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Phar 505 > Adnergic Nervous System > Flashcards

Adnergic Nervous System Flashcards

1
Q

What is the main neurotransmitter of the adrenergic synapse

A

Norepinephrine

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2
Q

What do all catecholamines have

A

amine group, benzene ring with two hydroxy groups ortho to one another

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3
Q

What structures are essential for binding to adernergic receptors

A

hydrogen bonding and pi-pi stacking from the catechol, ionic binding of the amino group, hydrogen bonding of the hydroxy group at the beta carbon

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4
Q

What are the two amino acids that are needed for biosynthesis of norepinephrine

A

Phenylalanine and tyrosine

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5
Q

T/F: Tyrosine is an essential amino acid (not made in the body) that is converted to phenylalanine to create catechols

A

False: Phenylalanine is an essential amino acid that is converted to tyrosine to create catechols

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6
Q

What is the enzyme that converts phenylalanine to tyrosine

A

L-phenylalanine hydroxylase

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7
Q

What is the rate limiting step enzyme for creating catechols, what is the MOA and result

A

L-tyrosine hydroxylase, adds a hydroxy group ortho to the other hydroxy group to create a L-DOPA (a catechol)

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8
Q

What is the inhibitor L-tyrosine hydroxylase, what kind of inhibition is it

A

alpha-methyltyrosine, competitive

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9
Q

What enzyme converts L-DOPA into a neurotransmitter, what neurotransmitter is L-DOPA converted to

A

L-aromatic amino acid decaboxylase, Dopamine

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10
Q

What are the two inhibitors of L-aromatic acid decarboxylase, which is used in combination with L-DOPA for parkinson’s disease

A

alph-methyldopa (aldomet) and Carbidopa, carbidopa

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11
Q

What is the enzyme that converts Dopamine into the adnergic neurotransmitter, what is this neurotransmitter

A

Dopamine Beta hydroxylase, norepinephrine

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12
Q

T/F: Vitamin C is a cofactor for dopamine Beta hydroxylase to create norepinephrine

A

True

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13
Q

What enzyme converts norepinephrine to epinephrine

A

Phenylethanolamine N-methyl Transferase (PNMT)

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14
Q

What are the two amino acids that deactivate, what is the MOA of each

A

MAO: turns amino group into an aldehyde, COMT: adds a methyl group to one of the hydroxy groups

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15
Q

T/F; COMT and MAO only deactivate norepinephrine and epinephrine

A

False: Both enzymes can deactivate dopamine as well

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16
Q

Why is COMT so essential to protecting the body

A

prevents ortho-quinones from forming since they are easily oxidized

17
Q

What are two common inhibitors of COMT

A

Entacapone and Tolcapone

18
Q

How are norepinephrine responses terminated

A

reuptake via norepinephrine transporter

19
Q

What enzyme repackages norepinephrine

A

Vesicular monoamine transporter (VMAT)

20
Q

What drug limits uptake of norepinephrine

A

Risperdone

21
Q

T/F: Adernergic receptors are G coupled protein receptors that are slightly different because binding happens in the cleft of the receptor

A

True

22
Q

T/F: Alpha 1 adernergic receptors can still have substrates bind even if it is not a catechol, while Alpha 2 cannot

A

True

23
Q

How does Alpha 1 adernergic activity become lost on a chemical structure

A

Adding a substituent to the alpha carbon

24
Q

Which drug is a prodrug for methoxamine analogue and is an alpha 1 agonist

A

Midodrine

25
Q

What is are therapeutic use of alpha 1 agonist

A

Decongestants and reduction of eye redness

26
Q

T/F: Alpha 2 receptors are usually preganglionic and can be used to turn down the entire adnergic nervous system

A

True

27
Q

What are two key components for alpha 2 agonist that penetrate the blood brain barrier

A

Guanidine group and electron withrdrawing groups

28
Q

What two drugs are alpha-1 agonist and partial alpha-2 antagonist, why

A

oxymetazoline and xylometazoline, bulky tertiary butyl group in the para-position of the aromatic ring greatly diminishes affinity for the alpha 2 receptors

29
Q

What are the uroslective alpha-1 antagonists

A

Tamsulosin, Sildosin

30
Q

What changes to nopepinephrine make it more selecitive towards Beta 2 receptors and no binding for any alpha receptor

A

adding a tertbutyl group or higher to bind the amine group, change the hydroxy groups

31
Q

T/F: To have a Beta 2 agonist function there must be one hydroxy similar to a catechol while the other functional group must be capable of hydrogen binding

A

True

32
Q

What is the functional group that allows for selective alpha-1 and alpha-2 agonists, what is the difference, what is need to allow for penetration of the BBB

A

Imidiazole ring, one substituent in the ortho position for alpha-1 agonsts, two substituents in the ortho positions, electron withdrawing group

33
Q

What is the one structural feature that is needed for B1 antagonists activity

A

Long meta substituent

34
Q

What gives Clonidine its selectivity as an alpha-2 agonists

A

Steric crowding by two bulky ortho-substituents forcing a 90 degree ring rotation

Phar 505 (33 decks)

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