Lecture 4: Adrenergic Drugs Flashcards
The α1 AR is what type of GPCR?
What are the downstream effects?
- Gq
- Activates PLC; increased IP3, DAG; Ca2; activates PKC
The α2 AR is what type of GPCR?
What are the downstream effects?
- Gi
- Decreased cAMP
The β AR’s is what type of GPCR?
What are the downstream effects?
- Gs
- Increased cAMP
There are 5 dopamine receptors, what type of GPCR is each and what are the downstream effects of each?
D1 = Gs = Increased cAMP
D2 = Gi = Decreased cAMP
D3 = Gi = Decreased cAMP
D4 = Gi = Decreased cAMP
D5 = Gs = Increased cAMP
What are 4 major effects produced by stimulation of α1 AR’s?
1) Contraction of most vascular smooth muscle
2) Contraction pupillary dilatory muscle (dilates pupil)
3) Contraction of the prostate
4) Increases force and contraction of the heart
What are 4 major effects produced by stimualtion of α2 AR’s?
1) Aggregation of platelets
2) Inhibition of NT release at adrenergic and cholinergic nerve terminals
3) Contraction of some vascular smooth muscle
4) Inhibition of lipolysis in adipocytes
What is the major effect of stimulation of β1 AR’s on the heart and juxtaglomerular cells?
- Increases force and rate of contraction
- Increases renin release
What are the major effects of stimulation of β2 AR’s on the liver, skeletal muscle, and respiratory, uterine, and vascular smooth muscle?
- Relaxation of respiratory, uterine and vascular smooth muscle
- Promotes skeletal muscle potassium uptake
- Activates glycogenolysis and gluconeogenesis in the liver
What is the major effect of stimulation of β3 AR’s on the bladder and fat cells?
- Relaxes detrusor muscle in bladder
- Activates lipolysis in adipocytes
What is the major effect of stimulation of D1 and D2 receptors?
- D1 = dilation of renal blood vessels
- D2 = modulation of transmitter release at nerve endings
What 2 drugs are direct adrenomimetic alpha agonists?
1) Phenylephrine - α1 > α2 >>>> β
2) Clonidine - α2 > α1 >>>>> β
What 2 drugs are direct adrenomimetic mixed alpha and beta agonists?
1) Norepinephrine - α1 = α2; β1 >> β2
2) Epinephrine - α1 = α2; β1 = β2
What 4 drugs are direct adrenomimetic beta agonists?
1) Dobutamine β1 > β2 >>> α
2) Isoproterenol β1 = β2 >>> α
3) Terbutaline β2 >> β1 >>> α
4) Albuterol β2 >> β1 >>>> α
What 2 drugs are direct adrenomimetic Dopamine agonists?
1) Dopamine D1 = D2 >> β >> α
2) Fenoldopam D1 >> D2
Which receptors does Norepinephrine act on?
α1 = α2; β1 >> β2
What are the major effects of Norepinephrine?
- Potent cardiac stimulant, but reduces HR
- Potent vasoconstrictor = increases peripheral vascular resistant and BP —> baroreflex will decrease the HR
Which receptors does Phenylephrine activate?
- α agonist
- α1 > α2 >>>> β
What is Phenylephrine used for and what are its effects?
- Effective mydriatic (pupil dilator) and decongestant
- Causes severe vasoconstriction, BP elevation and severe bradycardia
- Role of baroreflex in the severe bradycardia
Which receptors does Clonidine activate most specifically?
- Selective α2 agonist
- α2 > α1 >>>> β
What are the central effects of Clonidine?
- Act on α2 receptors in lower brainstem area
- Decrease sympathetic outflow; reduction in BP; bradycardia
- Local application produces vasoconstriction
Which receptors does Isoproterenol activate most specifically?
- Non-selective beta agonist
- β1 = β2 >>> α
What are the effects of Isoproterenol?
- Non-selective beta agonist
- Positive inotropic and chronotropic action, increases CO (β1)
- Vasodilator, decreases arterial pressure (β2)
- Bronchodilation (β2)
Which receptors does Dobutamine activate most specifically?
- Selective β1 agonist
- β1 > β2, α1
What is the effect of the (-) isomer vs. (+) isomer of Dobutamine on α1 receptors?
- (-) isomer is an agonist
- (+) isomer is an antagonist
What are the effects of Dobutamine?
- Potent inotropic action
- Less prominent chronotropic action as compared to isoproterenol
Which receptors do Terbutaline and Albuterol activate most specifically?
- Selective β2 agonists
- β2 > β1 >>>> α
What are the effects of Terbutaline and Albuterol?
- Selective β2 agonists
- Bronchodilation and relaxation of uterus