Lecture 6: Adrenergic Agonsists

Question 1

monoamines

Answer 1

-contain one amino group connected to aromactic ring by two-carbon chain
-serotonin, dopamine, norepinephrine, epinephrine, (histamine)

Question 2

Catecholamines

Answer 2

-monoamines with catechol group (benzene with 2 hydroxyl groups)
-dopamine, norepinephrine, epinephrine

Question 3

derivatives of trytophan

Answer 3

-serotonin

Question 4

Derivatives of tyrosine

Answer 4

-norepinephrine
-epinephrine
-dopamine

Question 5

NE transmission

Answer 5

1. tyrosine transported to noradrenergic ending by sodium-dependent carrier
2. tyrosine to dopamine
3. Dopamine transported to vesicle by VMAT
4. dopamine to NE
5. release NE when action potential opens Ca+ channels and fusion of vesicle with surface membrane
6. NE binds adrenergic receptors on postsynaptic cell
7. NE binds to regulatory receptors present on presynaptic terminal
8. NE diffuses

Question 6

Tyrosine to dopamine

Answer 6

1. tyrosine to dopa by tyrosine hydroxylase
2. dopa to dopamine by dopa decarboxylase

Question 7

VMAT

Answer 7

-vesicular monoamine transporter
-transport NE and dopamine

Question 8

dopamine-B-hydroxylase

Answer 8

-dopamine to NE
-happens in vesicle

Question 9

NE diffusion from synapse

Answer 9

-out of cleft
-reuptaken into cytoplasm by NET (NE transporter) where it is metabolized by MAO or taken back to vesicles by VMAT
-can also be degraded by COMT

Question 10

monoamine oxidase (MAO)

Answer 10

-metabolizes NE in cytoplasm

Question 11

COMT

Answer 11

-catechol-O-methyltransferase
-degrade NE released from synapse

Question 12

Biosynthesis of Catecholamines

Answer 12

1. L tyrosine (hydroxylase)
2. L-Dopa (decarboxylase)
3. Dopamine (hydroxylase in vesicle)
4. NE (PNM in adrenal medulla)
5. Epinephrine

Question 13

Metyrosine

Answer 13

-can inhibit L-tyrosine to L-Dopa step

Question 14

Carbidopa

Answer 14

-can inhibit L-dopa to dopamine step
-parkinson’s disease

Question 15

Metabolism of catecholamines

Answer 15

-COMT and MAO enzymes

Question 16

Epinephrine + COMT

Answer 16

-metanephrine

Question 17

metanephrine or normetanephrine + MAO

Answer 17

VMA

Question 18

NE or epinephrine + MAO

Answer 18

-dihydroxymandelic acid

Question 19

dihydroxymandelic acid + COMT

Answer 19

VMA

Question 20

NE + COMT

Answer 20

Normetanephrine

Question 21

Dopamine + MAO

Answer 21

dihydroxyphenylacetic acid

Question 22

Dopamine + COMT

Answer 22

-3-methoxtyramine

Question 23

Homovanillic acid

Answer 23

-from dihydroxyphenylacetic acid + COMT
-from 3-methoxytyramine + MAO

Question 24

Direct acting adrenergic receptor agonists

Answer 24

-norepinephrine
-epinephrine

Question 25

Sterochemistry of Adrenergic receptor agonists

Question 26

a1 agonist

Answer 26

-Gq -vasoconstriction -rise in BP -pupil dilation -ejaculation -inhibition of GI

Question 27

a2 agonist

Answer 27

-Gi -vasoconstriction -inhibit NE release -decrease CV SNS input

Question 28

B1 agonist

Answer 28

-Gs -cardiac stimulation -increase force and conduction -secrete renin

Question 29

B2 agonist

Answer 29

-cardiac stimulation -bronchodilation -uterine relaxation -GI inhibition -vasodilation -fall in BP

Question 30

Epinephrine receptor preference

Answer 30

-B1, B2, a1, a2

Question 31

NE receptor preference

Answer 31

-a1, a2, B1

Question 32

Norepinephrine activates

Answer 32

-a and B1 receptors

Question 33

Epinephrine activates

Answer 33

a and B receptors

Question 34

Dopamine activates

Answer 34

-D1 -B1 -a1

Question 35

D1 agonist

Answer 35

-vasodilation in renal, mesenteric, coronary arteries =increase blood flow

Question 36

Sodium bisulfate

Answer 36

-used in NE and epinephrine preparations to prevent oxidation -uhhh slide 20-21

Question 37

Epinephrine Beta activity

Answer 37

-stronger than alpha activity

Question 38

Epinephrine action at lower concentrations

Answer 38

-B1 and B2 effects predominate

Question 39

Epinephrine action at higher concentrations

Answer 39

-a1 effects prefominate

Question 40

Epinephrine clinical use

Answer 40

-treat anaphylaxis or cardiac arrest -adjunct with local anesthetics

Question 41

Epinephrine problems

Answer 41

-not orally active due to COMT and MAO in liver -can produce unwanted effects through broad activation of adrenergic receptors

Question 42

Epinephrine counters hypoglycemia

Answer 42

-B2: glycogenolysis, gluconeogenesis = INCREASE glucose -a2: inhibit insulin secretion

Question 43

Dipiveferin

Answer 43

-epinephrine -treat infant glaucoma -lipophilic -activated by esterase

Question 44

Dopamine (intropin)

Answer 44

-D1 agonist -renal dilation -B1 and a1 agonist -SNS activity -cardio stimulate and systemic vasoconstrictor outside the kidney

Question 45

Dopamine clinical use

Answer 45

-shock -acute congestive heart failure -must be given as IV

Question 46

selective D1 agonist

Answer 46

-Fenoldopam -severe HTN in hospitalized patients

Question 47

Phenylephrine

Answer 47

-a1 agonist -nasal decongestant (not that good tho most gets metabolized in liver) -mydriasis without cycloplegia -pressor -vasoconstrictor in regional anesthesia

Question 48

Phenylephrine administration

Answer 48

-parenteral -oral -local -substrate for MAO