Beta Blockers :- Types, Mechanism Of Action, Indications & Contraindications & Adverse Effects

beta blockers are a class of medications that are primarily used in the treatment of cardiovascular diseases including tachycardia hypertension myocardial infarction congestive heart failure coronary artery disease cardiac arrhythmias aortic dissection and portal hypertension in addition they are also used in the treatment of non-cardiovascular diseases such as hyperthyroidism essential tremor and as prophylaxis for migraine attacks before we begin our discussion on beta blockers let's recall our physiology knowledge on the sympathetic nervous system nervous system can be divided into the central nervous system which include brain and spinal cord and the peripheral nervous system peripheral nervous system can be further divided into somatic system which controls voluntary movements of the body and the autonomic system which controls involuntary movements autonomic system has two arms the sympathetic system and the parasympathetic system the autonomic system is made up of a relay between two neurons let's focus on just a sympathetic nervous system signals of the sympathetic system start from the hypothalamus these signals are transmitted down the spinal cord until they meet the cell bodies of sympathetic pre-ganglionic neurons from there signals exit the spinal cord through the pre-ganglionic neuronal axons and reach the nearby sympathetic ganglions which are made up of the cell bodies of postganglionic neurons post-ganglionic neurons are also called adrenergic neurons because they secrete the neurotransmitters epinephrine and norepinephrine these two catecholamines activate 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 slows down digestion and increases blood flow to the brain and muscles there are two types of adrenergic receptors alpha receptors and beta receptors which have two subtypes beta 1 and beta 2. beta 1 receptors are located in the heart activation of these receptors by the sympathetic system leads to increased heart rate and contractility which increase the cardiac output and blood pressure beta-1 receptors are also located in the juxtaglomerular cells of the kidneys activation of these receptors by the sympathetic system leads to the release of renin which activates the renin-angiotensin aldosterone system or ras this will lead to sodium and water retention by the kidneys and ultimately increased blood pressure 2 receptors are found in many parts of the body they are seen in the smooth muscle cells of the blood vessels supplying the brain and skeletal muscles activation of these receptors cause waso dilation and increased blood flow to these tissues they are also found in the bronchial smooth muscle cells activation of these receptors cause bronchodilation activation of beta-2 receptors in the gastrointestinal tract causes decreased motility beta-2 receptors found in the eyes help produce aqueous humor they are found in the liver too activation of these receptors causes increased release of glucose into the blood beta 2 receptors found in the pancreas cause increased release of glucagon which in turn increases blood glucose levels finally beta-2 receptors stimulate an enzyme called lipoprotein lipase which breaks down triglycerides into free fatty acids beta blockers are post-synaptic anti-adrenergic medications that prevent beta-1 and beta-2 receptors from being stimulated by catecholamines beta blockers are subdivided into three generations first generation medications are non-selective meaning that they act on both beta 1 and beta 2 adrenergic receptors these medications include propranolol timol natalyal satylal and pindal pindal is actually a partial agonist of beta receptors this means that when it binds to beta receptors it stimulates the receptor weekly but at the same time it prevents the binding of more potent catecholamines this is known as the intrinsic sympathomimetic effect by blocking the beta-1 receptors in the heart first-generation medications decrease the heart rate and contractility leading to reduced oxygen and energy demands as well as a drop in blood pressure at the same time beta-1 blockade in the juxtaglomerular cells of the kidney decreases renin release leading to less angiotensin and aldosterone release this will ultimately lead to excretion of more sodium and water and a reduced blood pressure however by blocking beta-2 receptors as well they also cause some vasoconstriction in the blood vessels supplying the brain and skeletal muscle this is typically very mild and does not have significant effects on blood pressure and it is important to know that propranolol is the only first generation medication that is able to penetrate the blood-brain barrier blocking of the beta-2 receptors in the bronchial smooth muscles causes bronchoconstriction which obstructs the airflow in the gastrointestinal tract beta-2 blockade causes increased motility in the eyes aqueous humor production decreases liver releases less glucose into the blood and pancreas also secretes less amounts of glucagon so blood glucose levels decrease finally inhibition of lipoprotein lipase by beta blockers leads to accumulation of triglycerides in blood non-selective beta blockers are widely used in the treatment of hypertension and coronary artery disease they are also used in the treatment of congestive heart failure however they should be used with caution in these individuals since they often rely on the sympathetic drive to maintain their blood pressure in addition non-selective beta blockers can be used to treat severe tachycardia like in thyroid storm which is an acute life-threatening complication of hyperthyroidism they are also being used in cases of severe anxiety moreover propranolol is also used as a prophylactic to prevent migraine attacks antimole helps reduce intraocular pressure when applied topically on the eye so it is used in the treatment of glaucoma main adverse effects of beta blockers include bradycardia and hypotension as well as fatigue in addition people may have dizziness insomnia and depression particularly due to the cns effects of propranolol since these medications can cause wheezing chest tightness and shortness of breath they are contraindicated in patients with obstructive lung diseases such as copd and asthma sometimes diarrhea may also occur additionally hypertriglyceridemia and hypoglycemia may also be seen it is important to know that hypoglycemia may go unnoticed since beta blockers blunt the counter regulatory effects and symptoms of catecholamines this is especially dangerous in patients with diabetes since they take a number of other hypoglycemic medications second generation beta blockers are selective for the heart and they are called cardioselective beta blockers these include atenyl metoprolol bizoprol azmal and acibutyl like pin doll acebutyl is a partial agonist of the beta receptor by blocking beta 1 receptors these medications reduce the heart rate and contractility and decrease renin release from the juxtaglomerular cells this makes them suitable for the treatment of hypertension coronary artery disease tachycardia and anxiety additionally metoprolol and bisoprolil are commonly used in the treatment of congestive heart failure since these medications do not block beta-2 receptors they do not cause bronchoconstriction and can be safely given to patients with copd and asthma moreover these are the preferred beta blockers for people with diabetes third generation beta blockers block both beta 1 and alpha 1 receptors alpha 1 receptors are located in blood vessels and they usually cause vasoconstriction administration of third generation beta blockers reduces vasoconstriction and they can be used in the treatment of hypertension common medications in this class include lebetoyle and carvedile lebetol is the preferred medication in the treatment of hypertension during pregnancy and it is also used to treat hypertensive emergency in addition to being an antihypertensive carvetalol also has antioxidant properties and it prevents blood vessel from thickening major adverse effect of these medications is orthostatic hypotension