Catecholamines Flashcards
What are drugs in the category of catecholamines?
Norepinephrine Epinephrine Isoproterenol Dopamine Dobutamine
What are the steps of NE synthesis?
Tyrosine –> DOPA by Tyrosine hydroxylase (rate limiting)
DOPA –> Dopamine by DOPA decarboxylase
Dopamine –> NE within the storage vesicle by Dopamine-beta-hydroxylase
What are contained in the storage vesicles of adrenergic nerves?
NE Dopamine-beta-hydroxylase ATP Neuropeptide Y Chromogranins
What is the transporter that takes up dopamine into vesicle and what drug inhibits it?
VMAT2
Inhibited by Reserpine
What is the enzyme in the adrenal medulla that methylates NE to EPI?
Phenylethanolamine-N-methyltransferase (PNMT)
What is the transporter that reuptakes NE back into presynaptic terminal and what drug inhibits it?
NE transporter (NET) Inhibited by cocaine
What are ways that the adrenergic receptors are regulated?
Desensitization
Sequestration
Down-regulation
All of these occur with prolonged activation.
What is the chaperone protein in the down-regulation and desensitization of beta-adrenergic receptors?
Beta-arrestin
What are the two enzymes involved in NE and EPI metabolism?
COMT
MAO
What are the intermediate metabolites produced in the adrenalmedullary pathway?
Metanephrine and normetanephrine
What are the final metabolites of NE and EPI metabolism?
MHPG and VMA
What are elevated free metanephrines in plasma diagnostic of?
Pheochromocytoma and CA-secreting paragangliomas
Which catecholamines have a higher affinity for alpha receptors?
EPI and NE»_space; ISO
When comparing EPI and NE, which has a higher affinity for Beta2 receptors?
EPI»_space; NE for Beta2 receptors
When comparing EPI and NE, which has a higher affinity for Beta1 receptors?
EPI = NE for Beta1 receptors