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17 Cards in this Set

  • Front
  • Back
Central Sympatholytics: MOA
-Central mediated inhibition of sympathetic activity
-Stimulation of postsynaptic A2 receptors (A2a subtype)
-Possible role of imidazoline receptors (I1, I2, I3 receptors)
-Endogenous substrate (clonidine displacing substrate)
Central Sympatholytics: Probable Sites of Action in Brain
-Nucleus of solitary tract (NTS)
-Ventral lateral medulla (VLM)
-Activation of these sites: decreases sympathetic nerve activity
Central Sympatholytics: General Hemodynamic Effects
-Decreased TPR
-Decreased HR
-Decreased CO
-Slight increase in sodium retention
-Slight decrease in renin release
Central Sympatholytics: Advantages
-Decreased TPR w/modest decrease in CO
-Efficacy independent of age, race, gender
-Suitable for monotherapy
-Works well in elderly
-No negative effects on lipids
Central Sympatholytics: General Side Effects
-Drowsiness/sedation (CNS)
-Dry mouth (CNS)
-Sexual dysfunction
-Narrow therapeutic range
-Abrupt withdrawal hypertension
-Potent A2 agonist
-Metabolized to a-methylnorepinephrine
-Taken up by reuptake pump, converted by normal enzymes in NE synthesis
Alpha-Methyldopa: Side Effects
-Sodium, fluid retention
-Positive Combs test in 20%, only 5% have true autoimmune response
-Hepatotoxicity (2%)
-Allergic skin reactions
-Hemolytic anemia
-Can be used during pregnancy
-2nd to 3rd line therapy
-A2 agonist, Imidazoline agonist
-Acute pressor response
-Lipid sol of analogues predicts potency
-Decrease SNS activity, increase PNS activity
-Increase blood glucose (inhibits insulin secretion)
-Decrease ADH secretion
-Causes Na+ retention (often given w/diuretic)
-Dry mouth (central effect)
-Analgesic activity - blunts opiate withdrawal reactions
Clonidine: Additional Side Effects
-Withdrawal reactions (may be severe)
-Orthostatic hypotension
Clonidine Analogues: Apraclonidine
-selective A2 agonist
-doesn't cross BBB
-decreases A2 mediated aqueous humor production
-short-term after laser surgery
-can be used w/other agents when pressure not well controlled
Clonidine Analogues: Brimonidine
-decreases A2-mediated aqueous humor production
-increases aqueous humor outflow
-crosses BBB, hypotension, sedation
-Less Na+/water retention
-More selectve for A2 receptors than Clonidine
-Dry mouth
-Less potent than Clonidine
-Most selective (A2>>A1)
-Less sedation
-Occasional withdrawal syndrome
-I1 receptor agonist (RVLM, NTS)
-Antihypertensive actions
-Few classical A2-adrenergic effects:
-Less dry mouth
-Minor sedation
-Little Na+/water retention
-No withdrawal syndrome
-No orthostatic hypotension
*Available in Europe only
-Blocks transport into vesicles, new synthesis of vesicles
-Depletes NE stores
-Decrease CO, TPR, HR, Renin
-Effective in elderly w/diuretic
-Both central and peripheral effects
Reserpine: Side Effects
-Sedation, drowsiness, fatigue
-Depression and suicide:
-Gradual onset, withdraw drug
-Guanethidine analog
-Slow displacement of vesicles:
-Orhostatic hypotension, CHF
-Weakness, fatigue, confusion, depression
-Sexual problems
-Withdrawal syndrome