Sympatholytics: Alpha-2 agonists

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Sympatholytics: Alpha-2 agonists

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A 28-year-old woman, gravida 2 para 1, at 30 weeks gestational age, comes to her primary care physician to evaluate joint pain and fatigue. The patient reports that her symptoms began two weeks ago. Her current pregnancy is notable for gestational hypertension, for which she is taking methyldopa, and an episode of cystitis at 20 weeks, which was successfully treated with antibiotics. Temperature is 37.8°C (100°F), blood pressure is 147/82 mmHg, and pulse is 73/min. Physical examination reveals a facial rash affecting the cheeks and nasal bridge. Bilateral lungs are clear to auscultation, and there is no abdominal tenderness. Uterine fundal height is consistent with gestational age. The bilateral wrist and metacarpophalangeal joints are noted with stiffness and pain with passive movement. Laboratory testing is shown below. Which of the following best describes the mechanism of action of the drug most likely responsible for this patient’s symptoms?  

Laboratory Value  
12.5 g/dL  

External References

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α-methyldopa p. 244

anemia and p. 417

gestational hypertension p. 667

Coombs-positive hemolysis

α-methyldopa p. 244

Lupus-like syndrome

α-methyldopa p. 244


Coombs-positive hemolytic anemia p. 251

hypertension in pregnancy p. 323


Central anti-adrenergics are a class of medications that’s not very commonly used these days. Their mechanism of action is to target the adrenergic neurons in the central nervous system, and prevent them from effectively releasing the catecholamines: norepinephrine and epinephrine.

So, the nervous system is divided into the central nervous system, so the brain and spinal cord; and the peripheral nervous system, which includes all the nerves that connect the central nervous system to the muscles and organs. The peripheral nervous system can be divided into the somatic nervous system, which controls voluntary movement of our skeletal muscles; and the autonomic nervous system, which controls the involuntary movement of smooth muscles and glands of our organs.

Now, the autonomic nervous system - which includes both the sympathetic and parasympathetic nervous systems - is made up of a relay that includes two neurons. We’ll focus on just the sympathetic nervous system. Signals for the autonomic nervous system start in the hypothalamus, at the base of the brain. Hypothalamic neurons have really long axons that carry signals all the way down to the thoracic and lumbar spinal cord nuclei, where they synapse with preganglionic neuron cell bodies. Here, they release the neurotransmitter norepinephrine, which causes the preganglionic neurons to transmit the signals down their relatively short axon, which exits the central nervous system via the spinal cord. These short nerve fibers reach the nearby sympathetic ganglion, which consists of many postganglionic neuron cell bodies. The postganglionic neurons are also called adrenergic neurons, because they release the neurotransmitter norepinephrine, which is also called noradrenaline; and to a much lesser degree, epinephrine, or adrenaline. These two catecholamines activate the adrenergic receptors on many different organs, which allow the sympathetic nervous system to trigger the fight or flight response that increases the heart rate and blood pressure, as well as slowing digestion. All of this maximizes blood flow to the muscles and brain, and can help you either run away from a threat, or fight it, which is why it’s also called the “fight or flight response.”


Alpha-2 agonists are a class of drugs that bind to alpha-2 adrenergic receptors and activate them, resulting in a range of physiological effects. Alpha-2 adrenergic receptor agonists include clonidine, guanabenz, and guanfacine. These medications stimulate alpha-2 adrenergic receptors on the presynaptic neurons in the CNS, especially those in the medulla. This decreases the release of norepinephrine in the sympathetic neurons, which leads to lower blood pressure. Alpha-2 agonists are used to treat various conditions such as anxiety, depression, attention deficit hyperactivity disorder (ADHD), and pain. Common side effects associated with the use of alpha-2 agonists include dry mouth, constipation, headache, dizziness, drowsiness, and fatigue.


  1. "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
  2. "Rang and Dale's Pharmacology" Elsevier (2019)
  3. "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
  4. "G-Protein–Coupled Receptors in Heart Disease" Circulation Research (2018)
  5. "α2A- and α2C-Adrenoceptors as Potential Targets for Dopamine and Dopamine Receptor Ligands" Molecular Neurobiology (2018)
  6. "Alpha-2 Adrenergic Receptor Agonists: A Review of Current Clinical Applications" Anesthesia Progress (2015)
  7. "Oral antihypertensive regimens (nifedipine retard, labetalol, and methyldopa) for management of severe hypertension in pregnancy: an open-label, randomised controlled trial" The Lancet (2019)

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