pharmacodynamics Flashcards
what are the three categories that determine the intensity of a drug response?
drug administration, PK, and PD
once the drug reaches the target tissue what processes determine the nature of and intensity of response?
PD
what are the four factors that determine the intensity/effect of drug response
number of receptors, affinity of drug, efficacy of the drug to initiate a response, and concentration of the drug
what is the difference in agonist and antogonist?
agonist has affinity and efficacy
antagonist has affinity but no efficacy
what drug class are antagonists for norepinephrine?
beta blockers
what is an agonist for NE that would increase cardiac output?
epinephrine
what are chiral molecules?
a lock and key fit between receptor and drug. % of medications are chiral. “Fits like a glove”
what are examples of a racemic mixture of chiral molecules
Adderall is the mixture of dextro 50% and levo 50% for ADHD without the strong amphetamine effects. Together they give a more prolonged result than levo given in code. Racemic epi may be used in the ER when stridor is present from croup
T or f, increasing the dose of a drug after all receptors have been saturated will increase the response?
False
a ligand is a substance that _____ to a receptor
binds
a ligand that mimics the effect of a hormone or neurotransmitter and augments its effects is called a _______
agonist
a molecule that exists in form that are mirror images of each other that are not superimposable on each other is called a _____ molecule
chiral
receptors exist in (finite/infinite) numbers on cell surfaces
finite
which occupancy theory says that the maximum effect would occur once all receptors are occupied?
single/simple occupancy theory
what is the single occupancy theory?
that there is a 1:1 relationship between ligands and receptors and that maximum response is obtained only when all of the receptors are occupied
What is the modified occupancy theory?
the response of a drug is not linearly proportional to the number of receptors that are bonded but that drugs with a strong affinity only need a low concentration and drugs with low affinity need high concentrations to initiate a response (movie analogy) if you are not interested in a movie you may need a few friends to convince you to go but if you are highly interested in the movie you would watch it by yourself
what is affinity?
the degree of attraction that a drug has for a receptor site
how does a drugs affinity affect its potency?
drugs with higher affinity are more potent and vice versa
what is Kd?
a value known as the disassociation constant or the dissociation-binding constant. it is the concentration of the drug required to occupy 50 % of the receptors. Equilibrium between bound versus unbound ligand. it is a measure of a drugs affinity.
when drug affinity is high Kd is _____
low
what is efficacy?
the maximum effect the drug can receive
what is potency?
a relative measure that compares doses of 2 drugs required to achieve the same effect
a drug is potent when it has high intrinsic activity at ____ doses
low
what is EC50?
the concentration of drug that produces a response 50% of the maximum response
If the EC50 of drug A is 20, drug B is 200, and drug C i s80 which drug is the most potent?
Drug A because it elicits the same response at a lower dose
what is MEC?
minimum effective concentration of drug to produce an effect
which drug is the most potent, fentanyl, morphine or aspirin?
fentanyl
T or F antagonist has an affinity and but no efficacy at a receptor
T
T or F an agonist has an affinity and efficacy at a receptor
T
maximal response depends on the efficiency of receptor _______
coupling
what is receptor coupling?
a cascade of effects starting at the binding site and leading to the observed biological effect
what is a full agonist?
100 % response. increased rate of signal transduction, efficacy = 1
what drugs are examples of full agonists?
isoproterenol and morphine
what is a partial agonist?
less than 100% response, efficacy between 0 and 1. weak partial agonists are also competitive antagonists
what drug is a example of partial agonists?
busbar
what is a inverse or negative agonist?
efficacy less than 0% (negative response) decreases the rate of signal transduction
what is a reversible agonist?
drug and receptor interaction are temporary, and action ceases when the drug leaves the receptor site
what is a irreversible agonist?
a drug that permanently occupies a receptor (rare)
what is a competitive antagonist?
it competes for the same binding site as an agonist. the agonist could still reach 100% response
how do you overcome a competitive antagonist?
higher doses of drug creating a higher drug concentration of the agonist
what is a example of a competitive antagonist
prazosin is a competitive antagonist with endogenous norepinephrine
what is a non-competitive antagonist
it strongly bonds to a different receptor than the agonist. it is irreversibly blocked, and agonist will never reach 100% response and Emax will decrease
what is down regulation?
the process in which a cell decreases the quality of one if its components. It happens when there are a decrease in number of receptors or an alteration in existing receptors decreasing responsiveness
what are two examples of drug classes that can cause down regulation?
SSRIs and opioids
what is up regulation?
when cells become more responsive to ligands by increasing the number of receptors on or in the cell increasing responsiveness
what are examples of up regulators?
rapid withdrawal of beta blockers or naloxone on opiate receptors
what is a allosteric site
agonist and antagonist may bind to a different site on the same receptor
what are the four superfamilies of receptors?
Cell membrane embedded enzyme, ligand gated ion channel, G protein coupled receptor system, transcription factor
how do transcription factor/ nuclear receptors work?
intracellular receptor proteins bind reside in the cytoplasm and bind to signa; molecules (ligands) like sex steroid and thyroid hormones that have crossed the cell membrane and entered the cell. once bound to the ligand the nuclear receptor complexes migrate to the nucleus of the cell where they directly affect gene transcription.
what kind of drugs and substances work on nuclear receptors/ transcription factors
estrogen, testosterone, progesterone, glucocorticoids, thyroid hormone, and Vitamin D
how do cell membrane embedded enzyme receptors work?
These substances are enzymes bound to cell membranes that serve as receptors for various ligands. There are 5 classes of cell membrane receptors, the most common are kinases. They all initiate signaling in essentially the same way but have different ligands and different target substrates. The signal molecule binds to the outside of the cell and the portion initiating the enzyme activity within the cell cytoplasm.
How do ligand gated channels work?
Receptors are located on the cell membrane, once receptor is activated a pore in the membrane opens allowing the passing of ions. This results in rapid meaning microsecond speed, changes in membrane potential. This changes the shape of the receptor allowing NA K Ca or Cl to pass through.
How do G protein coupled receptors work?
the ligand binds to the G protein coupled receptor on the outside of the cell; then binding triggers activation of a G protein located on the inner surface of the cell membrane and third the G protein separates from the receptor binds to the effector which bring the result.
what drugs work by G protein coupled receptors?
40% of drugs including, antihistamines, neuroleptics, antidepressants, and antihypertensive agents, serotonin, dopamine, GABA type B, acetylcholine, epinephrine, opioids.
What are receptor less drugs?
drugs that do not act through a specific target receptor. Their action is mediated through simple physical or chemical; interactions with other small molecules.
what are examples of receptor less drugs?
antacids, antiseptics, saline laxati8ves, chelating agents, binding agents.
lipid soluble drugs such as corticosteroids often activate receptors in which receptor superfamily?
Nuclear receptors
which type of receptor often in the cytoplasm binds to an agonist forming a complex which is then transported into the nucleus where it exerts its effect?
Nuclear receptors
which receptor system signal mechanism is responsible for the effects caused by beta receptor activation such as those seen with adrenergic bronchodilators?
G protein coupled receptors
examples of which receptor superfamily include acetylcholine (nicotinic) receptors on skeletal muscle and Gaba Type A?
ligand gated ion channel receptors
Which transmembrane signaling family is responsible for insulin and platelet growth factor?
Cell membrane embedded enzyme factor
What is the onset of action a measure of?
the time required for drug concentration to reach a minimum effective concentration (MEC)
what is time peak a measure of?
time required for maximal effect to occur after drug administration
what is the duration of action a measure of?
Time in which blood levels are above minimum effective concentration
what is EC50 a measure of?
Used only in vitro studies for the concentration which produces 50% of the maximum effect
what is potency the measure of
the comparison of EC 50 in two or more drugs. The drugs with a lower EC50 are more potent.
What is ED50 the measure of
dose required for 50% of peop0le to exhibit desired response. “average effective dose)
How do you calculate a drugs therapeutic index?
LD50 divided by ED50 (lethal animal dose divided by average effective human dose)
What drugs have narrow therapeutic indexes?
warfarin, lithium, digoxin, phenytoin, carbamazepine, gentamycin, amphotericin B, 5FU, theophylline, zidovudine
Why do drugs with narrow therapeutic indexes require frequent monitoring?
to prevent adverse reactions while maintaining a therapeutic effect
what are idiosyncratic variations?
rare responses that require multiple exposures to the drugs. genetic factors account for 20-95% of them. People can react less or much more than expected.
how does myasthenia gravis affect drug resposne?
it forms antibodies against acetylcholine receptors at the neuromuscular junction of skeletal muscles
What is tachyphylaxis?
rapid decrease or desensitization in the responsiveness to a drug
How does homeostatic reserve affect the elderly?
aging decreases homeostatic reserve and therefore the elderly cannot tolerate disease stresses as well as they could when they were younger
