Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
60 Cards in this Set
- Front
- Back
|
L-arginine
|
not usually deficient
|
|
|
antioxidants:
|
probucol, vitamin C, mimetics for SOD that breads down superoxide molecule. These lower free radicals which protects NO for it to do the desired job
|
|
|
statins:
|
have pleotropic effects, one of which is that they turn on eNOS :) a lot with vascular disease will be on statin even if cholesterol not particularly high
|
|
|
estrogen
|
beneficial CV effects so protected till after menopause for CV disease. positive effects on eNOS expression and signaling. Same thing with exercise, red grape wine.
|
|
|
all NO-related therapy (antioxidants, statins, estrogen, exercise, wine)
|
manipulate eNOS in a positive way.
|
|
|
type 5 PDE inhibitors
|
manipulate the levels of cGMP to incr
|
|
|
key concepts in regulation to the coronary circulation (ACS)
|
different modes of progression determines therapy. blood flow to heart ctrll'd by potent metabolic regulation: if anything increases oxygen consumption, work of the heart ->coronary blood flow will go up.
|
|
|
key determinants of myocardial oxygen consuption (metabolism)
(ACS) |
heart rate, cardiac contractility, exercise, potential drug effects.
|
|
|
affect of coronary heart disease on ACS:
|
exercise in CAD: cant dilate and supply as much blood.
|
|
|
drugs that lower heart rate or contractility lower metabolism so can get by with lower blood flow
|
if give drugs that increase heart rate or contractility can bring on chest pain. can't get adequate blood flow.
|
|
|
vasodilators for coronary vascular tone
|
NO, adenosine, prostacyclin, bradykinin (activates endothelial to release NO)
|
|
|
Vasoconstrictors that affect coronary vascular tone:
|
thromboxane (also promotes platelet agg), serotonin stored and released in platelets that becomes a powerful vasoconstrictor in diseased bv's, ATII (also
|
|
|
endothelium prostacyclin
adenylate cyclase |
diffusable and inhibit platelet aggregation like NO. Is lost with some NSAIDS. Uses adenylate cyclase and cAMP instead of NO's guanyl cyclase and cGMP
|
|
|
statins
|
reduce progression to CAD by stabilizing plaque and reducing the lipid pool and inflammation.
|
|
|
early atherosclerosis-->obstructed lumen
|
predictable chest pain seen here
|
|
|
early atherosclerosis-->vulnerable plaque
|
most dangerous because the wall between plaque and lumen becomes thinner and there is a large lipid pool, marked inflammation, oxidative stress..worst case scenario of plaque rupture and thrombosis, MI or stroke.
|
|
|
ACS warning signs:
|
chest pain/discomfort, pressure, SOB, other things possible such as nausea, cold sweat, light-headedness, impending doom...do an EKG, blood tests for biochemical markers of heart damage, angiogram
|
|
|
causes of ACS (CAD):
|
obstructive lesions/obstructed lumen
vasospasm (prinzmetal's angina) ser, TXA, NO decreased syndrome X (microvascular disease): most atherosclerosis happens in lrg coronary arteries..? unstable angina (plaque rupture, thrombosis) |
|
|
anti-anginal drugs: THERapeutic goals:
|
decrease work of heart
inhibi platelet aggregation, inhib clotting/thrombosis prevent vasospasm, dilate coronary arteries stabilize atherosclerotic plaques (most difficult) |
|
|
Nitrovasodilators/NG:
|
discovered by accident, HA is key SE
basic structure of RONO2 nitroglycerin/all agents in group are nitric oxide donors |
|
|
early atherosclerosis-->vulnerable plaque
|
most dangerous because the wall between plaque and lumen becomes thinner and there is a large lipid pool, marked inflammation, oxidative stress..worst case scenario of plaque rupture and thrombosis, MI or stroke.
|
|
|
ACS warning signs:
|
chest pain/discomfort, pressure, SOB, other things possible such as nausea, cold sweat, light-headedness, impending doom...do an EKG, blood tests for biochemical markers of heart damage, angiogram
|
|
|
causes of ACS (CAD):
|
obstructive lesions/obstructed lumen
vasospasm (prinzmetal's angina) ser, TXA, NO decreased syndrome X (microvascular disease): most atherosclerosis happens in lrg coronary arteries..? unstable angina (plaque rupture, thrombosis) |
|
|
anti-anginal drugs: THERapeutic goals:
|
decrease work of heart
inhibi platelet aggregation, inhib clotting/thrombosis prevent vasospasm, dilate coronary arteries stabilize atherosclerotic plaques (most difficult) |
|
|
Nitrovasodilators/NG:
|
discovered by accident, HA is key SE
basic structure of RONO2 nitroglycerin/all agents in group are nitric oxide donors |
|
|
nitrovasodilator mech of action:
|
BIOTRANSFORMATION of NG
|
|
|
role of diuretic in htn:
|
deplete volume to reduce CO
long-term reduction of TPR |
|
|
thiazide diuretics:
toxicity: |
inhibit NaCl reabsorption
XS sodium and potassium loss, contraction alkalosis, uric acid retention. also minor metabolic, weakness, impotentce, HA. |
|
|
Loop diuretics for htn:
|
incl ethacrynic acid. short acting. they increase blood flow incliding flow to kidney. reserved for complicated htn: renal or cardiac failure or if on minoxidil.
|
|
|
Loop toxicity:
|
hypokalemic metabolic alkalosis
ototox MAGNESIUM WASTING hyperuricemia nausea, cramp, dizzy, diarrhea |
|
|
potassium sparing diuretics
toxicity: |
may be used for EX mineralocorticoid such as Conn's disease/secondary causes.
hyperkalemia, nausea, HA, gynecomastia, impotence |
|
|
vasodilators for htn:
|
not first line but used where other therapies fail or in combo with b-blocker and diuretics
achieved by formation of NO or ACTIVATION of K+ channels to hyperpolarize. |
|
|
surprising good fact about direct acting vasodilators:
surprising bad fact: |
do not directly cause orthostatic hypotension (diuretics don't either) or impotence (thiazides and K sparing do).
can cause sympathetic activation, renin release, and sodium retention. |
|
|
hydralazine:
|
dilates just arteries, may release or mimic NO, may hyperpolarize VSM to reduce contractility
Lupus-like effect, reflex tachycardia, HA, nausea, palps |
|
|
Minoxidil (sulfate):
|
dilates arteries, prodrug, causes hyperpolarization via K+ increased permeability
tachycardia, edema, palps, hair growth |
|
|
diazoxide:
|
IV as opposed to minoxidil and hydralazine
dilates arteries, for BP>190, hyperpolarizes can cause severe hypotn, salt and water retention, hyperglycemia, reflex tachycardia and INCR CO, may stop labor due to relaxation of uterine SM. |
|
|
Sodium Nitroprusside:
|
for BP>190
Only one for both arteries and veins. REDUCES TPR via the NO mech severe hypotn, potent CN tox, naus, HA, restlessness (unlike thiazide, CCB esp), sweating, palps, retrosternal pain. |
|
|
CCB's: for HTN--which ones are used first-line?
|
Diltiazem, nicardipine, nifedipine, verapamil
can use alone or with ACEI or diuretic when severe. |
|
|
CCB ADEs:
|
dizziness, flushing, HA, fatigue, rhinitis, constipation, edema.
|
|
|
baroreceptors affect :
|
sympathetic outflow to bv's and heart and PS outflow to heart.
also affect renin release |
|
|
a-methyldopa and clonidine
|
chatecolamine related centrally acting sympatholytics that are not 1st line due to sedation effects.
|
|
|
a-methyldopa :
|
acts on brain a2-adrenergic receptors after being formed into a-MeNe in the CNS noradrenergic nerve terminals `which results in reduced symp outflow and reduced vasc resistance.
DOPA decarboxylase inhibitor. |
|
|
a-methyldopa toxicity:
|
sedation, chills, fever, metabolic effects, edema, orthostatic hypotension unlike the diuretics and direct vasodilators, lactation.
|
|
|
clonidine: toxicity:
|
sedation, dry mouth, dizziness.
|
|
|
a-2 agonists
|
a-methyldopa and clonidine.
reduce sympathetic outflow to peripheral vessels. |
|
|
a1 adrenergic receptors
|
located on arterioles postsynaptically therefore you need to inhibit them.
periferal a2 receptors are located presynaptically. more epi is sensed in synapse so more is not released. |
|
|
a-1 blockers adverse effects:
|
orthostatic hypotension, dizziness, palpitations, HA.
PRAZOSIN |
|
|
B-blocker
|
likely act thru CNS:
some ISA mimic action of catecholamines since NE can act on striated muscle and dilate bv's there. reason good for stress/anxiety. |
|
|
b-1 receptor location
|
heart
|
|
|
b-2 receptor location:
|
vascular SM
|
|
|
hybrid b-blocker:
|
labetalol etc
combines non-selective b-blocker with a1 receptor block. |
|
|
renin inhibitor:
|
aliskiren
can be used alone or in combo the block is at the rate-limiting step effective long lasting with similar tolerability to the other RAAS inhibitors, no AT1 or 2 buildup. |
|
|
unique fact about AcEI's:
|
do not cause baroreceptor reflex-mediated symp activation and can therefore be used in patients with ischemic heart disease
|
|
|
time of onset for losartan etc:
adverse effects: |
3-6 wks since works on brain RAS.
hypotension, hyperkalemia, reduced renal fxn. |
|
|
what do you need to produce NO?
|
O2, L-arginine, NADPH, BH4
|
|
|
additional effect of eNOS:
|
inhibit activation of transcription factor NF-kbeta, which stops expression of proinflammatory genes, inflammation.
|
|
|
pathophys related to eNOS
|
not well established
if deficient BH4 can have eNOS uncoupling and superoxide formation. changes in enzymes or cofactors can produce a free radical instead of NO. Reduced eNOS expression or reduced activity of eNOS. disfxn due to a variety of mech's. |
|
|
similarities between e and n NOS:
differences: |
expressed constitutively and use Ca++
more potential for pathophys with n: XS glutamate leading to stroke. lower concentrations only are good. |
|
|
nNOS;
|
releases glutamate in brain to increase postsynaptic Ca++. nNOS leads to same signaling possibilities as eNOS.
if nerve innervates non-neuronal tissue such as bv or GI, airway, nNOS is in PRESYNAPTIC just like with eNOS. |
|
|
iNOS:
|
good for infection but can lead to endotoxin shock, toxic shock syndrome, cytokine-induced hypotn
inflammation neurodegenerative/autoimmune diseases cerebral ischemia!!! |
