Flashcards in 10 Adrenergics I Deck (82):
which receptor when stimulated supplies parasympathetic activity to the heart?
Most organs/structures are innervated heavily by both the sympathetic and parasympathetic divisions. Which structures are solely sympathetic innervation?
1) blood vessels
2) sweat glands
where (generally) are adrenergic receptors found?
1) presynaptically (on postganglionic nerve terminals)
2) Postsynaptically (on target tissues)
which 2 adrenergic receptors are found on the nerve terminals of postganglionic nerves?
Alpha 2DA 2
T/F You find the Alpha 1, Beta 1, Beta 2, and DA 1 receptors on target tissues only?
What are the three catecholamines that are naturally occurring within the nervous system and clinically useful?
what is considered the primary NT of adrenergic nerves?
Where does the major source of epi come from?
Where is dopamine released in the PNS?
By postganglionic sympathetic nerves of the renal and splanchnic vascular smooth muscle.
How is epinephrine made?
1) Tyrosine (tyrosine hydroxylase)
What controls the rate of epinephrine formation?
The rate of neuronal firing.
What is the rate limiting step in epinephrine synthesis?
Tyrosine to DOPA through tyrosine hydroxylase because it is controlled by negative feedback.
What is COMT? Where is it found? What does it do?
COMT= Catechol o methyltransferase.It is found mainly in the liver.It methylates catecholamines rendering them inactive.
what is MAO? Where is it found? what does it do?
1) MAO= Monoamine oxidase
2) found mainly in the liver, adrenergic nerve terminals, and brain.
3) Deaminates catecholamines.
Isoproterenol, dobutamine, and terbutaline are all adrenergic receptor agonists that have large alkyl moieties. What does the large alkyl moiety do for the drug?
It increases Beta activity. (note: the alkyl group is the very end 'R' group)
T/F Catecholamines have an OH at the 3/4 postition?
What happens when you loose the hydroxyl group on the catecholamine?
1) Decreased potency
2) increased duration of action because COMT cant metabolize it easily.
Metaraminol, phenylephrine, and ephedrine all act as long lasting adrenergic agonist because?
These drugs all have a substitution to the benzene ring such as the loss of a hydroxyl.
what happens when you form a drug (catecholamine agonist) that has a substitution on the alpha carbon?
You end up getting a long lasting catecholamine type reaction because MAO is not able act on the molecule easily.
Metaraminol and ephedrine can have substitutions to the benzene ring to extend their half lives. What else can these two drugs do to extend their lives?
Have a substitution on the alpha carbon. They have this substitution to help slow/prevent the breakdown from MAO.
Agonists for the alpha 1 adrenergic receptor have what function? What is the exception?
1) In general, contraction and constriction of smooth muscle. 2) It causes relaxation of intestinal smooth muscle
An agonist of the alpha 2 receptor would act where?
1) postganglionic sympathetic nerve terminals
What happens when the presynaptic nerve terminal is stimulated at the alpha 2 receptor?
negative feedback will inhibit the release of more NE from the postganglionic neuron.
phenylephrine, methoxamine, clonidine, and methyl-NE are all drugs that do what?
selective agonists for alpha adrenergic receptor (Note they can also activate beta but its much much less)
Norepinephrine activates both alpha receptors equally. However, beta receptors are different. Which beta receptor is favored by NE?
NE favors Beta 1 >>Beta 2
T/F Epinepherine favors Beta 2 over Beta 1?
Beta 1=Beta 2
Also, Alpha 1=Alpha 2
Dobutamine, isoproterenol, albuterol, terbutaline, and metaproterenol are what type of drugs?
They are Beta agonists.
Where do you find Beta 1 receptors (Mainly)?
heart and adipose tissue
stimulation of Beta 1 receptors leads to?
What effects will you see with activation of the beta 2 receptor?
1) vasodilation in skeletal muscle
2) relaxation of smooth muscle
3) decreased intraocular pressure
what does the beta 3 receptor do?
Increases glycogenolysis in the liver and skeletal M.
Activation of the dopamine (D1 receptor) causes what? Where?
2) kidney and mesenteric
Where do you find the D2 receptor? What do they do?
1) Presynaptic nerve terminal
2) The D2 receptor acts as a negative feedback loop to prevent too much NE from being released.
Fenoldopam is a drug that does what?
Dopamine agonist. D1>>D2
What is NET?
AKA Amine 1 transport. Its a NE reuptake system located on the postganglionic nerve terminal.
what percent of NE is recycled back into the postganglionic nerve terminal? What about the rest of the NE?
50%The rest of the NE is degraded by MAO and COMT
What is the target of cocaine and tricyclic antidepressants?
They inhibit the function of Amine 1 transport
T/F vasoconstriction, tachycardia, and mydriasis are 3 symptoms associated with cocaine use. Why does this occur?
Cocaine block amine 1 transport (NET) and therefore causes further activation of the sympathetic nervous system.
What is DMI?
A tricyclic antidepressant that blocks NET.
what effects will you see with and alpha 2 and DA 2 antagonist?
Increased sympathetic activation. This is because the release of NE from the postganglionic synapse is not allowing for negative feedback.
T/F For Alpha 2 receptors, clinically relevant drugs are lacking?
T/F Antiphychotic drugs such as haloperidol and chlorpromazine act as antagonists to the D2 receptors and also elicit peripheral side effects?
NE is taken back into the synaptic terminal by NET (amine 1 transport). What other drugs/chemical does NET transport back into the nerve terminal?
Domamine, tyramine, ephedrine, and amphetamines all increase sympathetic responses. How do they do this?
They are all taken up through NET, and once inside the nerve terminal, they displace NE from storage vesicles causing NE to be released into the synapse.
Where can you get exogenous tyramine? When does this present as a problem?
1) cheeses, sausage, smoked products.
2) This only becomes an issue if you have problems with MAO.
How do amphetamines work?
They stimulate alpha 1 and beta 1 receptors, act as a NE releasing factor, and are vasopressors.
How does ephedrine act on the body?
It directly stimulates alpha 1 and beta 1 receptors, and acts as a releasing factor for NE.(Note: mild Beta 2 can occur=dilate bronchial/nasal decongestant)
where are alpha 1 receptors found?
most smooth muscle and elicit constriction/contraction(Exception: Inhibits the GI smooth muscle)
Where are beta 1 receptors found?
adipose tissue (Lipolysis)
where are beta 2 receptors found? what do they do?
1) bronchioles, intestines, uterus, arterioles of heart and skeletal muscle.
2) They all promote relaxation of smooth muscle. Ex: vasodilation.
What happens when you activate a DA 1 receptor?
You get increased blood flow to kidney and mesentary because of vasodilation to these structures.
T/F Beta 1 and beta 2 receptors are 10x more sensitive to Epi than are alpha 1 and alpha 2 receptors?
Epi stimulates which receptors?
all alpha, all beta (beta mainly)
NE stimulates which receptors?
all alpha, Beta 1 only.
Dopamine stimulates which receptors?
all dopamine, alpha 1, beta 1
Only 50% of the NE is recycled back into the nerve terminal. How does the nerve make up for the lost NE?
It transports tyrosine into the nerve terminal and converts tyrosine into DOPA--> dopamine--> NE
How does NE get into the vesicle ready to be released?
VMAT (vesicular monoamine transporter)
What triggers NE release?
Ca+ influx derived from an action potential.
Upon excitation of the adrenal medulla from the sympathetic nervous system, what is released?
what is pheochromocytoma?
A tumor of the adrenal gland that secretes a bunch of Epi and NE into the body. This causes an overwhelming sympathetic response.
Will you get excessive sweating with a pheochromocytoma?
Yes but only non thermoregulatory apocrine sweat glands will be stimulated.
Dopamine in the PNS is mainly secreted for what?
Activation of the DA 1 receptor in renal and splanchnic vasculature. (At high doses it can also stimulate alpha 1 and beta 1 receptors)
Why is dopamine used for shock?
increased vasoconstriction (alpha 1)
increased HR/contractability (Beta 1)
increased blood flow (DA 1)
Norepinephrine has its major effects on which receptors?
all alpha, beta 1 (It has little to no effect of beta 2)
what is Isoproterenol?
a very potent beta agonist. (very little alpha activity)
1) increased C.O. with beta 1
2) decreased M.A.P. with beta 2
what is considered the most potent vasopressor?
Epi because it has both full alpha and beta activity.
what is a vasopressor?
what happens when you give epi in low doses? high dose? bolus?
1) low dose (beta 1 and beta 2 dominate)
2) high dose (beta1, beta 2 and alpha 1 dominate)
3) bollus (Drop in MAP because due to vasovagal response)
what do you generally see with infusion of NE?
NE infusion increased MAP and decreases HR.
MAP increases because NE lacks Beta 2 receptor activity which would cause vasodilation( smooth muscle relaxation).
which 3 drugs are used to overcome hypotensive crisis?
NE, Phenylephrine, methoxamine
which 2 drugs are used to overcome chronic orthostatic hypotension?
which 1 drug is great for treating shock and why?
Dopamine. alpha 1, beta 1, and DA 1 activity.
which 2 drugs are great at slowing/stopping blood flow during surgery?
which 3 drugs are useful to help prevent diffusion of local anesthetics?
Epi, NE, phenylephrine
which 3 drugs help with reducing congestion of mucous membranes?
phenylephrine, ephedrine, pseudoephrine
which 1 drug is useful for rescuing cardiac function during a heart block of cardiac arrest?
which 1 drug is useful for rescuing cardiac function during heart failure?
metaproterenol, terbutaline, and albuterol are all beta 2 selective drugs designed to treat what?
what is anaphylaxis and how do you treat it?
2) mucous membrane congestion
4) hypotension(treated with epi)
which type of drug is used to treat glaucoma?
Beta antagonists generally.
terbutaline does what for the pregant woman?
relax pregnant uterus