Adrenergic Agonists

Question 1

Synthesis of NE

Answer 1

• starts with tyrosine
• tyrosine transformed into DOPA in neuron, rate limiting step
• formed into dopamine in the neuron
• goes into vesicles
• turns into NE inside the vesicle

Question 2

What is the rate limiting step in NE synthesis

Answer 2

Tyrosine into DOPA in the neuron

Question 3

Where is NE formed?

Answer 3

Inside the vesicle

-from dopamine

Question 4

Release of NE

Answer 4

• similar to Ach
• depolarize
• Ca2+ channels open
• Ca2+ rushes in
• vesicles go to membrane
• NE released into synapse

Question 5

What are the fates of NE once it is released into the synapse?

Answer 5

1. Bind to alpha or beta
2. Metabolized by COMT
3. NE reuptake into neuron
4. Negative feedback binding to presynaptic

Question 6

What does NE bind to

Answer 6

Alpha or beta

Question 7

What is NE metabolized by

Answer 7

COMT

-turned into inactive metabolites, just like Ach is with acetylcholinesterase

Question 8

NE reuptake into neuron

Answer 8

• very rapid
• goes back into the presynaptic neuron without being degraded (differnt for Ach)
• reason for short half life
• clears synapse even better than COMT

Question 9

What is the major reason for short half life of NE

Answer 9

Rapid reuptake into the presynaptic neuron

Question 10

What clears the synapse better, NE reuptake or COMT?

Answer 10

Reuptake

Question 11

What receptor does NE bind to presynaptic ally for negative feedback on the neuron

Answer 11

A2

• low CAMP
• closes Ca2+ channels
• vesicle wont migrate
• wont release NE

Question 12

Alpha 2 agonist

Answer 12

• stops NE release

- lowers BP

Question 13

Alpha 2 antagonist

Answer 13

Increases NE release

Increases BP

Question 14

COMT inhibitor

Answer 14

Increase NE in synapse

Question 15

Cocaine and NE

Answer 15

Blocks reuptake
Blocks major pathway to clear NE
Stimulant effect

Na/K ATPase is what gets blocked by cocaine

Question 16

TCA (tricyclic antidepressants) and NE

Answer 16

Work like cocaine

-block reuptake of NE

Question 17

MAO

Answer 17

• Monamine oxidase inhibitor
• Metabolizes amines in the cytoplasm (dopamine, NE, dopamine safe from it in the vesicle)
• when there is reuptake of NE, MAO waits for it in the cytoplasm and limits NE in the neuron by degrading excess of it

Question 18

MAOI (MAO inhibitor)

Answer 18

Increase recycling, increase NE

Question 19

What is the enzyme responsible for the rate limiting step of NE synthesis

Answer 19

Tyrosine hydroxylase

-tyrosine into DOPA

Question 20

there is one more step to NE synthesis that is not made int sympathetic nerves

Answer 20

NE into epi. This is done in adrenal medulla. Sympathetic nerves do not have the enzyme necessary to do this

Question 21

A1 receptor

Answer 21

Gq

Question 22

A2 receptors

Answer 22

Gi

Question 23

B receptors

Answer 23

Gs

Question 24

Tissues and receptor types

Answer 24

Different tissues have differnt receptors

Question 25

Catecholamines

Answer 25

Epinephrine NE Dopamine

Question 26

Duration of action of epi, NE, and dopamine

Answer 26

They are rapidly metabolized by COMT and MAO, so they have a short duration of action

Question 27

Epi, NE, and dopamine given as drugs and the CNS

Answer 27

Not much penetration into the CNS

Question 28

What type if receptors are found in most vascular smith muscle and what are the actions of it

Answer 28

A1 | Contracts, vasconstricts, increase TPR, increase BP

Question 29

What kind of receptors are in pupillary radial muscle and what is the action

Answer 29

A1 | Contracts (mydriasis)

Question 30

What kind of receptor is in the prostate and what does it do

Answer 30

A1a!!!! | Contracts and decreases urine output

Question 31

What kind of drug should be given for BPH (benign prostate hyperplasia)

Answer 31

A1 antagonsit

Question 32

What kind of drugs should be avoided in someone with BPH (benign prostate hyperplasia)

Answer 32

A1 agonist | M blockers

Question 33

What kind of receptors are on adrenergic and cholinergic nerve terminals and what do they do

Answer 33

A2 Inhibits transmitter release via negative feedback Don't worry too much about the cholinergic part

Question 34

What kind of receptors are on pancreatic Bcells and what do they do

Answer 34

A2 Inhibits insulin release Want to use nutrients in fight or flight, not store them

Question 35

What kind of receptors are on the heart and what do they do

Answer 35

B1 | Stimulates rate and force

Question 36

What kind of adrenoreceptors are on the juxtaglomerular cells and what do they do?

Answer 36

B1 Stimulates renin release Activates RAAS

Question 37

What drug can inhibit sympathetic induced renin release

Answer 37

B1 blocker

Question 38

What kind of adrenorecptors are on respiratory, uterine, and vascular smooth muscle and what do they do?

Answer 38

``` B2 Relaxes -bronchodilate -can stop premature labor -vasodilator BV and decrease TPR and BP ```

Question 39

What kind of drugs are good to give for asthma

Answer 39

B2 agonists and M antagonists

Question 40

What is a good drug to give someone going into premature labor?

Answer 40

B2 agonist

Question 41

What does a B2 agonist do to blood vessels and blood pressure

Answer 41

Vasodilate, decreases TPR and BP

Question 42

Which adrenoreceptor is not innervated?

Answer 42

B2

Question 43

What adrenorecptor is on the liver and what does it do

Answer 43

B2 Stimulates glycogenolysis -need glucose quick for fight or flight

Question 44

What adrenorecptor is on voluntary muscle and what does it do

Answer 44

B2 Causes tremor -they dont do much because they are not innervated. We dont expect a tremor, but when someone takes a B2 agonist for asthma way more than they need, they get a tremor because of decreased BP. Usually systemic. A premature labor patient would have a tremor too

Question 45

What adrenorecptors are found on fat cells and what do they do

Answer 45

B3 | Stimulates lipolysis

Question 46

What adrenoreceptors are found on renal and other splanchnic blood vessels and what do they do

Answer 46

D1 Relaxes (reduces resistance) Vasodilate in renal BV

Question 47

CNS effects of catecholamines

Answer 47

They do not enter the CNS effectively -amphetamines are an example of sympathmimetics which do enter the CNS and can cause reduced fatigue, euphoria, and insomnia

Question 48

What kind of sympathomimetic can get into the CNS

Answer 48

Amphetamines

Question 49

Effects of adrenorecptors on the eye

Answer 49

The radial muscle responds to a1 agonists with mydriasis

Question 50

Effects of adrenoreceptors on the bronchi

Answer 50

The smooth muscle of the bronchi relax in response to B2 agonists

Question 51

GI tract effect of adrenorecptors

Answer 51

A1 and b2 both mediate smooth muscle relaxation

Question 52

Effect of adrenorecptors on genitourinry tract

Answer 52

A1 receptors in the bladder mediate contraction of the sphincter, B3 agonists relax detrusor muscle

Question 53

A1 agonists in the vascular system

Answer 53

Constrict skin and splanchnic blood vessels and increase peripheral vascular resistance nad venous pressure; since these drugs increase BP they evoke a compensatory reflex bradycardia Response on heart is opposite of blood pressure Increased BP=decreased HR

Question 54

A2 agonists on the vascular system

Answer 54

When given orally, they accumulate in the CNS and reduce sympathetic outflow and blood pressure -would get reflected tachycardia