Miscellaneous CV Drugs Flashcards
Compare the effects of alpha-2 receptors in comparison with that ofthe beta-receptor.
Whereas the former is an inhibitory action mediated by Gi, the latter is stimulatory, mediated through Gs.
What does binding to B adrenoceptors cause?
stimulates adenylyl cyclase by activating the stimulatory Gprotein, Gs, which leads to the dissociation of its alpha subunit charged with GTP. This activated αs subunit directly activates adenylyl cyclase, resulting in an increased rateof synthesis of cAMP.
What does binding to a2 adrenoceptors cause?
Alpha2-adrenoceptor ligands inhibit adenylyl cyclase by causing dissociation of the inhibitory G protein, Gi, into its subunits; i.e., an activated αisubunit charged with GTP and a β-γ unit. The mechanism by which these subunits inhibit adenylyl cyclase is uncertain. cAMP binds to the regulatory subunit (R) of cAMP-dependent protein kinase, leading to the liberation of active catalytic subunits(C) that phosphorylate specific protein substrates and modify their activity. These catalytic units also phosphorylate the cAMP response element binding protein (CREB), which modifies gene expression.
Are there alpha-2 receptors in vasculature?
Yes, (although alpa1 dominate) acting via the Gi proteins.
T or F. vasculature alpha-2 receptors have little contribution to the pharmacology of alpha-2 agonists.
T, becausethe central hypotensive actions of the drugs prevail over peripheral vasoconstrictiveeffects.
When is the vasoconstriction mediated by alpha-2 agonists seen?
when the agonists are given locally, by rapid IV injection or in very high oral doses
What are the main effects of a2 agonists (clonidine) when given orally?
central effects dominate leading to inhibition of sympathetic tone and reduced blood pressure (thus, can be used to treat HTN)
When would a a2 agonist be indicated?
In patients with pure autonomic failure, characterized by neural degenerationof postganglionic noradrenergic fibers, alpha-2 agonist, like clonidine, may increase BP because the central sympatholytic effects of clonidine becomeirrelevant, whereas the peripheral vasoconstriction remains intact.
What are the a2 agonists?
-clonidine-guanfacine-methyldopa (prodrug)
What drugs causes NE storage depletion?
-reserpine-metyrosine
Increased sympathetic nervous system activity plays a significant role in HTN and therefore drugs that control sympathetic tone, or outflow, represent a reasoned approach to pharmacologic control of this disease.
Increased sympathetic nervous system activity plays a significant role in HTN and therefore drugs that control sympathetic tone, or outflow, represent a reasoned approach to pharmacologic control of this disease.
T or F. the central effects of alpha-2 receptor activity prevail over anyperipheral actions on vascular smooth muscle.
T.
What does activation of pre-synaptic alpha-2 receptors cause?
reduces the release of NE from the presynaptic terminal, and thereby reduce the stimulation of the heart and contraction of the vasculature that would normally ensue.
What can alpha-2 agonist stimulate in the CNS?
For example, dexmedetomidine a relatively selective,centrally acting, alpha2-adrenoceptor agonist produces sympatholytic, sedative, andanalgesic properties without significant ventilatory effects. It is used to produce andmaintain sedation.
What are the main effects of a2 agonists?
-withdrawal of SNS tone producing parallel and balanced fall in PVR and systolic/diastolic BP- NO reflex tachycardia; HR may reduce-decreased plasma renin activity-regression of left ventricular hypertrophy
