Term
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Definition
| Drugs that mimic endogenous ligands are called agonists |
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Term
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Definition
| - Drugs that block the action of an agonist (endogenous ligand) are called antagonist |
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Term
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Definition
o Receptor (7 transmembrane spanning)
o G-Protein from (heterotrimeric complex) αβγ-complex
GTP (activated)
GDP (inactivated)
o Effector system |
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Term
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Definition
- Enzyme that catalyzes the formation of cAMP from ATP
- Phosphodiesterase inactivates cAMP phosphorylating the AMP to ATP by incorporating an inorganic phosphate |
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Term
| - G-Protein coupled receptors |
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Definition
| - In this system when the ligand (neurotransmitter, hormone, drug molecule) binds to the recognition site on the receptor molecule (R) it activates a G-protein®ATP®cAMP (G; called a G-protein because it is always associated with a guanine nucleotide such as GTP), which in turn activates an effector molecule (E-an enzyme). This enzyme then catalyzes formation of a second messenger molecule inside the cell, which is responsible for the pharmacological effect produced. |
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Term
| Sequence of events for the AC system |
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Definition
1. Ligand (L) binds to recognition site on the receptor (R)
2. Receptor (R) activates G-protein (G)
3. Alpha subunit of G-protein activates adenylyl cyclase (AC)
4. Adenylyl cyclase converts ATP to cyclic AMP (cAMP) which acts as a second messenger
5. cAMP activates a protein kinase (PKA) which in turn activates various proteins in the cell’s metabolism®* pharmacological response
6. cAMP is inactivated by hydrolysis to AMP catalyzed by phosphodiesterase. The AMP is eventually phosphorylated to regenerate ATP. |
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Term
| Sequence of events for the PLC system |
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Definition
1. Ligand binds to recognition site on the receptor
2. Receptor activates G-protein
3. Alpha subunit of G-protein activates phospholipase (PLC)
4. PLC hydrolyzes phosphatidyl inositol diphosphate (PIP2) to give inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 and DAG both act as second messengers.
5. Second messenger actions:
a. IP3 migrates to an intracellular calcium storage vesicle
IP3 interacts with a specific IP3 receptor on the vesicle and promotes release of Ca2++ from the vesicle.
b. DAG remains in the membrane
c. The DAG and Ca2++ released by the IP3 act together to stimulate protein kinase C (PKC), an enzyme that phosphorylates the proteins which constitute a membrane Ca2++ ion channel. This causes the channel to open and allows Ca++ to enter the cell.
6. IP3 is stepwise dephosphorylated to IP whereupon it is conjoined with DAG and re-phosphorylated to give PIP2. |
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Term
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Definition
- Generates two 2nd messengers from PIP2
o IP3-- Inositol triphosphate
Phospholipids
Goes into the cell
o DAG-- Diacylglycerol
Stays in the membrane
Activates protein phosphokinase (PKC) |
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Term
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Definition
- Calcium containing vesicle
- Ligand gated ion channel
- Not multi-subunit (single protein)
- Releases calcium once it reacts with IP3 |
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Term
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Definition
| - Phosphorylates ion-channel (Ca2++) & activates it, which allows even more Ca2++ to enter the cell |
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Term
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Definition
| drug diminished effect over time |
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Term
| – Homologous desensitization |
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Definition
| the agonist’s affects are diminished at one type of receptor |
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Term
| – Heterologous desensitization |
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Definition
the agonist’s affects are coordinately diminished at two or more types of receptors
Drug induced alteration in a common point (i.e. shared effector molecule) |
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Term
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Definition
| - a required period of time to pass before the receptor can be stimulated again. |
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Term
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Definition
| activation of receptor is completely blocked and may cause removal of receptor from the cell surface |
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Term
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Definition
| ability of drug molecule or ligand; to bind to or interact with a receptor |
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Term
| • Intrinsic Activity or Efficacy |
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Definition
| ability of drug to initiate a response |
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Term
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Definition
| dissociation constant, concentration of the ligand at which 50% of the receptors are occupied. It is the equilibrium dissociation constant for a given drug receptor interaction… a lower Kd indicates a tighter receptor interaction (higher affinity) |
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Term
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Definition
| relative amount of drug needed to produce a given response, determined largely by the amount of drug that reaches the site of action and by the affinity of the drug for the receptor; describes strength of binding between a drug and its target (affinity or Kd). Often expressed as the dose of a drug required to achieve 50% of the desired therapeutic effect. |
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Term
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Definition
| drug effect as the maximum response it is able to produce and is determined by the number of drug-receptor complexes and the ability of the receptor to be activated once bound; the biological effect exerted on the target by virtue of the drug binding. |
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Term
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Definition
drug/ligand/molecule that can initiate a response. Activates receptor with
Must have the following
1. Affinity
2. Efficacy
R + D D - R ®®® E |
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Term
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Definition
| activates receptor but NOT with maximal efficacy. Cannot not produce 100% of the biological response even at high doses |
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Term
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Definition
| inactivates constitutively active receptors. Inverse agonist have the opposite effects from those of a full agonist and NOT the same as an antagonist, which blocks the effect of both agonist and inverse agonist. |
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Term
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Definition
substance that binds with a receptor and produces NO effect
- Has affinity but no efficacy
o Unable to initiate a response
- Can block the action of an agonist and inverse agonist |
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Term
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Definition
binds reversibly to the active site of receptor; competes with agonist for the same receptor or binding site. No effect on their own. Competitive antagonist makes an agonist look less potent.
o Depends on:
Concentration each receptor
Respective affinities for the receptor |
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Term
| • Non-competitive allosteric antagonist |
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Definition
blocks the action of agonist usually by changing the shape of the receptor; binds reversibly or irreversibly to a site other than the active site of the receptor; prevents conformational change required for receptor activation by the agonist
o Agonist can not overcome it (or out compete)
o May alter Kd for agonist binding or prevent intrinsic activity
o Reduces maximal response of an agonist |
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Term
| • Noncompetitive active site antagonist |
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Definition
| binds irreversibly (covalently) or very high affinity to the active site of the receptor; prevents agonist from binding to this site. Even high concentration of agonist are unable to activate receptor |
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Term
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Definition
| does not affect basal receptor activity |
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Term
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Definition
| inactivates the agonist by modifying or sequestering it, thereby making the agonist incapable of binding and activating the receptor (i.e. protamine binds to heparin to inactivate it) |
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Term
| • Physiological antagonist |
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Definition
| produces a physiological response opposite to that of an agonist, but does not involve the receptor. Counteracts physiological effects |
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Term
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Definition
| (Effective Concentration) refers to the drug concentration that produces 50% of the maximal response. |
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Term
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Definition
| (Effective median Dose) refers to the drug dose that is pharmacological effective in 50% of the population. |
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Term
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Definition
| (Median Toxic Dose) refers to the dose of drug that causes a toxic response in 50% of the population. |
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Term
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Definition
| (Median Lethal Dose) refers dose that will kill 50% of the population. |
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Term
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Definition
(Therapeutic Index) also called (Therapeutic Ratio) provides a single number that quantifies the relative safety margin of a drug in a population of people. A drug with higher therapeutic index is safer than one with a lower therapeutic index.
TI = TD50/ED50 |
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Term
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Definition
Absorption- rate at which a drug leaves its site of administration and the extent to which
this occurs
o Distribution- the transport of a drug in body fluids from the blood stream (at the site of
absorption) to various tissues in the body.
o Metabolism- chemical inactivation of a drug by conversion to a more water soluble
compound that can be excreted from the body
o Elimination- process by which drugs and their metabolites are removed from the body. Liver
and kidney are two major organs responsible for elimination |
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