of the cell and the enzyme catalytic site on the inside
-binding of a ligand on the outside of the cell activates the enzymes on the inside of the cell
-responses to activation of enzyme-linked receptors occur very rapidly (seconds)
what is an example of enzyme-linked receptors
-insulin receptor
-binding of insulin to the insulin receptor causes
enzymes mediated phosphorylation and activation of
an intracellular effector
-phosphorylated effector causes an increased translocation of glucose transporters to the cell membrane
-net effect of insulin binding to its receptor is increased cellular glucose uptake and utilization
how do intracellular receptors work?
-receptors reside completely inside the cell and are also called transcript factors
-to access these receptors, ligands must be able to cross the cell membrane either by diffusion or drug transport protein
-binding of ligand to the receptor causes translocation of the complex to the nucleus and binding to DNA
-when ligand/receptor complex binds to DNA, transcription of messenger RNA is stimulated
-protein synthesis occurs hours or days later
-ligands to these receptors are typically highly lipid soluble (testosterone & estrogen)
what is drug receptor selectivity?
-drugs that are selective will bind to only one type of receptor
-therefore will be less likely to produce side effects (still can have side effects - target therapy may be in the brain but the receptor may be located in the brain and the intestine, therefore side effects may occur in the intestine)
-AKA lock and key (lock is the receptor and the key is the drug, if it right shape and size, it can the lock)
