Adrenergic blocking agent
Adrenergic blocking agents are a class of drugs that exhibit its pharmacological action through inhibiting the action of the sympathetic nervous system in the body. The sympathetic nervous system is an autonomic nervous system that we cannot control by will. It triggers a series of responses after the body releases chemicals named noradrenaline and adrenaline. These chemicals will act on adrenergic receptors, with subtypes alpha-1, alpha-2, beta-1, beta-2, and beta-3, which ultimately allow the body to trigger a fight-or-flight response to handle external stress. These responses include vessel constriction in general vessels whereas there is vasodilation in vessels that supply skeletal muscles or in coronary vessels. Additionally, heart rate and contractile force increases when the SNS is activated, which may be harmful to cardiac function as it increases metabolic demand.
Adrenergic blocking agents treat certain diseases through blocking the adrenergic receptor, preventing it from being activated by noradrenaline and adrenaline. As a result, it stops the body from producing the fight-or-flight response.
Medical uses
There are drugs that are approved by the US Food and Drug Administration, whereas there are some off-label uses as well.Alpha-1 blocker
The alpha blockers mostly act in our smooth muscles, especially the ones that control the size of vessels. Thus, alpha1 blockers can dilate blood vessels and decrease the blood pressure. Depending on its site of action, it can be used to treat different diseases. They can be used to treat signs and symptoms of benign prostatic hyperplasia, hypertension, pheochromocytoma, extravasation management and reversal of local anesthesia.There are some off- label use as well, such as chronic prostatitis and lower urinary tract symptoms in males, ureteral calculus expulsion, ureteral stent-related urinary symptoms. It can be used in post-traumatic stress disorder, Raynaud phenomenon, hypertensive crisis, extravasation of sympathomimetic vasopressors, problem with urine related to neurogenic bladder, functional outlet obstruction and partial prostate obstruction.
Alpha-2 blocker
Alpha-2 blockers reduce the transmission of neurotransmitters circulating around the body, which contributes to contraction of smooth muscle. Instead of treating diseases, they are used as antidotes for reversing overdose of alpha-2 agonist, reducing the toxic effect of the agonist. Only limited indications are present for this drug. More research is in progress to investigate the possible use of alpha2 blockers.Beta-1 blocker
Since beta-1 receptors are mainly located in the heart, most beta-1 blockers take abnormalities associated with the heart as the target. It treats medical conditions like hypertension, arrhythmias, heart failure, chest pain, and myocardial infarction. It treats other symptoms unrelated to heart like migraines and anxiety.Beta-2 blocker
Beta-2 blockers promote vasodilation in some tissues as mentioned above. Currently, there is no beta-2 blocker with FDA approval. Butoxamine, an example of beta-2 blocker, has no clinical use but is used in research.Beta-3 blocker
Due to the relatively limited study on the beta-3 receptor, there is not much development of beta-3 blockers. Therefore, beta-3 blockers has no clinical use.Adverse effects
Selectivity
Some drugs, being non-selective, can exert actions on 2 or more different receptors. Examples include non-selective beta blocker, which block both beta-1 receptor and beta-2 receptor as well.Non-selective alpha blocker
The adverse effects of non-selective alpha blockers are caused by the autonomic response to the systemic changes induced by the adrenergic blocking agents. The common adverse effects of alpha blockers are due to the blockade of alpha-1 adrenergic receptors in tissue that requires high level of alpha adrenergic sympathetic input such as arterial resistance, vascular capacitance and the outflow tract of the urinary bladder. The undesirable symptoms are mentioned in the following 'selective alpha-1 blocker' part.Selective alpha-1 blocker
With the vasodilation and smooth muscle relaxation caused by alpha-1 blockers, around 10 to 20% of patients present undesirable effects of asthenia, dizziness, faintness and syncope. Other adverse outcomes that are even more uncommon include headache, drowsiness, palpitations, urinary incontinence and priapism. Mild body weight gain of 1–2 kg, which may be associated with secondary hyperaldosteronism, is also observed in some patients.The alpha-1 blockers are associated with the first-dose effect, which refers to the tachycardia response and orthostatic hypotension that caused by the systemic vasodilation at the initial administration of alpha-1 blockers. After the first administration, patients may experience a short period of orthostatic hypotension with a sensation of intense faintness, which is aggravated by upright posture, intravascular volume depletion or concurrent administration of other antihypertensive medications.
Selective alpha-2 blocker
Apart from increasing the noradrenaline release, the selective alpha-2 blockers have the potential to bind with other receptors such as the 5-HT receptor. However, the serotonin receptor antagonism has side effects such as weight gain and impaired movement. Hence, alpha-2 blockers are not used clinically due to its extensive binding.Similar to the alpha-1 blocker, the alpha-2 family will also present the first-dose effect, but it is generally less pronounced compared with the alpha-1 blockers.
Non-selective beta blocker
The Central Nervous System side effects of beta blockers including sleep impairment, dreaming, nightmares and hallucinations are generally small. Also, the effects on short-term memory are minimal.Selective beta-1 blocker
The cardio-selective beta-1 blockers could cause adverse effects including bradycardia, reduced exercise ability, hypotension, atrioventricular nodal blockage and heart failure. Other possible adverse effects include nausea and vomiting, abdominal discomfort, dizziness, weakness, headache, fatigue, and dryness in mouth and eye. Sexual impairment, memory loss, and confusion are regarded as rare side effects. For diabetic patients, there is an extra risk of masking hypoglycemia-induced tachycardia, while a continuous hypoglycemia could cause acute brain damage.Selective beta-2 blocker
The blockade of beta-2 receptors will result in vasoconstriction and smooth muscle constriction, and the effects are similar to the agonism of alpha-1 receptors. The side effects include hypertension, tachycardia, arrhythmia and subcutaneous ischemia at the site of injection. Other possible side effects include Raynaud phenomenon, hypoglycemia during exercise, muscle cramps, and increase of airway resistance.Selective beta-3 blocker
Due to the relatively limited study on beta-3 receptor, there is not much development of beta-3 blocker. Therefore, there is limited information on the adverse effects caused by beta-3 blocker.Contraindications
Alpha-1 blocker
As alpha 1 blocker will dilate blood vessels, it lowers the blood pressure. Thus, it contraindicate to patients with a history of orthostatic hypotension and in current use of phosphodiesterase inhibitors. Moreover, alpha 1 blocker should not be given to patients with heart failure since it expands blood volume.Alpha-2 blocker
There are limited information about the contraindication of alpha-2 blocker, since it has limited clinical uses.Beta-1 blocker
Traditionally, Beta-1 blocker has several contraindications, including, recent history of fluid retention without use of diuretics, and complete or second degree of heart block. Whilst some studies suggest that there are only minor differences in terms of adverse effect between asthma patients and non-asthma patients, beta-1 blockers are generally not prescribed to asthma patients or patients with chronic obstructive pulmonary disease, due to its potential blockage of beta 2 receptors. Additionally, beta1 blocker should not be given to patients with peripheral vascular diseases, diabetes mellitus, since blockage of beta-2 receptors may lead to vasoconstriction and delayed response to hypoglycemia respectively.Beta-2 blocker
Beta 2 blocker should be avoided for patients with asthma, COPD as it causes bronchoconstriction. It may also increase the chance of hypoglycemic comas in diabetic patients.Beta-3 blocker
Due to the relatively limited study on beta-3 receptor, there is not much development of beta-3 blocker. Therefore, beta-3 blocker has no clinical use. The contraindications of beta-3 blocker can not be observed.Overdose
Alpha-1 blocker
Overdose of alpha-1 blocker will lead to an unopposed parasympathetic activity. Symptoms include bradycardia, hypotension, miosis and sedation.Alpha-2 blocker
There is a lack of information regarding toxicity caused by overdose of alpha-2 blocker, due to its limited clinical uses.Beta-1 blocker
Toxicity of beta-1 blocker will contribute to symptoms including bradycardia, hypotension, due to its extensive blockage of beta-1 receptor. Moreover, overdose of beta-1 blocker may lead to the loss of their selectivity and bind to beta-2 receptor, causing bronchopulmonary symptoms. Overdose of lipophilic beta-1 blocker can disturb neurologic functioning, which eventually lead to altered mental states.To mitigate the toxicity of Beta-1 blocker, glucagon, salts like calcium and sodium bicarbonate, magnesium sulfate are used to reverse beta-1-blocker effect and treating hypotension respectively.