Drugs Affecting Adrenergic Neurotransmission Flashcards
General actions of sympathetic stimulation
increased rate + force of heart contraction, blood pressure, and blood glucose levels
shift of blood flow to skeletal muscles
dilation of bronchioles and pupils
Where is norepinephrine made?
within adrenergic neurons near the terminus of the axon near the junction with the effector cell
Where is epinephrine made?
the adrenal medulla
Which amino acid does epinephrine come from?
tyrosine
Alpha 1A receptor
causes contraction of smooth muscle, promotes cardiac growth and structure, vasoconstriction of large resistant arterials in skeletal muscle
Alpha 1 B receptor
promotes cardiac growth and structure
Alpha 1 C receptor
causes vasoconstriction in aorta and coronary artery
Alpha 2A receptor
predominant inhibitory receptor on sympathetic neurons
vasoconstriction of small procapillary vessels in skeletal muscle
Alpha 2B receptor
predominant receptor mediating alpha 2 vasoconstriction
Alpha 2c receptor
predominant receptor modulating dopamine neurotransmission
predominant receptor inhibiting hormone release from the adrenal medulla
Beta 1 receptor
predominant receptor in heart producing positive inotropic and chronotropic effects
Beta 2 receptors
predominant receptor in smooth muscle relaxation
skeletal muscle hypertrophy
beta 3 receptor
predominant receptor producing metabolic effects
How many transmembrane domains do adrenergic receptors have?
7
Which G protein are beta receptors coupled to ?
Gs
Which G protein is the alpha 2 receptor coupled to?
Gi
Which G protein is the alpha 1 receptor coupled to?
Gq
Direct acting agonists
norepinephrine
tetrahydrozoline
clonidine
dobutamine
albuterol
indirect acting agonists
increase the availability of norepinephrine or epinephrine to stimulate adrenergic receptors
Mixed Acting Agonists
indirectly release norepinephrine and also directly activate adrenergic receptors
A nitro group will deactivate the catechol which inhibits ?
COMT
Catechols are not recognized by ?
MAO
COMT inhibitors
treatment for parkinson’s
prolong half life of levodopa
MAO inhibitors
second line treatment for depression
may cause hypertensive crisis
increased norepinephrine leads to increased vasoconstriction
Phenylethanolamines
direct/mixed/indirect agonists
primary/secondary aliphatic amine separated by 2 carbon atoms from a benzene ring
a secondary hydroxyl group at the benzylic carbon
primarily ionized at physiological pH
pKa 9-11
What is significant about the N-CH3 on epinephrine?
it maximizes activity
For phenylethanolamines what happens as you increase the size of the N group
greatly decrease alpha activity due to differences in the binding pockets
What happens when you remove the 4’ OH on a phenylethanolamine
activity at the alpha receptor is reduced and almost eliminated at the beta receptors
Why does ephedrine have a greater duration of action than epinephrine?
no catechol, therefore no COMT metabolism
alpha-CH3 means steric hindrance ands blockage from MAO
Why does pseudoephedrine primarily act as an indirect mechanism?
has the wrong stereochemistry at OH group, overall too many changes for a direct mechanism
Ephedrine, pseudoephedrine and phenylephrine are commonly used as ?
Decongestants
What are the major therapeutic indications of selective alpha one receptor agonists?
nasal congestion
allergic and viral conjunctivitis
allergic/vasomotor rhinitis
conjunctival hypermedia
corneal abrasion
vernal keratoconjunctivitis
vasoconstriction
Which receptor accommodates a more diverse assortment of structural changes?
alpha 1
Oxymetazoline, Naphazoline, and Tetrahydrozoline are all available as ?
nasal sprays and ophthalmic solutions
