08.29 sympathetic nervous system

Question 1

How is Dopamine, NE and epi made in the nerve terminals?

Answer 1

-Tyrosine is taken up and converted (tyrosine hydroxylase) to DOPA (rate limiting step) which is then converted to Dopamine and put in storage vesicles.
Dopamine can then be converted to NE, and in the adrenal medulla can be converted to Epi

Question 2

Negative feed-back mechanism for Ne in the synaptic cleft:

Answer 2

-Alpha 2 auto receptors on the nerve terminal

Question 3

NE acts on which type of receptors?

Answer 3

alpha and beta

Question 4

What can block neuronal uptake?

Answer 4

Cocaine and TCA

*note, neuronal uptake is different than the negative feedback done by the alpha 2 receptors

Question 5

MAO

Answer 5

Mono Amine Oxidase
uptake 1
found in the nerve terminal,
metabolizes neurotransmitters (NE and dopamine)
found in the outer mitochondrial membrane
-two form/isotypes: MAO_A, and MAO_B
-attacks the amine portion thus substrates include: tyrosine, DOPA, dopamine, NE and epi, altho epi isn’t as good bc there is already a methyl group there

Question 6

COMT

Answer 6

similar to MAO, but found in the cytosol of post synaptic membrane

• extraneuronal, uptake 2
• attackes the 3’OH on the bezene ring, thus substrates include: NE, Epi, DOPA and dopamine

Question 7

What are the major metabolites of COMT and/or MAO?

Answer 7

VMA and MOPEG

Question 8

Isoprotenerol is what type of agonist?

Answer 8

Beta agonist

Question 9

alpha 1 receptors respond best to what agonist

Answer 9

EPI>or = NE»ISO

Question 10

alpha 2 receptors respond best to what agonist?

Answer 10

NE> EPI»ISO

Question 11

alpha 1 receptor location and second messenger

Answer 11

smooth muscle, glands, activates phopholipase C which mobilizes (increases) Ca++, and increases IP3 and DAG

Question 12

alpha 2 receptor location and second messenger

Answer 12

nerve endings, smooth muscle, they INHIBIT adenylate cyclase leading to a decrease in cAMP

Question 13

all beta receptors simulate what second messenger?

Answer 13

Adenylate cyclase which increases cAMP

Question 14

dopamine receptors couple to what?

Answer 14

adenylate cyclase, some stimulate, and some inhibit

Question 15

at a low dose, epi acts better on what receptors?

Answer 15

beta

Question 16

at a high dose, epi acts better on what receptors?

Answer 16

alpha 1

Question 17

NE

Answer 17

• “pressor agent” used to increase blood pressure (like during shock)
• activates alpha 1 and 2, and beta 1-3 receptors
• doesn’t cross BBB

Question 18

Epinephrine

Answer 18

-DOC for allergic reaction (anaphalaxis)
activates all alpha and betas
doesn’t cross BBB

Question 19

dopamine

Answer 19

-DOC for septic shock
-precursor of NE and EPI
doesn’t cross BBB
-at low dose; dopamine receptors (no clinical use)
-at moderate dose: activates beta 1 (acute treatment of cardiac failure)
-at high dose: activates alpha 1 receptors (vasoconstriction which elevates bp)

Question 20

Isoprotenerol

Answer 20

-asthma, cardiac stimulant
-artificial
-activates all beta receptors (non selective)
doesn’t cross BBB

Question 21

which drugs are selective beta 2 agonist?

Answer 21

• Albuterol
• Ritodrine
• Salmeterol (LABA, long activing)

Question 22

what is the clinical use for beta 2 agonists?

Answer 22

treatment of asthma and premature labor

Question 23

what drug is a selective beta 1 agonist

Answer 23

Dobutamine, used for congestive heart failure, it increases the force, but no change in HR or oxygen demand

Question 24

what are the adverse side effects of the selective beta-2 agonist?

Answer 24

-Cardiovascular (increased HR and decreased BP)

Question 25

What are the selective alpha 1-agonists? (pressor agents)

Answer 25

-Methoxamine, phenylephrine

Question 26

what are the selective alpha-1 agonists used for?

Answer 26

-hypotension or shock, nasal decongestant

causes an increase in BP

Question 27

what are the selective alpha-2 agonists?

Answer 27

Clonidine (activates the pre-synaptic alpha-2 receptors which inhibits NT (NE) release

• they do cross the BBB
• Dexmedetomidine
• Tizanidine

Question 28

what are the uses for alpha-2 agonists?

Answer 28

• they are used as anti-hypertensive agents and for opiod withdrawal (decrease severity)
• They decrease sympathetic outflow and work in the CNS

Question 29

what are the side effects of the selective alpha2 agonists?

Answer 29

-impotence, dry mouth, rebound HTN, sedation

Question 30

what drugs are dopamine agonists?

Answer 30

-Fenoldopam, and Pramiprexole

Question 31

Basics of Parkinson’s Disease

Answer 31

• CNS disorder, decreased dopamine released (adequate receptors, just not enough is released) thus they are more rigid and shuffle when they walk
• Pramiprexole is a drug used to treat this

Question 32

amphetamines

Answer 32

increase DA or NE in the synaptic cleft

Question 33

Cocaine

Answer 33

Neuronal uptake inhibition, potentiate the effects of NE (it’s not removed from the synaptic cleft

Question 34

what MAO inhibitor is used in the treatment of parkinsons?

Answer 34

MAO-B

Question 35

What is MAO-A inhibitor used for?

Answer 35

treatment of depression

Question 36

MAO inhibitors

Answer 36

MAO-A inhibitor used for treatment of depression

MAO-B inhibitor used for treatment of Parkinsons

Question 37

COMT inhibitors use

Answer 37

Parkinsons disease, but only used in late stage, it can cause liver failure