Adrenergic drugs are a broad class of medications that bind to adrenergic receptors throughout the body. These receptors include: alpha-1, alpha-2, beta-1, beta-2, beta-3. Adrenergic drugs will bind directly to one or more of these receptors to induce various physiologic effects. Some drugs indirectly act at these receptors to induce certain effects.
Adrenergic drugs must be classified based on the specific receptors they bind. Direct-acting drugs, which are the primary focus of this article, include vasopressors, bronchodilators, and other drugs. Examples of indirect drugs are amphetamines and cocaine.
Examples of adrenergic drugs which only bind on alpha-1 receptors are phenylephrine, oxymetazoline. Selective alpha-2 receptor drugs include methyldopa and clonidine. The key beta-1 selective drug is dobutamine. Lastly, beta-2 selective drugs are bronchodilators, such as albuterol and salmeterol.
Adrenergic drugs can also be non-selective and hence bind to a combination of adrenergic receptors. Norepinephrine binds to the alpha-1, alpha-2, and beta-1 receptors. Dopamine binds to the alpha-1, alpha 2, beta-1 receptors, and also the two dopamine receptors. Epinephrine binds to all of the adrenergic receptors. These drugs bind to more of the adrenergic receptors when administered at higher doses.
The following are key non-comprehensive indications of various adrenergic drugs:
Alpha-1 Receptor Agonists
Alpha-2 Receptor Agonists
Beta-1 Receptor Agonists
Beta-2 Receptor Agonists
Beta-3 receptors carry no clinical significance.
Many of these medications, especially the non-selective ones, are used in critical care and emergency settings. They are referred to as vasopressors. Side effects depend on the specific agent. However, changes in heart rate and blood pressure are the most common side effects.
Indirect acting adrenergic drugs increase norepinephrine and epinephrine through various mechanisms. Hence, their side effect profiles are similar to those seen with vasopressors. 
Adrenergic receptors, otherwise known as adreno-receptors, are classified as either alpha or beta receptors. Those two classes further subdivide into alpha-1, alpha-2, beta-1, beta-2, and beta-3. Alpha-1 and alpha-2 receptors both have three subtypes. These receptors are all G-protein-coupled receptors.
Alpha-1 receptors are Gq coupled-receptors, whereas alpha-2 receptors are Gi coupled-receptors. Beta-2 and beta-3 are also Gi coupled-receptors. All beta receptors are also Gs coupled-receptors.
Agonist binding to the adrenergic receptors induces the following cellular mechanisms:
Phospholipase C is activated, which leads to the induction of inositol triphosphate (IP3) and diacylglycerol (DAG). As a result, calcium rises.
Adenylate cyclase is inactivated, which leads to a decrease in cyclic adenosine monophosphate (cAMP).
Adenylate cyclase is activated, and cAMP increases.
Given adrenergic drugs are a broad class of medications, they are collectively available in almost every form. Common methods of administration are oral, intravenous, intranasal, and topical. Dosages for Beta 1 agonists such as dobutamine can begin with .5 to 1 mcg/kg/min and go up to 40 mcg/kg/min on the maximum end. The doses at the lower end can also be prescribed at 2.5mcg/kg/min to 5mcg/kg/min. While doses at the higher end can be prescribed at 5mcg/kg/min to 20mcg/kg/min. 
While other medications such as clonidine (alpha 2 agonists) may be prescribed as transdermal patches with dosages of 0.1mg/day to 0.3 mg/day while changing the patch every week. Clonidine can also be prescribed via an immediate-release tablet at 0.1 mg/day to 0.3 mg/day and an extended-release tablet with a dosage of 0.1 mg/day. Caution should be used when prescribing the medication to patients with renal failure as and it is recommended to begin with a low dose and increase as needed. 
The adverse effects seen with adrenergic drugs are broad. The most common side effects are changes in heart rate and blood pressure.
Selective agonist binding to the alpha-1 receptor can lead to hypertension. Certain drugs that bind to the alpha-1 receptor, such as phenylephrine, may cause bradycardia.
Drugs that selectively bind to alpha-2 receptors may cause hypotension, dry mouth, and sedation. At higher doses, respiratory depression and somnolence may occur. These effects are most pronounced with clonidine and similarly acting drugs.
Selective binding to beta-1 receptors commonly causes tachycardia, palpitations, and hypertension. Tachyarrhythmias and anxiety can also be common. High doses may induce dangerous arrhythmias. An example of a selective beta-1 receptor agonist is dobutamine.
Beta-2 receptor agonists can cause tremor, tachycardia, palpitations, and anxiety. Common examples are the various bronchodilator drugs such as albuterol and salmeterol.
Non-selective binding to the adrenergic receptors can cause different side effects that vary based on the specific agent as well as the dosage. The common non-selective agonists are norepinephrine, epinephrine, and isoprenaline. Common side effects are tachycardia, hypertension, arrhythmias, palpitations, and anxiety. Norepinephrine is less likely to cause arrhythmias than some of the other pressor medications. 
There is a broad variation in the therapeutic index of adrenergic drugs given the large number of medications. When prescribing beta 1 agonists care should be taken to monitor hypertension as well as potential arrhythmias. 
While prescribing alpha 2 agonists patients should be monitored for bradycardia, hypotension, and potential substance abuse. 
Recent research has also counseled caution when administering Beta 2 agonists as patients should be monitored for paradoxical bronchospasm, blood pressure, heart rate, and central nervous system penetration. 
Adrenergic receptors all have antagonists. Alpha-blockers are not generally indicated for the treatment of alpha-agonist overdoses. Beta-blockers may be used to treat adverse effects arising from adrenergic receptor agonists acutely. Beta-blockers can treat the tachycardia and hypertension that may occur from vasopressors. Toxicity should be monitored in the pediatric population when using Beta 2 agonists as they can increase levels of liver aminotransferase. 
In addition, when prescribing alpha 2 agonists there are instances where angioedema, Atrioventricular (AV) block, and Hypersensitivity may occur. Potential toxicities of Beta 1 agonists may include: tremors, headaches, and vomiting. 
There are many types of adrenergic agents and healthcare workers, including the nurse practitioner, physician assistants, and physicians who prescribe these agents, should be aware of their side effects and contraindications. It is essential to consult with a pharmacist if there is any question about the use of an adrenergic agent; this can include drug-drug interactions, appropriate dosing based on the condition treated, and adverse event profile. Nursing can also access this resource as they will often administer the drugs inpatient, and will need to know what signs to watch for in the event of an adverse reaction of any sort. An interprofessional team approach is vital to coordinate the care of patients taking these medications safely and effectively. [Level 5]
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