Adrenergics I Flashcards by Uche PM

What is the effect of epinephrine on bronchial smooth muscle, the heart and lastly, on vessels?

Bronchial muscle - vasodialation
Heart - Stimulation
Vessels - vasoconstriction

How well did you know this?

Not at all

Perfectly

What is the receptor through which epinephrine is able to induce vasoconstriction?

Alpha 1 receptors

How well did you know this?

Not at all

Perfectly

Epinephrine is used during what 2 emergency scenarios?

Elevated anterior eye chamber pressure (glaucoma)

Allegy / anaphylactic shock

How well did you know this?

Not at all

Perfectly

How is epinephrine used during surgery?

It can be used to cause vasoconstriction, reducing drug diffusion from administration site

How well did you know this?

Not at all

Perfectly

What is the effect of epinephrine on bleeding?

Causes vasoconstriction, reduces bleeding

How well did you know this?

Not at all

Perfectly

What is the clinical indication for norepinephrine? How is it administered?

Used only for shock therapy

IV infusion

How well did you know this?

Not at all

Perfectly

Norepinephrine is able to cause vasoconstriction and increase cardiac output via what two receptors, respectively?

Vasoconstriction - alpha 1

Cardiac output - beta 1

How well did you know this?

Not at all

Perfectly

What is the clinical indication for dopamine? How is it administered?

Used only for shock therapy

IV infusion

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

What are the 2 clinical uses of phenylephrine? What receptor is targeted?

Used as nasal decongestant (vasoconstriction)
Prevents shock
Alpha 1 adrenoreceptor

How well did you know this?

Not at all

Perfectly

What is Metaraminol? What receptors does it target?

Long acting agonist

Alpha 1 and beta 1 receptor stimulant

How well did you know this?

Not at all

Perfectly

What separates ephedrine from most of the other adrenergic agonists? What receptors does it target?

Orally effective

Targets most adrenoreceptors

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

What are the 5 organ systems that receive sympathetic innervation alone?

Blood vessels, sweat glands, liver, spleen and adrenal gland

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Where are adrenergic receptors found, preganglionic, post ganglionic, both? Presynaptic or post-synaptic?

Found in post ganglionic locations

Found both pre and post-synaptically

How well did you know this?

Not at all

Perfectly

What is the primary adrenergic neurotransmitter? What is the catecholamine released by the adrenal medulla?

Epinephrine

How well did you know this?

Not at all

Perfectly

The major adrenergic receptor controlling heart rate is

Muscarinic type 2

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

What are the 5 components / steps of catecholamine biosynthesis? i.e. what is made in what order?

Tyrosine - dopa - dopamine - NE - Epi

How well did you know this?

Not at all

Perfectly

What is the rate limiting enzyme in catecholamine synthesis? What is its substrate and product?

Tyrosine hydroxylase

Tyrosine - DOPA

How well did you know this?

Not at all

Perfectly

What is the main determinant of catecholamine synthesis rate?

Increased neuronal firing frequency = increased rate of NT synthesis

How well did you know this?

Not at all

Perfectly

Where is epinephrine synthesized?

In the adrenal medulla

How well did you know this?

Not at all

Perfectly

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