Alpha blockers

• Alpha blockers


  Drugs that block the alpha receptors
• Alpha receptors


  • Two types: alpha 1 and alpha 2
• Mechanism of action of alpha blockers

  1. Block alpha 1 receptors on vascular smooth muscle

  2. Cause vasodilation

  3. Decrease total peripheral resistance

  4. Decrease afterload on heart

  5. Decrease blood pressure
• Alpha 1 receptors


  • Located on prostatic smooth muscle and internal urethral sphincter
  • Activation causes contraction of these muscles
• Alpha blockers


  Relax internal urethral sphincter and prostatic smooth muscle
• Selective alpha 1 blockers

  • Terazosin
  • Doxazosin
  • Prazosin
  • Tamsulosin
• How selective alpha 1 blockers relax smooth muscle

  1. Inhibit binding of epinephrine/norepinephrine to alpha 1 receptors

  2. Decrease calcium influx and myosin light chain kinase activation

  3. Decrease smooth muscle contraction
• Non-selective alpha blockers


  • Phenoxybenzamine (allosteric inhibitor)
  • Phentolamine (active site inhibitor)
• Phenoxybenzamine binds to allosteric site, preventing epinephrine/norepinephrine from binding active site
• Phentolamine binds to active site, but can be displaced by high epinephrine/norepinephrine levels
• Indications for alpha blockers

  • Hypertension (second-line)
  • Benign prostatic hyperplasia (BPH)
  • Facilitate passage of ureteral stones
• Alpha blockers can be used in pheochromocytoma (adrenal tumor) to control hypertension
• Phenoxybenzamine is preferred in pheochromocytoma due to irreversible binding
• Flomax


  Brand name of drug that can dilate urine and help pass calculi in the ureter
• Pheochromocytoma


  Tumor in the adrenal medulla that secretes high levels of epinephrine and norepinephrine
• Phenoxybenzamine


  Drug that binds tightly to allosteric site and prevents norepinephrine and epinephrine from binding, helping to lower blood pressure
• Monoamine oxidase inhibitors


  Drugs used for resistant or refractory depression, can interact with certain foods to cause hypertensive crisis
• Phentolamine


  Drug that can be used to treat hypertensive crisis caused by monoamine oxidase inhibitor-food interactions
• Using cocaine


  Beta blockers should be avoided as they can lead to unopposed alpha receptor activation and further increase in blood pressure
• Using cocaine or methamphetamine

  Phentolamine or phenoxybenzamine can be used to control hypertension and reduce risk of aortic dissection
• Alpha blockers


  • Can cause vasodilation, leading to potential side effects like hypotension, flushing, peripheral edema, reflex tachycardia
• Miosis


  Pupillary constriction
• Alpha blockers like tamsulosin can cause intraoperative floppy iris syndrome during cataract surgery, where the iris can prolapse through the corneal incision
• Retrograde ejaculation


  Semen entering the bladder instead of being ejaculated through the urethra, due to relaxation of the internal urethral sphincter
• Decreased ejaculatory response


  Caused by relaxation of the vas deferens smooth muscle
• Alpha-2 receptor blockade by drugs like phenoxybenzamine and phentolamine


  Leads to increased norepinephrine release and reflex tachycardia