Adrenergics I Flashcards
What is the effect of epinephrine on bronchial smooth muscle, the heart and lastly, on vessels?
Bronchial muscle - vasodialation
Heart - Stimulation
Vessels - vasoconstriction
What is the receptor through which epinephrine is able to induce vasoconstriction?
Alpha 1 receptors
Epinephrine is used during what 2 emergency scenarios?
Elevated anterior eye chamber pressure (glaucoma)
Allegy / anaphylactic shock
How is epinephrine used during surgery?
It can be used to cause vasoconstriction, reducing drug diffusion from administration site
What is the effect of epinephrine on bleeding?
Causes vasoconstriction, reduces bleeding
What is the clinical indication for norepinephrine? How is it administered?
Used only for shock therapy
IV infusion
Norepinephrine is able to cause vasoconstriction and increase cardiac output via what two receptors, respectively?
Vasoconstriction - alpha 1
Cardiac output - beta 1
What is the clinical indication for dopamine? How is it administered?
Used only for shock therapy
IV infusion
Dopamine is able to cause vasoconstriction and increase cardiac output and dialate renal blood vessels via what three receptors, respectively?
Vasoconstriction - alpha 1
Cardiac output - beta 1
Renal blood vessels - DA 1
What is the major clinical use of isoproterenol, what receptor is targeted? When used for cardiac stimulation, what receptor is targeted then?
Relaxation of bronchial smooth muscle
Beta-2 adrenoreceptors
Beta 1 receptors
What are the 2 clinical uses of phenylephrine? What receptor is targeted?
Used as nasal decongestant (vasoconstriction)
Prevents shock
Alpha 1 adrenoreceptor
What is Metaraminol? What receptors does it target?
Long acting agonist
Alpha 1 and beta 1 receptor stimulant
What separates ephedrine from most of the other adrenergic agonists? What receptors does it target?
Orally effective
Targets most adrenoreceptors
True or false: The parasympathetic NS plays a major role in determining periperal vascular resistance, contractile force and venous tone.
False, these are all determined by sympathetic output
What are the 5 organ systems that receive sympathetic innervation alone?
Blood vessels, sweat glands, liver, spleen and adrenal gland
What are the six major adrenergic receptors? Which 2 are feedback mediators?
alpha 1,2
beta 1,2
DA 1,2
Feedback, alpha 2 and D2
Where are adrenergic receptors found, preganglionic, post ganglionic, both? Presynaptic or post-synaptic?
Found in post ganglionic locations
Found both pre and post-synaptically
What is the primary adrenergic neurotransmitter? What is the catecholamine released by the adrenal medulla?
NE
Epinephrine
The major adrenergic receptor controlling heart rate is
Muscarinic type 2
Where within the sympathetic NS is dopamine released from? What type of sweat glands receive adrenergic stimulation?
Splanchnic vascular smooth muscle and Renal vascular smooth muscle
Non-thermoregulatory sweat glands
What are the 5 components / steps of catecholamine biosynthesis? i.e. what is made in what order?
Tyrosine - dopa - dopamine - NE - Epi
What is the rate limiting enzyme in catecholamine synthesis? What is its substrate and product?
Tyrosine hydroxylase
Tyrosine - DOPA
What is the main determinant of catecholamine synthesis rate?
Increased neuronal firing frequency = increased rate of NT synthesis
Where is epinephrine synthesized?
In the adrenal medulla
What are the 2 enzymes involved in catecholamine metabolism? What are their main sites of action?
catechol-o-methyltransferase (COMT) - Liver Monoamine oxidase (MAO) - Adrenal nerve terminals, liver
What is the function of COMT? MAO? What is the net effect? What order do they work?
COMT - Methylation
MAO - Deamination
Reduce the biologic activity of the target catecholamines
No specific order of function
When NE or Epi are metabolized by COMT and or MAO, what are the two products that can be found in plasma or urine?
MHPG - methoxyhydroxyphenylglycol
VMA - vanillylmandelic acid
Among adrenergic receptor agonists, what is the effect of substituting the amino group? What are the examples (3)?
Increase beta-receptor activity
Isoproterenol, dobutamine, terbutaline
Among adrenergic receptor agonists, what is the effect of substituting the benzene ring? What are the examples (3)?
Increases duration of action (reduced COMT binding) but reduced potency.
Metaraminol, ephedrine, phenylephrine
Among adrenergic receptor agonists, what is the effect of substituting the alpha carbon? What are the examples (2)?
Increased duration of action (blocks MAO metabolism), displaces NE in storage vesicles
Metaraminol, Ephedrine
Alpha 1 receptor stimulation generally [contracts / constricts] muscles. What is the exception?
Relaxes intestinal smooth muscle
Arterial and venoconstriction, ejaculation, piloerection are all regulated by _ receptor activation
Alpha 1
Iris radial muscle contraction and glycogenolysis are all regulated by _ receptor activation
Alpha 1
What are the 2 alpha 1 selective agonists drugs provided as examples?
Phenylephrine
Methoxamine
What are the 2 alpha 2 selective (relatively) drugs provided as examples?
Clonidine
Methyl-NE
What are the 2 mixed alpha and beta receptor agonists provided as examples?
NE
Epi
What is the pharmacological difference between NE and Epi?
Epi is able to bind beta1 and beta2 equally, while NE binds beta1 alot better than beta2
What are the 3 beta 2 selective agonist provided as examples?
Albuterol, Terbutaline, metaproterenol
Isoproterenol is a beta selective agonist. How does its binding of the 2 main beta receptors compare?
It binds both of the receptors equally
What is the single example if a beta 1 selective agonist provided?
Dobutamine
Where are alpha 2 receptors found? What is their g-protein? What is their function
Presynaptically located
Gi
Negative feedback, reduce NE release
Activation of what receptor will increase heart rate, contractile force, CO and lypolysis?
Beta 1
Mydriasis, contraction of the iris muscle, is mediated by which adrenergic receptor?
Alpha 1
Where are beta 1 receptors found? What is the assoc. g protein? Generally, what is the net effect of stimulation?
Heart
Gs
Increase heart function, including lipolysis
What is the major effect of beta 2 stimulation?
Counters alpha 1 (mostly)
- skeletal muscle vasodilation
- bronchodialation, myometrial replaxation,
- decreased intraoccular pressure
- intestinal relaxation (exception)
What is the effect of beta 3 stimulation?
Increased glycogenolysis in liver and skeletal muscle
How does dopamine binding to DA1 and DA2 compare? What is the example of a DA1 selective agonist provided?
Equivalent binding
Fenoldopam
What is the G-protein assoc. with DA1? DA2?
Gs and Gi, respectively
What is the effect of DA1 stimulation? DA2?
DA1 - vasodialation of renal and mesenteric vessels
DA2 - Presynaptic, reduce neurotransmitter release
What is the Amine 1 transporter? What is the effect of its inhibition?
It is the reuptake system for norepinephrine
If inhibited, NE levels increase in the synapse
What are the specific inhibitors of the Amine 1 transporter mentioned?
Cocaine
Desmethylimipramine (DMI), a tricyclic antidepressant
What are they 2 presynaptically located adrenergic receptors? What are their functions? What is the effect of antagonists?
Alpha 2 and DA 2
They are feedback regulators, decrease release
Antagonists will block feedback, increase synaptic NT levels
How are amine 1 transporter inhibitors (cocaine, DMI) related to antagonists of presynaptic adrrenergic receptors?
Their net effect is the same (increased synaptic NT), the mechanism of action is different
What are the 2 DA2 specific antagonists provided as examples? What are they used for?
Haloperidol
Chlorpromazine
Antipsychotics
There are 4 drugs that are provided as examples of releasing agent (Increase NE release). What are they?
Dopamine
Ephedrine
Tyramine
Amphetamine
Why is tyramine (found in certain cheeses) dangerous for patients on MAO inhibitors?
Tyramine blocks MAO activity as well as increases NE release, can lead to increased arterial pressure
What are they 2 ways amphetamines increase synaptic NE?
Block NE reuptake
Reverse NE transport (release NE already within the nerve terminals)
What are the effects of ephedrine (2)?
Acts as releasing agent
Directly stimulates alpha 1 and beta 1 receptors
Where are beta 1 receptors located? What is the effect of stimulation?
Heart and adipose tissue
Increased cardiac function, lipolysis
As a rule, alpha 1 receptor stimulation leads to smooth muscle constriction. What organ system is the exception?
The intestines
While epinephrine is able to stimulate both alpha and beta receptors, which of the 2 is more sensitive to epi i.e. which receptors will be affected first by low doses of epinephrine?
Beta receptors, 10X more sensitive
Under what conditions will dopamine affect receptors other than DA1 and DA2? What receptors will now be affected?
High doses of dopamine stimulate alpha 1 and beta 1. No effect on beta 2 and alpha 2
Where is NE made? What protein is responsible for its packaging into vessicles?
In the nerve terminal
vesicular monoamine transporter (VMAT)
NE release is dependent on which cation? What is the protein that recycles NE back into the synapse?
Calcium dependent exocytosis
The Amine 1 Transporter
Upon stimulation, what is released from the adrenal medulla? Where is “X” released into?
Epinephrine (80%) and NE (20%)
Directly into venous circulation
What is a pheochromocytoma?
A tumor of the adrenal medulla, causes increased catecholamine release.
What are the 4 major symptoms associated with pheochromocytoma?
Severe tachycardia
Hypertension
Headaches
Increased sweating
What is the function of dopamine in the PNS? What is the clinical use of dopamine? Why?
PNS - Stimulates alpha 1 and beta 1 receptor at higher doses
Used in treatment of shock because it can stimulate alpha 1 and beta 1 receptors
Both alpha 1 and beta 2 receptors are activated by several drugs. However, which one dominants regarding peripheral effects (constriction vs relaxation)?
Alpha 1 will usually dominate, i.e. you will see constriction of peripheral blood vessels
Epinephrine is considered a potent vasoconstrictor and a cardiac stimulant. What receptors mediate each of these characterizations?
Potent vasoconstrictor - Because of alpha 1 stimulation
Cardiac stimulant - Because of beta 1 stimulation
Epinephrine can decrease total peripheral resistance. What receptor subtype mediates this action and what is the mechanism?
Stimulation of beta 2 receptors in skeletal muscle blood vessels leads to vasodilation
What is the effect of NE administration? What receptor subtype won’t be activated?
Increases both peripheral resistance and blood pressure. No effect on beta 2 receptors
Isoproterenol is considered a potent vasodialator. Why?
It will selectively affect the beta receptors, but no vasoconstriction because no alpha 1 activity
How will infusion of low dose epinephrine affect HR and MAP, compared to high dose? What receptors mediate its low dose effects?
Either dose will increase HR
Low dose will decrease MAP (beta 2), high dose will increase MAP (alpha 1)
Only affects beta receptors
Bolus injection of epinephrine can result in a paradoxical immediate drop in MAP. Why?
This is a vagal reflex, increasing parasymp. activity
Why does NE infusion consistently lead to increased MAP?
No stimulation of the beta 2 receptors
Clinically used beta agonists for the treatment of hypotensive crisis are _ (3)
NE
Phenylephrine
Methoxamine
Clinically used beta agonists for the treatment of chronic orthostatic hypotension are _ (2)
Midodrine
Ephedrine
Clinically used adrenergic agonists for the treatment of shock (1)
Dopamine
Clinically used adrenergic agonists for the treatment of cardiogenic shock following MI (2)
Dopamine, dobutamine
Clinically used beta agonists for reducing blood flood during surgery (2)
epinephrine, cocaine
Clinically used beta agonists for reducing diffusion of local anesthetics (3)
Epi, NE, phenylephrine
Clinically used beta agonists for the treatment of congested mucus membranes (3)
Phenylephrine
Ephedrine
Pseudoephedrine
Clinically used beta agonists for the treatment of heart block or cardiac arrest
Epinephrine
Clinically used beta agonists for the treatment of heart failure
Dobutamine
Clinically used beta agonists for the treatment of bronchial symptoms (beta 2 selective, (3))
MEtaproterenol
Terbutaline
Albuterol
Clinically used beta agonists for the treatment of anaphylaxis
Epinephrine
Clinically used beta agonists for achieving mydriasis
Phenylephrine
Clinically used beta agonists for relaxing a pregnant uterus
Terbutaline
Clinically used beta agonists for the treatment of stress incontinence
Ephedrine
Generally, Alpha 1 and Beta 2 receptors [complement / counteract] each other. What is the exception?
Counter act
Intestinal smooth muscle, both cause relaxation
