Pharmacology – ALPHA & BETA BLOCKERS – ADRENERGIC ANTAGONISTS ( MADE EASY)

Pharmacology – ALPHA & BETA BLOCKERS – ADRENERGIC ANTAGONISTS ( MADE EASY)

September 3, 2019 100 By Bertrand Dibbert


in this lecture I’m going to talk about
adrenergic antagonists so let’s get right into it
adrenergic antagonists also called sympatholytics bind to adrenergic receptors but instead of stimulating them they actually prevent their
activation and just like with adrenergic agonists we can divide antagonists based
on their affinity for alpha or beta receptors so we can divide adrenergic
antagonists into two main groups that is alpha blockers and beta blockers so
let’s start with alpha blockers first alpha-1 adrenergic antagonists block
the binding of norepinephrine to the smooth muscle receptors which results in
vasodilation and thus lowering of blood pressure this is why alpha blockers are
useful in the treatment of hypertension now alpha blockers can be subdivided
into two groups that is non-selective alpha blockers and selective alpha
blockers as you might have guessed non-selective agents can block both alpha-1
and alpha-2 receptors example of these are Phentolamine and Phenoxybenzamine which are used in the treatment of hypertension specifically caused by
pheochromocytoma which is a tumor of the adrenal glands that secrete
norepinephrine and epinephrine now we know that through alpha-1 blockade these
drugs cause vasodilation but since they are non-selective they also block alpha-2 receptors which as you may remember from the previous lecture are mainly
located on presynaptic nerve endings now norepinephrine acts on alpha-2
receptors to inhibit its own release so blockade of these receptors results in
more norepinephrine release norepinephrine then can stimulate beta-1
receptors on the heart this is why non-selective drugs such as Phentolamine and Phenoxybenzamine can cause tachycardia and even cardiac arrhythmias
now the main difference between these two
drugs is that Phenoxybenzamine is a irreversible antagonist and the only way
the body can overcome its effects is by making new adrenergic receptors which
takes about 24 hours or so on the other hand Phentolamine is a reversible
antagonist and that’s why its effect lasts only about four hours or so now
let’s move on to selective alpha blockers and let’s discuss alpha-1
blockers first so these agents selectively and reversibly block alpha-1 receptors located mainly in vascular smooth muscle which reduces peripheral
resistance and leads to decrease in blood pressure and they also block
receptors in the smooth muscle of the bladder neck and prostate gland which
causes smooth muscle there to relax leading to relief of the urinary
difficulties associated with benign prostatic hypertrophy BPH for short or
simply enlarged prostate now examples of alpha-1 selective
blockers include Prazosin Doxazosin Terazosin Tamsulosin Alfuzosin and Silodosin and note that this ending with “-osin” is a pretty good
giveaway when it comes to identifying alpha-1 blocker now the first three of
these that is Prazosin Doxazosin and Terazosin are effective treatment
for hypertension but have lesser effects on relieving symptoms of enlarged
prostate on the other hand Tamsulosin Alfuzosin and Silodosin have little
effect on blood pressure but are much more effective for relieving symptoms
associated with enlarged prostate and this is because these agents have
increased selectivity for alpha-1 receptors in the prostate specifically
alpha-1a subtype now when it comes to side effects orthostatic hypotension is
one of the main concerns when initiating alpha-1 blocker
although it’s not as severe as that observed with non-selective alpha
blockers additionally vasodilation produced by alpha-1 blockers can lead
to headaches and nasal congestion finally what about alpha-2 selective
blockers well alpha-2 selective blockers have very limited clinical
application in humans and they’re used mainly in research one example of alpha-2 blocker that you may encounter is Yohimbine which can be found in some
dietary supplements however there is not much beneficial evidence supporting its
use in humans on the other hand Yohimbine is used sometimes in veterinary medicine to reverse sedative effects of alpha-2 agonist such as Xylazine now
let’s switch gears and let’s move on to beta blockers so just like alpha
blockers beta blockers can also be subdivided into selective and
non-selective agents however unlike alpha blockers beta blockers can also be
grouped in generations beta blockers are competitive inhibitors at beta
adrenergic receptors and they counter the effects of catecholamines such as
epinephrine and norepinephrine which leads to decrease in sympathetic effects
mainly on cardiovascular system this is why beta blockers are useful in the
treatment of hypertension heart failure heart attacks angina and cardiac
arrhythmias additional uses include treatment of glaucoma and migraine
prophylaxis so now let’s start by discussing first generation beta
blockers which also happen to be non-selective that is they block beta-1 and
beta-2 receptors throughout the body example of these agents include
Propranolol Pindolol or Nadolol Sotalol and Timolol now practically all
the applications of these agents are based on blockade of beta-1 receptors on
the heart which results in decreased heart rate delayed conduction through AV
node and reduced contractility so now the final outcome is decreased cardiac
output and decreased oxygen demand of heart muscle besides being useful in
treatment of hypertension angina and arrhythmia
note that Propranolol due to its lipophilicity can also penetrate into the CNS
and was found to be effective for migraine prophylaxis on the other hand Timolol when applied topically to the eye was found to decrease intraocular
pressure which is why it is often used for a treatment of glaucoma
however all that being said let’s not forget about blockade of beta-2 receptors by
these non-selective agents and as you may recall beta-2 receptors are predominant
in lungs so their blockade can actually lead to bronchoconstriction for this
reason these non-selective beta blockers are not recommended in patients with
COPD or asthma now let’s move on to the second generation beta blockers which
happen to be selective for beta-1 receptors and because of that we also
call them cardio-selective beta blockers now this cardio-selectivity makes these
agents more suitable in patients with chronic lung disease however keep in
mind that at high enough doses this beta-1 selectivity can be lost and beta-2
receptor blockade may occur example of these agents include Atenolol Acebutolol
Bisoprolol Esmolol and Metoprolol now let’s move on to the third generation
beta blockers and here you need to pay special attention because things can get
a little tricky so unlike the first generation group that included non-selective agents and unlike the second generation group that included selective
agents the third generation group includes both non-selective and
selective beta blockers however what makes the third generation beta blockers
different from the other two is that they also act on blood vessels to cause
vasodilation so here we have non-selective agents
such as Carvedilol and Labetalol which produce peripheral vasodilation by
blocking not only beta but also alpha-1 receptors and on the other hand we
have beta-1 selective agents such as Nebivolol which produce vasodilation by
inducing the release of nitric oxide from endothelial cells and Betaxolol
which is thought to produce vasodilation by additionally blocking calcium
channels and just as a side note here Betaxolol due to its ability to
decrease intraocular pressure when applied topically to the eye just like
Timolol it is often prescribed for glaucoma but the bottom line here is
that vasodilation produced by the third generation beta blockers make
these agents especially effective in treatment of hypertension furthermore
Carvedilol and Nebivolol have been also shown to have antioxidant properties
which make them beta blockers of choice for heart failure alongside commonly
prescribed Bisoprolol and Metoprolol lastly I wanted to briefly discuss intrinsic
sympathomimetic activity of couple beta blockers namely Pindolol and Acebutolol now these two beta blockers are a little special in that they have ability
to not only block but also to weakly stimulate both beta-1 and beta-2
receptors which leads to diminished effect on cardiac rate and cardiac output this
so called intrinsic sympathomimetic activity can actually be beneficial in
patients who cannot tolerate other beta blockers because of pre-existing
bradycardia or heart block and now before we end you may wonder well what
about beta-2 blockers and the short answer is at this time we don’t have
clinically useful beta-2 blockers and with that I wanted to thank you for
watching I hope you enjoyed it and as always stay tuned for more videos