Receptors 1 Flashcards

Question

**Dose-Response Curve**

Answer 1

**Fraction of Receptors Bound (B) Vs Drug Concentration (D)** * Pysiological responses are NOT simple fxn of the amount of dose given * May be *INITIALLY LINEAR* * *but level off @ higher doses* * ****B_max**= **100% of receptors bound** * *B IS NOT the same as effect or efficacy (vs EC₅₀)*

Answer 2

**Drug-Receptor Dissociation Constant** * When drug cocentration (D) shows **HALF SATURATION** * **[D]** when **[B = 50%]** * ****half of receptors are occupied * **Smaller the K_D = Greater the affinity** * ****less drug is needed to saturate the receptor * K_Dis related to the **free energy** of ligand-receptor interactions * *not the same as EC₅₀*** * *inverse of K_a*

Answer 3

**Association Constant = AFFINITY** *inverse of dissociation constant K_D* **K_a= k₁/ k_-1** * **Greater the K_a= greater the affinity**

Answer 4

* **Scale @ low concentration** (where binding changes rapidly) * compresses **[D]** @ *HIGH concentration (where binding changes slowly* * **_Does not change value of B_max & K_D_**

Answer 5

* Better **defined Plateau** * Plotting of **wide range** of [D] * Enables **comparison of drugs w/ different affinites due to compression of x axis**

Answer 6

**_Drug Efficacy [E]_ vs Drug Concentration [D]** * **E_max** = maximum response (**effect)** achieved by agonist * = **drug efficacy** * ******ED₅₀**= druc conc. (dose) at which**50% of E_maxis achieved** * ****= **drug potency** * *different units of E vs B*

Answer 7

* Agonist w/ **High Affinity** * ****shit curve to the **LEFT** * ****binding & drug action start @ *LOWER concentrations of agonist* * Agonist w/ ***LOW AFFINITY*** * *causes curve to move to the **RIGHT*** * ****MORE agonist** is needed to make the drug-receptor complex

Answer 8

**Individuals Responsing (%) Vs Drug Dose [D]** * Describe POPULATION rather than single individual responses * based on plotting **comulative frequency of distribution of responsers** * **vs log of drug dose** * **E_max& ED₅₀****** * like **GRADED** dose response curve

Answer 9

**INFINITE Number of intermediate stages** * Blood vessel dialation * Bood Pressure Change * Heart Rate Change

Answer 10

**BINARY all-or-none** * Death * Pregnancy * Cure * Pain relief * Effect of a given magnitude

Answer 11

Have an efficacy of 0 Similar to **Antagonist** bind to receptor without exerting an intracellular effect

Answer 12

* **blockage of the action of a drug-recepter interaction** * by another compound * ex. cimetidine --\> blocks interaction of: * histamine --\> H2 Receptors * --\> *lower gastric acid secretion*

Answer 13

* Interaction of **two drugs in solution** * such that the **effect of the active drug is lost** * ****Ex. _metal chelators + toxic metals_

Answer 14

**Agonist is DESTROYED by biochemical reaction** * Ex. _Sodium bicarb neutralizes Gastric acid secretion_ * Ex. _Protamine antagonizes heparin_ * __protamine = alkaline w/ +e charge * heparin = acid w -e charge

Answer 15

* Interaction of two drugs with **opposing physiological actions** * ****Ex. _Histamine vs Epinephrine_ * __Histamine *LOWERS* arterial pressure thru **VASODILATION** (h1 receptor) * Epinephrine **RAISES** arterial pressure thru *VASOCONSTRICTION* * ****B-adrenergic receptors** * Ex. _Insulin antagonizes gluticocorticoids_ * __hyperglycemic effects counteracted

Answer 16

* **prevent biological actions of agonist** * Bind to **SAME SITE** on receptor as agonist * inhibition **CAN** **be overcome** by increasing agonist concentration * = **reversible** * ****primarily affect agonist **POTENCY** * *****DO NOT alter receptor function* * **May also bind to another site on receptor that **BLOCKS** the action of an agonist * **SHIFT RIGHT**

Answer 17

* **Bind Covalently** to **SAME SITE** as agonist (**IRREVERSIBLE)** * or to a site distinct from that agonist (irreversible or reversible) * Inhibition *_CAN NOT be overcome_* by increasing agonist concentration * primarily affect **EFFICACY** * **SHIFT DOWN**

Answer 18

**u-opioid receptor ligand** **COMPETATIVELY ANTAGONIZES** action of _morphine / heroin_ opiate overdose treament

Answer 19

**NONcompetative antagonist of AMPA** ionotropic glutamate receptor Treatment of epilepsy (antiepileptic)

Answer 20

**Agonist + Competative Agonist (B)** Agonist has ***_REDUCED POTENCY_*** *but still MAXIMUM EFFICACY* * Produce a **PARALLEL** **RIGHT-SHIFT** * **Magnitide of the shift** is dependent on: * **[B]** , concentration of antagonist * **K_B ,** potency of antagonist

Answer 21

* Depends on the **plasma concentration** of the Antagonist: * **dose of the antagonist** * **rate of clearance of the antagonist** * ****_concentration of the agonist_ * __--\> can OVERCOME competative antagonist * **prescription must take into account possible changes in the endogenous agonist concentration** * ****ex. norepinephrine **vs** Propranolol

Answer 22

**Agonist + Non-Competitive Antagonist** Agonist has **Maximum Potency** *but REDUCED EFFICACY* * ****_curve moves DOWN_****__** (depressed response) * **__***no horizontal shift*

Answer 23

Allosteric Antagonist (modulator) Effect **modulator *REDUCES* mGlu1R signaling** ***DECREASES effect (shift down)*** *_without effecting binding or potency (no lateral shift)_*

Answer 24

Allosteric Antagonist (modulator) Effect **INCREASES Gaba POTENCY** (\<**shift left\<)** **&** **Maximal Effect (^shift up^)**

Answer 25

**Allosteric Antagonist** (modulator) **Effect** *DECREASES EFFICACY (moves down)* **Increases Potency (moves left)**

Answer 26

**More Agonist Sites can be occupied** INCREASE maximal GABA response * Examples: * Etomidate / Neurosteroids * **Barbiturates / Benzodiazapenes** * **Alcohols /Isoflurane / Propofol**

Answer 27

**Positive Allosteric Agent (propofol) on Gaba-ar** * ****Receptor binds GABA **more TIGHTLY** * dose response curve shifts to the **LEFT** * ****@ particular GABA concentration, **more agonist sites are occupied** in the presence of propofol * **response increases -- shift ^^UP^^**

Answer 28

Agonist occupies receptor --\> Trigers Response Strength of response : **directly related** to fraction of receptors occupied *does not explain all observations*

Answer 29

* **DR\*-** Agonist binding --\> conformational change * R-\>R\* active * **R\*** - Conformational change occurs SPONTANEOUSLY * in absense of agonist * --\> is active * small fraction of R\* is in EQ without athe agonist * agonist drives the conformational change, stabilizes R\*

Answer 30

* **Occupency model is *INSUFFICIENT*** *to explain these facts:* * Experimentally shown: * **Maximal response** can be found when only a **fraction** of total receptor population is occupied * **spare receptors** are present * Diff. Drugs have **different capacities** to initiate response when bound * = **different efficacies** * ***Certain receptors are active even in absence of agonist*** * Certain drugs act as "inverse" agonist * shut down **intrinsically active receptors******

Answer 31

* *assume that response (E) is :proportional: to receptor bound drug*, *where E_max= maximum effect* * **Magnitude of effect (**E**) is dependent on: * **Drug Concentration [D]** * **Affinity K_D**(receptor occupancy) * **Ability to activate the receptor "e"** * ****aka **intrinsic activity**

Answer 32

**Potency INCREASE as response shift to the LEFT \>\>\>** **_Efficacy INCREASES as maximal effects of receptor shift ^^UP^^_**

Answer 33

**Maximal Response produced by a drug** analogous to _Maximal Velocity for Enzyme_ * Depends on 3 factors: * **Intrinsic Activity (e)** * **Number** of drug receptor complexes formed * **Efficiency** of signal transduction in producing physiological response * Possible to have **High Affinity** w/ low efficacy * or vice verse

Answer 34

**FULL Agonist** **Max Potency = lowest drug conc to reach max effect** **Max Efficacy = reaches max effect**

Answer 35

***Partial Agonist*** **Maximum Potency** = reaches it max potential *Reduced Efficacy = Is not as Effective as a full agonist*

Answer 36

**FULL Agonist** *Reduced Potency* = *requires more drug to reach max efficacy* **Maximum Efficacy** *=* **Reaches its full effect**

Answer 37

***Partial Agonist*** * Reduced Potency = requires more drug to be effective* * Reduced Efficacy = Is not as Effective as a full agonist*

Answer 38

**Agonist with efficacy \<1 (e\<1)** _can serve as competitive agonist_ (also lower efficacy) **Shifts RIGHT! *but can also shift down*** * May completely occupy receptor sites * *BUT the response reaches a plateau at a value less than the maximal 100%* * *reduced effect SHIFT DOWN* * **Agonist binding may **favor new conformation** of receptor * --\> but has *LESS intrinsic activity (lower efficacy)* * *= poor contact w/ "downstream" partners in signal path* * *or more receptor states may need to be considered*

Answer 39

* **Heroin =** MOST efficacious agonist of opiod receptor * FULL AGONIST * ***Codeine** = most potent **partial agonist*** of opiod receptor * *Nalaxone = antagonist* * ***effect of antagonist needs agonist to be present to be observed* * *otherwise silent*

Answer 40

Has **Independent** impact upon receptor activity produces **Opposite effect to agonist** * *Unlike antagonist*, they are active in the absence of agonist * **intrinsically / constitutively active** * ****Ex. * **cimetidine --\> H2 receptors** * **Haloperidol --\> D2 receptors**

Answer 41

* Applicable to: * Simple Occupency model (esp. for enzyme INHIBITION) * Binding to Noncatalytic proteins (receptors) * Only consider **competitive antagonism** * **K_L=** dissociation constant of **AGONIST** (ligand) used in **displacement assay** * obtained from literature / determined beforehand * **{1 + [L]/KL}** = **Dose Ratio**

Answer 42

**EC50 is ALWAYS HIGHER than KD** * **K_D= thermodynamic paramater** * interaction between receptor / antagonist * (absolute value / constant, like melting point) * **EC₅₀= functional strength of a ligand** * ****depends on **experimental conditions** * ex. conc of **L** / presence of spare receptors * **EC₅₀**would INCREASE if **L** was at a higher conc.

Answer 43

**if NO LIGAND IS PRESENT** **when, [L] = 0**

Answer 44

E**D**₅₀= **DOSE** for 50% of **population** to obtain therapeutic effect Vs E**C**₅₀= **DOSE that reduces response** to 50% of maximal value (invidual)

Answer 45

* Expressed as the **Dose or Concentration** * that produces 50% of **maximal response ED50 or EC50** * ****_under experimental conditions_ * __*LOWER EC₅₀ = GREATER Potency* * **less drug needed to produce same effect

Answer 46

* Affinity of drug for receptor **K_D** * ****But also: * metabolism * distribution * Presence of other ligands

Answer 47

**Dissociaition constant of AGONIST** used in displacement assay _Obtained from literature or determined beforehand_ * *K_D = dissociation constant of the receptor-antagonist complex* * *= affinity*

Answer 48

**Molar Fraction of occupied receptor** * When [L] = KD, 50% protein is bound * When [L] = 0.1 KD only 9% of the protein is bound * When [L] = 10 KD, the protein is 91% saturated

Receptors 1 Flashcards

(72 cards)