Term
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Definition
| the study of drugs effects and mechanisms of action |
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| stimulators are also called: |
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Definition
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| blockers are also called: |
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Definition
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Term
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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 |
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Term
| broad definition of receptor: |
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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. |
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Term
| an example of drug binding to an enzyme and inhibiting its activity: |
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Definition
| digoxin inhibiting sodium potassium atpase |
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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 ____. |
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Definition
- specialized
- bind
- transduce and amplify
- cascade
- response |
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Term
| An ___ ___ receptor gets bound by its ligand, which causes a ___ ___ that opens up the ___ ___ so that ___ can flow either way depending on the ____ ___. |
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Definition
- ion channel
- confirmational change
- ion channel
- ions
- electrochemical gradient |
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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? |
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Definition
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Term
| with the lock and key model, the ___ or ___ is the lock, while the ___ or ___ ___ is the key. |
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Definition
- enzyme or receptor is the lock
- drug or endogenous ligand is the key |
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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. |
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Definition
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| 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 |
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Definition
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| ___ is a measure of affinity or of how "tightly" the ligand binds the receptor. |
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Definition
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Term
| Potency is affected by the ___ and ____ of the drug. |
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Definition
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| ___ ___ refers to the capacity of a drug agonist to activate the receptor. This is also known as ____. |
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Definition
- intrinsic activity
- efficacy |
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Term
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Definition
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| 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 |
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Definition
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Term
| Increasing ____ makes a difference, but increasing ___ is pointless. |
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Definition
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| A __ ___ can never cause a full response, they have lower ___ or ___ ___ than full agonists. |
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Definition
- partial agonisty
- efficacy or intrinsic actvity |
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Term
| what makes a drug a partial vs. a full agonist? |
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Definition
| - different chemical properties that make or dont make the drug good a fitting and turning the receptor |
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Term
| Drugs that are agonists mimic __ ___ ___ and ___ receptors. |
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Definition
- endogenous signal molecules
- activate receptors |
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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. |
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Definition
- do not activate them
- occupying
- prevent
- NO effects |
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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. |
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Definition
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Term
| Most, but not all, drugs bind their receptors ____. |
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Definition
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Term
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Definition
| Kd= equillibrium dissociation constant, a measure of affinity, units are drug concentration |
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Term
| Kd is the drug concentration at which __ of the ___ are ___ and half are ___. This is a direct measure of ___. |
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Definition
- half of the receptors are bound and half are unbound
- affinity |
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Term
| Drug A has a nanomolar Kd, while Drug B has a millimolar Kd. Which drug has a higher affinity for its receptor? |
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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. |
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Term
| the smaller the Kd the ___ the affinity |
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Definition
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Term
| if drug x has low affinity, ___ concentrations will be needed. |
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Definition
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Term
| define x and y axises for a concentration-effect curve. |
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Definition
x-axis: concentration
y-axis: effect |
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Term
| define x and y axises for a dose response curve. |
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Definition
x-axis: dose
y-axis: responseWit |
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Term
| With in vitro studies you have to use ___ ____ curve instead of dose response curve. |
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Definition
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Term
| explain the concentration dependent effect: |
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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 |
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Term
| dose response curves are hyperbolic why? |
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Definition
| b/c receptors become saturated |
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Term
| The EC50 is the ___ ___ that produces __% of the __ ___. |
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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 |
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Term
| EC50 is used when you are looking at a ___ from a drug, whereas Kd is used when looking at how many ___ are bound. |
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Definition
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Term
| Kd is the concentration at which ___ of the receptors are ___ and ___ are ____. |
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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 |
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Term
| why does a highly plasma protein bound drug require higher concentrations? |
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Definition
| b/c have to bind up all plasma proteins before any free drug is available to act |
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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 ___. |
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Definition
- hyperbolic
- "S" shape
- EC50 |
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Term
| dose reponse curves in log scale will be: |
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Definition
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Term
| 4 important parameters of log dose response curves: |
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Definition
1. Efficacy
2. Potency
3. Slope
4. Variability
Every Pretty Saddle Varies. |
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Term
| When looking at the log dose response curve if you want to look at efficacy look at __ ___. |
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Definition
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Term
| when looking at log dose response curve if what to compare potencies look at ___. The __ this number the more ___ the drug is. |
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Definition
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Term
| The slope on a log dose response curve tells us about ___. |
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Definition
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Term
| Potency refers to the ___ or ___ of drug required to produce a ___. |
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Definition
amount
concentration
response |
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Term
| on dose response curve, potency is measured on the ___ axis. |
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Definition
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Term
| __, ___, and ___ are all measures of potency. |
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Definition
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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. |
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Definition
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Term
| No drug is ____, but some are ___ ___ for a particular receptor or in a producing a particular effect. |
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Definition
- no drug is specific
- highly selective |
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Term
| Selectivity is due to differential ___at differential ____. |
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Definition
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Term
| Selectivity is ___ dependent. |
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Definition
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Term
| selectivity depends on what 2 things? |
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Definition
- different potencies for different receptors
- dose |
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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. |
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Definition
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Term
| Most receptors for endogenous agonists exist as a ___. of structurally related ___ ___ |
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Definition
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Term
| Each subtype probably sends a different type of signal and may be present on different cell types. |
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Definition
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Term
| The more recptors you have in one family, the ___ it is to make the drug selective. |
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Definition
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Term
| efficacy refers to the capacity of a drug to produce a ___ |
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Definition
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Term
| the continuum of efficacy includes: |
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Definition
- full agonists
- partial agonists
- antagonists |
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Term
| full agonists can produce max response. Partial agonists produce less than maximal response. Antagonists, in the absense of agonists, produce no response. |
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Definition
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Term
| If a drug can stimulate a receptor it is said to have ___ ___. |
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Definition
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Term
| If a drug stimulates a full response, it might to said to be a full agonist and to be very efficacious |
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Definition
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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. |
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Definition
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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. |
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Definition
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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. |
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Definition
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Term
| In an individual subject, a continuously increasing response, or ___ ____, up to a certain maximum can be achieved as doses of drugs are increased. |
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Definition
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Term
| A quantal response is a __ or __ type respnse, like ___, ___, or ___ ___. |
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Definition
- yes or no
- death, sleep, anesthesia |
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Term
| Quantal dose effect curves. In a population of subjects, the number of subjects responding at ___ ___ ___, often can be represented by a ___ ____ ___, a ___ ___ curve. |
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Definition
- any give dose
- normal frequency distribution
- bell shaped |
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Term
| A graph of the ___ ___ of ___ of subjects responding vs. the log of the ___ yields a ___ ______ curve. |
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Definition
- cumulative frequence
- dose
- quantal dose-effect curve |
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Term
| Quantal dose effect curve important variables include: |
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Definition
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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. |
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Definition
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Term
| formula for therapeutic index: |
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Definition
| TD50/ED50= therapeutic index (TI) |
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Term
| Therapeutic index (TI) is a measure of relative __ ___. |
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Definition
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Term
| the larger the TI, the ___ the drug. |
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Definition
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Term
| quantal dose response curves define the ____ ____. |
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Definition
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Term
| recommended effective doses are established in ___ ___. |
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Definition
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Term
| toxic doses in humans are estimated from preclinical tests using ___. |
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Definition
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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. |
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Definition
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Term
| A synergistic response is when the response to two chemicals is ___ than the __ of the effect of each agent when given alone. |
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Definition
greater than the sum
1+1=3 |
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Term
| Physiological functional antagonism is when two chemicals produce the ___ effect on the same physiolocigal function. |
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Definition
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Term
| Chemical antagonism is when one chemical ____ the effects of another. |
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Definition
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Term
| An example of chemical antagonism: |
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Definition
| EDTA chelating lead to get it out of body |
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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. |
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Definition
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Term
| An inverse agonist has ___ ___ activity, meaning that occupying the receptor induces effects ____ those of an agonist. |
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Definition
- negative receptor
- opposite |
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Term
| Competetitive antagonists compete with agonists for the receptors. A blockade by competitive antagonists can be overcome by ____ concentrations of ____. |
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Definition
| increasing concentrations of agonist |
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Term
| The ED50 for an agonist ____, meaning the curve shifts to the ____, in the presence of competitive antagonists. |
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Definition
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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 ____ ___. |
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Definition
- irreversibly aka covalently to the same site as the agonist
- different site and reduce the receptors activity |
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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. |
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Definition
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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. |
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Definition
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Term
| Pharmocokinetic tolerance is about altering the ___ ____ of drug. This can be done by induction of _____ _____ or other drug metabolizing enzymes. |
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Definition
- body's clearance
- P450 enzymes |
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Term
| Pharmacodynamic tolerance is about ___ ___ ___ via ____ or ____. |
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Definition
- target cell adaption
- desensitization
- supersensitivity |
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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. |
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Definition
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