PCOL FINALS

• Adrenergic antagonists


  Also called adrenergic blockers or sympatholytics, drugs that block the action of norepinephrine and epinephrine in adrenergic receptors
• Alpha-receptor antagonist drugs

  • Bind reversibly or irreversibly with alpha receptors, preventing the binding of NE or Epinephrine
• Phenoxybenzamine


  • Binds covalently to alpha receptors (both 1 and 2), causing irreversible blockade of long duration (14-48 hours or longer)
  • Major use is in the treatment of phaeochromocytoma
  • Side effects: orthostatic hypotension and tachycardia; nasal stuffiness and inhibits male ejaculation
• Phaeochromocytoma

  A tumor of the adrenal medulla or sympathetic ganglion cells that secretes norepinephrine and epinephrine
• Phentolamine


  • A potent competitive antagonist at both alpha 1 and alpha 2 receptors (short-acting)
  • Used in the treatment of Phaeochromocytoma
  • Side effects: severe tachycardia, arrythmia and myocardial ischemia
• Selective alpha-1 antagonists


  • Selectively bind to alpha-1 receptors, blocking the effects of catecholamines
• Prazosin


  • Effective in the management of hypertension
  • Selective alpha-1 receptor antagonist
  • Relaxes both arterial and venous vascular smooth muscle, as well as smooth muscle in the prostate
• Terazosin


  • Another reversible alpha-1 selective antagonist that is effective in hypertension
  • Also approved in men with urinary symptoms due to benign prostatic hyperplasia
• Doxazosin


  • Efficacious in the treatment of hypertension and BPH
  • Has longer half-life compared to prazosin and terazosin
• Tamsulosin


  • A competitive alpha-1 receptor antagonist with a structure quite different from that of most other alpha-1 antagonists
  • Greater potency in inhibiting contraction in prostate smooth muscle
• Alfuzosin


  An α1-selective quinazoline derivative that is approved for use in BPH
• Adverse effects of alpha-1 antagonists

  • First Dose Syncope/Phenomenon - sudden decrease in BP after taking the drug
  • Should be taken with lower dose at bedtime
• Other alpha-adrenoceptor antagonists

  • Indoramin - used as an antihypertensive, not available in the USA
  • Urapidil - an α1-antagonist that also has α2-agonist actions and weak antagonist action at β1-receptors, used in Europe as an antihypertensive agent and for benign prostatic hyperplasia
  • Labetalol - has both α1-selective and β-antagonistic effects
  • Neuroleptic drugs (e.g. Chlorpromazine and Haloperidol) - are potent dopamine receptor antagonists but are also antagonists at α-receptors, antagonism of α receptors probably contributes to some of their adverse effects, particularly hypotension
  • Trazodone - an antidepressant that has the capacity to block α1-receptors
  • Ergot derivatives (e.g. Ergotamine and Dihydroergotamine) - cause reversible α-receptor blockade, probably via a partial agonist action
  • Yohimbine - an indole alkaloid, an α2-selective antagonist, sometimes used in the treatment of orthostatic hypotension because it promotes norepinephrine release through blockade of presynaptic α2 receptors, once used to improve male erectile dysfunction but has been superseded by phosphodiesterase-5 inhibitors like sildenafil, can reverse the antihypertensive effects of an α2-adrenoceptor agonist such as clonidine
• Propranolol


  • The prototype beta-adrenergic antagonist and blocks both beta-1 and beta-2 receptors with equal affinity
  • Effects on the cardiovascular system: if given chronically can lower blood pressure in patients with hypertension, valuable in the treatment of angina pectoris, chronic heart failure and myocardial infarction (negative inotropic and chronotropic effect)
  • Effects on the respiratory tract: blockade of β2-receptors in bronchial smooth muscle will increase in airway resistance, particularly in asthma patients
  • Effects on the eye: can reduce intraocular pressure, especially in glaucoma, mechanism of action is decreased aqueous humor production
  • Metabolic & endocrine effects: can inhibit sympathetic nervous system stimulation of lipolysis, can mask hypoglycemic signs and symptoms
• Non-selective β antagonists


  • Nadolol
  • Timolol - used for chronic management of glaucoma because it can lower IOP (Betaxolol, carteolol can also be used for glaucoma)
• Antagonists with partial agonist activity

  • Acebutolol - effective in treating hypertension with moderate bradycardia, should not be given to patients with angina and arrhythmias
  • Pindolol - effective in treating hypertension with moderate bradycardia, should not be given to patients with angina and arrhythmias
• Antagonists of both α and β adrenoceptors

  • Labetalol - alternative to methyldopa for hypertensive pregnant women
  • Carvedilol - beneficial for stable chronic heart failure
• Make a FARM Note of the case study presented in Chapter 7 (KATZUNG)