Medical Pharmacology Chapter 5:  Autonomic Pharmacology:  Adrenergic Drugs

 
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  • *GU--genitourinary; ** IP3: Inositol trisphosphate; DAG:  diacylglycerol

     

    • IP3:DAG Second Messengers

      IP3

      DAG

       

    • α2 Receptors49,46

      Receptor type: α2 (includes α2A, α2B, α2D)

      example agonist:  clonidine;

       α2Aagonist: oxymetazoline

      example α2: antagonist:  yohimbine;

      α2A,α2B:  prazosin

      Signal transduction: G protein (Gi adenylyl cyclase activity);

      Gi (βγ subunits): K+ channel conductance;

      Go : Ca2+ channel conductance (L- and N-type)

      cAMP (true for all α2 receptor subtypes)

    • Receptor type: α2

      Agonist effectiveness: 

      Epinephrine ≥ Norepinephrine >> Isoproterenol;

      clonidine (classical α2 agonist)

      • Tissue Effects following α2-receptor activation

        • Platelets:  aggregation

        • Pancreatic islet β cells:  reduction in insulin release

        • Synaptic endings:  reduction in norepinephrine release

        • Vascular smooth muscle:  contraction

    •  

      β Receptors49,46

      Receptor type: β (includes β1, β2, β3)

      example agonist:  isoproterenol;

       β1 agonist: dobutamine;

      β2 agonist : albuterol

      example β: antagonist: propranol;

       β1 antagonist: bextaxolol, metaprolol;

      β2 antagonist: butoxamine

       

       

      Signal transduction: G protein (Gs)

      cAMP (true for all β receptor subtypes),

       adenylyl cyclase, L-type Ca2+ channels

      Receptor type: β1

      Agonist effectiveness: 

      Isoproterenol > Epinephrine = Norepinephrine;

      dobutamine (antagonist:  CGP 20712A)

      • Tissue Effects following β1 -receptor activation

        • Renal:  juxtaglomerular cells:  increased renin secretion

        • Cardiac: increased myocardial contractility (positive inotropism)

          • increased rate of contraction

          • increased AV nodal conduction velocity

      Receptor type: β2

      Agonist effectiveness: 

      Isoproterenol > Epinephrine >> Norepinephrine (antagonist ICI 118551);

      terbutaline (antagonist:  CGP 20712A)

       

      • Tissue Effects following β2-receptor activation

        • Smooth muscle (including bronchial, vascular, GI and GU):  relaxation

        • Skeletal muscle:  glycogenolysis and increased K+ uptake.

        • Hepatic effects::  glycogenolysis and gluconeogenesis

       

      Receptor type: β3

      Agonist effectiveness: 

      Isoproterenol = Epinephrine > Norepinephrine (antagonist ICI 118551);

      BRL 37344 (antagonist:  CGP 20712A)

      • Tissue Effects following β3-receptor activation

        • Adipose:  lipolysis

    •  

      Dopamine Receptors49,46

      Receptor type: Dopamine (includes D1, D2,D3, D4,D5 )

      example D1 agonist: fenoldopam;

      example D2 agonist:  bromocriptine

      example D4: antagonist: clozapine

      Signal transduction:

      D1: cAMP;

      D2-D5: cAMP

 

 

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