L6

Question 1

What is the rate limiting step in NE synthesis?

Answer 1

Tyrosine –> DOPA

Tyrosine hydroxylase

Question 2

What enzyme converts DOPA –> dopamine?

Answer 2

DOPA decarboxylase

Question 3

What enzyme converts dopamine –> NE?

Answer 3

Dopamine beta hydroxylase

Question 4

What transporter brings dopamine into vesicles in the adrenergic nerve terminal?

Answer 4

VMAT2

H+ counter transport

Question 5

Which drug can be used to deplete NE by inhibiting VMAT2?

Answer 5

Reserpine

Question 6

When enzyme converts NE –> E? In what organ?

Answer 6

PNMT inside vesicles

Adrenal medulla

Question 7

What is the mechanism of NE feedback inhibition?

Answer 7

Alpha 2 auto-receptors on the pre-synaptic side

Question 8

What is the primary mechanism for NE inactivation?

Answer 8

NET reuptake into pre-synapse

Question 9

What is the secondary mechanism for NE inactivation?

Answer 9

Facilitated diffusion out of cleft by OCT3 into the post-synaptic side

Question 10

How does cocaine work at adrenergic nerve terminals?

Answer 10

Inhibits NET

Increases NE time in synapse

Question 11

What are the 3 ways NE adrenergic receptors can be regulated on the post-synaptic membrane?

Answer 11

1. Desensitization (sec)
   - Phos the receptor, uncouple action from ligand binding
2. Sequestration (mins) = aggregation, internalization
3. Down regulation (hrs) via less mRNA

Question 12

If the receptor is G protein independent, what is the mechanism by which it will be regulated?

Answer 12

B arrestin = signaling molecule to inactivate

Question 13

If the receptor is G protein dep, what is the mechanism by which it will be regulated?

Answer 13

B arrestin = chaperone for INTERNALIZATION

Question 14

Does MAO or COMT metabolize NE in the pre-synaptic neuron?

Answer 14

MAO

Question 15

Does MAO or COMT metabolize NE in the post-synaptic neuron?

Answer 15

COMT

Question 16

Describe the sympathetic nerve metabolism of NE/E

Answer 16

1. NE/E + MAO –> DHPG
2. • COMT –> MHPG
3. MHPG reduced = glycol
   MHPG oxidized (liver) = VMA

Question 17

Describe the adrenergic nerve metabolism of NE/E

Answer 17

1. N/E + COMT –> normet/met
2. • MAO –> MHPG
3. MHPG reduced = glycol
   MHPG oxidized (liver) = VMA

Question 18

What is elevated plasma free (unconj) metanephrines diagnostic of?

Answer 18

Pheochromocytoma
Catecholamine secreting paraganliomas
Or pt is on drugs that release or inhibit reuptake of NE

Question 19

A1 agonist

Answer 19

Phenylephrine

Question 20

A2 agonist

Answer 20

Clonidine

Question 21

B1 agonist

Answer 21

Dobutamine

Question 22

B2 agonist

Answer 22

Albuterol

Question 23

B3 agonist

Answer 23

Mirabegron

Question 24

3 effects of A1 agonist

Answer 24

1. Smooth muscle contraction - vascular, iris, GU
2. Secretion - salivary & sweat glands
3. K+ release from liver

Question 25

4 effects of A2 agonist

Answer 25

1. ↓NE @ nerve term 2. Contract vasc smooth muscle 3. ↓ insulin secretion 4. Platelet aggregation

Question 26

4 effects of B1 agonist

Answer 26

1. ↑HR 2. ↑contractility 3. ↑conduction velocity 4. ↑renin from kidney

Question 27

4 effects of B2 agonists

Answer 27

1. Dilate BVs in skeletal muscle & liver 2. ↑glucose & K in skeletal muscle 3. ↑glucose @ liver 4. Mast cell stablization

Question 28

2 effect of B3 agonists

Answer 28

1. Relax bladder | 2. Lypolysis

Question 29

What is the difference between B1 & 2 receptors with NE/E?

Answer 29

B1: E=NE agonism B2: E > NE

Question 30

Are catecholamines hydrophobic or philic - explain effects.

Answer 30

Hydrophobic - poor penetration | - Injector topical

Question 31

Do catecholamines have long or short half lives?

Answer 31

SHORT

Question 32

What is NE's receptor selectivity?

Answer 32

A1, 2 | B1; 3

Question 33

What is E's receptor selectivity?

Answer 33

A1, 2 | B1, 2

Question 34

What is isoproterenol's receptor selectivity?

Answer 34

= 100% beta agonist | B1, 2, 3 only

Question 35

What is dopamine's receptor selectivity?

Answer 35

B1 - need ↑[ ] | D1 - dilate renal & GI vascular beds, ↑NA excretion at kidneys

Question 36

What is dobutamine's receptor selectivity?

Answer 36

B1 only

Question 37

What is the main adrenergic receptor in the heart?

Answer 37

B1 Some B2 NO ALPHA

Question 38

What happens if E + SA node?

Answer 38

``` Epi + beta receptor - AC --> cAMP --> PKA ↑HR and contractility - Faster depol & repol due to ↑PKA - Faster pacemaker potential due to ↑cAMP ↑freq of impulses ```

Question 39

What is a downside of using B agonists in the heart?

Answer 39

↑risk arrhythmia | ↑risk cardiac arrest due to VFib

Question 40

What do A1 & 2 receptors do to vascular smooth muscle: cuteanous, mesenteric, renal, muscle, liver?

Answer 40

Vasoconstrict

Question 41

What is the baroreceptor reflex in context of slow NE infusion?

Answer 41

+ NE A1 vasocontrict --> ↑TPR --> ↑BP B1 at heart means you'd expect ↑HR... but vagal reflex dominates so ↑BP overrides to ↓HR ACh acts on muscarinic receptors

Question 42

What happens with slow E infusion?

Answer 42

``` B2 - vasodilation in skeletal muscle ↓TPR --> ↓DBP ↑CO --> ↑SBP Not dramatic enough rise BP to warrant vagal response - ↑HR & BP at same time (EXERCISE) ```

Question 43

What happens with slow isoproterenol infusion?

Answer 43

B effects only Dilation --> ↓DBP ↑HR & CO but overall BP ↓s even if systolic increases slightly due to CO

Question 44

Why use E for cardiac arrest?

Answer 44

Peripheral vasoconstriction - ↑coronary perfusion

Question 45

Why use E for anaphylatic shock?

Answer 45

↑CO ↑BP (alpha) Bronchodilate (alpha & B2) Stabilize mast cells (B2)

Question 46

Why use NE or E for mucosal decongestion?

Answer 46

Alpha - vasocontrict to ↓swelling and secretions

Question 47

Why use NE or E for hypotension?

Answer 47

Vasopressor short term

Question 48

Why use DO during acute heart failure?

Answer 48

Selectively B1 -↑CO

Question 49

Adverse effects E/NE

Answer 49

MI Arrythmia Hypoxia Necrosis at IV sites