Autonomics IV-VI Flashcards
How is NE removed from the synapse?
Primarily reuptake, extraneuronal uptake followed by metabolism, dissemination into blood
Synthesis of NE
Tyrosine -> DOPA -> Dopamine -> NE -> E
Alpha 1 receptor mechanism
Simulatory G-protein increases phosphotidyl inositol hydrolysis
Alpha 2 receptor mechanism
inhibitory G-protein decreases cAMP
B1, 2, 3 receptor mechanism
Stimulatory G-protein increases cAMP; B1 also activates voltage-sensitive Ca2+ channels in heart
D1 receptor mechanism
stimulatory G-protein increases cAMP
Enzymes involved with NE, Epi metabolism. Location?
Monoamine oxidase (MAO) - mitochondrial surface, Catechol-O-methyltransferase (COMT) - cytoplasm of many cells, notably liver
Beta 1 receptor, prominent effector organs and response
Heart - Increased HR and force of contraction; Kidney - Renin secretion
Beta 2 receptor, prominent effector organs and response
Arterioles in skeletal muscle/coronaries - dilation; Bronchial Muscle - Relaxation; Uterus - Relaxation; “Several sites” - Increased metab.
Beta 3 receptor, prominent effector organs and response
Adipose tissue (lipocytes) - lipolysis, thermogenesis
Alpha 1 receptor, prominent effector organs and response
Arterioles in skin, mucosa, viscera, kidney - Constriction; Veins - Constriction; Uterus and Spleen - Constriction
Alpha 2 receptor, prominent effector organs and response
Presynaptic nerve endings - Inhibit NE release and ACh release (gut); Postsynaptic nerves in CNS - Decreased Peripheral Sympathetic Tone
D1 receptor, prominent effector organs and response
Renal, mesenteric and cerebral arterioles - dilation
How does autoregulation work in the sympathetic NS?
Alpha2 receptors on presynaptic nerves regulate NE release.
Describe heteroreceptor control. What substance does this process regulate?
Gut relaxation. Activation of Alpha 2 receptors by Sympathetic NS NE on parasympathetic neurons decrease release of ACh which relaxes gut.
Describe the dose-dependent effects of Epinephrine on skeletal muscle blood vessels
Skeletal muscle vessels have Alpha 1 and Beta 2. Beta 2 dominant a physiological (low) concentrations and therefore you get vasodilation. At therapeutic levels, Alpha 1 effects predominate and vessels constrict.
What receptors do Phenylephrine activate?
Alpha 1
What receptors do Clonidine activate?
Alpha 2
What receptors do Norepinephrine activate?
Alpha 1, Beta 1, Alpha 2
What receptors do Epinephrine activate?
Alpha 1, Beta 1, Beta 2, Alpha 2
What receptors do Isoproterenol activate?
B1, B2
What receptors do Dopamine activate?
DA, A1, B1
What are the four main agonists for B1?
ISO > Epi >= NE > DA
Four main agonists for B2?
ISO > Epi»_space; NE»_space; DA
Four main agonists for A1?
Epi >= NE > DA»_space; ISO
Four main agonists for A2?
Clonidine > Epi >= NE»_space; ISO
Two Indirect adrenergic agonists
Tyramine and amphetamine
Effects of low, medium and high doses of Dopamine
Low: Direct action of DA on D1 receptors - vasodilation at renal, mesenteric and cerebral arteries resulting in lower BP and increased urine output; Medium: Same as low with some direction action on B1 receptors in heart - increase hr; High: More of above and some direct activation of A1 resulting in vasoconstriction (including renal because A1 dominates D1)
How does fenoldopam work and what is it used for?
D1 selective agonist that increases blood flow to renal, mesentery, and cerebral arteries. Used in hypertensive emergencies
What would be the results of giving NE injection?
A1 increases peripheral resistance B1 increase HR. Because baroreceptors detect increase in BP, their action results in an overall decrease in HR with a slight increase in BP.
What would be the results of giving Epinephrine injection?
Peripheral resistance decrease due to B2 activation although there is an increase in HR due to B1 activity. Net slight increase in BP with increase in PP.
What would be the results of an Isoproterenol injection?
Isoproterenol is strictly a beta agonist. B1 increases HR while B2 causes massive decrease due to vasodilation. PP increases with a slight decrease in BP.
Describe the physiological process of sweating
Sympathetic fibers travel to eccrine sweat glands and release ACh onto (probably) M3 receptors on the secretory cells
Uses of Epinephrine
Control hemorrhage (A1 vasocon), Nasal Decongestion (A1 vasocon decrease swollen mucosa), Allergic/Anaphylactic Shock (A1 Vasoconstriction, B2 bronchodilation, decrease histamine release), Hypotension, (A1 vasocon)
In shock, why would you want to administer alpha blockers and dopamine?
To perfuse organs. Shock results in sympathetic vasoconstriction to raise BP. By giving alpha blocker you facilitate vasodilation and by giving dopamine you cause vasodilation of the kidney, mesentery and cerebral arteries
What does Ergonovine treat?
Post partum bleeding (Alpha agonist)
What does Ergotamine treat?
Acute migraine (A agonist)
What does bromocriptine treat?
Hyperprolactenemia and Parkinsonism
Use of Alpha2 agonists
Central control of BP in NTS by acting on regulatory A2 receptors in the midbrain. Therefore BP decreases
Clonidine uses
HTN, prevent withdrawal from opioids and alcohol
B1 agonists and their uses
Epinephrine, Isoproterenol, - Cardiac Arrest, A-V block, CHF Dobutamine - candidate for treadmill stress test
B2 agonists and their uses
Smooth muscle relaxation - tx of bronchial asthma - terbutaline and albuterol b/c they are B2 selective, Uterine smooth muscle relaxation
What are amphetamines used for?
Narcolepsy, hyperkinesis (ADHD)
First generation Beta blocker
classic nonselective B1 and B2 blocker; Propanolol
Second generation beta blockers
B1 selective, metoprolol, atenolol
Third generation beta blockers
Nonselective B blocker with additional actions (A1 receptor antagonism), Labetalol Tx: hypertension, lower TPR with little tachycardia
Conditions treated with Beta blockers
HTN, Arrhythmias, Angina Pectoris, Glaucoma, Migraine, Stage Fright, HF
What Beta blockers should you use for CHF? Why?
ONLY SECOND OR THIRD GENERATION; Second generation slows down heart, third generation slows down heart and has A1 antagonism so the heart pumps against less peripheral resistance. If you use first generation, you will slow the heart down but there will be unopposed A1 action causing massive vasoconstriction!
Nonselective Alpha blockers
Phentolamine, Phenoxybenzamine
A1 selective blockers
Prazosin, Terazosin
Major application of Alpha blockers
HTN
Mechanism explaining less tachycardia with Prazosin compared to nonselective Alpha blockers
NSABs block A1 on effector organ and autoregulator A2s. NE goes to B1 receptor causing tachycardia. A1SBs disallow for NE to bind to A1 but can still bind autoregulator A2s. This decreases overall NE in synaptic cleft and thus resulting in less NE binding to B1. Less tachycardia!
Uses for Alpha blockers
Hypertension, Raynauds, Frostbite, Pheochromocytoma, Shock, BPH
