Term
| What stimulates the receptor so as to produce the response; active by itself? |
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Definition
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Term
| What blocks the action of agonist; has no activity in absence of agonist? |
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Definition
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Term
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Definition
| Saturable and Stereospecific |
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Term
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Definition
| Effect produced by agonist |
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Term
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Definition
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Term
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Definition
| Maximum effect produced by the agonist or Efficacy |
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Term
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Definition
| Concentration of agonist that produces 50% of Emax or Potency |
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Term
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Definition
| Concentration (read from X-axis) |
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Term
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Definition
| Response (read from Y-axis) |
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Term
| Are potency and efficacy dependent on each other? |
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Definition
| No, they are independent; neither can predict the other |
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Term
| What is more important in therapeutics? |
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Definition
| Efficacy over potency; however higher potency can mean greater selectivity, few side effects |
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Term
| Why not always use a dose much bigger than EC50 to insure the maximum therapeutic effect? |
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Definition
1) To avoid side (adverse) effects
E.g., opiate analgesics cause constipation, respiratory depression, death at high doses.
E.g., high doses of aspirin cause tinnitus (“ringing in the ears”). |
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Term
| What is the Therapeitic Index (TI)? |
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Definition
TI= LD50/ED50
Typically 3 to 8 for prescription drugs; sometimes <2 |
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Term
| What is the Margin of Safety (MS)? |
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Definition
MS= LD1/ED99
Typically 1 to 3 for prescription drugs; sometimes <1 |
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Term
| Why would a cell want to have spare receptors? |
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Definition
1) With spare receptors, a cell is MORE SENSITIVE to agonist
2) Spare receptors facilitate repeated responses to agonist. RESISTS DESENSITIZATION. |
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Term
| Desensitization can also be called? |
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Definition
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Term
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Definition
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Term
| How fast do drugs come off their receptors? |
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Definition
| Depends on their affinity |
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
| DO ALL AGONISTS AT A GIVEN RECEPTOR HAVE THE SAME EFFICACY (SAME Emax)? |
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Definition
| NO. THERE ARE FULL AGONISTS AND THERE ARE PARTIAL AGONISTS. |
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Term
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Definition
| lower efficacy than full agonist |
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Term
| What the drug does to the body? |
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Definition
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Term
| What the body does to the drug? |
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Definition
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Term
| What can have affects on prescribed dose? |
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Definition
1) Pt compliance
2) Medication errors
3) Drug side effects/ Pharmacokinetics
4) Prescription writing |
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Term
| What can have affects on administered dose? |
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Definition
1) Rate and extent of absorption
2) Body size and composition
3) Distribution of body fluids
4) Binding in plasma and tissues
5) Rate of elimination
6) ADME/ Drug delivery
7) Pharmacokinetics
8) Pt Characteristics |
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Term
| What can have affects on concentration at locus of action? |
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Definition
1) Physiological variables
2) Pathological factors
3) genetic factors
4) Interaction with other drugs
5) Development of tolerance
6) Pt liver/kidney function
7) Pharmacogenomics
8) Desensitization |
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Term
| What can have affects on the intensity of effect? |
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Definition
1) Drug-receptor interaction
2) Functional state
3) Placebo effects
4) Pharmacodynamcis
5) Receptor signaling |
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Term
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Definition
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Term
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Definition
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Term
| What are some examples of ADE? |
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Definition
1) ADRs-side effects in the body
2) Errors in Prescribing
3) Errors in Pharmacy
4) Errors in Administration |
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Term
| What is the main goal of Pharmacology? |
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Definition
| Right drug, right dose, right route, right pt, and right time. |
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Term
| Most preventable ADE's occur due to? |
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Definition
| Errors in prescribing or at administration of meds- cost is about $10,000 per event and more than one occur per day in hospital per pt |
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Term
| What are two main types of ADRs? |
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Definition
A) Based on specific drug action (mechanism based; predictable)
B) Based on action on the other receptors ("off target") or atypical processing by the body |
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Term
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Definition
-Drug-Drug
-Drug-Food
-Hepatic
-Renal
-Idiosyncratic
--Genetic(caused by SNPs)
--Immunological |
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Term
| How mant US adults take prescription or over-the-counter or dietary supplements in any given week? |
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Definition
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Term
| How many adults will take ≥ than 5 of these daily? |
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Definition
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Term
| What is the most common iatrogenic (caused by medical exam or treatment) illness? |
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Definition
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Term
| What are some examples of "personalized medicine"? |
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Definition
-Matching drug to genetic make up of pt
-Pharmacogenomics and specific cancer therapy |
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Term
| What is important in taking a pt's drug history? |
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Definition
-Pharmaceuticals
-OTC meds
-"Dietary Supplements"
-"Allergies"- Distinguish ADRs due to action of drug versus true immunological allergy |
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Term
| What are some ethical issues dealing with Pharmacology? |
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Definition
1) Accept no favors from “Pharma” that would make you uncomfortable if your patients knew about them! (not allowed to accept pens and other trinkets. . . .)
2) Prescribe only in your patient’s best interest-including cost-effectiveness (generic vs. proprietary)
3) Formulary Issues (insurance companies, Hospitals, Medicaid) |
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Term
| What can a proper dose of partial agonist do? |
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Definition
| It can raise the baseline response or tone of the system, while maintaining some ability to respond to a full agonist |
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Term
| A drug with a high affinity and slow dissociation is? |
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Definition
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Term
| A drug with low affinity and fast dissociation is? |
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Definition
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Term
| How do a partial agonist and a full agonist compare in terms of potency? |
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Definition
| can be lower, higher or equal in potencies |
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Term
| If there are no spare receptors then how do EC50 and Kd sompare? |
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Definition
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Term
| What offers a potential for therapeutic intervention which is different from that of full agonists or antagonists? |
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Definition
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Term
| What is a practical example of partial agonists? |
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Definition
| Physiological responsiveness to a native neurotransmitter could be maintained while the baseline (resting tone of the system) is raised, or the maximal response diminished, or both. |
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Term
| Drugs acting on receptors may be... |
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Definition
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Term
| What bind to receptors, and activate them to produce various changes in cell function? |
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Definition
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Term
| What bind to receptors, and activate them to produce various changes in cell function? |
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Definition
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Term
| What bind to receptors without activating them? |
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Definition
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Term
| Agonist dose-response is characterized by... |
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Definition
| potency (EC50) and efficacy (Emax) |
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Term
| Relate antagonists, agonists, and partial agonists to efficacy... |
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Definition
antagonists-zero efficacy
agonists- 100% efficacy
partial agonists- intermediate efficacy |
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Term
| Can we account for full agonists, partial agonists, and antagonists by one simple model? |
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Definition
| Yes, there is a model. It even accommodates some other concepts (e.g., the inverse agonist). Many people find the R -> R* model helpful as a way of integrating multiple concepts of pharmacodynamics. |
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Term
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Definition
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Term
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Definition
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Term
| A receptor exists in equilibrium between... |
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Definition
| an inactive state R and an active state R*; Only R* produces the response |
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Term
| What causes an opposite response compared to an agonist, and can do so even in the absence of any endogenous agonist? |
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Definition
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Term
| When can an inverse agonist exist? |
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Definition
| Only exist in the situation where a receptor is partially activated in the absence of any agonist (i.e., there is some receptor in the activated R* state even with no agonist present). |
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Term
| If it causes a response, it's an... |
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Definition
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Term
| If it causes a response, at a saturating dose, that is smaller than the response to another agonist, it's a |
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Definition
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Term
| If it inhibits the response caused by an agonist, it's an... |
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Definition
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Term
| If there is some baseline level of receptor activity (in the absence of agonist), and the drug inhibits that, it's an... |
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Definition
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Term
| What does a competitive antagonist do to the dose-response curve? |
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Definition
| It shifts the curve right. doesn't change efficacy, but increases potency. |
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Term
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Definition
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Term
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Definition
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Term
| C=concentration of agonist |
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Definition
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Term
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Definition
| concentration of antagonist |
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Term
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Definition
| dissociation constant of antagonist |
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Term
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Definition
| It takes twice as much agonist to produce the same pharmalogical response as it did when I=0 |
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Term
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Definition
| concentration of agonist to give response E in presence of competitive antagonist dissociation with constant Ki at concentration I=Ki |
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Term
| What PERMANENTLY disables a receptor so it could NEVER again respond to agonist? |
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Definition
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Term
| What changes in a dose-response curve in the presence of a irreversible antagonist(no spare receptors)? |
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Definition
| Potency stays the same, but the efficacy lowers(only true if there is no spare receptors) |
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Term
| What are the main concepts of Irreversible Antagonists (if there is no spare receptors)? |
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Definition
-Potency (EC50) constant
-Efficacy drops as [antagonist] increases
-Nonparallel shift in Dose-Response curve
-Makes some receptors "disappear" without altering affinity or response of those receptors which are left |
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Term
| What are the clinical implications of irreversible antagonists? |
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Definition
-Effect of drug remains long (days-weeks) after drug has been cleared (hours-days)
-Overdose is particularly dangerous
-Time course of drug action depends on biosynthesis of new receptors, not on clearance of drug |
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Term
| Overdose with a competitive antagonist may be surmounted with... |
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Definition
| an agonist at that same receptor (In some cases, the agonist may be ready as an "antidote" at the bedside if needed) |
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Term
| Overdose with an irreversible antagonist will... |
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Definition
NOT be surmounted with agonist. The receptors which have reacted with the irreversible antagonist are dead.
[It may be possible to retrieve the error with a drug which works on an opposing physiological system with different receptors.] |
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Term
| What are the known transmembrane signaling mechanisms? |
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Definition
1) Lipid-soluble chemical signal crosses the plasma membrane and acts on an intracellular receptor (which may be an enzyme or a regulator of gene transcription)
2) the signal binds to the extracellular domain of a transmembrane protein, thereby activating an enzymatic activity of its cytoplasmic domain
3) the signal binds to the extracellular domain of a transmembrane receptor bound to a separate protein tyrosine kinase, which it activates
4) the signal binds to and directly regulates the opening of an ion channel
5) the signal binds to a cell-surface receptor linked to an effector enzyme by a G protein |
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Term
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Definition
| G protein Coupled Receptors |
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Term
| Half of known drugs target what? |
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Definition
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