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Sympatholytics: Alpha-2 agonists
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|Laboratory Value ||Result|
|Hemoglobin||12.5 g/dL |
anemia and p. 417
gestational hypertension p. 667
α-methyldopa p. 244
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.
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