11/12 Pharmadynamics Flashcards
what is pharmacodynamics?
the drugs effects on the body.
what are the five different types of biochemical receptors
- Intracellular. 2. Ligand-regulated enzyms. 3. Cytokine 4. ligand-gated ion channel. 5. G-protien linked
describe an intracellular biochemical receptor
a receptor that will bind a lipophilic drug or other drug that enters the cell and binds in the cytoplasm.
describe a ligand regulated enzyme
this is a receptor that will bind a ligand on the outside of the cell and then on a transmembrane component: cause a conformational change or other change in the receptor that will turn it into a an active enzyme on the intracellular portion of the receptor.
describe a cytokine biochemical receptor:
receptor binds the drug, causing the receptor to bind a ligand on the intracellular portion and then the intercellular portion will act to phosphorilate intracellular molecules
Describe ligand-gated ion channel biochemical receptors:
they bind a ligand or other drug that will cause the ion channel to open and allow ions to flow through
Describe G-protein coupled biochemical receptors:
they are7 transmembrane receptors, interact with a G-protien and have an effector element and second messenger.
what are the possible effector elements of a G-protein?
Enzymes (protien kinase A) or ion channels
what are the second messengers of G proteins
cAMP, IP3 and cGMP
Non-superimposable mirror images of a drug:
Chiral molecules
why would chirality be important for drug delivery?
50% of useful drugs have different chrality with different potentcy or toxicity.
Most common drug-receptor interactions use what type of bond?
Electrostatic
a drug that binds a physicologic receptor and mimics the regulatory effects of the endogenous signaling compounds
Agonist
partial agonist
binds and activates the receptor but does not evoke as great a response as full agonists
Allosteric agonist
binds to a site on the receptor remote from the agonist binding site.
Inhibiting drug action
mimics agonist drugs by inhibiting the molecules responsible for terminating the action of an endogenous agonist
inverse agonist drug action
reduces receptor activity below basal levels observed in the absence of bound ligand (clinical effets similar to competitive antagonist)
The level of response vs. log of the drug conc. for a full agonist; partial agonist , inactive compound, and inverse agonist.
a drug without regulatory effect that interferes with the ability of the endogenous agonist to activate a receptor
Antagonist
Describe Reversible competitive antagonists
reversibly binds to the same site as the agonist. Increases the agonist concentration required for a given degree of response.
Irreversibly binds the same site as the agonist. Reduces the maximal effect the agonist can achieve
Allosteric
What types of antagonist are non-Competitvie
Irreversible;
Allosteric;
Graph of a competitive antagonist
% max effect vs. Log [drug] as you add more and more antagonist
Graph of Non-competitive Antagonist in the form of irreversible antagonist:
% max effect vs. [drug] for different amounts of antagonism added
Graph of Non-competitive Antagonist in the form of Allosteric antagonist:
% max effect vs. [drug] for different amounts of antagonism added
What is the concentration of drug where 50% effect has been achieved?
the EC50 or effective concentration 50
What is the difference in potency vs. efficacy?
the potency is the conc. of drug needed to be able to reach % max effect
(greater conc. needed then less potency– look at the right shift in the % effect vs. log[] graph – farther to the right the less potent)
The Efficacy is the ability of the drug to reach a high % effect.
(less % effect reached at high conc. then less efficacy – look at the hight of the final equilibrium of the % effect vs. Log [] graph – smaller height is less efficacy)
The graphical representation of the ED-50 dose and the LD-50 dose
The dose at which 50% of individuals exhibit the specified effect
Median effective dose (ED-50)
I’m prescribing a drug, and I want to know how likely a high dose of the drug is going to kill by patient…given that I work with an average patient that is :-) what do I want to calc?
the Therapeutic Index
TI = TD-50/ED-50 or TI = LD-50/ED-50
where TD=toxic dose; LD = lethal dose; ED=Effective dose
as the number gets smaller, and closer to one, then the drug is more likely to cause problems with any kind of large dose!
The dose at which 50% of the individuals exhibit the specified toxic effect
Median toxic dose (TD-50)
Median Lethal dose (LD-50)
the does at which 50% of the individuals die
hmmm, the patient just had a really infrequent reaction to the drug…what kind of variability is this?
Idiosyncratic variability
This person just does not have a very intense effect from this dose of the drug that most people see a large effect from…what do I call this?
Hyporeactive
This perosn has a very intense effect from this drug that most have a mild effect…what do I call this variability
Hyperreactive
This person takes this drug every day and now it doesn’t seem to effect them at all….?
Tolerance
The intensity of response is rapidly diminshed in response to continued drug administraition?
Tachyphylaxis
