Adrenic agonist/antagonist

• Adrenergic Agonists (sympathomimetics)

  Exert effects by activating adrenergic receptors
• Adrenergic Agonists

  • Effects are similar to sympathetic nervous system activation, due to using the same receptors
  • Often referred to as sympathomimetics
• Mechanisms of Adrenergic Receptor activation

  1. Direct: Receptor binding

  2. Indirect: Promotion of norepi release

  3. Indirect: Blockade of norepi reuptake

  4. Indirect: Inhibition of norepi inactivation
• Classes of Adrenergic Agonists

  • Catecholamines
  • Noncatecholamines
• Catecholamines

  • Contain catechol group and amine group
  • Cannot be used orally
  • Have brief durations of action
  • Cannot cross blood-brain barrier
  • Quickly metabolized by enzymes: Monoamine oxidase (MAO) and Catechol-O-methyltransferase (COMT)
  • Will turn brown or pink in solution once oxidated
• Noncatecholamines

  • Metabolized slower, not metabolized by COMT, metabolize slowly by MAO
  • Can be given orally
  • Can cross blood-brain barrier
• Receptor Specificity


  Ability of drug selectivity is based on dose
• Alpha1 Receptor


  • Activation causes vasoconstriction, mydriasis
  • Therapeutic applications: Hemostasis, Nasal decongestion, Adjunct to local anesthesia, Elevation of blood pressure
  • Adverse effects: Hypertension, Necrosis, Bradycardia
• Alpha2 Receptor


  • Located presynaptically in CNS, Activation inhibits norepinephrine release
  • Activation in CNS reduces sympathetic outflow to the heart and blood vessels, Provides relief of severe pain
• Beta1 Receptors


  • Activation stimulates the heart
  • Therapeutic applications: Heart failure, Shock, Atrioventricular heart block, Cardiac arrest
  • Adverse effects: Altered heart rate or rhythm, Angina pectoris
• Beta2 Receptors


  • Located in lungs and uterus
  • Therapeutic applications: Asthma, Delay of preterm labor
  • Adverse effects: Hyperglycemia, Tremor
• Dopamine Receptors


  • Activation of peripheral dopamine receptors causes renal vasodilation
  • Can treat shock by improving the perfusion of kidneys
  • Dopamine also stimulates heart rate due to beta1 activation
• Adrenergic Agonists


  • Epinephrine
  • Norepinephrine
  • Isoproterenol
  • Dopamine
  • Dobutamine
  • Phenylephrine
  • Albuterol
  • Ephedrine
• Epinephrine


  • Receptor specificity: A1, A2, B1, B2
  • Therapeutic uses: Delay absorption of local anesthetics, Control superficial bleeding, Increase blood pressure, Overcome atrioventricular heart block, Restore cardiac function, Bronchodilation, Treating anaphylactic shock
  • Pharmacokinetics: Topical or injection, Slow absorption due to vasoconstriction, Short half-life
  • Adverse effects: Hypertensive crisis, Dysrhythmias, Angina pectoris, Necrosis following extravasation, Hyperglycemia
  • Drug interactions: MAO inhibitors, Tricyclic antidepressants, General anesthetics, Alpha-adrenergic blocking agents, Beta-adrenergic blocking agents
• Norepinephrine


  • Receptor Specificity: A1, A2, B1
  • Therapeutic applications: Hypotensive states, Cardiac arrest
  • Adverse Effects: Tachydysrhythmias, Angina, Hypertension, Local necrosis on extravasation
• Isoproterenol


  • Receptor: B1 and B2
  • Therapeutic uses: AV block, Cardiac arrest, Increase cardiac output during shock
  • Adverse Effects: Tachyarrhythmias, Angina, Hyperglycemia in diabetics
  • Drug interactions: MAO inhibitors, Tricyclic antidepressants, General anesthetics, Alpha-adrenergic blocking agents, Beta-adrenergic blocking agents
• Dopamine


  • Receptors: Low doses activate dopamine in kidney, Moderate doses activate beta1 in heart, High doses activate alpha1 causing vasoconstriction
  • Therapeutic uses: Shock, Heart failure
  • Adverse effects: Tachycardia, Dysrhythmia, Anginal pain
• Dobutamine


  • Receptor: B1
  • Therapeutic use: Heart failure
  • Adverse Effects: Tachycardia
  • Drug interactions: Not be taken with MAOIs
• Phenylephrine


  • Receptor: A1
  • Therapeutic use: Reduce nasal congestion, Epistaxis, Increase blood pressure, Dilate pupils, Delay absorption of local anesthetic
• Albuterol


  • Receptor: B2, High dose activates B1 as well
  • Therapeutic use: Asthma through bronchodilation
  • Adverse Effects: Tremor, Tachycardia
• Ephedrine


  • Receptor: A1, A2, B1, B2 (poor selectivity)
  • Therapeutic use: Asthma, Shock, Anesthesia induced hypotension
  • Adverse Effects: Hypertension, Dysrhythmias, Angina, Hyperglycemia in diabetics, Insomnia
• Adrenergic Antagonist


  Cause direct blockade of adrenergic receptors, Most are more selective than the adrenergic agonists
• Major Groups of Adrenergic Antagonists

  • Alpha-adrenergic blocking agents
  • Beta-Adrenergic blocking agents
• Alpha-adrenergic blocking agents


  • Therapeutic applications: Essential hypertension, Reversal toxicity from alpha1 agonist, Extravasated necrosis, Benign prostatic hyperplasia, Pheochromocytoma, Raynaud's
  • Adverse effects: Orthostatic hypotension, Reflex tachycardia, Nasal congestion, Inhibition of ejaculation, Sodium retention
• Selective Alpha1 blocking agents

  • Prazosin
  • Terazosin
  • Doxazosin
  • Tamsulosin
  • Alfuzosin
  • Silodosin
• Nonselective alpha blockers


  • Block A1 and A2

  Phentolamine: Uses - Diagnosis and treatment of pheochromocytoma, Prevention of tissue necrosis, Reversal of soft tissue anesthesia

  Phenoxybenzamine: Noncompetitive receptor agonist, Effects are long lasting, Used for pheochromocytoma
• Beta-adrenergic blocking agents


  • Therapeutic uses: Angina pain, Hypertension, Arrhythmias, Heart failure, Migraine, Glaucoma
• Hycardia


  Nasal congestion
• Alpha blockers


  • Terazosin
  • Doxazosin
  • Tamsulosin
  • Alfuzosin
  • Silodosin
• Tamsulosin


  • Abnormal ejaculation
  • Increased risk for rhinitis
• Alfuzosin


  • Prolong QT interval
  • Do not give with inhibitors of CYP34A
• Silodosin


  • Abnormal ejaculation
  • Increased risk for rhinitis
• Nonselective alpha blockers


  Block A1, A2
• Nonselective alpha blockers


  • Phentolamine
  • Phenoxybenzamine
• Phentolamine


  Noncompetitive receptor agonist
• Phenoxybenzamine


  • Receptor blockade not reversible
  • Effects are long lasting
• Uses of Phentolamine


  • Diagnosis and treatment of pheochromocytoma
  • Prevention of Tissue necrosis after extravasation that produce A1 mediated vasoconstriction
  • Reversal of soft tissue anesthesia
• Adverse effects of Phentolamine

  • Orthostatic hypotension
  • Reflex tachycardia
  • Nasal congestion
  • Inhibition of ejaculation
• Therapeutic uses of beta-adrenergic blocking agents

  • Angina pain
  • Hypertension
  • Cardiac dysrhythmias
  • Myocardial infarction
  • Heart failure
  • Hyperthyroidism
  • Migraine prophylaxis
  • Stage fright
  • Pheochromocytoma
  • Glaucoma
• Angina pain


  • Mainstay
  • Block B1 receptors in heart → decrease cardiac workload
  • Decrease oxygen demand → bring balance of oxygen supply