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
What receptors in NE selective for?
Alpha1 and Alpha2
Beta1 and Beta3
What receptors is EPI selective for?
Alpha1 and Alpha2
Beta1 and Beta2
What receptors is ISO selective for?
Beta 1, 2, 3
What receptors is dopamine selective for?
Beta1 and D1
What receptors is dobutamine selective for?
Beta1
How does Beta1 receptor activation impact pacemaker rate?
Increases pacemaker rate
How does Beta1 receptor activation impact automaticity?
Increases automaticity
- Recruit latent pacemaker cells
- Shift pacemaker locus, can result in ectopic pacemaker and arrhythmia
How does Beta1 receptor activation imact action potnetial and conduction velocity in nonpacemaker fibers?
shortened AP and increased conduction velocity
How does Beta1 receptor activation impact atria and ventricles?
Increased contractility, increased O2 consumption Shortened systole (faster repolarization)
Stimulation of Alpha1 and 2 receptors in blood vessels will result in _____?
Vasoconstriction
Stimulation of dopamine receptors in renal vascular beds will result in ______?
Vasodilation
Stimulation of Beta2 receptors in muscle and liver vascular beds will result in _____?
Vasodilation
Why does infusion of NE cause a decreased heart rate?
NE has little effect on Beta2 receptors and therefore almost exclusively constricts vasculature
Increased TPR = increased BP = activated baroreceptor vagal reflex = decreased HR
Why does infusion of epinephrine cause a slight decrease in TPR?
At low doses, EPI has more effect on Beta2 than Alpha receptors
Hence the vasodilation of vascular beds in muscle and liver due to Beta2 receptors overrides the vasoconstriction of vessels due to Alpha receptors
Slightly more vasodilation = slightly decreased TPR
Why does infusion of isoproterenol cause a dramatic decrease in TPR?
ISO is beta selective, will cause vasodilation
What are clinical uses of EPI?
Anaphylactic shock (increases cardiac output and BP, relaxes laryngeal and bronchial smooth muscle, stabilizes mast cells) Hypotension (short term vasopressor effect e.g. during surgery) Decongestion (reduces swelling of mucosa)
What are clinical uses of NE?
Hypotension (short term vasopressor effect e.g. during surgery)
Decongestion (reduces swelling of mucosa)
What are clinical uses of Dopamine?
Maintain urine production via renal vasodilation
What are clinical uses of Dobutamine?
Selectively increases cardiac output, can be used in heart failure
What effect does epinephrine have on blood glucose?
Causes hyperglycemia
- Beta1 receptors - increase lipolysis and FFA
- Beta2 receptors - increase muscle glycogenolysis
- Alpha2 receptors - decrease secretion of insulin by pancreatic beta cells
What effect does epinephrine have on K+ levels?
Transient hyperkalemia (due to release of K+ from liver) Followed by sustained hypokalema (potentiation of Na/K pump in skeletal muscle)
What effect does epinephrine have on tonic skeletal muscle?
Tremor
EPI reduces contraction time –> shorter contraction –> incomplete fusion –> increased tremor
Can adrenergic receptor stimulation cause salivary secretion and sweating?
Yes, stimulates alpha 1 receptor
Produces a much more viscous secretion than with the usual cholinergic stimulation
