Term
| what do adrenergic or sympathomimetic drugs do? |
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Definition
| mimic the sympathetic nervous system |
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Term
| what does the sympathetic nervous system do? |
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Definition
| it is involved in homeostatic regulation of heart rate, force of cardiac contraction, vasomotor tone, BP, bronchial airway tone, and carbohydrate and fatty acid metabolism |
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Term
| what are the 3 NTs in the sympathetic nervous system? how do they compare in terms of structure? |
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Definition
| dopamine, epinephrine, and norepinephrine. they are all catecholamines (6C ring w/hydroxyls on Cs 3 & 4) with differences on the beta carbon and amine group |
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Term
| what is the structure of dopamine? |
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Definition
| the beta carbon has no OH, and the functional group is just an amine |
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Term
| what is the structure of norepinephrine? |
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Definition
| OH on the beta carbon, and the functional group is just an amine |
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Term
| what is the structure of epinephrine? |
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Definition
| OH on the beta carbon, and the functional group is a methylated amine |
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Term
| what is possible due to the subtle differences between the catecholamines? |
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Definition
| they each work primarily in certain areas, but can also function as one of the others |
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Term
| what is the synthesis pathway for dopamine? |
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Definition
| tyrosine ->(tyrosine hydroxylase)->DOPA->(DOPA decarboxylase)->dopamine->(DA-B-hydroxylase)->norepinephrine->(phenylethanolamine N-methyltransferase)-> epinephrine |
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Term
| what is different about storage sacs in dopaminergic cells vs non-dopaminergic cells in the adrenergic system |
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Definition
| in non-dopaminergic cells, DA-B-hydroxylase is in the membrane to convert it to norepinephrine, while in dopaminergic cells, that enzyme is not present so in uptake, the molecule remains dopamine (DA) |
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Term
| how is epinephrine produced? |
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Definition
| in the chromaffin cells of the adrenal glands, which have phenylethanolamine N-methyltransferase which convert norepi to epi |
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Term
| what are the 3 main pathways for NT response termination? |
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Definition
| metabolism, uptake, and dilution |
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Term
| what are the 2 enzymes that carry out metabolic NT termination for all 3 catecholamines? |
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Definition
| monoamine oxidase (MAO) and catechol O-methyltransferase (COMT) |
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Term
| where is monoamine oxidase found? what does it do? |
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Definition
| in the mitochondria of nerve terminals it oxidatively deaminates the alpha carbon. (MAO: Mitochondria, Alpha carbon) |
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Term
| where is catechol O-methyltransferase found? what does it do? |
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Definition
| in the cytoplasm, esp in the liever, and there are moderate amounts in the adrenergic synapse itself. it transfers a methyl group to the 3 position of the catechol, inactivating it. (COMT: Cytoplasm, Oxygen) |
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Term
| can both metabolic enzymes work on the same catecholeamine? |
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Definition
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Term
| what does the uptake1/reuptake system do? |
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Definition
| this is an active transport system that takes up various amines (not just catecholamines), removing them from the synapse, and into the cytoplasm - where MAO deaminates them or they are repackaged into vesicles for further use. |
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Term
| what is the process of dilution? |
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Definition
| diffusion out of the synapse, drifting away to lower concentrations. once this occurs, uptake can happen at extraneuronal sites such as the glial (astroglia) cells in the CNS. |
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Term
| what is the most important method for terminating norepinephrine? |
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Definition
| the uptake1 pump, which reuptakes 80% of the released NT and repackages it back into the vesicles |
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Term
| what usually happens to the 20% norepinephrine that is not reuptaken by uptake1? |
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Definition
| that 20% is usually metabolized by MAO in the nerve terminal, diffused away or metabolized by COMT and taken up by non-neuronal cells |
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Term
| what can norepinephrine do once release from into the synaptic cleft? |
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Definition
| once released, norepinephrine can bind to pre/postsynaptic receptors, it can be taken up by the post synaptic uptake system or the pre synaptic uptake system (if this happens – some of it metabolizes by MAO, but majority comes right back in to synaptic vesicle), and if it is taken up by extra neuronal uptake pumps it will be acted on by COMT |
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Term
| where are the alpha1 adrenergic receptors? |
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Definition
| postsynaptic (on target tissue) |
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Term
| where are the alpha2 adrenergic receptors? |
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Definition
|
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Term
| where are the beta1 adrenergic receptors? |
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Definition
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Term
| where are the beta2 adrenergic receptors? |
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Definition
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Term
| what 4 things happen when the alpha1 receptor (postsynaptic) is activated by NE? |
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Definition
| 1) vasoconstriction of all blood vessels, leading to an increase in TPR, which will increase BP (allows for higher level of activity in more extreme body positions) and mucosal decongestion (allows greater flow of O2). 2) radial muscles of the eye conract:mydriasis/dilation -which allows more light into the eyes, improving vision. 3) pilomotor muscles of the skin will contract - hair sticks up (evolutionary advantage in hair standing up scaring off predators). 4) hyperglycemia: want to develop high blood sugar level for higher level of muscle activity |
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Term
| what 2 things happen when the alpha2 receptor (presynaptic) is activated by NE? |
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Definition
| at the synapse, the release of NE is reduced and in the CNS sympathetic outflow is reduced |
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Term
| what 3 things happen when the beta1 receptor (heart) is activated by NE? can dopamine also accomplish the same effect? |
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Definition
| HR is increased, force of contraction is increased, and velocity of contraction is increased, (to increase CO for increased muscle use). dopamine as well as NE can also accomplish this same effect in the heart. |
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Term
| what 4 things happen when the beta2 receptor (blood vessels) is activated by NE? |
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Definition
| 1) vasodilation in the skeletal muscle, pulm, and coronary vessels (NOT smooth like GI, this allows better nutrient transfer to muscles of mobility). 2) bronchodilation (higher O2 availability). 3) uterine relaxation (prevents labor under stress, but can be overridden). 4) hyperglycemia, lactic acidemia, and lipolysis |
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Term
| why do drugs designed to affect specific receptors such as alpha1 or beta2 still have varying effects? |
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Definition
| there are different subtypes of each receptor which different drugs designed for that same receptor have a varying affinity for. |
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Term
| where are beta 3 receptors? |
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Definition
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Term
| out of the catecholamines, what is the order of agonist potency for alpha receptors? |
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Definition
| epi -> norepi -> dopamine -> isoproterenol |
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Term
| what is the order of agonist potency for beta 1 receptors? |
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Definition
|
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Term
| what is the order of agonist potency for beta 2 receptors? |
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Definition
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Term
| what 2 things will affect alpha receptors and cause contraction? |
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Definition
| NR or high dose EPI (like in local anesthetics, makes them last longer b/c they won't be carried away) |
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Term
| what 2 things will affect beta receptors and cause dilation? |
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Definition
| ISOP and low dose EPI (like in asthma inhalers) |
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Term
| what is the mechanism for drugs acting at alpha receptors? |
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Definition
| the phosphatidylinositol second messenger system (IP turnover) |
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