EXAM #1: AND PHARMACOLOGY - ADRENERGIC

Question 1

What is the rate limiting step in catecholamine synthesis? What enzymes catalyzes this reaction?

Answer 1

Tyrosine–>DOPA, which is catalyzed by the enzyme “Tyrosine Hydroxylase”

Question 2

What drug blocks the conversion of Tyrosine to DOPA?

Answer 2

Metyrosine

Question 3

How are synthesized catecholamines transported into vesicles?

Answer 3

VMAT (vesicular monoamine transporter)

Question 4

What drug blocks VMAT?

Answer 4

Reserpine

Question 5

Clinically, how is reserpine used?

Answer 5

To treat resistive HTN

Question 6

What facilitates binding of vesicles containing catecholamines to the nerve terminal membrane?

Answer 6

VAMPs

Question 7

What drug blocks VAMPs?

Answer 7

Bretyilum

Question 8

What are the three methods that terminate catecholamine action?

Answer 8

1) Simple diffusion
2) Neuronal reuptake
2) Extra-neuronal uptake

Question 9

What enzyme metabolizes catecholamines that diffuse into the circulation?

Answer 9

COMT

“Catechol-O-methyl-transferase”

Question 10

What transporter facilitates the neuronal reuptake of NE?

Answer 10

NET1

Question 11

What drugs can inhibit NET1? What is the effect of these drugs?

Answer 11

• Cocaine
• Tricyclic antidepressants

These drugs increase the concentration of NE in the synaptic cleft

Question 12

What are the analogs to NET for DA and 5-HT?

Answer 12

DAT

SERT

Question 13

What transporter facilitates extraneuronal reuptake of catecholarmines? What drugs can block these transporters?

Answer 13

• ENT/ NET2

Corticosteroids can block these transporters.

Question 14

What is the fate of catecholamines that have been reuptaken into a nerve terminal?

Answer 14

1) Restored in vesicles for release
2) Metabolism by monoamine oxidase (MAO)

Note that there are two isoforms of MAO, MAO-A and MAO-B.

• MAO-A= NE, 5-HT, and tyramine
• MAO-B= DA

Question 15

What drug can inhibit MAO?

Answer 15

Phenelzine

Question 16

Draw the mechanisms G-protein linked second messenger activation.

Answer 16

p. 244 First Aid

Question 17

What is the mnemonic to remember the receptor types and their associated g-protein class?

Answer 17

“Qiss and qiq till you’re siq of sqs.”

Question 18

Outline the mnemonic to remember the receptor types and their associated g-protein class.

Answer 18

p. 244 First Aid

Question 19

List the Gq-coupled receptors. What is the mnemonic to remember these receptors?

Answer 19

H1
Alpha-1 
V1 
M1 
M3 

“HAVe 1 M and M”

Question 20

List the Gs-coupled receptors.

Answer 20

B1
B2
D1
H2 
V2

Question 21

List the Gi-coupled receptors. What is the mnemonic to remember these receptors?

Answer 21

M2
Alpha-2
D2

“MAD 2s”

Question 22

Where are alpha-1 receptors located?

Answer 22

Vascular smooth muscle

• Arterioles
• Veins

Radial (dilator) muscle of the eye

Bowel and bladder sphincters

• Bladder trigone and sphincter
• Male sex organ

Liver
Kidney

Question 23

What is the consequence of alpha-1 activation in the eye?

Answer 23

Contraction–>mydriasis

Question 24

What is the effect of alpha-1 activation in the arterioles?

Answer 24

Contraction leading to:

• Increased TPR
• Increased diastolic pressure
• Increased afterload

Question 25

What is the effect of alpha-1 activation in the veins?

Answer 25

Contraction leading to: - Increased venous return - Increased preload

Question 26

What is the effect of alpha-1 activation in the bladder trigone and sphincter?

Answer 26

Contraction leading to urinary retention

Question 27

What is the effect of alpha-1 activation in the male sex organ?

Answer 27

Ejaculation

Question 28

What is the effect of alpha-1 activation in the liver?

Answer 28

Increased glycogenolysis

Question 29

What is the effect of alpha-1 activation in the kidney?

Answer 29

Decreased renin release

Question 30

List the locations of alpha-2 receptors.

Answer 30

Prejunctional nerve terminals - Decreased SNS output Platelets - Aggregation Pancreas - Decreased insulin release - Decreased lipolysis

Question 31

What is the effect of alpha-2 activation in the prejunctional nerve terminal?

Answer 31

Decreased NE synthesis and release

Question 32

What is the effect of alpha-2 activation in the platelets?

Answer 32

Platelet aggregation

Question 33

What is the effect of alpha-2 activation in the pancreas?

Answer 33

Decreased insulin secretion

Question 34

List the locations of B1 receptors.

Answer 34

Heart - Increased rate - Increased contractility Kidney - Increased renin release Increased lipolysis

Question 35

What is the effect of Beta-1 activation in the heart?

Answer 35

SA Node= positive chronotrope AV node= positive dromotrope Atrial and ventricular muscle= - positive ionotrope - increased conduction velocity, CO, and O2 consumption

Question 36

What is the effect of Beta-1 activation in the kidney?

Answer 36

Increased Renin release

Question 37

List the locations of Beta-2 receptors.

Answer 37

- Heart= increased rate and contractility - Liver= increased lipolysis - Pancreas= Increased insulin release - Eye 1) Ciliary epithelium= aqueous humor production 2) Ciliary m.= relaxation - Vascular smooth muscle= vasodilation - Bronchioles= bronchodilation - Uterus= decreased uterine contraction

Question 38

What is the effect of Beta-2 activation in the vasculature?

Answer 38

Vasodilation leading to: - Decreased TPR - Decreased diastolic BP - Decreased afterload

Question 39

What is the effect of Beta-2 activation in the uterus?

Answer 39

Relaxation

Question 40

What is the effect of Beta-2 activation in the bronchioles?

Answer 40

Bronchodilation

Question 41

What is the effect of Beta-2 activation in the skeletal muscle?

Answer 41

- Glycogenolysis | - Muscle contraction/ tremors

Question 42

What is the effect of Beta-2 activation in the liver?

Answer 42

Glycogenolysis

Question 43

What is the effect of Beta-2 activation in the pancreas?

Answer 43

Insulin secretion

Question 44

What is the effect of muscarinic stimulation of the eye?

Answer 44

Stimulation of M receptors causes: 1) Miosis (sphincter m.) 2) Spasm of accomodation and opening the Canal of Schlemm

Question 45

What is the result of muscarinic blockade on the eyes?

Answer 45

1) Mydriasis | 2) Paralysis of accommodation, or "cycloplegia"

Question 46

What is the effect of sympathetic alpha-1 stimulation on the eye?

Answer 46

Myrdiasis

Question 47

How does the mydriasis caused by adrenergic stimulation differ from that caused by muscarinic stimulation?

Answer 47

Alpha-1= pupillary radial muscle; thus, there is NO cycloplegia Muscarinic= mydriasis WITH cycloplegia b/c of effects of ciliary m.

Question 48

Where are D1 receptors located?

Answer 48

Renal, mesenteric, and coronary vasculature

Question 49

What is the effect of D1 stimulation?

Answer 49

Vasodilation In the kidney, this leads to: - Increased GFR, RBF and Na+ excretion

Question 50

Draw the autonomic feedback loop controlling arterial blood pressure. Draw the hormonal ANS feedback loop controlling blood pressure.

Answer 50

N/A

Question 51

What is the meeting point between the autonomic and hormonal feedback loops controlling blood pressure?

Answer 51

Mean Arterial Pressure (MAP)

Question 52

What will changes in the MAP evoke?

Answer 52

Powerful homeostaic responses *****Note that if a drug has induced a change in MAP, homeostatic responses to that change may produce the OPPOSITE action of the intended drug,*****

Question 53

What is reflex bradycardia?

Answer 53

Reflexive lowering of heart rate in response to an increase in MAP or increase in TPR-->increase in MAP

Question 54

What is reflex tachycardia?

Answer 54

Reflexive raising of heart rate in response to a decrease in TPR-->decrease in MAP