Lecture 6: Adrenergic Agonsists Flashcards
monoamines
-contain one amino group connected to aromactic ring by two-carbon chain
-serotonin, dopamine, norepinephrine, epinephrine, (histamine)
Catecholamines
-monoamines with catechol group (benzene with 2 hydroxyl groups)
-dopamine, norepinephrine, epinephrine
derivatives of trytophan
-serotonin
Derivatives of tyrosine
-norepinephrine
-epinephrine
-dopamine
NE transmission
- tyrosine transported to noradrenergic ending by sodium-dependent carrier
- tyrosine to dopamine
- Dopamine transported to vesicle by VMAT
- dopamine to NE
- release NE when action potential opens Ca+ channels and fusion of vesicle with surface membrane
- NE binds adrenergic receptors on postsynaptic cell
- NE binds to regulatory receptors present on presynaptic terminal
- NE diffuses
Tyrosine to dopamine
- tyrosine to dopa by tyrosine hydroxylase
- dopa to dopamine by dopa decarboxylase
VMAT
-vesicular monoamine transporter
-transport NE and dopamine
dopamine-B-hydroxylase
-dopamine to NE
-happens in vesicle
NE diffusion from synapse
-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
monoamine oxidase (MAO)
-metabolizes NE in cytoplasm
COMT
-catechol-O-methyltransferase
-degrade NE released from synapse
Biosynthesis of Catecholamines
- L tyrosine (hydroxylase)
- L-Dopa (decarboxylase)
- Dopamine (hydroxylase in vesicle)
- NE (PNM in adrenal medulla)
- Epinephrine
Metyrosine
-can inhibit L-tyrosine to L-Dopa step
Carbidopa
-can inhibit L-dopa to dopamine step
-parkinson’s disease
Metabolism of catecholamines
-COMT and MAO enzymes
Epinephrine + COMT
-metanephrine
metanephrine or normetanephrine + MAO
VMA
NE or epinephrine + MAO
-dihydroxymandelic acid
dihydroxymandelic acid + COMT
VMA
NE + COMT
Normetanephrine
Dopamine + MAO
dihydroxyphenylacetic acid
Dopamine + COMT
-3-methoxtyramine
Homovanillic acid
-from dihydroxyphenylacetic acid + COMT
-from 3-methoxytyramine + MAO
Direct acting adrenergic receptor agonists
-norepinephrine
-epinephrine
Sterochemistry of Adrenergic receptor agonists
a1 agonist
-Gq
-vasoconstriction
-rise in BP
-pupil dilation
-ejaculation
-inhibition of GI
a2 agonist
-Gi
-vasoconstriction
-inhibit NE release
-decrease CV SNS input
B1 agonist
-Gs
-cardiac stimulation
-increase force and conduction
-secrete renin
B2 agonist
-cardiac stimulation
-bronchodilation
-uterine relaxation
-GI inhibition
-vasodilation
-fall in BP
Epinephrine receptor preference
-B1, B2, a1, a2
NE receptor preference
-a1, a2, B1
Norepinephrine activates
-a and B1 receptors
Epinephrine activates
a and B receptors
Dopamine activates
-D1
-B1
-a1
D1 agonist
-vasodilation in renal, mesenteric, coronary arteries
=increase blood flow
Sodium bisulfate
-used in NE and epinephrine preparations to prevent oxidation
-uhhh slide 20-21
Epinephrine Beta activity
-stronger than alpha activity
Epinephrine action at lower concentrations
-B1 and B2 effects predominate
Epinephrine action at higher concentrations
-a1 effects prefominate
Epinephrine clinical use
-treat anaphylaxis or cardiac arrest
-adjunct with local anesthetics
Epinephrine problems
-not orally active due to COMT and MAO in liver
-can produce unwanted effects through broad activation of adrenergic receptors
Epinephrine counters hypoglycemia
-B2: glycogenolysis, gluconeogenesis
= INCREASE glucose
-a2: inhibit insulin secretion
Dipiveferin
-epinephrine
-treat infant glaucoma
-lipophilic
-activated by esterase
Dopamine (intropin)
-D1 agonist
-renal dilation
-B1 and a1 agonist
-SNS activity
-cardio stimulate and systemic vasoconstrictor outside the kidney
Dopamine clinical use
-shock
-acute congestive heart failure
-must be given as IV
selective D1 agonist
-Fenoldopam
-severe HTN in hospitalized patients
Phenylephrine
-a1 agonist
-nasal decongestant (not that good tho most gets metabolized in liver)
-mydriasis without cycloplegia
-pressor
-vasoconstrictor in regional anesthesia
Phenylephrine administration
-parenteral
-oral
-local
-substrate for MAO
