AssessmentsSympathomimetics: Direct agonists
Sympathomimetics: Direct agonists
Content Reviewers:Yifan Xiao, MD
Alpha agonists and beta agonists are two types of adrenergic medications that stimulate their respective receptors and mimic the effect of endogenous catecholamines, like norepinephrine and epinephrine.
The peripheral nervous system can be further 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 the smooth muscles and glands of our organs; this system is then further divided into the sympathetic and parasympathetic nervous systems.
Now, the autonomic nervous system 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.
From there, the signal goes from the preganglionic neurons down its relatively short axon, exits the spinal cord, and reaches the nearby sympathetic ganglion, which is made up of lots of postganglionic neuron cell bodies.
The postganglionic neurons are also called adrenergic neurons, because they release the neurotransmitter norepinephrine, which is also called noradrenalin; and to a much lesser degree, epinephrine also known as adrenaline.
These two catecholamines activate the adrenergic receptors on many different organs, which allows the sympathetic nervous system to trigger the fight or flight response that increases the heart rate and blood pressure, as well as slowing down digestion.
This response 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.
There are 2 types of alpha receptors: alpha-1 and alpha-2.
And in males, they trigger ejaculation.
Now, alpha-2 adrenergic receptors are primarily found on the presynaptic neuron. So when a presynaptic nerve ending is stimulated to release noradrenaline in the synaptic cleft, some of that norepinephrine turns around and binds to alpha-2 receptors on the presynaptic membrane. This inhibits further release of norepinephrine and serves as a mechanism of negative feedback control.
On the other hand, beta receptors have two main subtypes: beta-1 (β1) and beta-2 (β2).
Beta-1 receptors are also found in the kidney, where they stimulate a very special kind of cell, called juxtaglomerular cells, to release renin. Renin is a part of the renin- angiotensin- aldosterone system, which increases sodium and water retention by the kidneys and helps increase blood pressure.
Moving on to beta-2 adrenergic receptors, these are found on smooth muscle cells in the walls of blood vessels supplying skeletal muscles and the brain, which leads to vasodilation and increased blood flow to these tissues.
In the lungs, beta-2 adrenergic receptors cause bronchodilation, and that increases oxygen delivery to cells.
In the gastrointestinal tract, they decrease motility and slow digestion.
Now, in the liver, they cause more glucose to be released into the blood; and in the pancreatic islets of Langerhans, they promote the release of glucagon, which again, helps raise blood glucose levels.
Finally, beta-2 receptors stimulate an enzyme found on the surface of the cells lining capillary walls called lipoprotein lipase, which breaks down triglycerides into free fatty acids and cholesterol.
Alright, so medications that stimulate adrenergic receptors are called sympathomimetic medications or sympathomimetic agonists; and based on their mechanism of action, they are subdivided into three main categories: direct-acting agonists, which directly activate adrenergic receptors to produce the desired effect; indirect-acting agonists like amphetamines and cocaine, which increase the release of endogenous catecholamines and enhance their effect; and mixed-acting agonists like ephedrine, which utilize both of these mechanisms.
Now, we’re going to focus only on direct-acting agonists and we’ll subdivide them into three main groups: alpha agonists; beta agonists; and catecholamines and dobutamine.
First let’s start with alpha agonists, which are subdivided into two groups of their own; alpha-1 agonists and alpha-2 agonists.
Moreover, it can also be used as a topical agent in ophthalmological procedures to cause mydriasis.
On the other hand, midodrine is primarily used to treat autonomic dysfunction and orthostatic hypotension, which is a condition in which the blood pressure falls significantly when a person stands up too quickly.
Norepinephrine (NE), also called noradrenaline (NA) is a chemical in the catecholamine family that functions in the human brain and body as a hormone and neurotransmitter. Norepinephrine is synthesized and released by the CNS, and also by the sympathetic nervous system. The site of synthesis of norepinephrine is the locus ceruleus, located in the pons. In the sympathetic nervous system, norepinephrine is used as a neurotransmitter by sympathetic ganglia located near the spinal cord or in the abdomen, and it is also released directly into the bloodstream by the adrenal glands as sympathetic effector organs. Regardless of how and where it is released, norepinephrine acts on target cells by binding to and activating noradrenergic receptors located on the cell surface.
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