RCS 08 - Adrenergic Agonists & Antagonists 1

Question 1

Answer 1

C

Question 2

Is E or NE a better bronchodilator? Why?

Answer 2

E, because the receptors in bronchial smooth muscle are β2 receptors, which have low affinity for NE and high affinity for E

Question 3

Discuss the adrenergic receptor distribution/density among blood vessels and what this means about the effects of NE and E on these vessels.

Answer 3

• Skin BVs have almost only α1 receptors which cause vasoconstriction
• Skeletal Muscle BVs have mostly α1 but also some β2 (vasodilation)

NE and E both cause vasoconstriction in skin BVs

NE will cause vasoconstriction in muscle BVs

Because β2 receptors have a higher affinity for E than α1 receptors, physiological concentrations of E will cause vasodilation in muscle BVs. However, at higher concentrations, E will begin to activate the more numerous α1 receptors, leading to vasoconstriction

Question 4

List the different classes of adrenergic agonists we need to know.

Answer 4

• Direct-Acting
  
  • Endogenous catecholamines
  • β-adrenergic agonists
  • α-adrenergic agonists
• Indirect-Acting
  
  • Releasing agents
  • Uptake inhibitors
• Mixed-Acting (direct acting + releasing agents)

Question 5

List the direct acting adrenergic agonists we need to know and specify which ones are endogenous catecholamines. List the receptors these drugs activate.

Answer 5

• Endogenous Catecholamines
  
  • Epinephrine - β1 and β2 at low concentrations, α1 at high []
  • Norepinephrine - α1, α2, β1, and slightly activates β2
  • Dopamine - D1 > β1 > α1, but it does activate all three
• Isoproterenol - β1 and β2 (aka - non selective)
• Dobutamine - β1
• Albuterol, Salmeterol, & Formoterol - β2
• Phenylephrine - α1
• Clonidine, Methyldopa, Brimonidine - α2

Question 6

List the effects of epinephrine on the following tissues/actions and include the mediating receptor:

• HR and Contractile Force
• Renin release
• Skin arterioles
• Viscera Arterioles
• Skeletal Muscle arterioles
• Bronchial smooth muscle
• Liver Glycogenolysis
• Glucagon release
• Lipolysis

Answer 6

• Increases HR and contractile force - β1 effect
• Increases Renin release - β1 effect
• Constricts arterioles in skin and viscera - α1 effect
• Dilates arterioles in skeletal muscle - β2 effect
• Bronchodilation - β2 effect
• Increases liver glycogenolysis - β2 effect
• Increases glucagon release - β2 effect
• Increases lipolysis - β1 and β2 effect

Question 7

Describe the effects of epinephrine on systolic, diastolic, and mean arterial pressure when given in large and small doses. Name the relevant receptors.

Answer 7

• When a large dose is given
  
  • Increase in SP from increase in ventricular contraction and HR (β1)
  • Increase in DP due to vasoconstriction (α1)
  • Increase in MAP because of the previous two
• When a low dose is given
  
  • Increase in SP from β1 effect on heart
  • Decrease in DP from β2 effect on vasculature
  • No change in MAP, which means no baroreceptor reflex

Question 8

What are the uses for epinephrine?

Answer 8

• Anaphylactic shock
• Acute asthmatic attacks (when other drugs have failed)
• Cardiac arrest
• Used with local anesthetics to increase the duration of their effectiveness (by producing vasoconstriction at the site of injection)

Question 9

Describe the effects NE has on TPR, HR, contractility, CO, SP, DP, and MAP. Name the receptors involved. How does this effect change if atropine is given before NE?

Answer 9

• Increases TPR (and therefore DP as well) - α1 effect
• Increases Contractility (and therefore SP as well) - β1 effect
• NE would also increase HR (and therefore CO as well) via the β1 effect except that the baroreceptor reflex counteracts this effect and the HR actually decreases, leading to no net change (or a decrease) in CO

If atropine is given first, NE will cause tachycardia because atropine will block the M2 receptors in the heart (the receptors through which the baroreceptor reflex decreases HR).

Question 10

What are the primary uses of NE?

Answer 10

To treat shock because it increases TPR thereby increasing MAP

Question 11

Describe the baroreceptor reflex and include the names of the relevant heart receptors and their actions.

Answer 11

1. Baroreceptors in the carotid sinus sense an increase in MAP and they send signals to vagal and sympathetic centers in the brain
2. Stimulation of vagal centers of the brain leads to an increase in PSNS stimulation to the M2 receptors in the atria, causing a decrease in HR
3. Inhibition of sympathetic centers in the brain leads to a decrease in SNS stimulation of the β1 receptors in the atria, causing a decrease in HR. There is also a decrease in the SNS stimulation of the β1 receptors in the myocardium, causing a decrease in contractility

The reverse happens when there is a decrease in MAP

Question 12

Describe the CVS effects of dopamine at low, intermediate, and high doses.

Answer 12

• Low Doses - only activates D1 receptors, which are located in the renal and other vascular beds. This causes vasodilation of the renal vascular beds leading to incresaed GFR and Na+ excretion
• Intermediate Doses - cardiac β1 receptors now get activated by dopamine directly and by the increased release of NE from nerve terminals, which dopamine also causes. This leads to increased SP and MAP (DP and TPR unchanged)
• High Doses - α1 receptors are now actiavted leading to a larger increase in MAP, DP, and TPR

Question 13

List the uses of dopamine

Answer 13

• Treatment of severe CHF
• Treatment of cardiogenic and septic shock. Intermediate to high doses need to be used for this

Question 14

Describe the CVS and respiratory system effects of isoproterenol. Name the relevant receptors.

Answer 14

• Increases HR. contractility, and CO via the β1 effect
• Dilates arterioles or skeletal muscle (causing a decrease in TPR) via the β2 effect
• DP falls, SP usually remains unchanged (it might rise), and MAP typically falls
• Bronchodilation via the β2 effect

Question 15

What are the primary uses of isoproterenol?

Answer 15

May be used in emergencies to stimulate HR in patients with bradycardia or heart block

Question 16

List the CVS effects of dobutamine. Name the relevant receptors

Answer 16

• Potent inotrope (contractility), with comparatively mild chronotropic (HR) effects (less than isoproterenol)
• Causes mild vasodilation (less than isoproterenol)

Question 17

What are the primary uses of dobutamine?

Answer 17

• Management of acute heart failure
• Management of cardiogenic shock
• Used during a stress ECG because it increases myocardial O2 consumption

Question 18

List the β2 agonists we need to know and their uses

Answer 18

Used to evoke bronchodilation for asthma patients

• Albuterol - short but fast acting for management of acute asthma symptoms
• Salmeterol & Formoterol - slow but prolonged action for 12 hr relief of chronic asthma symptoms. Not for prompt relief of acute symptoms

Question 19

What are the adverse effects of β2 agonists? How are these effects managed?

Answer 19

• Tremor
• Restlessness
• Apprehension
• Anxiety
• Tachycardia

These effects are less likely to occur if medication is adminstered via inhalation instead of parenteraly or orally.

Question 20

List the actions of phenylephrine

Answer 20

• Direct effect
  
  • Vasoconstriction (thereby causing an increase in TPR and MAP)
• Indirect effects via the baroreceptor reflex
  
  • Decrease in HR

Question 21

List and explain the uses of phenylephrine

Answer 21

• Nasal decongestant - vasoconstriction decreases the volume of the nasal mucosa
• Evoke mydriasis
• To increase BP in cases of hypotension caused by vasodilation in septic shock or anesthesia
• Used to terminate episodes of supraventricular tachycardia via the baroreceptor reflex (by causing vasoconstriction which will increase MAP)

Question 22

List the MOA, uses, and adverse effects of clonidine.

Answer 22

• Partial α2 agonist that only activates central presynaptic α2 receptors which essentially leads to a reduction in SNS outflow.
• These drugs are used to reduce BP (antihypertensive).
• Adverse Effects - lethargy, sedation, and xerostomia

Question 23

What are the MOAs, effects, uses, and adverse effects of methyldopa

Answer 23

• Taken up by noradrenergic neurons and converted to α-methylnorepinephrine which activates central α2 receptors, decreasing BP.
• The drug of choice for treatment of HTN during pregnancy.
• Adverse Effects - sedation, impaired mental concentration, xerostomia

Question 24

What are the MOAs, effects, uses, and adverse effects of brimonidine?

Answer 24

• Highly selective α2 agonist.
• Reduces aqueous humor production and increases outflow.
• Given ocularly to lower IOP in glaucoma patients

Question 25

List the indirect acting adrenergic agonists we need to know and briefly describe how they work.

Answer 25

• Releasing Agents, meaning they cause NE release from presynaptic terminals and potentiate effects of NE produced endogenously - Amphetamine, methylphenydate, tyramine
• Uptake Inhibitors - cocaine, atomoxetine, modafinil

Question 26

List the effects and uses of amphetamine.

Answer 26

• It has central stimulatory action which can increase BP by α-agonist action on vasculature as well as β-stimulatory effects on the heart
• Used to treat ADHD and Narcolepsy

Question 27

List the effects and uses of methylphenidate

Answer 27

• It’s a structural analogue of amphetamine so it has the same effects
• Used to treat ADHD in children

Question 28

List the effects and special considerations for Tyramine.

Answer 28

Tyramine has the same effects as the other releasing agents. It is normally oxidized by MAOs. It is also commonly found in fermented foods like ripe cheeses and Chianti wine so patients on MAOIs should not eat these foods in order to avoid a vasopressor episode.

Question 29

List the MOA, effects, and uses of cocaine.

Answer 29

• Blocks monoamine reuptake causing it to accumulate in the synaptic space, resulting in potentiation and prolongation of their central and peripheral actions
• No approved uses

Question 30

List the MOA and uses of atomoxetine.

Answer 30

• Selective inhibitor of the NE reuptake transporter
• Indicated for treatment of ADHD

Question 31

List the MOA, effects, and uses of modafinil.

Answer 31

• MOA not fully known but it appears to inhibit NE and DA transporters
• It increases synaptic concentrations of NE, DA, serotonin, and glutamate while decreasing GABA levels.
• Acts as a psychostimulant and is used for the treatment of narcolepsy

Question 32

List the mixed-acting adrenergic agonists we need to know and describe their MOA.

Answer 32

• Ephedrine and Pseudoephedrine (an enantiomer of ephedrine)
• They induce release of NE and activate adrenergic receptors

Question 33

List the uses of ephedrine and explain why it’s useful for these purposes.

Answer 33

• Used as a pressor agent during spinal anesthesia and used to treat myasthenia gravis.
• It’s use is preferred for these purposes because it is not a catecholamine and is readily non-polar which means it can penetrate the CNS and is not readily broken down by COMT or MAO (longer duration)

Question 34

What are the uses of pseudoephedrine.

Answer 34

As a component of many nasal decongestant mixtures