Term
| what is the qualification of a drug that binds to a receptor |
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Definition
| it must induce a biological response |
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Term
| what drugs dont use receptors |
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Definition
| diuretics and anesthetics |
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Term
| where are drug receptors located |
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Definition
| membrane proteins, cytoplasmic enzymes, extracellular enzymes, nucleic acids |
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Term
| why are drugs/receptors specific |
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Definition
| differnet tissues have receptors with different conformations that will only accept certian drugs |
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Term
| what is the purpose of innert binding sites |
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Definition
| drug binds a non-regulatory molecule (most commonly plasma membrane) and causes no changes but hitches a ride because it is lipid soluble and cannot travel in the blood |
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Term
| how does innert binding sites affect drug effects |
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Definition
| they ability or need of a drug to bind to them effects distribution and amount of the drug availiable |
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Term
| explain the role of ionization in drug binding to receptor, what is the down side of needing to be ionized for bonding |
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Definition
when drug nears receptor various ionic bonds form but to participate the drug needs to be ionized first.
some drugs are already ionized
pH will alter non-ionized drugs |
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Term
| what is the down side of a pre-ionized drug, what is the up side |
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Definition
it is water solube and will not distribute as well in the body because it cant get through membranes well (so no BBB or placenta crossing)
pH will not alter these as much |
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Term
| where are nicotinic ACh receptors located |
|
Definition
neuromuscular junction muscle end plate
autonomic ganglic
CNS |
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Term
| what type of receptors are nicotinic ACh receptors |
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Definition
| ligand gated ion channels |
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Term
| what is the general function of a nicotinic ACh receptor, how does it work |
|
Definition
depolarization of a cell
2ACh bind to 2 alpha subunts on recpetor and electrically open Na or K channels causing depolarization |
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Term
| what is the down side of using nicotinic ACh receptors as a drug target, why |
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Definition
| they can become desensitized if they have prolonged ACh exposure because the conformation of the receptor is altered so even if ACh binds there is no depolarization |
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Term
| where are sodium channels located |
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Definition
| excitable tisses like nerve, cardiac, skeletal muscle |
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Term
| what type of channel are sodium channels, how do they work |
|
Definition
voltage gated ion channels
resting state channel is closed and intracellular Na is low due to Na/K pump. depolarization of the membrane opens the channel allowing Na into the cell |
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Term
| what drugs target Na channels, why |
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Definition
| anesthetics to block nerve transmission by stopping Na influx |
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Term
| where are g-protein coupled receptors located, describe their general structure |
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Definition
on almost all cells
heterotrimetric receptor with 7 transmembrane domains |
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Term
| explain the process of a Gs or Gi protein once a ligand binds them |
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Definition
alpha subunit catalizes exchange of GDP to GTP and releases from beta and gamma creating alpha-GTP
alpha-GTP activates adenylyl cyclase then hydrolyzes GTP back to GDP
adenylyl cyclase converts ATP to cAMP
cAMP activates protein kinase A |
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Term
| explain the process of a Gq protein once a ligand binds them |
|
Definition
alpha subunit catalizes exchange of GDP to GTP and releases from beta and gamma creating alpha-GTP
alpha-GTP activates phospholipase C then hydrolyzes GTP back to GDP
phospholipase C releases IP3 and DAG from the phosphatidylinositol in the plasma membrane
IP3 activates Ca and calmodulin dependent kinase
DAG activates protein kinase C |
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Term
| give examples of receptors Gs proteins are on |
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Definition
|
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Term
| give examples of receptors Gi proteins are on |
|
Definition
M2 muscrinic
a2 adrenergic
D2 dopamine |
|
|
Term
| give examples of receptors Gq proteins are on |
|
Definition
a2 adrenergic
M2 and M3 muscerinic
5HT2 serotonin |
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Term
| what agonists can activate a tyrosine kinase receptor |
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Definition
| insulin, EGF, PDGF, HGF, ANF, TGF-beta |
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Term
| describe the structure of a tyrosine kinase receptor |
|
Definition
extracellular ligand binding domain
single transmembrane domain
intracellular binding domain with an INTRINSIC tyrosine kinase (means it is not activated by the receptor, it is ON the receptor) |
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Term
| explain how a tyrosine kinase receptor works |
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Definition
| ligand binds the extracellular domain, receptor dimerizes, tyrosine kinase signals within the cell |
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Term
| what agonists can activate a cytokine receptor |
|
Definition
| growth hormone, erythropoetin, interferons |
|
|
Term
| explain how a cytokine receptor works |
|
Definition
ligand binds, receptor dimerizes
JAK activates STATs
STATs signal transcription of genes |
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|
Term
| agonists to intracellular receptors (6) |
|
Definition
| corticosteroids, mineralcorticoids, sex steroids, thyroid hormones, vitamin D, NO |
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|
Term
| how does a steroid agonist activate a receptor |
|
Definition
| agonist goes through cell membrane to intracellular cytoplasmic receptor, receptor ligand complex travels to nucleus and signals transcription of genes |
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Term
| explain how NO activates the receptor and changes within the cell |
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Definition
| NO is generated in endothelial cells and diffuses into smooth muscle cells and reacts with gyanylyl cyclase which stimulates cGMP which activates protein kinase G which phosphorlyates to relax smooth muscle |
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