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Pharmacology Exam 1: Pharmacodynamics
pharmacodynamics
91
Anatomy
Graduate
01/24/2011

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Term
define pharmacodynamics:
Definition
the study of drugs effects and mechanisms of action
Term
stimulators are also called:
Definition
agonists
Term
blockers are also called:
Definition
antagonists
Term
receptor concept:
Definition
As a drug is absorbed and distributed to many sites in the body, it will bind to a number of types of macromolecules.
This binding reaction may result in:
1. No change.
2. An undesirable change.
3. A change that ultimately leads to a desirable therapeutic effect
Term
broad definition of receptor:
Definition
Drug target; site of action of a drug
Examples:
1. Drug binds to an enzyme and inhibits activity.
2. Drug binds to tubulin and inhibits microfilament formation.
3. Drug binds to a transport protein and inhibits uptake of endogenous chemical into the cell.
4. Drug binds to DNA and disrupts gene transcription.
Term
an example of drug binding to an enzyme and inhibiting its activity:
Definition
digoxin inhibiting sodium potassium atpase
Term
Receptors are highly ___ proteins that have evolved to ___ endogenous signal molecules, ___ and ____binding into an intracellular signal that involves a ___ of biochemical reactions ultimately resulting in a ____.
Definition
- specialized
- bind
- transduce and amplify
- cascade
- response
Term
An ___ ___ receptor gets bound by its ligand, which causes a ___ ___ that opens up the ___ ___ so that ___ can flow either way depending on the ____ ___.
Definition
- ion channel
- confirmational change
- ion channel
- ions
- electrochemical gradient
Term
Receptor = lock
Drug = key

Two key properties:
will key fit in lock and how tightly?
Will key turn in the lock and open it?
Definition
Term
with the lock and key model, the ___ or ___ is the lock, while the ___ or ___ ___ is the key.
Definition
- enzyme or receptor is the lock
- drug or endogenous ligand is the key
Term
If a drug binds a lot of receptors at a low concentration, then the drug has a ___ affinity. When we talk about how tightly will the key fit, we are talking about affinity.
Definition
high
Term
Agonist could bind and fit and cause confirmational change and cause downstream event, but antagonist would just sit there and not fit so no conformational change
Definition
Term
___ is a measure of affinity or of how "tightly" the ligand binds the receptor.
Definition
Potency
Term
Potency is affected by the ___ and ____ of the drug.
Definition
size and charge
Term
___ ___ refers to the capacity of a drug agonist to activate the receptor. This is also known as ____.
Definition
- intrinsic activity
- efficacy
Term
efficacy is aka:
Definition
intrinsic activity
Term
Efficacy: to what extent does the drug produce an effect, think about graded response of a drug you have 0-100% response, ddrug that makes 100% at receptor is fully efficaceous, but a partial agonist is one that can never cause full response
Definition
Term
Increasing ____ makes a difference, but increasing ___ is pointless.
Definition
- efficacy
- potentcy
Term
A __ ___ can never cause a full response, they have lower ___ or ___ ___ than full agonists.
Definition
- partial agonisty
- efficacy or intrinsic actvity
Term
what makes a drug a partial vs. a full agonist?
Definition
- different chemical properties that make or dont make the drug good a fitting and turning the receptor
Term
Drugs that are agonists mimic __ ___ ___ and ___ receptors.
Definition
- endogenous signal molecules
- activate receptors
Term
Drugs that are antagonists bind to receptors but do not ___ them. Thus by ___ the receptor binding site, antagonists ___ binding and activation by endogenous signal molecules. But remember antagonists have __ effects.
Definition
- do not activate them
- occupying
- prevent
- NO effects
Term
Antagonist is like putting key in neighbors door, it can go in, but won’t do anything. Antagonists can be used to reduce ability of endogenous molecule to bind and thereby dampening normal signal the body produces. Antag are just place holders with no molecular effects but does have physiological effect b/c dampening normal endogenous signal.
Definition
Term
Most, but not all, drugs bind their receptors ____.
Definition
reversibly
Term
define Kd:
Definition
Kd= equillibrium dissociation constant, a measure of affinity, units are drug concentration
Term
Kd is the drug concentration at which __ of the ___ are ___ and half are ___. This is a direct measure of ___.
Definition
- half of the receptors are bound and half are unbound
- affinity
Term
Drug A has a nanomolar Kd, while Drug B has a millimolar Kd. Which drug has a higher affinity for its receptor?
Definition
Drug A b/c its Kd is in the nanomolar range, which is smaller than the millimolar range, meaning at lower concentrations it is bound to more receptors.
Term
the smaller the Kd the ___ the affinity
Definition
higher
Term
if drug x has low affinity, ___ concentrations will be needed.
Definition
greater
Term
define x and y axises for a concentration-effect curve.
Definition
x-axis: concentration
y-axis: effect
Term
define x and y axises for a dose response curve.
Definition
x-axis: dose
y-axis: responseWit
Term
With in vitro studies you have to use ___ ____ curve instead of dose response curve.
Definition
concentration effect
Term
explain the concentration dependent effect:
Definition
- as you increase concentration, you see a response, but at some point the response won't increase even if you keep increasing concentration= ceiling effect
Term
dose response curves are hyperbolic why?
Definition
b/c receptors become saturated
Term
The EC50 is the ___ ___ that produces __% of the __ ___.
Definition
- effective concentration
- 50%
- max response

so draw EC50 at half way point on y-axis and drop it down to x-axis to get concentration of EC50
Term
EC50 is used when you are looking at a ___ from a drug, whereas Kd is used when looking at how many ___ are bound.
Definition
- response
- receptors
Term
Kd is the concentration at which ___ of the receptors are ___ and ___ are ____.
Definition
- 50%
- bound
- 50% are unbound

to find this draw a line half way on y axis and drop it down to x-axis to find concentration at which this happens
Term
why does a highly plasma protein bound drug require higher concentrations?
Definition
b/c have to bind up all plasma proteins before any free drug is available to act
Term
You can see a concentration effect curve arthymatically with a ___ shape, or you can see it on a log scale with a __ shape, which makes it easier to identify ___.
Definition
- hyperbolic
- "S" shape
- EC50
Term
dose reponse curves in log scale will be:
Definition
S-shaped/sigmoidal
Term
4 important parameters of log dose response curves:
Definition
1. Efficacy
2. Potency
3. Slope
4. Variability

Every Pretty Saddle Varies.
Term
When looking at the log dose response curve if you want to look at efficacy look at __ ___.
Definition
max response
Term
when looking at log dose response curve if what to compare potencies look at ___. The __ this number the more ___ the drug is.
Definition
EC50s
- lower
- potent
Term
The slope on a log dose response curve tells us about ___.
Definition
cooperativity
Term
Potency refers to the ___ or ___ of drug required to produce a ___.
Definition
amount
concentration
response
Term
on dose response curve, potency is measured on the ___ axis.
Definition
x-axis
Term
__, ___, and ___ are all measures of potency.
Definition
ED50, EC50, and Kd
Term
look at slide 23 and 24 of pharmacodynamics lecture and understand. So if 2 drugs start at same point, but one is lower on yaxis, then they may have same ED50 and potency, but have differnt efficicacies. But if start at same point on x and have same efficacy, probably have different potencies.
Definition
Term
No drug is ____, but some are ___ ___ for a particular receptor or in a producing a particular effect.
Definition
- no drug is specific
- highly selective
Term
Selectivity is due to differential ___at differential ____.
Definition
potency
receptors
Term
Selectivity is ___ dependent.
Definition
dose
Term
selectivity depends on what 2 things?
Definition
- different potencies for different receptors
- dose
Term
If give drug A at concentration of ED50 for A, you are not effecting receptor B very much, but if increase dose of drug A, then the drug starts affecting receptor B and causes unwanted side effects.
Definition
Term
Most receptors for endogenous agonists exist as a ___. of structurally related ___ ___
Definition
family
receptor subtypes
Term
Each subtype probably sends a different type of signal and may be present on different cell types.
Definition
Term
The more recptors you have in one family, the ___ it is to make the drug selective.
Definition
harder
Term
efficacy refers to the capacity of a drug to produce a ___
Definition
response
Term
the continuum of efficacy includes:
Definition
- full agonists
- partial agonists
- antagonists
Term
full agonists can produce max response. Partial agonists produce less than maximal response. Antagonists, in the absense of agonists, produce no response.
Definition
Term
If a drug can stimulate a receptor it is said to have ___ ___.
Definition
intrinsic activity
Term
If a drug stimulates a full response, it might to said to be a full agonist and to be very efficacious
Definition
Term
Partial agonists are also partial antagonists.

Partial agonists can be very useful drugs. They can block the effects produced by a natural full agonist, but partially stimulate the receptor. Thus, receptor signaling can be toned down without being completely silenced.
Definition
Term
IF YOU HAVE A RECEPTOR THAT IS REACTING TO ENOGENOUSLY RELEASED NEUROTRANSMITTER, AND YOU GIVE PARTIAL AGONIST IN APPROPRIATE RANGE YOU CAN REALLY REDUCE RESPONSE OF NORMAL ENDOGENOUS RESPONSE DOWN TO THE PARTIAL AGONIST RESPONSE, SO ITS WORKING LIKE A PARTIAL ANTAGONIST.
Definition
Term
Examples
b blockers with ISA = intrinsic sympathomimetic activity. These drugs are not blockers, i.e., full antagonists; they are partial agonists.

Opioid mixed agonist-antagonists. The term mixed agonist-antagonist means partial agonist.
Definition
Term
In an individual subject, a continuously increasing response, or ___ ____, up to a certain maximum can be achieved as doses of drugs are increased.
Definition
- graded response
Term
A quantal response is a __ or __ type respnse, like ___, ___, or ___ ___.
Definition
- yes or no
- death, sleep, anesthesia
Term
Quantal dose effect curves. In a population of subjects, the number of subjects responding at ___ ___ ___, often can be represented by a ___ ____ ___, a ___ ___ curve.
Definition
- any give dose
- normal frequency distribution
- bell shaped
Term
A graph of the ___ ___ of ___ of subjects responding vs. the log of the ___ yields a ___ ______ curve.
Definition
- cumulative frequence
- dose
- quantal dose-effect curve
Term
Quantal dose effect curve important variables include:
Definition
- ED50
- LD50
- TD50
Term
For the quantal dose effect curve, the ED50 is the dose at which 50% of the population had a specific response. The LD50 is the dose at which 50% of the population died. The TD50 is the dose at which 50% of the population expressed a specified toxic effect.
Definition
Term
formula for therapeutic index:
Definition
TD50/ED50= therapeutic index (TI)
Term
Therapeutic index (TI) is a measure of relative __ ___.
Definition
drug safety
Term
the larger the TI, the ___ the drug.
Definition
safer
Term
quantal dose response curves define the ____ ____.
Definition
therapeutic window
Term
recommended effective doses are established in ___ ___.
Definition
clinical trials
Term
toxic doses in humans are estimated from preclinical tests using ___.
Definition
animals
Term
An additive response, is one in which the response to two chemicals is equal to the ___ of the effect of each agent when given alone.
Definition
sum

1+1=2
Term
A synergistic response is when the response to two chemicals is ___ than the __ of the effect of each agent when given alone.
Definition
greater than the sum

1+1=3
Term
Physiological functional antagonism is when two chemicals produce the ___ effect on the same physiolocigal function.
Definition
opposite
Term
Chemical antagonism is when one chemical ____ the effects of another.
Definition
reduces
Term
An example of chemical antagonism:
Definition
EDTA chelating lead to get it out of body
Term
Antagonists have no intrinsic activity/efficacy in terms of molecular action at receptors. However, antagonists can be very efficacious drugs in term of physiological effects.
Definition
Term
An inverse agonist has ___ ___ activity, meaning that occupying the receptor induces effects ____ those of an agonist.
Definition
- negative receptor
- opposite
Term
Competetitive antagonists compete with agonists for the receptors. A blockade by competitive antagonists can be overcome by ____ concentrations of ____.
Definition
increasing concentrations of agonist
Term
The ED50 for an agonist ____, meaning the curve shifts to the ____, in the presence of competitive antagonists.
Definition
- increases
- right
Term
There are two types of non-competitive antagonists. There are the type that bind ___ aka ____ to the ___ site as the agonist. Or there are the kind that bind a ___ site and ___ the ____ ___.
Definition
- irreversibly aka covalently to the same site as the agonist
- different site and reduce the receptors activity
Term
Noncompetitive antagonists bind covalently (irreversibly) with receptors.
Blockade by a noncompetitive antagonist is very prolonged or permanent.
Shift agonist dose-response curves downward.
Omeprazole binds to the proton pump covalently and inhibits it for the lifetime of the molecule.
Definition
Term
non competitive antagonists also Binds at a site other than the agonist site
Phencylidine (PCP) binds to a channel lining amino acid in the NMDA receptor and blocks ion flow.
Definition
Term
Pharmocokinetic tolerance is about altering the ___ ____ of drug. This can be done by induction of _____ _____ or other drug metabolizing enzymes.
Definition
- body's clearance
- P450 enzymes
Term
Pharmacodynamic tolerance is about ___ ___ ___ via ____ or ____.
Definition
- target cell adaption
- desensitization
- supersensitivity
Term
noncompetetive antagonism cannot be overcome by adding more agonist. with noncompetitive antagonism the curve will shift right and it will not rise as high.
Definition
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