Non-Autonomic Agents that Alter Vascular Tone Flashcards
how does increasing cGMP cause vasodilation?
what drugs activate guanylyl cyclase and how is this related to cGMP?
cGMP facilitates MLC de-phosphorylation and prevents myosin-actin interaction
Nitric oxide or donors of NO: guanylyl cyclase is converted to cGMP to cause relaxation
how does decreasing intracellular calcium cause vasodilation?
intracellular calcium is required to activate MLC kinase to promote actin-myosin interaction causing contraction
what is the mechanism of action of Ca channel antags?
vasodilation by reducing intracellular Ca in smooth muscle and reduce Ca influx into cardiac muscle fibers to reduce rate, contractility, and oxygen requirement
how are beta blockers related to the concentration of intracellular calcium?
they reduce Ca influx in cardiac muscle fibers to reduce rate, contractility, and oxygen requirement
how do K+ channel openers work to promote vasodilation?
what is a drug that acts this way?
they increase K-channel permeability to stabilize or prevent depolarization of the vascular smooth muscle cell membrane
minoxidil
how do beta-agonists promote vasodilation?
increase cAMP in vascular smooth muscle which increases the rate of inactivation of MLC-kinase
cardiac output is determined by?
stroke volume and heart rate
stroke volume is determined by?
inotropy (force of muscular contractions) and ventricular preload
ventricular preload is altered by changes in?
venous compliance and blood volume
when does a decrease in venous compliance occur? what is the outcome?
when veins constrict. ventricular preload increases by increasing central venous pressure
how is blood volume regulated?
by renal function by handling sodium and water
neurohumoral factors strongly influence which factors?
heart rate, inotropy, venous compliance
the most important mechanism for changing systemic vascular resistance involves changes in?
vessel lumen diameter
dilation of arterial vessels leads to what which causes a fall in arterial blood pressure
reduction in systemic vascular resistance
the heart pumps against a constant pressure and can be damaged if ______ ______ _______ is too high
total peripheral resistance (hypertension)
drugs that are arterial dilators reduce arterial pressure by decreasing systemic vascular resistance, how does the benefit patients with heart failure? how about angina?
helps with heart failure by reducing the afterload on the left ventricle, enhancing stroke volume and cardiac output, and decrease in ventricular preload and venous pressures
helps with angina by reducing the afterload on the heart, decreases oxygen demand of the heart, and improves the oxygen supply/demand ratio
hydralazine, a direct acting vasodilator, is highly selective for?
arterial resistance vessels
which drugs are selective for venous dilation?
organic nitrate dilators
what factors do venous dilators reduce?
cardiac output
arterial pressure
myocardial oxygen demand
capillary fluid filtration and tissue edema
venous pressure and therefore cardiac preload
what is the mechanism of action of nitric oxide?
it is an endogenous vasodilator that increases the level of vascular cGMP and causes smooth muscle relaxation
which type of cells produce nitric oxide?
endothelial cells
describe endothelial cells
they form a continuous lining at the interface between blood and tissue and are present in all blood vessels
explain the conversion process of nitric oxide and how it promotes smooth muscle relaxation
acetylcholine and bradykinin stimulate production of nitric oxide. in addition, calcium influx into endothelial cell activates endothelial nitric oxide synthase (eNOS) which converts L-Arg to NO. NO is then diffused into vascular smooth muscle cells to activate guanylyl cyclase and promote smooth muscle relaxation or activate Ca-dependent K+ channels to cause the cell to hyperpolarize and relax
what role does endothelin play towards vascular smooth muscle cells?
mediates both contraction and relaxation
where are ETA receptors located and what is their function?
smooth muscle cells to mediate vasoconstriction
where are ETB receptors located and what is their function?
primarily on vascular endothelial cells, but also on smooth muscle cells where they mediate vasoconstriction
when ETB receptors are activated in endothelial cells, what does it stimulate? what is the final result?
COX and eNOS
vascular smooth muscle relaxation
what is the difference between ACEs and ARBs?
ACEs prevent AT-II production, but allow increased AT-II levels that activate AT2 receptors. ARBs reduce AT-II production and allow activation of AT2 receptors while reducing activation of AT1 receptors
list the drugs that are calcium channel blockers
nifedipine, amlodipine, diltiazem, and verapamil
which CCBs are dihydropyridines?
nifedipine and amlodipine
which CCB is a benzothiazepine?
diltiazem
which CCB is a phenylalkylamine?
verapamil
how do KATP channel openers work?
cause arterial vasodilation by opening ATP sensitive K channels: when enough K channels open, normal excitatory stimuli cannot promote membrane depolarization and Ca channels don’t open
what is an example drug of a KATP channel opener? where does it act? when do we use it? adverse effects?
minoxidil
acts on arterial smooth muscle
used for hypertension in pts with the most severe and drug-resistant form of hypertension
adverse effects include fluid and salt retention, activation of baroreceptor (inc HR), and hypertrichosis (excessive hair growth)
what is the role of alpha1 A receptors?
contraction of vascular smooth muscle, promote cardiac growth, vasoconstriction of large resistant arterioles in skeletal muscle
what is the role of alpha1 B receptors?
promotes cardiac growth, most abundant in heart
what is the role of alpha1 D receptors?
causes vasoconstriction in aorta and coronary artery
what drug class is Bosentan and what does it do? what is it used to treat? adverse effects? specific drug toxicities?
non-selective ETA and ETB receptor antagonist to cause vasodilation. used to treat pulmonary hypertension.
adverse effects include: incr HR, facial flushing or edema, HAs, vomiting, constipation
can cause fatal hepatotoxicity, req monthly liver test and negative pregnancy tests are req
what drug class are Amrinone and Milrinone and what do they treat?
PDE inhibitors in heart and blood vessels to treat CHF
what drug class is sildenafil? what is its mechanism of action?
PDE inhibitor. it enhances the effect of NO by inhibiting PDE5 which normally causes degradation of cGMP in the corpus cavernosum
what are some adverse effects of PDE inhibitors?
vascular events, ventricular arrhythmia, hypertension
what drugs should sildenafil not be mixed with to avoid a severe fatal drop in BP?
nitrates such as nitroglycerin
PDE5 prevents the activation of what enzyme? therefore inhibiting it will promote the activation of this enzyme to promote smooth muscle relaxation
protein kinase G
what increases due to release of NO during sexual stimulation to promote smooth muscle relaxation and inflow of blood to the corpus cavernosum? PDE5 promotes the formation of ____ from ______ and thus to inhibit PDE5 allows relaxation
cGMP
GMP, cGMP
what is Aliskiren? what does it do?
renin-angiotensin system blocker: inhibits renin production to treat hypertension
why avoid combining Aliskiren with ARBs or ACE-Is in patients with diabetes?
risk of kidney impairment, low BP, and high lvls of potassium in blood
what is the mechanism of action of Hydralazine?
SEs?
inhibits IP3-induced release of intracellular calcium, opens K+ channels, and stimulates the formation of NO leading to cGMP-mediated vasodilation
HA, nausea, flushing, dizziness, tachycardia
what is the mechanism of action of nitric oxide?
increases the lvl of vascular cGMP and causes smooth muscle relaxation
describe the process of acetylcholine leading to smooth muscle relaxation
acetylcholine activates muscarinic acetylcholine receptor on endothelial cells. this activates Gq that stimulates IP3 synthesis and Ca release. Ca activates NO synthase to produce NO which diffuses out of endothelial cells into smooth muscle to activate guanylyl cyclase to produce cGMP. cGMP causes smooth muscle relaxation
how is amyl nitrite administered?
as an inhalant
what is sodium nitroprusside used for?
hypertensive emergencies or when we need rapid and controlled hypotension
when would we use NO gas inhalation?
pulmonary hypertension, acute hypoxemia, cardiopulmonary resuscitation, or short term improvement of pulmonary function
when do we give pts a combo of hydralazine and nitrate?
for pts who cannot take an ACE-I or ARB, or need extra control for HF
vasodilators cause renal retention of sodium and water, what would the outcome be?
increased blood volume and cardiac output
