Sympatholytics

• Sympatholytics


  Also known as "adrenergic antagonists" or "adrenergic blockers"
• Antagonists


  Drugs with affinity but no intrinsic activity
• Sympatholytics


  • Bind to adrenoceptors but do not trigger the usual receptor-mediated intracellular effects
  • Do not cause activation of the receptors but limit access of activators to the receptor site
  • Agents that inhibit responses mediated by adrenoceptor activation
  • Primarily used to treat diseases associated with the cardiovascular system
  • Divided into primary subgroups on the basis of their receptor selectivity
• Alpha-adrenergic blocking agents


  • The pharmacologic effects are predominantly cardiovascular and include the lowered peripheral vascular resistance and blood pressure (profoundly)
  • All active by the oral as well as the parenteral route
  • Subdivisions are based on selective affinity for alpha1 versus alpha2 receptors
• Non-selective alpha receptor antagonists

  Classified based on reversibility of action
• Phenoxybenzamine


  • Nonselective, linking covalently (strong bond) to both alpha1 and alpha2-receptors
  • The block is irreversible and noncompetitive
  • Has long duration of action (15–50h)
• Phentolamine


  • Competitive, reversible blocking agent of alpha1 and alpha2 receptors
  • The blockage effects can be surmounted by increasing the concentration of agonists
  • Effects last for approximately 4 hours after a single injection
• Selective alpha1 receptor blockers

  • Prototype is Prazosin
  • Slow onset of action (2-4 hours)
  • Long duration of action (approximately 10 hours)
  • Extensively metabolized by the liver
• Selective alpha2 receptor blockers


  • Block the activity of alpha2 adrenoceptors, exerting effects that oppose those of receptor activation
• Beta-adrenergic blocking agents


  • Decrease peripheral vascular resistance and cardiac output, contributing to the antihypertensive effect
  • Block the positive chronotropic and inotropic actions of endogenous catecholamines at beta1 receptors
  • Generally do not lower blood pressure in normotensive individuals
• Non-selective beta receptor antagonists

  • Propranolol is the prototype, blocking both beta1 and beta2 receptors with equal affinity
  • Have both negative inotropic and chronotropic effects causing bradycardia
  • Blocking beta2 receptors in the lungs causes bronchiolar smooth muscle contraction, which may exacerbate COPD and asthma
• Blocking β2 receptors in the lungs

  Causes bronchiolar smooth muscle contraction (may result in the exacerbation of COPD and asthma)
• Receptors in the lungs activated

  Causes bronchodilation, but since the drug blocks, it results into bronchoconstriction
• Timolol


  More potent than propranolol
• Timolol


  Reduces the production of aqueous humor in the eye
• Timolol


  Used topically in the treatment of chronic open angle glaucoma
• These agents neither affect the ability of the eye to focus for near vision nor change pupil size
• Selective beta1 receptor antagonists

  • Lower blood pressure in hypertension and increase exercise tolerance in angina
• Selective beta1 receptor antagonists


  • Have fewer effects on pulmonary function, peripheral resistance, and carbohydrate metabolism compared to propranolol
• Esmolol


  Lowest duration action
• Beta receptor antagonists with intrinsic sympathomimetic activity


  Stimulate β-receptors to which they are bound, yet they inhibit stimulation by the more potent endogenous catecholamines
• Beta receptor antagonists with intrinsic sympathomimetic activity

  Opposing effects lead to cancellation of effects
• Beta receptor antagonists with intrinsic sympathomimetic activity


  Minimize the disturbance of lipid and carbohydrate metabolism that are seen with other beta-blockers
• Beta blockers with intrinsic sympathomimetic activity are infrequently used in clinical practice
• Beta blockers with local anesthetic activity


  Can serve as adjuvants to traditional local anesthetics to enhance efficacy and prolonging the duration of anesthesia
• Beta blockers with local anesthetic activity


  Can be applied topically or injected into specific areas to block nerve signals and induce numbness
• Use of beta blockers for local anesthesia or pain management may require careful consideration of individual patient factors, potential side effects, and drug interactions
• Beta blockers with alpha1 blocking activity

  Produce peripheral vasodilation, thereby reducing blood pressure
• Carvedilol


  Decreases lipid peroxidation and vascular wall thickening (beneficial in heart failure)
• Labetalol


  Used as an alternative to methyldopa in the treatment of pregnancy-induced hypertension
• Labetalol


  Most cardio selective blocker which causes vasodilation
• Labetalol


  Stimulates the releases of nitric oxide (an endogenous vasodilator) / ↑Nitric Oxide (NO)
• Selective beta-blockers used in management of stable heart failure

  Bisoprolol, Metoprolol (salt form must be succinate), Carvedilol, Nebivolol
• Beta-blockers when it comes to the management of arrhythmia, they are classified as Class II Anti-arrhythmic agents