SYMPATHOLYTICS

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SYMPATHOLYTICS

• Philip J. Kadowitz, Ph.D.

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Learning Objectives

• Described the actions of adrenergic blocking
  drugs with regard to receptor subtype and
  selectivity.
• Explain the use of alpha-receptor blocking drugs
  in the treatment of hypertension and benign
  prostatic hyperplasia (BPH).
• Explain the use of beta-receptor blocking drugs
  in the treatment of hypertension, angina, and
  heart failure.
• Drugs Alpha blockers phenoxybenzamine,
  phentolamine, prazosin, yohimbine.
• Beta blockers propranolol, metoprolol,
  pindolol, labetolol, butoxamine
  (experimental drug)
• (Other alpha blockers in top 200 terazosin,
  tamsulosin. Other beta blockers in top 200
  atenolol, carvedilol, timolol)

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Receptor Blocked
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Agents

• Phentolamine short-acting, nonselective alpha
  blocker (competitive)
• Phenoxybenzamine long-lasting efeect binds to
  receptor irreversible (non-competitive)
• Prazosin (Minipress) ?1 gt ? 2 effects
• Yohimbine ?2 gt ? 1 effects
• ? -blockers
• a. Prototypical nonselective beta blocker
  Propranolol (Inderal)
• Clinical uses
• angina antiarrhythmic (propranolol only)
• hypertension alcoholism
• heart failure migraine
• glaucoma behavioral disturbances
• pheochromocytoma

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Contraindications

• asthma (due to bronchoconstriction) careful
  use of ? 1 selective agents in asthma??
• Cautions careful in patients with acute CHF
  but are used in the treatment of chronic CHF
• b. Prototypical cardioselective (?1) blocker
• Metoprolol (Lopressor) and atenolol
• ? antianginal
• ? antihypertensive
• ? used in asthmatic patient with caution
• ? used in hypertensive with CHF
• ? used in CHF

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c. Other Betablockers

• carvedilol
• esmolol
• nadolol
• pindolol
• timolol

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Figure 10-6. The effect in an anesthetized dog of
the injection of epinephrine before and after
propranolol. In the presence of a
beta-receptor-blocking agent, epinephrine no
longer augments the force of contraction
(measured by a strain gauge attached to the
ventricular wall) nor increases cardiac rate.
Blood pressure is still elevated by epinephrine
because vasoconstriction is not blocked.
(Reproduced, with permission, from Shanks RG The
pharmacology of beta sympathetic blockade. Am J
Cardiol 196618312.)
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Figure 10-8. Effects of beta-blocker therapy on
life-table cumulated rates of mortality from all
causes over 6 years among 1884 patients surviving
myocardial infarctions. Patients were randomly
assigned to treatment with placebo (dashed line)
or timolol (color). (Reproduced, with permission,
from Pederson TR Six-year follow-up of the
Norwegian multicenter study on timolol after
acute myocardial infarction. N Engl J Med
19853131055.)