AlphaAdrenergic Blockers

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Alpha-Adrenergic Blockers

• Type of blockade Phenoxybenzamine
  non-competitive slow onset and long duration.
  2-stage blockade. All the rest
  competitive
• Selectivity Nonselective
  Phenoxybenzamine and phentolamine alpha-1
  selective Prazosin, terazosin, others
  alpha-2 selective Yohimbine
  alpha/beta blockers Labetalol
  
• Others phenothiazines, tricyclic antidepressants

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Phenoxybenzamine
Prazosin
Yohimbine
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EPI
Receptors no longer available
EPI Phenoxybenzamine
Phenoxybenzamine alone
Maximal Increase
Decrease in the maximal efficacy of Epi due to
a decrease in the number of receptors
Agonist, mg/kg
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Pharmacological Effects -Phenoxybenxamine

• Cardiovascular system Blood pressure
  Cardiac Effects Organ Blood
  Flow Capillaries
• Central nervous system
• Respiratory system

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Pharmacological Effects contd

• Eye - miosis
• GI tract Increased motility
• Urinary bladder decreased tone in sphincter
• Metabolic effects increased insulin secretion

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Adverse effects

• Postural hypotension
• Tachycardia
• Sedation
• Nasal stuffiness
• Miosis
• Impotence (inhibits ejaculation)
• Exercise care in hypovolemic patients

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Imidazoline derivatives - phentolamine

• Many other effects including
• Parasympathomimetic
• Increased gastric acid secretion
• Cardiac stimulation
• Increased secretion from exocrine glands, such as
  salivary, sweat, lacrimal, pancreatic
• Coronary artery disease and peptic ulcer relative
  contraindication to it.

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Alpha-1 selective blockersPrazosin

• Less cardiac stimulation since it preserves
  alpha-2 mediated negative feedback other
  mechanisms
• Used in congestive heart failure and in
  hypertension but tolerance develops with time,
  maybe due to fluid retention.
• Adverse effects First dose phenomenon.
• Favorable effect on plasma lipids increase
  HDL/LDL ratio

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Effect of Adrenaline (ADR) on Blood Pressure and
Heart Rate Before and After Prazosin
ADR (µg/Kg)
HR
1
10
100
500
0.1
BP
500
1
10
100
PRAZOSIN
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Alpha-2 selective blockersYohimbine

• Cardiovascular effects peripheral and central
  effects
• Blocks other receptors also serotonin, dopamine
• Increases ADH release
• Enhances sexual activity aphrodisiac
• Potential uses depression, obesity, NIDDM

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Ergot alkaloids

• Interact with serotonin and dopamine receptors
  also
• Direct smooth muscle contraction
• Structure-activity relationships
• Coronary vasoconstriction
• Toxicity GI, vascular insufficiency ergotism
• Use in migraine and post-partum

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Therapeutic Uses ofAlpha-Adrenergic Blockers

• Hypertension - alpha-1 selective
• Conditions associated with increased sympathetic
  activity e.g. pheochromocytoma
• Hemodynamic shock
• Peripheral vascular disease Raynauds
• Congestive heart failure
• Benign prostatic hyperplasia
• Pulmonary hypertension tolazoline
• Yohimbine or intracavernous phentolaminepapaverin
  e for impotence