【Pharmacology】Adrenergic drug (adrenergic antagonists)

Adrenergic antagonists

also called sympatholytics
bind to adrenergic receptors and prevent activation
Two main groups: Alpha blockers & Beta blockers

Review: 【Pharmacology】Adrenergic drug (adrenergic agonists)

Content:

1. Alpha blockers
   a. Non-selective alpha blockers
   b. Selective alpha blockers
2. Beta blockers
a. 1st generation (non-selective)
   b. 2nd generation (selective)
   c. 3rd generation (non-selective & selective)
3. Reference

【Pharmacology】Adrenergic drug (adrenergic antagonists)

1. Alpha blockers

Alpha-1 adrenergic antagonists: Used in hypertension treatment
→ block the binding of norepinephrine to the smooth muscle receptors
→ results in vasodilation
→ lowering of blood pressure

Two groups: non-selective alpha blockers and selective alpha blockers

a. Non-selective alpha blockers

block both alpha-1 and alpha-2 receptors
eg, Phentolamine and Phenoxybenzamine
treatment of hypertension specifically caused by pheochromocytoma (tumor of the adrenal glands)
through alpha-1 blockade, these drugs cause vasodilation. But since they are non-selective, they also block alpha-2 receptors, which will lead to norepinephrine acts on alpha-2 receptors to inhibit its own release.
results in more norepinephrine release to stimulate beta-1 receptors on the heart 👉 cause tachycardia and even cardiac arrhythmias

Difference between Phentolamine and Phenoxybenzamine

Phentolamine

reversible antagonist
effect lasts only about four hours

Phenoxybenzamine

irreversible antagonist
the body can overcome its effects is by making new adrenergic receptors which takes about 24 hours

b. Selective alpha blockers

Selectively and reversibly block alpha-1 receptors located mainly in vascular smooth muscle which reduces peripheral resistance and leads to decrease in blood pressure

they also block receptors in the smooth muscle of the bladder neck and prostate gland which causes smooth muscle relax, leading to relief of the urinary difficulties associated with benign prostatic hypertrophy (BPH) / simply enlarged prostate

Alpha-1 selective blockers

Prazosin
Doxazosin
Terazosin

effective treatment for hypertension
lesser effects on relieving symptoms of enlarged prostate

Tamsulosin
Alfuzosin
Silodosin

have little effect on blood pressure
more effective for relieving symptoms associated with enlarged prostate
This is because have increased selectivity for alpha-1 receptors in the prostate specifically alpha-1a subtype

Side effects

Alpha-1 selective blockers: orthostatic hypotension

as it initiating alpha-1 blocker

Non-selective alpha blockers: additionally vasodilation produced by alpha-1 blockers 👉 headaches and nasal congestion

Alpha-2 selective blockers

limited clinical application in humans
Drug: Yohimbine (found in some dietary supplements)
veterinary medicine to reverse sedative effects of alpha-2 agonist such as Xylazine

2. Beta blockers

can be divided into selective and non-selective agents
but can also be grouped in generations
competitive inhibitors at beta adrenergic receptors
they counter the effects of catecholamines such as epinephrine and norepinephrine
catecholamines decrease in sympathetic effects mainly on cardiovascular system
useful in the treatment of

hypertension
heart failure
heart attacks
angina
cardiac arrhythmias

additional uses

glaucoma
migraine prophylaxis

a. 1st generation (non-selective)

block beta-1 and beta-2 receptors throughout the body

Drug:

Propranolol
Pindolol
Nadolol
Sotalol
Timolol

blockade of beta-1 receptors on the heart, result in

decreased heart rate
delayed conduction through AV node
reduced contractility

final outcome: decreased cardiac output & decreased oxygen demand of heart muscle

useful in treatment of Hypertension, Angina & Arrhythmia

Propranolol due to its lipophilicity, can also penetrate into the CNS

effective for migraine prophylaxis

Timolol when applied topically to the eye, can decrease intraocular pressure

treatment of glaucoma

blockade of beta-2 receptors

predominant in lungs 👉 lead to bronchoconstriction

not recommended in patients with COPD or asthma

b. 2nd generation (selective)

also known as cardio-selective beta blockers
selective for beta-1 receptors
more suitable in patients with chronic lung disease
due to cardio-selectivity
At high enough doses this beta-1 selectivity can be lost and beta-2 receptor blockade may occur
Drug:

Atenolol
Acebutolol
Bisoprolol
Esmolol
Metoprolol

c. 3rd generation (non-selective & selective)

Different from the other two: act on blood vessels to cause vasodilation

Non-selective agents

Carvedilol
Labetalol

produce peripheral vasodilation by blocking beta & alpha-1 receptors

Beta-1 selective agents

Nebivolol

produce vasodilation by inducing the release of nitric oxide from endothelial cells

Betaxolol

produce vasodilation by additionally blocking calcium channels
applied topically to the eye to decrease intraocular pressure

used in glaucoma

Both:
effective in treatment of hypertension

vasodilation produced by the third generation beta blockers

have antioxidant properties

which make them beta blockers of choice for heart failure alongside (commonly prescribed Bisoprolol and Metoprolol)

Intrinsic sympathomimetic activity of couple beta blockers

Pindolol
Acebutolol

have ability to block & weakly stimulate both beta-1 and beta-2 receptors
leads to diminished effect on cardiac rate and cardiac output (intrinsic sympathomimetic activity)
beneficial in patients who cannot tolerate other beta blockers because of pre-existing bradycardia or heart block

Beta-2 blockers

don't have clinically useful beta-2 blockers

3. Reference

https://youtu.be/41Xloc_vvX8

【Pharmacology】Adrenergic drug (adrenergic agonists)

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