Drugs Affecting the Sympathetic Nervous System

Key Terms

Adrenergic Neuronal Blocker: A drug that acts at the neuronal nerve endings to reduce the formation or release of norepinephrine (NE).
Alpha-Adrenergic Drug: A drug that stimulates alpha-adrenergic receptors.
Alpha-1 Adrenergic Blocker: A drug that blocks the alpha-1 effects of norepinephrine (NE) and epinephrine (EPI).
Alpha-1 Adrenergic Receptor: A receptor, located on smooth muscle, that mediates smooth muscle contraction.
Alpha-2 Adrenergic Receptor: A receptor located on adrenergic nerve endings that reduces the release of norepinephrine (NE).
Beta-1 Adrenergic Receptor: A receptor located in the heart that increases heart rate and force of contraction.
Beta-2 Adrenergic Receptor: A receptor located on smooth muscle that relaxes smooth muscle when stimulated.
Catecholamine: A term referring to norepinephrine, epinephrine, and other sympathomimetic compounds possessing the catechol structure.
False Transmitter: A substance formed in nerve endings that mimics and interferes with the action of the normal neurotransmitter.
Nonselective Beta-Adrenergic Blocker: A drug that blocks both beta-1 and beta-2 adrenergic receptors.
Nonselective Beta-Adrenergic Drug: A drug that stimulates both beta-1 and beta-2 receptors.
Selective Beta-1 Adrenergic Blocker: A drug that blocks only beta-1 receptors.
Selective Beta-2 Adrenergic Drug: A drug that stimulates only beta-2 receptors at therapeutic doses.
Sympatholytic: Refers to the action of an adrenergic blocking drug or an action that decreases sympathetic activity.
Sympathomimetic: Refers to the action of an adrenergic drug or an action that increases sympathetic activity.

Learning Outcomes

Explain how adrenergic nerve endings function to form and release norepinephrine (NE).
Explain the mechanism of action of adrenergic drugs used to treat a variety of diseases.

Introduction

The sympathetic nervous system regulates activity of internal organs and glands during energy expenditure, physical exertion, and stressful situations.
Stressful conditions like mental anguish, anxiety, physical trauma, and serious disease activate the sympathetic nervous system.
Peripheral sympathetic nerves (adrenergic nerves) release norepinephrine (NE).
Norepinephrine (NE) binds to adrenergic receptors, producing effects associated with sympathetic stimulation.
The adrenal medulla releases epinephrine (EPI), which travels in the blood and stimulates adrenergic receptors.
Epinephrine (EPI, adrenaline) is released in larger amounts during stress and emergencies (fight or flight).
Norepinephrine (NE) and epinephrine (EPI) are chemically similar and called catecholamines.
Drugs affecting sympathetic activity:
- Adrenergic drugs (agonists): Increase sympathetic activity.
- Adrenergic blockers (antagonists): Decrease sympathetic activity.
Adrenergic drugs are used to:
- Increase blood pressure.
- Stimulate the heart.
- Produce bronchodilation.
Adrenergic blockers are used to:
- Lower blood pressure.
- Reduce cardiac stimulation in excessive sympathetic activity.

Adrenergic Nerve Endings

Nerve endings primarily form NE.
Adrenergic nerve ending takes up tyrosine, forms dihydroxyphenylalanine (DOPA), then dopamine (DA), which is converted into NE.
Norepinephrine (NE) is stored within vesicles inside nerve endings.
When adrenergic nerves are stimulated, norepinephrine (NE) is released.
Norepinephrine (NE) travels across the synaptic cleft to smooth or cardiac muscle, attaches to adrenergic receptors, producing the sympathetic response.
Most of the norepinephrine (NE) rapidly passes back into the nerve endings (reuptake).
Inside nerve endings:
- NE may be reused.
- NE may be destroyed by monoamine oxidase (MAO).
Figure 6.1 illustrates these actions.

Schematic Representation of Neurohumoral Transmission at Adrenergic Nerve Endings

Tyrosine (Tyr) is taken up into the nerve ending and enzymatically converted to dihydroxyphenylalanine (DOPA).
DOPA converted to dopamine (DA), which enters storage vesicles and is synthesized/stored as norepinephrine (NE).
Upon adrenergic stimulation, norepinephrine (NE) is released from the adrenergic nerve ending into the synaptic cleft.
Norepinephrine (NE) then can:
- Stimulate adrenergic receptors on internal organs and glands.
- Stimulate alpha-2 receptors on the postganglionic nerve ending to inhibit further release of norepinephrine (NE).
- Undergo reuptake back into nerve ending for restorage in vesicles or metabolism to inactive metabolites by MAO.

Norepinephrine Versus Epinephrine

Norepinephrine (NE) and epinephrine (EPI) are both adrenergic neurotransmitters but have important differences.
Both stimulate internal organs to increase sympathetic activity.
Epinephrine (EPI) is only produced in the adrenal medulla and released during stressful situations (fight or flight).
Epinephrine (EPI) is released into bloodstream; acts as a hormone to stimulate all adrenergic receptors.
One action of epinephrine (EPI) is to relax smooth muscle; norepinephrine (NE) does not.
Epinephrine (EPI) relaxes respiratory smooth muscle, promoting bronchodilation.
Increased oxygen passes into lungs when respiratory tract is dilated.
Due to response differences, several adrenergic receptor types have been identified.

Adrenergic Receptors

Two main types: alpha- and beta-adrenergic receptors.
Alpha Receptors:
- Divided into alpha-1 and alpha-2 subtypes.
Beta Receptors:
- Divided into beta-1 and beta-2 subtypes.
Some organs contain more than one receptor type, but one predominates and determines overall response.
Alpha-1 Adrenergic Receptors:
- Found predominantly on smooth muscle membranes of arteries, veins, and sphincters of urinary and gastrointestinal tract.
- When stimulated by norepinephrine (NE) or epinephrine (EPI), they produce contraction (e.g., vasoconstriction of most blood vessels).
- During fight or flight, vasoconstriction diverts blood from organs not involved (GI, urinary tract) to heart and skeletal muscle.
Alpha-2 Adrenergic Receptors:
- Located on adrenergic nerve endings.
- Activated by norepinephrine (NE) and epinephrine (EPI) to activate a negative feedback mechanism that reduces and regulates the release of additional norepinephrine (NE).
- Drugs affecting this receptor are used in hypertension treatment.
Beta-Adrenergic Receptors:
- Found on both cardiac and some smooth muscle membranes.
- In the heart, predominant receptors are beta-1:
  - Stimulation by norepinephrine (NE) or epinephrine (EPI) increases heart rate and force of contraction.
- In smooth muscle of coronary and skeletal muscle blood vessels and bronchiolar smooth muscle, the predominant receptor is beta-2:
  - Stimulation by epinephrine (EPI) produces vasodilation and bronchodilation (relaxation of bronchiolar smooth muscle).
  - Increases blood flow to skeletal muscle and the heart, delivers more oxygen to the lungs (necessary during fight or flight).
Alpha-receptor stimulation causes smooth muscle contraction at some sites, while beta-2 receptor stimulation causes smooth muscle relaxation at other sites.

Effects of Norepinephrine and Epinephrine on Alpha and Beta Receptors

Alpha-1:
- Organ: Most arteries and veins, Iris muscle (eye).
- Epinephrine effect: Vasoconstriction, Contraction-pupillary dilation.
- Norepinephrine effect: Vasoconstriction, Contraction-pupillary dilation.
Alpha-2:
- Organ: Adrenergic nerve ending.
- Epinephrine effect: Decrease release of NE.
- Norepinephrine effect: Decrease release of NE.
Beta-1:
- Organ: Heart.
- Epinephrine effect: Greater increase in heart rate, force of contraction, and atrioventricular conduction.
- Norepinephrine effect: Moderate increase in heart rate, force of contraction, and atrioventricular conduction.
Beta-2:
- Organ: Bronchiolar smooth muscle, Uterus, Coronary and smooth muscle.
- Epinephrine effect: Bronchodilation, Relaxation, Vasodilation.
- Norepinephrine effect: Norepinephrine does not stimulate beta-2 receptors

Adrenergic Drug Classes

Classification system for adrenergic receptors is used for classifying drugs.
Two general terms to categorize drugs affecting the sympathetic nervous system:
- Sympathomimetics: Adrenergic drugs (alpha and beta agonists) that produce effects similar to stimulating or mimicking the sympathetic nervous system.
- Sympatholytics: Adrenergic blocking drugs (alpha, beta, and neuronal blockers) that antagonize or decrease sympathetic activity.

Sympathomimetic Drug Classes

Sympathomimetic drugs (including norepinephrine (NE) and epinephrine (EPI)) that produce contraction of smooth muscle by stimulating the alpha-1 adrenergic receptors are called alpha-adrenergic drugs.
Drugs (including epinephrine (EPI)) that both stimulate the heart (beta-1 receptors) and cause relaxation of smooth muscle (beta-2 receptors) are called nonselective beta-adrenergic drugs.
Epinephrine (EPI) stimulates all alpha and beta receptors
Beta-adrenergic drugs that selectively stimulate only the beta-2 receptors at therapeutic doses are referred to as the selective beta-2 adrenergic drugs and are used primarily as bronchodilators.

Sympatholytic Drug Classes

Sympatholytic drugs that block the alpha effects of norepinephrine (NE) and epinephrine (EPI) are known as alpha-adrenergic blockers.
- Most alpha blockers today are selective and only block the alpha-1 receptor (relaxation of smooth muscle).
Drugs that block both the beta-1 and beta-2 effects of epinephrine (EPI) are known as the nonselective beta-adrenergic blockers.
Drugs that block only beta-1 receptors are known as selective beta-1 adrenergic blockers.
The effect of these alpha- and beta-blockers is to decrease sympathetic activity, especially in the cardiovascular system.
The blocking drug competes with norepinephrine (NE) or epinephrine (EPI) for the receptor sites.
When the blocking drug occupies the receptor, it prevents norepinephrine (NE) and epinephrine (EPI) from producing an effect.
Another method to inhibit the sympathetic system is to decrease the formation or the release of norepinephrine (NE) from the adrenergic nerve ending.
Drugs that act at the adrenergic nerve endings to reduce the formation or release of norepinephrine (NE) are known as the adrenergic neuronal blockers.

Summary of Major Adrenergic Drug Classes and Receptor Sites Acted Upon

Sympathomimetics (Agonists)
- Alpha Drugs
  - Receptor Site: Alpha-1
  - Main drug effect: Alpha-1 effect, contraction of alpha-1-mediated smooth muscle.
- Nonselective beta drugs
  - Receptor Site: Alpha-2, Beta-1, Beta-2
  - Main drug effect: Alpha-2 effect, negative feedback effect to decrease release of NE. Beta-1 effect, cardiac stimulation; increased heart rate and force of contraction. Beta-2 effect, relaxation of beta-2-mediated smooth muscle, bronchodilation, and increased blood flow to the heart and skeletal muscle.
- Selective beta-2 drugs
  - Receptor Site: Beta-2
  - Main drug effect: Beta-2 effect, relaxation of beta-2-mediated smooth muscle, bronchodilation, and increased blood flow to the heart and skeletal muscle.
Sympatholytics (Antagonists)
- Selective alpha-1 blockers
  - Receptor Site: Alpha-1
  - Main drug effect: Alpha-1 blockade, relaxation of alpha-1-mediated smooth muscle (vasodilation), decreased blood pressure.
- Nonselective beta-blockers
  - Receptor Site: Beta-1, Beta-2
  - Main drug effect: Beta-1 blockade, decreased cardiac function; decreased heart rate and force of contraction. Beta-2 blockade, beta-2-mediated smooth muscle contraction (nontherapeutic).
- Selective beta-1 blockers
  - Receptor Site: Beta-1
  - Main drug effect: Selective beta-1 blockade, decreases cardiac function; decreases heart rate and force of contraction.
- Neuronal blockers
  - Receptor Site: Adrenergic nerve ending
  - Main drug effect: Interferes with synthesis and/or release of NE from nerve ending, decreases all sympathetic activity, lowers blood pressure and cardiac function.

Alpha-Adrenergic Drugs

Norepinephrine (NE) is the prototype drug for the alpha drug class.
Alpha-adrenergic drugs have chemical structures and effects similar to norepinephrine (NE).
Disadvantage of norepinephrine (NE) as a drug: must be injected, short duration.
The most important clinical effect produced by alpha-adrenergic drugs is stimulation of alpha-1 receptors to cause contraction of smooth muscle.
- Vasoconstriction of most blood vessels.
- Contraction of sphincter muscles in the gastrointestinal (inhibits movement of intestinal contents) and urinary (restricts passage of urine) tracts.
- Contraction of ocular muscles that causes dilation of the pupil of the eye (mydriasis).
Actions on sphincters of GI and urinary tracts are not therapeutic and are potential side effects.

Clinical Indications

Alpha drugs are administered intravenously in hypotensive states (e.g., after surgery) to increase blood pressure and maintain circulation.
Vasoconstriction of blood vessels in mucous membranes of nasal sinuses decreases mucous secretions and produces a decongestant effect.
- Included in over-the-counter (OTC) cold and allergy preparations for relief of nasal congestion.
A few alpha drugs are used:
- In ophthalmology to dilate pupils (mydriatic drugs).
- As ocular decongestants.

Representative Alpha-Adrenergic Drugs

Drugs used to treat hypotension
- Midodrine (ProAmatine): Tablets, Increase blood pressure
- Norepinephrine (Levophed): Parenteral injection, Increase blood pressure
- Phenylephrine (Neo-Synephrine): Parenteral injection, Increase blood pressure
Drugs used for nasal and ocular decongestion
- Naphazoline (Privine): Nasal solution, spray, Nasal decongestant
- Naphazoline (Naphcon): Ophthalmic solution, drops, Ocular decongestant
- Oxymetazoline (Afrin/Mucinex/Dristan): Nasal spray, Nasal decongestant
- Phenylephrine (Neo-Synephrine): Nasal solution, spray, tablets, ophthalmic solution, Nasal decongestant
- Pseudoephedrine (Sudafed): Tablets, capsules, syrups, Nasal decongestant
- Tetrahydrozoline (Tyzine): Nasal solution, drops, Nasal decongestant
- Tetrahydrozoline (Visine): Ophthalmic solution, drops, Ocular decongestant
- Xylometazoline (Otrivin): Nasal drops, Nasal decongestant

Adverse Effects

The major adverse effect of IV alpha-adrenergic drugs is excessive vasoconstriction of blood vessels.
- May result in increased blood pressure and hypertensive crisis.
- Can lead to hemorrhage (usually cerebral) or cardiac arrhythmias.
- Extreme caution must be observed with hypertensive or cardiac patients.
- Blood pressure recordings should be taken at frequent intervals.
The most common side effect of decongestant use is irritation of the nasal sinuses or eyes due to excessive dryness caused by vasoconstrictive decrease in blood flow.

Caution for Health-Care Professionals

During intravenous infusion of alpha-adrenergic drugs, the IV needle should be checked frequently to make certain that the drug is not infiltrating the skin.
Infiltration by alpha drugs causes intense vasoconstriction of skin blood vessels, which can lead to death of skin cells and gangrene.

Beta-Adrenergic Drugs

Beta-adrenergic drugs have a selective action to stimulate beta receptors.
With the exception of norepinephrine (NE) and epinephrine (EPI), most beta drugs produce very few alpha effects.

Beta Drug Effects

The most important actions of the beta drugs are stimulation of the heart (beta-1) and bronchodilation (beta-2).
Isoproterenol is the most potent beta-adrenergic drug that produces both of these effects.
This dual action (heart and respiratory passages) is the main disadvantage of isoproterenol.
- Often overstimulation of the heart along with the bronchodilator effect.
- Isoproterenol is rarely used due to this disadvantage.
Selective beta-2 drugs are now widely used as bronchodilators.
Beta-2 adrenergic drugs are more extensively discussed in Chapter 32 with the treatment of asthma.
Beta-2 receptors are also found in uterine smooth muscle.
- Stimulation of beta-2 receptors in the uterus relaxes smooth muscle and inhibits uterine contractions (can occur during premature labor).
- Selective beta-2 drugs such as terbutaline may be used to arrest premature labor.

Beta-Adrenergic Drugs

Nonselective drugs
- Dopamine (Intropin): Alpha, beta-1, IV infusion, Circulatory shock
- Ephedrine (generic): Alpha, beta-1, beta-2, Parenteral, Bronchodilator
- Epinephrine (Adrenaline): Alpha, beta-1, beta-2, Parenteral SC injection, Acute allergy/asthma
- Epinephrine (EpiPen): Alpha, beta-1, beta-2, Parenteral IM/SC injection, Acute allergy
- Epinephrine (Primatene mist): Alpha, beta-1, beta-2, non-aerosol inhalant, Bronchodilator
- Isoproterenol (Isuprel): Beta-1, beta-2, Parenteral IV injection, Cardiac stimulant
Selective drugs
- Albuterol (Proventil): Beta-2, Non-aerosol inhalant, (MDI), nebulizer, tablets, syrup, Bronchodilator
- Dobutamine (Generics): Beta-1, IV infusion, Acute heart failure
- Levalbuterol (Xopenex): Beta-2, Nebulization, non-aerosol MDI, Bronchodilator
- Metaproterenol (Alupent, generics): Beta-2, Non-aerosol inhalant, Bronchodilator
- Salmeterol (Serevent): Beta-2, Non-aerosol inhalant, Bronchodilator

Adrenergic Neuronal Blocking Drugs

The main activity inside adrenergic nerve endings is the formation and storage of norepinephrine (NE).
Norepinephrine (NE) is synthesized from amino acids: phenylalanine or tyrosine.
Drugs that interfere with the formation or storage of norepinephrine (NE) are classified as adrenergic neuronal blockers.
Neuronal blockers were reserved for severe hypertension.
Older drugs (reserpine and guanethidine) have been discontinued due to serious adverse effects.
Methyldopa is the most important neuronal blocker that is still available.

Sites of Action of Adrenergic Neuronal Blocking Drugs

Alpha-methyldopa inhibits the enzyme that normally converts DOPA to DA. In the process, DOPA is converted into alpha-methyldopamine (alpha-MDA) and then into the false transmitter alpha-methylnorepinephrine (alpha-MNE).
Reserpine depletes the nerve ending vesicles of NE, which is then metabolized by MAO to inactive metabolites.
Guanethidine acts on the nerve ending to block the release of NE and also depletes vesicles of NE, which is metabolized by MAO.

Patient Administration and Monitoring

Check vital signs frequently with parenteral drug administration.
Observe patient frequently for signs of cardiac depression (beta-blockers) and hypotension (alpha- and beta-blockers).
Explain to patient the common drug side effects: weakness, fatigue, dizziness, and sedation.
Instruct patient to report slow pulse rate, chest pain, respiratory difficulties, mental confusion, nightmares, or impotency.
Diabetic patients should be warned that beta-blockers may affect insulin and blood glucose levels, and that they should report any changes.

Methyldopa (Aldomet)

Methyldopa (alpha-methyldopa) interferes with the synthesis of norepinephrine (NE) in the nerve endings and greatly reduces the amount of norepinephrine (NE) that is formed.
Less norepinephrine (NE) is released, and the activity of the sympathetic system is decreased.
The adrenergic nerve ending also converts methyldopa into alpha-methylnorepinephrine, which is stored and released by the nerve endings like norepinephrine (NE).
The term false transmitter is used to describe drugs that produce neurotransmitter-like substances but that interfere with and reduce neuronal activity.
The main use of methyldopa is in the treatment of hypertension to lower blood pressure.
The most important site of action of methyldopa to reduce blood pressure is in the vasomotor center of the medulla oblongata (central effect).
In the medulla, the formation and release of alpha-methylnorepinephrine activates alpha-2 receptors and leads to a decrease in sympathetic activity to vascular smooth muscle, which produces vasodilation and a lowering of blood pressure.
The usual oral dose is 250 to 2000 mg/day (divided doses).
During initial treatment with methyldopa, many patients experience drowsiness and/or sedation, but these effects tend to disappear as drug treatment continues.
Other side effects include nausea, vomiting, diarrhea, nasal congestion, and bradycardia.
In some patients, adverse reaction may cause one or more of the following: drug fever, liver dysfunction, hemolytic anemia, or a lupus like syndrome resulting in skin eruptions and symptoms of arthritis.

Reserpine

Reserpine is obtained from a plant, Rauwolfia serpentina, found mainly in India.
The site of action of reserpine is the adrenergic nerve endings.
Reserpine prevents the storage of norepinephrine (NE) inside the storage granules.
Consequently, the adrenergic nerve endings are depleted of norepinephrine (NE).
When this occurs, the level of sympathetic activity is greatly reduced.
By reducing sympathetic activity, reserpine produces vasodilation and a lowering of blood pressure.
Reserpine is rarely used today because of its numerous adverse effects.
Most of the side effects of reserpine are caused by the decreased sympathetic activity.
Side effects are similar to parasympathetic stimulation and include increased salivation, diarrhea, nasal congestion, bradycardia, and excessive hypotension.
In the CNS, reserpine may produce excessive sedation, psychic disturbances such as confusion and hallucinations, or mental depression.

Guanethidine (Ismelin)

Guanethidine is a potent adrenergic neuronal blocker rarely used.
There are two main actions that guanethidine exerts on the nerve endings:
- Guanethidine prevents the release of norepinephrine (NE) from the nerve endings.
- Guanethidine depletes the norepinephrine (NE) storage granules similarly to reserpine.
These two effects produce a significant reduction of sympathetic activity and blood pressure.
The main adverse effects of guanethidine are caused by the decreased sympathetic activity and include diarrhea, nasal congestion, bradycardia, orthostatic hypotension, and impotency in males.
Many patients cannot tolerate the adverse effects.

Guanadrel (Hylorel)

Guanadrel produces effects similar to those produced by guanethidine.
It is used in the treatment of hypertension and generally produces a lower incidence of adverse effects than does guanethidine.

Preferred Treatment for Selected Conditions

Acute Allergic Reactions/Anaphylaxis

The drug of choice for treating acute allergic reactions caused by insect stings, drugs, or other allergies is epinephrine, administered by subcutaneous injection.
Self-injectable preparations (EpiPen) are available and must be carried and administered as soon as possible.
In addition, corticosteroids (Chapter 36) and antihistamines (Chapter 31) also can be administered but require time before the onset of action.
Other supportive measures such as oxygen and IV fluids also may be required.

Benign Prostatic Hyperplasia

Alpha-blockers such as tamsulosin (Flomax) and alfuzosin (Uroxatral) are generally preferred to increase urine flow.
In addition, finasteride (Proscar) and dutasteride (Avodart) are steroid inhibitors that block conversion of male testosterone to its active form and cause some reduction in the size of the prostate gland.

Bronchodilation

The selective beta-2 drugs such as albuterol (Proventil) or terbutaline (Brethine) with durations of action of 4 to 6 hours are usually the preferred drugs used to treat mild to moderate asthma.
If longer-acting drugs are required, formoterol (Foradil) and salmeterol (Serevent) may be indicated.
Preparations that combine either formoterol or salmeterol with anti-inflammatory corticosteroids are available and indicated for moderate to severe asthma.
Bronchodilators and the treatment of asthma are more extensively discussed in Chapter 32.

Hypertension

There are 11 different drug classes that can be considered for the treatment of hypertension.
- These include diuretics, angiotensin-converting enzyme inhibitors (ACEIS), angiotensin receptor blockers (ARBS), vasodilators, alpha-2 receptor agonists, calcium channel blockers, combined alpha- and beta-receptor blocking agents, central agonists, peripheral adrenergic inhibitors, and alpha- and beta-adrenergic blocking drugs.
The preferred treatment usually depends on what other diseases and conditions the patient is experiencing.
The treatment of hypertension is discussed in Chapter 26.

Summary of Sites of Action for Adrenergic Drugs

Figure 6.4 provides a diagrammatic summary of typical adrenergic nerve fibers, adrenergic receptors, and representative drugs that act on each receptor site.
Table 6.7 summarizes the major sympathetic drug classifications and receptor site terminology with drug examples.

Summary of Sympathetic Drug Classification and Receptor Site Terminology

Sympathomimetics (Agonists)
- Alpha-adrenergic drugs
  - Site of action: Alpha-1 receptor
  - Main effect: Smooth muscle contraction, vasoconstriction
  - Drugs: NE, EPI, metaraminol, phenylephrine
- Nonselective beta-1 and beta-2 adrenergic drugs
  - Site of action: Beta-1 and beta-2 receptors
  - Main effect: Cardiac stimulation, smooth muscle relaxation, bronchodilation
  - Drugs: EPI, isoproterenol, dopamine, dobutamine
- Selective beta-2 adrenergic drugs
  - Site of action: Beta-2 receptors
  - Main effect: Smooth muscle relaxation, bronchodilation
  - Drugs: Albuterol, formoterol, salmeterol, terbutaline
Sympatholytics (Antagonists)
- Alpha-1 adrenergic blockers
  - Site of action: Alpha-1 receptor
  - Main effect: Smooth muscle relaxation, vasodilation
  - Drugs: Doxazosin, prazosin, tamsulosin, terazosin
- Nonselective beta-1 and beta-2 adrenergic blockers
  - Site of action: Beta-1 and beta-2 receptors
  - Main effect: Cardiac depression, smooth muscle contraction (beta-2 organs)
  - Drugs: Nadolol, pindolol, propranolol, timolol
- Selective beta-1 adrenergic blockers
  - Site of action: Beta-1 receptors
  - Main effect: Cardiac depression (decrease HR/force of contraction)
  - Drugs: Atenolol, acebutolol, esmolol, metoprolol, nebivolol
- Adrenergic neuronal blockers
  - Site of action: Adrenergic nerve ending
  - Main effect: Decrease sympathetic activity
  - Drugs: Methyldopa