Adrenergic antagonists: Alpha blockers

Definitions & Key takeaways

Adrenergic antagonists are a type of drug that blocks the action of adrenaline in the body. Adrenaline is a hormone that is released in response to stress or excitement, and it causes the heart rate to speed up and the blood vessels to narrow.

Alpha-blockers are a type of adrenergic antagonist that blocks the action of adrenaline on the alpha receptors. The alpha receptors are found in the muscles around the blood vessels, and when they are activated, they cause the blood vessels to narrow. Alpha-blockers, therefore, cause the blood vessels to widen, which lowers blood pressure and improves symptoms of congestive heart failure.

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Introduction0:00–0:53

Alpha blocker and beta blockers are two types of postsynaptic anti-adrenergic medications that prevent their respective receptors from being stimulated by catecholamines, like norepinephrine and epinephrine.
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 is further divided into the sympathetic and the parasympathetic, and controls the involuntary movement of the smooth muscles and glands of our organs.
Now, the autonomic nervous system - which includes both the sympathetic and parasympathetic nervous system - is made up of a relay that includes two neurons.

Physiology0:53–2:20

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.
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, or adrenaline.These two catecholamines activate the adrenergic receptors on the 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.Now, there are two main groups of adrenergic receptors: the alpha receptors, and beta receptors.

Mechanism of action2:20–3:47

Let’s focus on alpha receptors, which have two subtypes: alpha-1 and alpha-2. alpha-1 adrenergic receptors are mainly located on the walls of blood vessels, and when stimulated, they cause vasoconstriction, thus decreasing blood flow to tissues.
In the eyes, alpha-1 adrenergic receptors also trigger mydriasis, or pupil dilation. In the bladder, they cause sphincter constriction and urinary retention, or holding the urine within the bladder.
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. Alright, so medications that inhibit peripheral postsynaptic adrenergic neurons are called peripheral postsynaptic anti-adrenergics.And based on the type of receptors they block, they are divided into two main categories - alpha blockers, and beta blockers.
Now, alpha blockers are subdivided into two groups of their own; non-selective alpha blockers and selective alpha blockers.

Non-selective alpha blockers3:47–6:27

Non-selective alpha blockers work on both alpha-1 and alpha-2 adrenergic receptors and include phenoxybenzamine and phentolamine.By blocking alpha-1 receptors, they cause vasodilation and lower blood pressure.
But what sets these two apart is that phenoxybenzamine is an irreversible, noncompetitive antagonist, while phentolamine is a reversible, competitive antagonist.
So, phenoxybenzamine binds irreversibly, to a different site on the receptor from catecholamines, and changes the shape of the receptor so it can no longer bind to catecholamines.
This effect cannot be overcome, even if the levels of catecholamines increase. In fact, the only way out is to synthesize new adrenergic receptors, which takes about 24 hours.
This makes phenoxybenzamine perfect for the treatment of pheochromocytoma, a rare tumor of the adrenal medulla, which secretes too much of the catecholamines; adrenaline and noradrenaline.
On the other hand, phentolamine competes with catecholamines for the exact same binding site on the receptor, but is reversible; meaning that it can be kicked off after a while, especially if there’s a lot of catecholamines around.
Now, phentolamine can also be used in pheochromocytoma, but it’s mainly used to treat hypertensive crisis caused by the combination of a Monoamine oxidase inhibitors, or MAOIs for short, and tyramine-rich food and drinks, such as cheese, wine, and beer.Okay, so since alpha-1 receptor inhibition causes vasodilation, we get side effects like hypotension; headache, due to vasodilation in the brain; and nasal congestion, due to vasodilation of nasal mucosa.In men, it can cause difficulty in ejaculation, due to alpha-1 receptor inhibition in the seminal tract.When blood pressure drops, the body compensates by increasing the heart rate, leading to tachycardia.
Now, remember these medications also inhibit the alpha-2 receptors on the presynaptic neurons, which normally regulate catecholamine release through feedback inhibition.
This leads to uncontrolled catecholamine release, which also act on other receptors like the beta receptors in the heart, causing it to beat even faster, which could worsen the tachycardia and turn it into an arrhythmia.
Alright, now selective alpha blockers work on either alpha-1 or alpha-2 adrenergic receptors. Alpha-1 blockers mainly include prazosin, terazosin, doxazosin, and tamsulosin so they all end in –osin.

Selective alpha blocker6:27–8:43

By blocking alpha-1 receptors and inducing vasodilation, prazosin, terazosin, and doxazosin are effective in lowering blood pressure, so they are used in cases of hypertension.Once again, there’s a risk of causing hypotension, especially when given for the first time; and tachycardia, through the baroreceptor reflex.
These side effects are less severe compared to non-selective alpha blockers since the negative feedback inhibition through the alpha-2 adrenergic receptors is still working.
The rest of the side effects, though, such as headache, nasal congestion, and difficult ejaculation are still present. On the flip side, tamsulosin is much less effective on alpha-1 receptors found in blood vessels.
Instead, it’s selective for a specific subtype of alpha-1 receptors, called alpha-1A, found in the smooth muscle of the bladder neck, and the prostate itself.
So, it can be used to relieve urinary retention in cases of benign prostatic hyperplasia, or BPH for short, where the prostate is enlarged and might obstruct urine flow.
Despite its specificity, tamsulosin can also cause relaxation of the iris dilating muscle, and has been associated with intraoperative floppy iris syndrome, or IFIS for short.
This is when the iris prolapses during a standard cataract surgery. On the other hand, there are no commonly used peripheral selective alpha-2 blockers.The main medication that inhibits this receptor is mirtazapine, which works in the central nervous system.
It’s an atypical antidepressant that works by inhibiting the alpha-2 receptor, which increases the release of serotonin, along with norepinephrine.
Now, we want to make a simple and fun mnemonic that’ll help you efficiently memorize and retain all these pharm facts! Let’s have a highway with 2 lanes, where the top lane has the word alpha-1 on it, and the bottom lane is alpha-2.
The line in the middle of the street is where we put the 2 nonselective alpha blockers. We have a phoenix driving a Benz, for phenoxybenzamine, and it’s running over a bird that’s half-crow and half-phoenix, since it’s ideal for pheochromocytoma.

Memory palace8:43–10:53

Also on the line is phentolamine, which is represented by the Phantom of the opera. He’s taking wine and cheese from chairman Mao, which represents MAOI and tyrosine containing foods, that when combined could cause hypertensive crisis.
Next, farther down the road on the alpha-1 side, we have a sinful devil with a big “O” on his chest for some of the medications that end in -”osin.” He’s holding the leashes to his pet duck, for doxazosin; a pterodactyl, for terazosin; and a parrot, for prazosin.
These three are sitting on a blood vessel to help you remember the main target for these drugs.On the other side of the devil is a urinal with a discarded tiramisu cake, for tamsulosin, which is mainly used to treat urinary retention in BPH.
Now under the alpha-1 area, the alpha-2 side of the street is blocked off with traffic barriers, to help you remember there are no clinically relevant medications that are selective for alpha-2 blockers in the peripheral nervous system.
Now for side effects shared by all alpha blockers, let’s use a group of jogger.Running along the middle line, closer to the non-selective alpha blockers, is a heart wearing a sweat band, to help you remember that tachycardia and arrhythmia are more common with these drugs.
Next is a guy with a runny nose, wearing nothing but his sexy shorts, for nasal congestion and sexual dysfunction. Finally, there’s a guy who got orthostatic hypotension and passed out on the street.
For drug-specific side effects, the tiramisu cake has an iris flower growing out of it, to represent intraoperative floppy iris syndrome.
##SummaryAll right, as a quick recap, alpha blockers are divided into non-selective blockers, which include phenoxybenzamine, an irreversible antagonist, mainly used for the treatment of pheochromocytoma; and phentolamine, a reversible antagonist, mainly used to treat hypertensive crisis caused by the combination of Monoamine oxidase inhibitors, or MAOIs, and tyramine-rich foods.
Selective blockers are subdivided into alpha-1 blockers, including prazosin, terazosin, and doxasozin, used in hypertension treatment; and tamsulosin, which relieves the symptoms of benign prostatic hyperplasia.But wait, there’s more: Here’s a mind map with all of the mnemonics.

Recap10:53–11:39

Go ahead and pause the video so you can test yourself to see what you remember. Stay tuned for the answers after the credits.
Tamsin which relieves the symptoms of benign prostatic hyperplasia But wait there's more Here's a mind map with all the mnemonics Go ahead and pause the video so you can test yourself to see what you remember Stay tuned for

Mind Map11:39–11:49