Catecholamines

Question 1

What are drugs in the category of catecholamines?

Answer 1

Norepinephrine
Epinephrine
Isoproterenol
Dopamine
Dobutamine

Question 2

What are the steps of NE synthesis?

Answer 2

Tyrosine –> DOPA by Tyrosine hydroxylase (rate limiting)
DOPA –> Dopamine by DOPA decarboxylase
Dopamine –> NE within the storage vesicle by Dopamine-beta-hydroxylase

Question 3

What are contained in the storage vesicles of adrenergic nerves?

Answer 3

NE
Dopamine-beta-hydroxylase
ATP
Neuropeptide Y
Chromogranins

Question 4

What is the transporter that takes up dopamine into vesicle and what drug inhibits it?

Answer 4

VMAT2

Inhibited by Reserpine

Question 5

What is the enzyme in the adrenal medulla that methylates NE to EPI?

Answer 5

Phenylethanolamine-N-methyltransferase (PNMT)

Question 6

What is the transporter that reuptakes NE back into presynaptic terminal and what drug inhibits it?

Answer 6

NE transporter (NET)
Inhibited by cocaine

Question 7

What are ways that the adrenergic receptors are regulated?

Answer 7

Desensitization
Sequestration
Down-regulation

All of these occur with prolonged activation.

Question 8

What is the chaperone protein in the down-regulation and desensitization of beta-adrenergic receptors?

Answer 8

Beta-arrestin

Question 9

What are the two enzymes involved in NE and EPI metabolism?

Answer 9

COMT

MAO

Question 10

What are the intermediate metabolites produced in the adrenalmedullary pathway?

Answer 10

Metanephrine and normetanephrine

Question 11

What are the final metabolites of NE and EPI metabolism?

Answer 11

MHPG and VMA

Question 12

What are elevated free metanephrines in plasma diagnostic of?

Answer 12

Pheochromocytoma and CA-secreting paragangliomas

Question 13

Which catecholamines have a higher affinity for alpha receptors?

Answer 13

EPI and NE&raquo_space; ISO

Question 14

When comparing EPI and NE, which has a higher affinity for Beta2 receptors?

Answer 14

EPI&raquo_space; NE for Beta2 receptors

Question 15

When comparing EPI and NE, which has a higher affinity for Beta1 receptors?

Answer 15

EPI = NE for Beta1 receptors

Question 16

What receptors in NE selective for?

Answer 16

Alpha1 and Alpha2

Beta1 and Beta3

Question 17

What receptors is EPI selective for?

Answer 17

Alpha1 and Alpha2

Beta1 and Beta2

Question 18

What receptors is ISO selective for?

Answer 18

Beta 1, 2, 3

Question 19

What receptors is dopamine selective for?

Answer 19

Beta1 and D1

Question 20

What receptors is dobutamine selective for?

Answer 20

Beta1

Question 21

How does Beta1 receptor activation impact pacemaker rate?

Answer 21

Increases pacemaker rate

Question 22

How does Beta1 receptor activation impact automaticity?

Answer 22

Increases automaticity

• Recruit latent pacemaker cells
• Shift pacemaker locus, can result in ectopic pacemaker and arrhythmia

Question 23

How does Beta1 receptor activation imact action potnetial and conduction velocity in nonpacemaker fibers?

Answer 23

shortened AP and increased conduction velocity

Question 24

How does Beta1 receptor activation impact atria and ventricles?

Answer 24

Increased contractility, increased O2 consumption
Shortened systole (faster repolarization)

Question 25

Stimulation of Alpha1 and 2 receptors in blood vessels will result in _____?

Answer 25

Vasoconstriction

Question 26

Stimulation of dopamine receptors in renal vascular beds will result in ______?

Answer 26

Vasodilation

Question 27

Stimulation of Beta2 receptors in muscle and liver vascular beds will result in _____?

Answer 27

Vasodilation

Question 28

Why does infusion of NE cause a decreased heart rate?

Answer 28

NE has little effect on Beta2 receptors and therefore almost exclusively constricts vasculature Increased TPR = increased BP = activated baroreceptor vagal reflex = decreased HR

Question 29

Why does infusion of epinephrine cause a slight decrease in TPR?

Answer 29

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

Question 30

Why does infusion of isoproterenol cause a dramatic decrease in TPR?

Answer 30

ISO is beta selective, will cause vasodilation

Question 31

What are clinical uses of EPI?

Answer 31

``` 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) ```

Question 32

What are clinical uses of NE?

Answer 32

Hypotension (short term vasopressor effect e.g. during surgery) Decongestion (reduces swelling of mucosa)

Question 33

What are clinical uses of Dopamine?

Answer 33

Maintain urine production via renal vasodilation

Question 34

What are clinical uses of Dobutamine?

Answer 34

Selectively increases cardiac output, can be used in heart failure

Question 35

What effect does epinephrine have on blood glucose?

Answer 35

Causes hyperglycemia - Beta1 receptors - increase lipolysis and FFA - Beta2 receptors - increase muscle glycogenolysis - Alpha2 receptors - decrease secretion of insulin by pancreatic beta cells

Question 36

What effect does epinephrine have on K+ levels?

Answer 36

``` Transient hyperkalemia (due to release of K+ from liver) Followed by sustained hypokalema (potentiation of Na/K pump in skeletal muscle) ```

Question 37

What effect does epinephrine have on tonic skeletal muscle?

Answer 37

Tremor | EPI reduces contraction time --> shorter contraction --> incomplete fusion --> increased tremor

Question 38

Can adrenergic receptor stimulation cause salivary secretion and sweating?

Answer 38

Yes, stimulates alpha 1 receptor | Produces a much more viscous secretion than with the usual cholinergic stimulation