8) Sympathomimetics Flashcards
Sympathomimetics
- Used for cardiovascular, respiratory, and other conditions
- Divided into subgroups based on their spectrum of action (α-, β-, or dopamine-receptor affinity) or mode of action (direct or indirect)
Adrenoceptors are classified as
- α, β, or dopamine receptors
Epinephrine may be considered
- Single prototype agonist
- Effects at all α- and β-receptor types
Separate prototypes of epinephrine
- Phenylephrine (α agonist)
- Isoproterenol (β agonist)
Endogenous adrenoceptor agonists
- Epinephrine
- Norepinephrine
- Dopamine
Catecholamines (endogenous adrenoceptor agonists)
- Rapidly metabolized by COMT and MAO
- Inactive by oral route
- Given parenterally
Phenylisopropylamines
- Resistant to MAO and COMT
- Most are not catecholamines
- Orally active (enter CNS, last much longer than catecholamines)
Tyramine
- Rapidly metabolized by MAO (inactive orally) except in patients who are taking a MAO inhibitor drug
MAO inhibitors
- Sometimes used in the treatment of depression
- Tyramine is found in fermented foods so patients taking MAO inhibitors may have hypertensive reactions to such foods
Two major enzymes are responsible for catecholamine catabolism in the brain
- Catechol-O- methyltransferase (COMT)
- Monoamine oxidase A (MAO-A)
- Either can catalyze the first step in catecholamine catabolism
Alpha 1-receptor effects
- Mediated by Gq
- Gq activated > a moiety activates phospholipase C > (IP3) and (DAG) released from membrane lipids
IP3 acts on/causes
- Acts on intracellular IP3 receptors
- Causes calcium release from stores in smooth muscle cells
Alpha2-receptor activation results in
- Inhibition of adenylyl cyclase via Gi
- Leads to the decrease of cAMP
β receptors (β1, β2, and β3) effects
- All stimulate adenylyl cyclase via Gs
- Increase cAMP concentration in the cell
Dopamine D1 receptor effects (D1 and D5)
- Gs activates adenylyl cyclase
- Increase cAMP in neurons and
vascular smooth muscle - Vasodilation
Dopamine D2 receptors effects (D2, D3, D4)
- Gi reduces cAMP
- More important in the brain
- Role as presynaptic receptors on peripheral nerves
Alpha 1 agonists
- Increase blood pressure
- Evoke compensatory reflex bradycardia (mediated by vagus)
Alpha 2 agonists
- Topical or IV = vasoconstriction
- Oral = accumulate in CNS, reduce sympathetic outflow and BP
Beta 2 agonists and nonselective β agonists cause a significant reduction in
- Arteriolar tone in the SkM vascular bed
Beta 1 agonists
- Relatively little effect on vessels
- Potent cardiac stimulants
Dopamine
- Vasodilation in renal vascular beds (via D1 receptor activation)
- Treatment of renal failure
- Higher doses = activates β receptors in the heart and elsewhere
- Even higher doses = α receptor activation
β1 and β2 receptors mediate
- Increased rate of SA node/pacemaker (normal and abnormal)
- Increased AV node conduction velocity
- Increased cardiac force
Baroreceptor
- Mechanoreceptor
- Relays info derived from BP within the ANS
Sympathomimetics with both α and β1 effects may cause
- Reflex increase in vagal outflow (higher BP evokes baroreceptor)
- This effect may dominate any direct beta effects on the heart rate
A pure α agonist
- Slows heart rate via the baroreceptor reflex
A pure β agonist
- Increases heart rate
The reduction in heart rate caused by norepinephrine is the result of
- Baroreceptor reflex activation of vagal nerve
Diastolic blood pressure is affected mainly by
- Peripheral vascular resistance and the heart rate
The adrenoceptors with the greatest effects on vascular resistance are
- α and β2 receptors
The systolic pressure is the sum of
- Diastolic and the pulse pressures
- thus, a function of both α and β effects
Pulse pressure
- Difference between systolic and diastolic
- Measures the heart force generated in every contraction
