Sympathomimetics

1
Sympathomimetics
2
Sympathomimetics

• Naturally occurring catecholamines
• Synthetic catecholamines
• Synthetic non-catecholamines
• (Direct and Indirect)

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Pharmacological effects

• 1. Vasoconstriction (renal circulation, and
  cutaneous)
• 2. Vasodilatation (skeletal muscle)
• 3. Bronchodilation
• 4. Cardiac stimulation (increase heart rate)
• 5. Myocardial Contractility (increases
  irritability)
• 6. Hepatic glycogenolysis
• 7. Liberation of free fatty acids
• 8. CNS stimulation
• 9. Modulation of Insulin, renin and pituitary
  hormone

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Structure Activity

• Derived from beta-phenylethylamine. A hydroxyl
  group on positions three and four on the benzene
  ring. (these are catechols).

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Structure Activity

• Receptors Need the hydroxyl group on the 3,4
  position to maintain maximal alpha and beta
  stimulation.

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Structure Activity

• CNS stimulation occurs when the drugs lack
  substitutes on the benzene ring
• Substitutes on ring decrease lipid solubility,
  decreasing passage through the blood brain
  barrier

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Clinical uses

• 1. Most often used as positive inotropes
• 2. Vasopressors
• 3. Treatment of brochospasm (including allergic
  rxn)
• 4. Prolong duration of action of local
  anesthetics

8
Metabolism

• Catecholamines
• All catecholamines are inactivated by MAO
  (monoamine oxidase)
• They contain 3,4 dihydroxy benzene structure.

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Metabolism

• COMT (catechol-o-methyltransferease) methylates
  hydroxyl group

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Structure Activity

• Principle mechanism
• Uptake into the postganglionic sympathetic nerve
  endings.

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Non-Catecholamines

• Not effected by COMT (lack hydroxyl group)
• Relies on MAO

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NATURALLY OCCURRING CATECHOLAMINES

• Epinephrine
• Norepinephrine
• Dopamine

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SYNTHETIC CATECHOLAMINES

• Isuprel
• Dobutamine

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SYNTHETIC NON-CATECHOLAMINES

• Indirect Acting
• 1. Ephedrine
• 2. Mephentermine (Wyamine)
• 3. Metaraminol (Aramine)
• Direct Acting
• 1. Phenylephrine (Neosynephrine)
• 2. Methoxamine (Vasoxyl)

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Selective Beta 2 Agonist

• 1. Metaproterenal (Alupent)
• 2. Albuterol (Proventil)
• 3. Terbutaline (Brethine)
• 4. Ritordine
• 5. Theophyilline