AssessmentsAdrenergic antagonists: Beta blockers
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A 75-year-old man comes to the primary care clinic because of tea colored urine for the past 2 weeks. He has been feeling more fatigued for the last few weeks, but denies any other recent changes. He has a history of hyperlipidemia and insulin-dependent diabetes mellitus, as well as a 40-pack-year smoking history. His blood pressure in the room is 201/95 mm Hg. Urinalysis shows 3+ protein and red blood cells. A renal biopsy is obtained and is shown below. Which of the following is the most appropriate medication for this patient?
Content Reviewers:Yifan Xiao, MD
Alpha blockers 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 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. 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 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.
Now, there are two main groups of adrenergic receptors: the alpha receptors, and beta receptors.
Let’s focus on beta receptors, which have two main subtypes: beta1 (β1) and beta2 (β2). Beta1 adrenergic receptors are mainly located in the heart, where they increase the heart rate and contractility, which helps pump out more blood.
Beta1 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 beta2 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, beta2 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.
Alright, so medications that act on peripheral post-synaptic adrenergic neurons to block adrenergic receptors are called peripheral post-synaptic anti-adrenergics.
And based on the type of receptors they block, they are divided into two main categories - alpha blockers and beta blockers.
Now, beta blockers are subdivided into three generations.
The first generation of beta blockers are non- selective blockers, meaning that they work as antagonists on both beta1 and beta2 adrenergic receptors.
Actually, pindolol is not a pure antagonist, but a partial agonist. This means that, when bound to a beta receptor, it very weakly stimulates it, but at the same time, it prevents binding and stimulation by the more potent catecholamines.
This is known as intrinsic sympathomimetic effect. Or more simply, pindolol has the same but weaker effects compared to the other first generation beta blockers.
Now, by blocking beta1 receptors in the heart, these medications decrease the heart rate and contractility, which lets the heart work less hard, and pump less blood out, resulting in a drop in its oxygen and energy demands, as well as a drop in blood pressure.
At the same time, beta1 blockade in the juxtaglomerular cells in the kidney decreases renin release, which in turn decreases angiotensin II and aldosterone, letting more sodium and water be lost in the urine and lowering the blood pressure even more.
Okay, but by blocking beta2 receptors as well, they also cause some vasoconstriction of blood vessels supplying the skeletal muscles and the brain.
This is typically very mild though, and doesn’t have a significant effect on blood pressure.
In the brain, in fact, beta2 receptors in blood vessels are only reached by propranolol, which is lipid- soluble enough to penetrate the blood- brain barrier and induce some degree of vasoconstriction.
Now, moving on to the lungs, blocking beta2 receptors causes bronchoconstriction, or narrowing of the respiratory airways, which obstructs airflow, and lets in less oxygen.
In the gastrointestinal tract, beta2 blockade speeds up motility.
In the eye, aqueous humor production decreases, so intraocular pressure or the pressure within the eye falls.
And finally, inhibition of lipoprotein lipase leads to the accumulation of triglycerides in the blood.
Alright, so looking at the indications of non- selective beta blockers, they are widely used in the treatment of hypertension; and coronary artery disease, in the form of angina pectoris or a heart attack.
It has also been suggested that beta blockers slow down the progression of congestive heart failure, or CHF for short.
This remains controversial though, since individuals with heart failure often rely on sympathetic drive to maintain some degree of heart function.
So in this situation, beta blockers might actually make things worse, especially in a situation of acute CHF exacerbation.
- "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
- "Rang and Dale's Pharmacology" Elsevier (2019)
- "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
- "Chronotropic incompetence, beta-blockers, and functional capacity in advanced congestive heart failure: Time to pace?" European Journal of Heart Failure (2008)
- "Beta-blockers for hypertension" Cochrane Database of Systematic Reviews (2017)
- "Blood pressure lowering efficacy of beta-1 selective beta blockers for primary hypertension" Cochrane Database of Systematic Reviews (2016)
- "Treatment of Angina: Where Are We?" Cardiology (2018)
- "Bisoprolol compared with carvedilol and metoprolol succinate in the treatment of patients with chronic heart failure" Clinical Research in Cardiology (2017)
- "A Review of Nebivolol Pharmacology and Clinical Evidence" Drugs (2015)
- "Management of arrhythmia in sepsis and septic shock" Anaesthesiol Intensive Ther (2017)