Term
| What are the different kinds of adrenergic receptors? What G protein do they use? What is their overall effects? |
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Definition
-α1; Gq, vasoconstriction, **increased BP, mydriasis (dilation), closure of internal sphincter of bladder (urinary retention
-α2; Gi, inhibits NE and insulin release
-β1; Gs, tachycardia, increased lipolysis
-β2; Gs, vasodilation, **decreased BP, bronchodilation, increased glucagon and glycogenolysis, relaxation of uterine smooth muscle
-Notice that α1 and β2 are somewhat antagonistic with α1 acting to increase BP and β2 acting to decrease BP |
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Term
| What are catecholamines? What are the endogenous ones? What are the synthetic ones (2)? |
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Definition
-They are adrenergic agonists with catechol groups (benzene with a meta and para OH); can act on α or β
-Endogenous; DA,NE,EPI (all from Tyr-->L-Dopa-->DA)
-Synthetic; **Dobutamine, **isoproterenol |
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Term
| What is the catecholamine structure? Give the structures of dopamine, NE, EPI, and isoproterenol? Give the receptor they prefer? |
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Definition
-It has the catechol group; benzene with meta & para OH
-For the R group, it has an ethylamine (-C-C-N) which can bear various substitutions
Dopamine;
(OH)2-Φ-CH2-CH2-NH2
-Binds D receptors, some β, no α
Norepinephrine;
(OH)2-Φ-CHOH-CH2-NH2
-Binds both α's, and some β1, but not β2**
Epinephrine;
(OH)2-Φ-CHOH-CH2-NHCH3
-Binds both α and β
Isoproterenol;
(OH)2-Φ-CHOH-CH2-N(CH3)2
-Both β's, but not α's**
-Note that the α carbon is next to the N |
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Term
| Where are the three places on catecholamines we can substitute, and what changes do they produce? Give an example? |
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Definition
At the N group;
-Larger alkyl subs on the amino group gives increased preference for β receptors (e.g. Isoproterenol)
On benzene ring;
-Removing the OHs will increase lipid solubility, thereby increasing bioavailability and duration of action (e.g. all the noncatecholamine sympathomimetics, like ephedrine)
On the α carbon (one N is attached to);
-Blocks oxidation by MAO and prolongs duration of action (e.g. ephedrine and some of the other noncat drugs)
On the β carbon (one Φ is attached to);
-Putting an OH there allows optical isomerism, which is important in vesicle storage apparently ( |
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Term
| Overall, what are we doing by exciting the adrenergic receptors? |
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Definition
-We are stimulating the sympathetics
-Their end synapses are all adrenergic (except for sweat glands, which are cholinergic) |
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Term
Clinically, for what do we use;
-Dopamine
-NE
-EPI
-Isoproterenol |
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Definition
-Dopamine; Shock
-NE; Hypotension (α1, no β2)
-EPI; Anaphylaxis, cardiac arrest, glaucoma (topical)
-Isoproterenol; Congestive heart failure (CHF) (β2, no α1) |
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Term
| What do NE, EPI, & isoproterenol do to BP and HR? Which have a greater effect on pulse pressure |
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Definition
-NE; raises BP, lowers HR
-EPI; raises both
-Isoproterenol; lowers BP, raises HR
-The HR is compensatory in NE and iso
-EPI is more α stimulating at higher doses (similar to norepinephrine)
-EPI & Iso give a much greater effect on pulse pressure. |
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Term
| What are the non-catecholamine adrenergic agonists (2 direct and 2 indirect)? What are the advantages to using these? |
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Definition
Direct acting;
-Phenylephrine
-Albuterol
Indirect acting agents;
-Amphetamine
-Ephedrine
-These have substitutions that make them last longer (block MAO & COMT, increase bioavailability, etc.)
-Keep in mind, the indirect acting increase release of endogenous catecholamines (esp. NE) |
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Term
| What are the side effects of stimulating the sympathetic system with catecholamines? Give the stimulated receptor in each case? |
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Definition
-Hyper/hypotension (α1/β2)
-Arrhythmias and infarct (β1) |
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