Flashcards in 08.29 sympathetic nervous system Deck (37):
How is Dopamine, NE and epi made in the nerve terminals?
-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
Negative feed-back mechanism for Ne in the synaptic cleft:
-Alpha 2 auto receptors on the nerve terminal
NE acts on which type of receptors?
alpha and beta
What can block neuronal uptake?
Cocaine and TCA
*note, neuronal uptake is different than the negative feedback done by the alpha 2 receptors
Mono Amine Oxidase
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
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
What are the major metabolites of COMT and/or MAO?
VMA and MOPEG
Isoprotenerol is what type of agonist?
alpha 1 receptors respond best to what agonist
EPI>or = NE>>ISO
alpha 2 receptors respond best to what agonist?
alpha 1 receptor location and second messenger
smooth muscle, glands, activates phopholipase C which mobilizes (increases) Ca++, and increases IP3 and DAG
alpha 2 receptor location and second messenger
nerve endings, smooth muscle, they INHIBIT adenylate cyclase leading to a decrease in cAMP
all beta receptors simulate what second messenger?
Adenylate cyclase which increases cAMP
dopamine receptors couple to what?
adenylate cyclase, some stimulate, and some inhibit
at a low dose, epi acts better on what receptors?
at a high dose, epi acts better on what receptors?
-"pressor agent" used to increase blood pressure (like during shock)
-activates alpha 1 and 2, and beta 1-3 receptors
-doesn't cross BBB
-DOC for allergic reaction (anaphalaxis)
activates all alpha and betas
doesn't cross BBB
-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)
-asthma, cardiac stimulant
-activates all beta receptors (non selective)
doesn't cross BBB
which drugs are selective beta 2 agonist?
-Salmeterol (LABA, long activing)
what is the clinical use for beta 2 agonists?
treatment of asthma and premature labor
what drug is a selective beta 1 agonist
Dobutamine, used for congestive heart failure, it increases the force, but no change in HR or oxygen demand
what are the adverse side effects of the selective beta-2 agonist?
-Cardiovascular (increased HR and decreased BP)
What are the selective alpha 1-agonists? (pressor agents)
what are the selective alpha-1 agonists used for?
-hypotension or shock, nasal decongestant
causes an increase in BP
what are the selective alpha-2 agonists?
Clonidine (activates the pre-synaptic alpha-2 receptors which inhibits NT (NE) release
-they do cross the BBB
what are the uses for alpha-2 agonists?
-they are used as anti-hypertensive agents and for opiod withdrawal (decrease severity)
-They decrease sympathetic outflow and work in the CNS
what are the side effects of the selective alpha2 agonists?
-impotence, dry mouth, rebound HTN, sedation
what drugs are dopamine agonists?
-Fenoldopam, and Pramiprexole
Basics of Parkinson's Disease
-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
increase DA or NE in the synaptic cleft
Neuronal uptake inhibition, potentiate the effects of NE (it's not removed from the synaptic cleft
what MAO inhibitor is used in the treatment of parkinsons?
What is MAO-A inhibitor used for?
treatment of depression
MAO-A inhibitor used for treatment of depression
MAO-B inhibitor used for treatment of Parkinsons