Term
| regulation of vsmc contraction |
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Definition
calcium channels lead to contrcaction, binds to almodulin. calcium-calmodulin aciated mlck-? mlck phosphylariotn light chains, interacti wth actin leading to contraction.
CAMP worksi n opposite way- activation of camp kinase - leading to inactivation of myosine lc kianse- resulting in relaxation. |
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Term
| mechanicsms for relaxing arterial smoht muscle |
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Definition
hyperpolarization (cllsoure of l type channels) .
blockade calcium l channels.
increase cGMP via NO.
icnrease camp via b adrenergic agonists. |
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Term
| organic nitrates principel agents |
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Definition
| nitroglycerin, amyl nitrite, and isobiride dinatirate |
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Term
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Definition
| relase NO in smooth muscle cells. Leadst to activation fo guanylate cyclase- > increase in cyclic GMP. protein kianse phosphorylation cascade leads to dephosphorylation of myosin light chain and msucle relaxation. |
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Term
| cardoiovascular effects of organci nitrates |
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Definition
low doses- capacitance vessels- venodilation, decresed diastolic fillign pressure and pulmonary vessel restiatnce .
side effects:
hypotension, flushing, headache, orthostatic hypotension adn cornoary vasodilation.
Hi doses: resistance vesel fffects- systemic peripheralr esitance. Reflex cardiac stimulation.
overall effects- decrased heart size and awl ltension durin sytole and reflex cardiac stimulation. |
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Term
| pharmacokinetics of nitrates |
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Definition
subject to first pass inactivationby ntirate reductase in liver. Diferentially resitant to dentiration i ntisuses.
Agents more reistant to metabolism are less potent (paradoxically)-longer doses and logner halflife.
tolerance and physcial depepdnance can occur. |
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Term
| duration of action of nitrites |
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Definition
| short (minutes) and long acting (hours) |
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Term
| sildenafil (viagra on vsmc contracition |
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Definition
NO relaxation of smooth msucle in corpora cavernosa. PDE5 mediates cgmp breakdown in tissue.
sildenafil inhbiits pde5 adn increases concnetration oc GMP.
potentiates actions of nitrates us ed for angina. |
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Term
| calcium channels nad smooth msucle contraciton |
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Definition
VSMC contraciton is tonic , not phasic ,toen is maintained by intracellular free calcium.
Sources of calcium: sarcoplasmic reticuluc mediated by IP3
entry through calciu mcselectiev chnensl: votlage dependant or receptor operated.
or entry throu calcium sodiu exchange |
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Term
| calcium channel type in smooth muscle contraction |
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Definition
| L type channels mediate contraction in smooth smmucles |
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Term
| factors that mediate l type channel oepning |
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Definition
tone matinained by entry exit blalcne of calcium. Entry via voltage dependant L channels.
Proabilyt of l channe loepning increased via a1a arenergic recptors, icnrse in embmrane potenail.
and stretch icnreases membrane potential. |
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Term
| calcium chanenl blcloerks tyeps |
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Definition
| verapail, niphopine, diltiadim |
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Term
|
Definition
| is a dihydroperidine- blcoks transition of clsoed channels int oopen state . Decrese frequency of oepning . nifedipine causes strogner vasodilation than others . |
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Term
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Definition
| itneracts iwth open channels. and blocks them. |
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Term
| location of theraputic effects of calcium channelblockers |
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Definition
| myocardial cells and vascular smooth muscle |
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Term
| cardiovascualf effect of nifedipien and verapamil at clinical doses |
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Definition
vasodilation: nifedipine- strong, verapamil-moderate.
direct cardiac suppresio: nifedidpine-modest to mdoerate. Verapamil-moderate
reflex cardiac activation: nifedipine-modest tostrong. Verapamil-moderate.
Net balance- nifedipine- vasodilation with mdoest cardiac stimulation. verapamil- vasodilation with mdoerate cardiac suprpesion. |
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Term
| nifedpine pharmacology effects. |
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Definition
at clincial doses- vasodialtor efects predmoinate- systemic vvasodialtion fo resistance, but not capacistance vesels.
coronary arteyr vasodialtion adn increased blood flow.
cardiac suppressive effects balanced by reflex acivation. |
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Term
| adverse effects of nifedipine |
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Definition
| flushign, headache, hypoetnsion and eripheral edema. |
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Term
| nifedippine admiintation /metbaolism |
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Definition
| orally effective, halflife in hours range. large firs pass metabolism. |
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Term
| pharmacology of verapamil |
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Definition
| mdoerate vasodilation. cardaic suprpesion alrgely balanlced by felex activation. co andh r modestly decreased only. alhpa adrenergic blockade |
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Term
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Definition
| flushign, gi distrubances, left ventricular dysfunction |
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Term
| verapamil adminsitration/metabolism |
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Definition
orally effective, half life in hours range. large first passm etabolism in liver.
Dilitizaem is ismilair but less upreesive herat effects. |
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Term
| alium entry blockers advantages |
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Definition
no aggravtion of diabetes, peripheral vascular disease, bronchospasm, blodo profiels of lipids , or glucose or ptoassium.
tolerance does nto develop. |
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Term
| nitroglycerin effects on perfusion |
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Definition
no overal increasei n coronary blodo flow.
some redistrubtion from epicardial to endocardia lischemic regions: preferential dilation of larger vesels.
dilation at occlued (hyperreactiev sites). |
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Term
| nitroglycerin effects on cardiac work |
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Definition
| alot of venodilation, some arteiroalar dilation, reflex cardiac stimualtion of rate and cotnracitlity. |
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Term
| utility for typical angina nitro |
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Definition
| lowers work of heart. useful for suprepsing acute attacks |
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Term
| calcium ntry blcokers effects on pefrfusion |
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Definition
| icnreaseo f conronary blodo flow |
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Term
| calcium entry blockers cardiac work effects |
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Definition
| eresistance vessel dilation. reflex cardiac efefcts vary with agent. work ofh eart is decreased. |
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Term
| calcium etnry lbockers utility for typical angina |
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Definition
reduce frequuncy of attacks, reduce ntirate requirements. icnreaase excercise performance. no reduction in MI incidence.
used hwen ntirate/b-blocekrs are poorly toleraetd. |
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Term
| b adrenergic recetor antatognist effect on cardiac work |
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Definition
| block b adnrecetporsi n eahrt. suppress cardiac acvitiy, lower o2 consumption, prologn diastole |
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Term
| b adrenergic receptors antagonists uitlity for typical angin |
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Definition
| most effectie agents currently availble for reduiton of cardiac ischemia . reduces ferquency adn severit of attacks. toleranc doesnt develop. useful for suprressiong MI |
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Term
| b aderenergic antaognist adverse efefcts |
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Definition
possible aggravation of peripheral insufficiency, icnresed airways resistance.
bradycardia and hypotension. not for patients with congestive heartfailure.
may produce rebound agnina or mi on sudden withdrawal |
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Term
| therapy of variatn angina |
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Definition
| organic nitrates, calcium etnry blocekrs, but NOT b adrenergic antagonists |
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