the RAAS system helps to regulate_,_,__ and can mediate____

the RAAS system helps to regulate BP, blood volume, and fluid and electrolyte balance and can mediate cardiovascular pathology (HTN, heart failure, MI)

1. the RAAS acts through production of

2. angiotensin II has much greater biologic activity than

3. angiotensin II is formed by the actions of two enzymes

4. angiotensin II causes vasoconstriction (primarily in__a__).  The release of alsodteronse.  In addition, angiotensin II can promote___b___

1. angiotensin II and aldosterone

2. than angiotensin I or angiotensin III

3. rennin and ACE

4. a. arterioles

b.pathologic changes in the heart and blood vessels (increases blood pressur)

aldosterone acts on kidneys to promote retention of __a__.  In addition, aldosterone can also mediate pathologic changes in __b__.

a. sodium and water

b.cardiovascular function

The RAAS system raises BP by causing___a___ and by increasing blood volume (secondary to aldosteron-mediated retention of Na and water)

In addition to the traditional RAAS, in which angiotensin II is produced in the blood and then carried to target tissues, angiotensin II can be produced __b__

a. vasoconstriction

b. locally by individual tissues

By inhibition of ACE, ACE inhibitors decrease production of __a__.  The result is___b___, decrease BV, and prevention or reversal of pathologic changes in the heart and blood vessels mediated by c, d, & e

a. angiotensin II

b. vasodialiation

c. angiotension II

d. aldosterone

Beneficial effects of ACE inhibitors result largely from inhibition of __a__ and partly from inhibition of__b__

a. ACE

b. kinase II

a. ACE stands for

b. if angiotensin II is decreased

vasodiliation or vasoconstriction?

blood volume ____

potassium excretion_____

cardiac remodeling_____

fetal injury risk_____

a. angiotensin converting enzyme

b. if angiotensin II is decreased

vasodiliation

blood volume goes down-pooling in vascular system

potassium excretion goes down

cardiac remodeling goes down

fetal injury risk increases

ACE inhibitors (prils) are used to treat patients with

• Hypertension
• Heart Failure
• MI
• Diabetic neuropathy

• also used to prevent MI, stroke, and death from cardiovascular causes (for pts at risk)

What are the potential adverse effects of ACE inhibitors?

•    First dose hypotension

•    Cough

•    Hyperkalemia

•    Renal failure

•    Angioedema

•    Fetal injury (2^nd and 3^rd trimester)

a. this happens due to a sharp drop in circulation angiontensin II.  Taking an ACE inhibitor can cause this to occur

b. secondary to accumulation of bradykinin, this is the most common reason for dicontinuing ACE inhibitors

c. By suppressing aldosterone released potassium is reabsorbed and Na is released in the urine.  This Potential build up of potassium warrants caution if taking K supplements, salt substitutes, or K-sparing diuretics.  Can be a result of taking an ACE inhibitor. 

a. first dose hypertension

b. cough

c. hyperkalemia

 ACE inhibitors can cause a precipitous drop in BP in patients with bilateral renal artery stenosis or stenosis in the artery to a single remaining kidney.  If the patient starting on an ACE inhibitor has a history of renal failure what action should be taken? why?

The dose should be decreased because of lowered excretion of the drug by the kidneys

advantages of ACE inhibitors

1. after an MI

2. with heart failure

3. with activity (cardiovascular refelx)

4. if person has asthma

5. with increased potassium

6. cost-wise

7. if patient has diabetic neuropathy

1. reduce mortalilty after an MI (captopril, lisinopril, trandonapril)

2. with heart failure: works to lower tone of arterioles (increases cardiac output)

3. doesn't interfere with cardiovascular refelx: can stay active

4. safe if person has asthma

5. doesn't promote hyperkalemia

6. inexpensive

7. reduces pressure in glomerulur (good for people with diabetic neuropathy)

aldosterone secretion is enhanced when sodium levels are ____and when potassium levels are ____

aldosterone secretion is enhanced when sodium levels are low and when potassium levels are high

Angiotensin II may cause structural changes in the heart and blood vessels.  In the heart the compound may cause remodeling, which is __A___, and hypertrophy, which is__B__

A. Remodeling is redistribution of mass within the heart

B. Hypertrophy is increased cardiac mass

In hypertension, angiotensin II may be responsible for___a___.  In atherosclerosis, it may be responsible for___b___.  In heart failure and MI it may be responsible for __c__.

Angiotensin II:

a. HTN: for increasing the thickness of the blood vessel walls

b. atherosclerosis: for thickening the intimal surface of the blood vessels

c. heart failure & MI: causign cardiac hypertrophy and fibrosis

Renin is produced by juxtaglomerular cells of the kidney and undergoes contrlled release into the bloodstream where it cleaves (divides)

angiotensinogen into angiotensin I

Release of renin can be triggered by multiple factors release increases in response to a decline in:

blood pressure, blood volume, plasma sodium content, or renal perfusion pressure. 

ACE can act on several substrates.  When the substrate is angiotensin I, we refer to the enzyme as ACE. When the substrate is a hormone known as bradykinin, we refer to the enzyme as

Kinase II (it is the same thing as ACE)

angiotensin II works in two ways to promote renal retention of water (increases BP)

1. by constricting______

2. stimulates release of______

1. constricting renal blood vessels

2. angiotensin II stimulates relase of aldosterone from renal cortex (acts on renal tubules to promote Na and water retention, and excretion of K)

Beneficial effects from ACE inhibitors result from suppressing

formation of angiotensin II

a. nearly all ace inhibitors are administered____

b. except for captopril and moexipril, all oral ACE inhibitors are administered with____

c. With the exception of captopril, all ACE inhibitors have ______ half lives, and hence can be administered_____

a. orally

b. food

c. all ACE inhibitors have prolonged half lives and can be administred just once or twice a day.  Captopril is administered 2-3 times/day.

a. with the exceptio nof lisinopril, all ACE inhibitors are _____ that must undergo conversion to their active form in the _______.  Lisinopril is active as given. 

b. All ACE inhibitors are excreted by the _____.  As a result, nearly all can accumulate to dangerous levels in patients with _____disease, and hence dosages must be reduced in these patients.  Only one agent, fosinopril, does not require a dosage reduction.

 a. with the exceptio nof lisinopril, all ACE inhibitors are prodrugs that must undergo conversion to their active form in the small intestine and liver.  Lisinopril is active as given. 

b. All ACE inhibitors are excreted by the kidneys.  As a result, nearly all can accumulate to dangerous levels in patients with kidneys disease, and hence dosages must be reduced in these patients.  Only one agent, fosinopril, does not require a dosage reduction. 

When Kinase II (form of ACE) is blocked by an ACE inhibitor there is an increase in bradykinin, which results in

- vasodilation

-cough

-angioedema (rarely)

With prolonged therapy of an ACE inhibitor, blood pressure often undergoes _______

an additional decline

a. ACE inhibitors (unlike sympatholytic agents, which oppose effects of SNS) do not interfere with______

b.  In addition, these drugs can be used safely in patients with______

c. they do not promote or induce

a. with cardiovascular reflexes- exercise capacity is not impaired and orthostatic hypotenstion is minimal

b.bronchail asthma

c. hypokalemia, hyperuricemia (high uric acid in blood), hyperglycemia, lethargy, weakness, or sexual dysfunction

a. Most importantly, ACE inhibitors reduce the risk of cardiovascular mortality caused by

b. By lowering arteriolar tone, ACE inhibitors improve

c. By reducing cardiac afterload, they

d. by causing venous dialation, they reduce

a. hypertension

b. regional blood flow

c. increase cardiac output

d. pulmonary congestion and peripheral edema

a. By dialating vessles in the kidney, ACE inhibitors increase renal blood flow, and

b.  Two benefical effects of this fluid loss include:

a. promote excretion of sodium and water

b. reduced edema & and lowering blood volume (decreases venous return to the heart, and reduces right-heart size)

By suppressing aldosterone and by reducing local production of angiotensin in the heart, ACE inhibitors may prevent or reverse

pathologic changes in cardiac structure

a. ACE inhibitors can reduce the mortality following acute MI.  In addition, they decrease the chance of developing

b. Treatment should begin as soon as possible after infarction and should continue

a. overt heart failure

b. for at least 6 weeks

a. Diabetic Nephropathy is the leading cause of end-stage renal disease in the U.S.  In patients less with advanced neuropathy ACE inhibitors can

b. ACE inhibitors reduce glomerular filtration pressure by

a. delay the onset of overt neuropathy (slow progression of renal disease)

b. reducing levels of angiotensin II (can raise filtration pressure)

Angiotension II raises glomerular filtration pressure by two mechanisms:

a.angiotensin II raises systemic blood pressure, which ___

b. it constricts the efferent artiole______

*the resulting increase in filtration pressure promotes injury

a. angiotensin II raises systemic blood pressure, which raises pressure in the afferent arteriole of the glomerulus

b. it constricts the efferent artiole thereby generating back-pressure in the glomerulus

*at this time the only ACE inhibitor approved for neuropathy is Captopril

a. one ACE inhibitor is approved for reducign the risk of MI, stroke, and death from cardiovascular causes in patients at high risk for a cardiovascular event it is...

b. High Risk is defined as

-a history of_______ combined withat least one other risk factor such as_________

a. ramipril (altace)

b. a history of: stroke, coronary artery disease, peripheral vascular disease, or diabetes combined with at least one other risk factor, such as: hypertension, high LDL cholesterol, low HDL, or cigarette smoking

 ACE inhibitors are generally well tollerated. Some adverse effects are due to a reducion in angiotensin II

a. a precipitous drop in blood pressure may occur following the first dose of an ACE inhibitor.  This reaction is due to widespread dialation. 

b. Diuretics should be temporally discontinued

a. first-dose hypotension

b. 2-3 days before start of an ACE inhibitor

A persistant, dry, irritating, nonproductive cough can develop with______.  The underlying cause is accumulation of bradykinin as a result of inhibition of kinase II. 

ACE inhibitors (kinase II is another name for ACE)

Inhibition of aldosterone release (as a result of angiotensin II production inhibition) can cause ____ build up in the kidneys, and can lead to_____

K build up (retention)

Hyperkalemia

A potentially fatal reaction to an ACE inhibitor that develops in 1% of patients.  Symptoms, which result from increased capillary permeability, include giant wheals and edema of the tongue, glottis and pharynx

[image][image]

angioedema

a. Diuretics may intensify first-dose hypotension.  To prevent this interaction, diuretics should be_______

b. the hypotensive effects of ACE inhibitors are often additive with those of other antihypertensive drugs like_________

c. when an ACE inhibitor is added to an antihypertensive regimen,

a. withdrawn 1 week prior to ACE inhibitor treatment and can be resumed later if needed

b. diuretics, sympatholytics, vasodiliators, calcium channel blockers

c. doses of other drugs may require reduction

ACE inhibitors increase the risk of hyperkalemia caused by potassium supplements and potassium-sparing diuretics.  The risk of hyperkalemia is increased because

by suppressing aldosterone secretion, ACE inhibitors can reduce excretion of potassium.

a. what is the effect of ACE inhibitors on lithium?

b. How do NSAIDs effect ACE inhibitors?

a. ACE inhibitors can cause lithium to accumulate to toxic levels

b. Aspirin, Ibuprofen, and other NSAIDs may reduce the antihypertensive effects of ACE inhibitors

a. The angiotensin II receptor blockers (ARBs) are approved for........

b. like the ACE inhibitors, ARBs decrease the influence of

c.ACE blocks production of angiotensin II, but ARBs block

a. heart failure, diabetic nephropathy, myocardial infarction, and stroke prevention

b. angiotensin II

c. the actions of angiotensin II

*they are very similiar, but ARBs do not cause cough or hyperkalemia*

ARBs block access of angiotensin II to its receptors in blood vessels, the adrenals, and all other tissues. 

a. By blocking angiotensin II receptors in the heart, ARBs can

b. By blocking angiotensin II receptors in the adrenals, ARBs

c. by blocking angiotension II receptors in blood vessels, ARBs cause

a. prevent angiotensin II from inducing pathologic changes in cardiac structure

b. ARBs decrease release of aldosterone, and can thereby increase renal excretion of sodium and water

c. ARBs cause dilation of arterioles and veins

*ARBs do not inhibit kinase II, and hence do not increase levels of bradykinin in the lung*

All ARBs are approved for HTN.  Reductions in BP equal that of those seen with ACE inhibitors. 

a. Currently only two ARBs are approved for heart failure_

b. in clinical trails these drugs reduced symptoms, decreased hospitalizations, improved functional capacity, and increased left ventricular ejection fraction.  More importantly they....

a. valsartan (diovan) and candesartan (atacand)

b. prolonged survival

a. Two ARBs ___&___ are approved for managing nephropathy in hypertensive patients with type II diabetes.  They also delayed development of overt nephropathy and slowed progression of established renal disease

b. Benefits are due in part to

c. Although both ACE inhib and ARBs can delay development of renal complications, only the ACE inhibitors

a.  irbesartan (avapro) and losartan (cozaar)

b.reductions in BP and in part to mechanisms that have not been determined. 

c. have been shown to reduce mortality

a. This ARB was approved for reducing cardiovascular mortality in post-MI patients with heart failure or LV dysfunction. 

b.one ARB is approved for reducing risk of stroke in patients with HTN and LV hypertrophy

c. All of the ARBs are well tolerated.  In contrast to ACE inhibitors, ARBs do not cause

a. valsartan (diovan)

b. losartan (Cozaar)

c. clinically significant hyperkalemia, accumulation of bradykinin in the lung, cough

a. Like ACE inhibitors, ARBs can cause angioedema.  If this happens..

b. how do ARBs cause angioedema?

c. like ACE inhibitors, ARBs can injure the developing fetus if taken during _____. 

* Like the ACE inhibitors, ARBs can cause renal failures in patients with kidney problems*

a. ARBs should be withdrawn immediately and never used again.  Severe rxns: sub-q epinephrine

b. By increasing bradykinin.  Unlike ACE inhibitors, ARBs do not inhibit bradykinin breakdown, and may contribute to local bradykinin synthesis

c. the second or third trimester

a. when the ARB is added to a antihypertensive regimen

b. All ARBs are all administered PO, and all may be taken with or without food.  In addition, all are available alone and in fixed combitions with _______

a. doses of other drugs may require reduction

b.HCTZ

a. Direct renin inhibitors (DRIs) are drugs o that act on renin to

b.By decreasing production of angiotensin I, DRIs can suppress

c. The only DRI available, ___, is approved for HTN with less cough and angioedema than the ACE inhibitors, but poses similar risk to the developing fetus

a. inhibit the conversion of angiotensinogen into angiotensin I. 

b.the entire RAAS

c. Aliskiren

a. Aliskiren is a DRI, and is approved for

b. Aliskiren binds tightly with renin, and thereby inhibits the cleavage of angiotensinogen into antiotensin I.  Since this is the first, and rate-limiting step in the production of ____&____, Aliskiren can reduce the influence of the entire RAAS system

a. for hypertension (only)

b. angiotensin II and aldosterone

note: in clinical trials the drug decreased the plasma renin activity by 50-80%

a. Aliskiren is administered orally and bioavailability is low. About _____% of the drug is eliminated unchanged in the urine and the half life is______

b. At high therapeutic doses, some patients experience

c. like other drugs that affect the RAAS, aliskired should be avoided

a. 25% eliminated, half life 24 hours

b. diarrhea

c. during pregnancy

a. a cough and angioedema are usually the result of inhibiton of ____.  Since aliskiren does not inhibit ____, these are not much of a concern. 

b.Aliskiren causes ______ mostly in women and the elderly

c. like ACE inhibitors, aliskiren rarely causes hyperkalemia alone, but it might be expected if

a. kinase II, kinase II

b. dose-dependent diarrhea (300mg/day).  Excessive doses 600mg/day are associated with abdominal pain

c. when combined with an ACE inhibitor, potassium-sparing diuretic, or potassium supplement

a. aldosterone anatgonists are drugs that block receptors for alsodterone.  Two such agents are available: 

b. Both drugs have similar structures and actions, and both are used for the same disorders:

c. The selective aldosterone blocker aldosterone antaganist (has less side effects)

d. In the kidney, activation of aldosterone receptors promotes excretion of potassium and retention of sodium an water.  Receptor blockade...

a. eplerenone and spironolactone

b. HTN and heart failure

c. eplerenone- produces selective blockade of aldosterone receptors, having little or no effect on receptors for other steroid hormones

d. has the opposite effect: retention of potassium and increased excretion of sodium and water.

a. Blockade of aldosterone receptors at nonrenal sites may prevent or reverse pathologic effects of aldosterone on

b. for treatment of HTN, eplerenone may be used alone or in combination with

c. In patients with heart failure, eplerenone can improve symtpoms, reduce hospitalizations and prolong life. Benefits appear to derive from....

a. on cardiovacular structure and function

b.other antihypertensive agents

c. blocking the adverse effects of aldosteron on cardiovaxcular structure and function

a. Eplerenone is generally well tolerated, with the greatest risk being

b. inhibitors of CYP3A4 can increase levels of eplerenone, thereby posing a risk of toxicity.  Weak inhibitors can _____, and strong inhibitors can_______

c. If eplerenone is combined with a weak inhibitor,

a. Hyperkalemia

b. inhibitors of CYP3A4 can increase levels of eplerenone, thereby posing a risk of toxicity.  Weak inhibitors can can double eplernone levels, and strong inhibitors can increase levels fivefold.

c. eplerenone dosage should be reduced.  Eplerenone should not be combined with strong inhibitors

a. Cacium channel blockers are drugs that prevent

b. CCBs are used widely to treat

c. There has been controversy about the safety of CCB, especially in patients with

d. Calcium channels are gated pores in the cytoplasmic membrane that........

a. calcium ions from entering cells

b. HTN, agnina pectoris and cardiac dysrhythmias

c. HTN and diabetes

d. regulate entry of calcium ions into cells

a. calcium entry into channels play an important role in the function of

b. when an action potential travels down the surface of a smooth muscle cell, calcium channels open and calcium ions flow inward, therby

c. If calcium channels are blocked, contraction will be

d. At therapeutic doses CCBs act selectively on

a. vascular smooth muscle and the heart (regulate contraction)

b. initiating the contractile process

c.prevented and vasodialation will result

d. peripheral arterioles, and arteries, and arterioles of heart.  CCBs have no significant effect on veins

a. in the heart, calcium channels help regulate function of the

b.calium channels at all three sites are coupled to

c. In cardiac muscle (myocardium) calcium entry has a positive intropic effect which means......

d. If calcium in atrial and ventricular muscle are blocked

a. myocardium, the SA node, and the AV node

b. beta 1-adrenergic receptors

c. calcium increases the force of contraction.

d. contractile force will diminish

a. Pacemaker activity of the SA node is regulated by

b. when calcium channels are open, spontaneous discharge of the SA node increases.  When calcium channels are closed pacemaker activity declines, hence the effect of calcium channel blockade is to....

c. Impulses that originate in the SA node must pass through the AV node on their way to the ventricles.  Because of this arrangement, regulation of AV conduction plays a critical role in

a. calcium influx

b. reduce heart rate

c. coordination of the ventricles with contraction of the atria

a. the excitability of AV nodal cells is regulated by

b.The effect of calcium channel blockade is to

c. Calcium channels in the heart are connected to beta 1 receptors.  When these receptors are activated calcium

d. Because of this relationship, CCBs (like beta blockers) have this effect on the heart.....

a. calcium entry

b. decrease velocity of conduction through the AV node (discharge of AV node is suppressed)

c. influx is suppressed. 

d. reduced force of contraction, slow HR, and suppressed conduction through the AV node

a. CCB used in the U.S. belong to three chemical families:

b.These act on the arterioles, doesn't affect the heart at therapeutic doses, but toxic doses can produce dangerous cardiac suppression

c. The differences in selectivity among CCBs are based on

a. dihydropyridines (ie nifedipine), phenylalkylamine (verapamil) and benzothiazepine (diltiazem)

b.dihydropyridines

c. structural differences among the drugs themselves and structural differences among calcium channels.

a. this blocks calcium channels in blood vessels and in the heart.  Major indications are angina pectoris, essential HTN, and cardiac dysrhythmias. 

b.was the first dihydropyridine available.  It blocks calcium channels in the VSM and therby promotes vasodialation.  It does not, however produce much blockade of calcium channels in the heart, and can't be used for dysrhythmias & doesn't cause cardiac suppression, but is more likely to cause reflex tachycardia

a. verapamil

b. nifedipine

a. the overall hemodynamic response to verapamil is the net response of

b. By blocking calcium channels in the heart and blood vessels, verapamil has five direct effects:

1.blockade at peripheral arterioles causes:

2.blockade at arterioles and arteries of the heart:

3. blockade at the SA node:

4. blockade at the AV node (most important)

5. blockade at the myocardium

a. direct effects on the heart and blood vessels and refelx responses

b.

1. causes dilation, and thereby reduces arterial pressure

2. increases coronary perfusion

3. reduces heart rate

4. decreases AV nodal conduction

5. decreases force of contraction

a. verapamil-induced lowering of blood pressure activates the

b. norepinepherine released from sympathetic nerves acts to increase

c. Because direct effects of verapamil on the heart are counterbalanced by indirect effects, the drug

d. The overall cardiovascular effect of verapamil is

a. barorecptor reflex, causing increased firing of sympathetic nerves to the heart (indirect actions)

b. heart rate, force of contraction, and AV conduction (these three are suppressed by direct actions of verapamil- direct and indirect actions tend to neutralize eachother)

c. has little or no net effect on cardiac performance

d. vasodialation accompanied by reduced arterial pressure and increased coronary perfusion

a. verapamil may be administered

b. the drug is well absorbed following oral administration, but undergoes

c. Effects begin within___and peak___

d. elimination is primarily by the___

a. orally and IV

b.extensive metabolism on its first pass through the liver (only 20% of an oral dose reaches systemic circulation)

c. within 30 minutes and peak within 5 hours

d. liver- doses must be reduced substantially for patients with hepatic impairment

a. verapamil is used widely to treat

b. Verapamil is a first-line agent for chronic hypertension.  It lowers BP by:

c. Verapamil, administered IV, is used to slow ventricular rate in patients with atrial flutter, atrial fibrillation, and paroxysmal supraventricular tacycardia.  It does this by:

a. angina pectoris (vasospastic angina & angina of effort)

b.  by promoting dilation of arterioles

c. suppressing impulse conduction through the AV node, thereby preventing the atria from driving the ventricles at an excessive rate

a. verapamil is genrally well tolerated with____as a frequent complaint of taking the drug. 

b. This complaint (side effect) results from

c. Other common side effects

a. constipation

b. blockade of calcium channels in smooth muscle

c. dizziness, facial flushing, headace and edema of the ankles and feet (r/t vasodilation)

a. blockade of calcium channels in the heart can

b.  In the SA node, calcium channel blockade can cause

c. in the AV node

d. in the myocardium blockade can

*in patients with certain cardiac diseases, verapamil can seriously exacerbate dysfunction*

a. compromise cardiac function

b. bradycardia

c. blockade can cause partial or compete AV block

d. blockade can decrease contractility

a. Like verapamil, ____ suppresses impulse conduction through the AV node.

b. accordingly, when these drugs are used concurrently,

c. Beta blockers and verapamil have the same effect on the heart: they decrease heart rate, AV conduction, and contractility.  Hence there is a risk of ____when used together

a. digoxin

b.the risk of AV block is increased.

c. excessive cardiosuppression

a. the direct effects of nifedipine on the cardiovascular system are limited to

b. blockade of calcium channels in peripheral arterioles

causes

c. Channel blockade in arteries and arterioles of the heart

d.  Because nifedipine does not block cardiac calcium channels at usual therapeutic doses,

a. blockade of calcium channels in VSM

b.vasodiliation, and therefore lowers arterial pressure

c. increases coronary perfusion

d. the drug has no direct suppressant effects on automaticity (cardiac muscle cell firing impulse on its own), AV conduction, or contractile force

a. by lowering BP, nifedipine activates the baroreceptor relfex, thereby

b. Because nifidepine lacks direct cardiosuppressant actions, cardiac stimulation is

c. Reflex effects occur primarily with the fast-acting formulation of nifidepine, but not with the sustained-release formulation.  Why?

a. causing sympathetic stimulation of the heart

b.not inhibited, and heart rate and contractile force increase

c. because the baroreceptor reflex is turned on by rapid fall in blood pressure; a gradula decline will not activate the reflex

a. the overall hemodynamic response to nifedipine is simply the sum of its direct effect (___) and indirect effect (____)

b.the net effect of nifidipine:

a. vasodilation, reflex cardiac stimulation

b. lowers BP, increases HR, increases contractile force

(increases in HR and contractile force are transient-occur primarily with rapid-acting formulation)

a. Nifedipine is indicated for vasospastic angina and angina of effort.  The durg is usually combined with a beta blocker to prevent

b. long term use reduces the rates of overt heart failure, coronary angiography, and coronary bypass surgery, but not rates of

a. reflex stimulation of the heart, which could intensify anginal pain. 

b. stroke, MI or death

a. adverse effects of nifidipine include

b. though nifedipine causes only minimal blockage of calcium channels in the heart, and doesn't exacerbate AV block. heart failure, bradycardia, or sick sinus syndrome, it does, however cause reflex tachycardia, which

c. Rapid acting nifidepine has been associated with increase mortality in patients with

a. flushing, dizziness, headache, peripheral edema, and gingival hyperplasia (causes very little constipation)

b. increases cardiac oxygen demand and can increase pain in patients with angina (helps to combine with a beta blocker)

c. myocardial infarction and unstable angina

a. Beta blockers are combined with nifedipine to prevent

b. When taken in excessive dosage, nifedipine loses selectivity.  Hence toxic doses affect the

a. reflex tachycardia

b. heart in addition to the blood vessels

 Some vasodialators act on veins, some on arterioles, and some act on both.

a. Some agents____produce selective dilation of arterioles

b. others, produce selective dilation of veins.

c. Still others dilate arterioles and veins

a. hydralazine

b. nitroglycerine

c. prazosin

a. drugs that diliate resistant vessels (arterioles) cause

b. drugs that diliate capacitance vessels (veins)

c. reducing ventricular filling causes

d. by doing this, venous dilation causes a decrease in cardiac work, along with a decrease in CO and tissue perfusion

a. a decrease in cardiac afterload (the force the heart works agains to pump blood)

b. reduce the force with which blood is returend tot he heart, which reduces ventricular filling

c. cardiac preload (the degree of stretch of the ventricular mucle prior to contraction)

d. decreasing preload

a. the vasodilators indications are

b. Postural (orthostatic) HTN is defined as a fall in blood pressure when moving from a supine/seated position to an upright position.  The underlying cause is

c.  Patients receiving vasodilators should be informed about symptoms of hypotension and be advised to sit or lie down if this happens.  Failure to follow advice may lead to

a. essential HTN, Hypertensive crisis, angina pectoris, heart failure, and MI

b. relaxation of smooth muscle in veins.  Because of venous relaxation, gravity causes blood to pool in veins, thereby reducing venous return to the heart (drop in BP)

c. fainting

 Reflex tachycardia can be produced by dilation of arterioles or veins.  the mechanism of this:

a. arteriolar dilation causes a

b. venous dialation

c. baroreceptors in the aoritc arch and carotid sinus sense

d. in an attempt to bring BP back up, the medulla

a. direct decrease in arterial pressure

b. reduces cardiac output, which in turn reduces arterial pressure

c. the drop in pressure and relay this information to the vasomotor center of the medulla

d. impulses along sympathetic nerves instructing the heart to beat faster

Reflex tachycardia is undesirable for two reasons:

a. tachycardia can

b. If the vasodilator was given to reduce blood pressure, tachycardia would

a. put and unacceptable burden on the heart

b. would raise pressure and thereby counteract the desired effect

prolonged use of arteriolar or venous dilators can cause an increase in blood volume

a. this increase in blood volume represents

 Why does blood volume increase?

b1. reduced BP triggers secretion of aldosterone by the adrenal glands

b2. by reducing arterial pressure, vasodilators decrease both renal blood flow and glomerular filtration rate

a. an attempt by the body to restore BP to pretreatment levels

b1. (aldosterone acts on kindey to promote retention of salt & water)

b2. b/c the filtrate volume has decreased, the kindey reabsorbes a fracion of filtered Na and water. 

a. hydralazine, minoxidil, diazoxide, and sodium nitroprusside are all

b. causes selective dilation of arterioles, and has little or no effect on veins. 

c.arteriolar dilation results from a direct action on

d.In response to arteriolar dilation, ___and ___ fall.  In addition ___&____increase

a. vasodialators

b.hydralazine

c.vascular smooth muscle (selectivity= minimal postural hypotension)

d.In response to arteriolar dilation, peripheral resistance and arterial BP fall.  In addition HR& myocardial contractility increase

a. Hydralazine is readily absorbed following ____administration

b. effects being within ___minutes and last ____hours

c. with parental administration effects begin within ____minutes and last ____to____hours

d. Hydralazine is inactivated by a metabolic process known as....

a. oral

b. within 45 minutes, last 6 hours

c. 10 minutes, 2-4hours

d. acetylation

a. Oral hydralazine can be used to lower BP in patients with

b. Hydralazine regimen to treat BP also includes

c. Parenteral hydralazine is used

d. hydralazine and isosorbide dinitrate can be used short term to

a. essential hypertension (most prevalent type)

b. a diuretic and a beta blocker

c. to lower BP in a severe hypertensive episode

d. reduce afterload in patients with heart failure

a. by lowering arterial BP, hydralazine can trigger reflex stimulation of the heart, thereby causing

b. because reflex tachycardia is usually severe

c. hydralazine-induced hypotension can cause

 d. Hydralazine is combined with beta blocker to protect against ___, and with diuretics to prevent _______.

a. cardiac work and myocardial oxygen demand to increase

b. the drug should be combined with a beta blocker

c. sodium and water retention and a corresonding increase in blood volumeclear antibodies. 

d. Hydralazine is combined with beta blocker to protect against reflex tachycardia , and with diuretics to prevent sodium and waterretention and expansion of blood volume.  

a. Minoxidil produces selective dilation of ____

b. Arteriolar dilation decreases___ and ___.  In response, reflex mechanisms ___ and ___.

c. Both responses can increase cardiac oxygen demand, and can thereby exacerbate ___.

d. the only cardiovascular indication ofr minoxidil is

a. arterioles (little or no dilation occurs)

b. Arteriolar dilation decreases peripheral resistance and arterial blood pressure.  In response, reflex mechanisms increase heart rate and myocardial contractility

c.angina pectoris

d. severe HTN

adverse effects of minoxidil include

 reflex tachycardia (r/t BP reduction),

sodium and water retention (loop diuretic may be added),

hypertrichosis (excessive hair growth),

pericardial effusion (fluid accumulation beneath pericardium)

a. this is a potent and effective vasodialator.  It is also the fastest acting antihypertensive agent available.

 It causes venous dilation and arteriolar dilation, but reflex tachycardia is minimal.   

b. This med contains five cyanide groups which are split free in the first step of metabolism.  Once freed, cyanide groups are converted to ___by the liver.

c. The active component of this drug is released next:

a. Sodium Nitroprusside

b. thiocynate- eliminated by kidneys over several days.

c. nitric oxide

*both reactions take place in the smooth muscle*

a. nitroprusside is used to lower BP rapidly in hypertensive emergencies.  If administered too rapidly,

b. Cyanide buildup is most likely in patients with

c. when given nitroprusside for several days, thiocyanate may accumulate.  Adverse effects include

a. nitroprusside can cause a precipitous drop in BP (results in headache, palpitations, nausea, vomiting, and sweating)

b. liver disease

c. CNS issues: disorientation, psychotic behavior, and delirium

a. left untreated this can lead to heart disease, kidney disease and stroke

b. JNC 7 is

c. the four categories listed by JNC7 are

a. hypertension- can't cure, can only treat (lifelong)

b. the seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high BP

c. normal BP, prehypertension, stage 1 HTN, stage 2 HTN

a. normal BP is

b. prehypertension

c. hypertension

a. systolic below 120/ diastolic below 80 mmHg

b. systolic BP of 120-139, diastolic of 80-89

c. systolic BP above 140 or diastolic BP above 90 mmHg

a. primary (essential) hypertension is HTN that

b. Primary HTN is a chronic, progressive disorder.  In the absence of treatment, patients will

c. Primary HTN affects ___% of adults in the US

a. has no identifiable cause

b. experience a continuous, gradual rise in BP for the rest of their lives

c. 30%

a. Secondary hypertension has an identifible primary cause so it is possible

b. Chronic HTN is associated with increased morbidity and mortality.  Left untreated, prolonged elevation of BP can lead to

c. The degree of injury is related to

d. treatment reduces risk of stroke by ___-___%

a. to treat that cause directly (cure)

b. heart disease (MI, heart failure, angina pectoris), kidney disease, stroke

c.  the degree of pressure elevation

d. 35-40%

Risk factors for HTN include these types of target-organ damage:

Heart disease

-left ventricular hypertrophy

-angina pectoris

-prior MI

-prior coronary revascularization

-heart failure

Stroke or transient ischemic attack

chronic kindey disease

peripheral arterial disease

retinopathy

The major Cardiovascular risk factors for HTN are:

cigarette smoking

obesity

inadequate exercise

dyslipidemia

diabetes

microalbuminuria

advancing age

family hx of premature cardiovascular disease

the following tests should be done for all patients with HTN

electrocardiogram

complete urinalysis

hemoglobin and hematocrit

and blood levels of sodium, potassium, calcium, creatinine, glucose, uric acid, triglycerides, and cholesterol (LDL, HDL, and total)

a. there is a direct relationship between obesity and elevation of BP.  Studies indicate that weight loss can reduce BP ___-___% in overweight hypertensive people.

b. reducing sodium chloride (salt) intake can

b the DASH diet includes foods

a. 60-80%

b.lower BP in people with HTN and can help prevent overt HTN in those with prehypertension. 

c. fruits & veggies, lowfat dairy, and low in total fat, sat fats, and cholesterol.  In addition the plan encourages intake of whole-grain products, fish, poultry, and nuts, and recommends minimal intake of meat and sweets

a. lifestyle modifications for HTN include

b. Arterial pressure is the result of

c. cardiac output is influenced by (what) four factors:

a. weight loss, sodium restriction, DASH diet, alcohol restriction, aerobic exercise, smoking cessation, maintenance (increased) of K and Ca intake. 

b. cardiac output and peripheral resistance

c. HR, myocardial contractility, blood volume, and venous retur of blood to the heart

*an increase of any of these will increase CO, causing BP to rise*

a. Drugs that effect BP are

b. Three regulatory systems are of particular importance when considering BP

c.The sympathetic nervous system employs a reflex circuit (the ___) to keep BP at present

a. beta blockers, verapamil and diltiazem, diuretics,  venodialators

b. the SNS, the RAAS, and the kidney

c. the barorecptors

a. we can suppress renin release in the RAAS by

b. can prevent conversion of angiotensinogen to angiotensin I by

c. we can prevent the conversion of angiotensin I into angiotensin II by

d. we can block the receptors for angiotensin I with

e. we can block receptors for aldosterone with

a. beta blockers

b. direct renin inhibitor

c. ACE inhibitor

d. angiotensin II receptor blocker

e. aldosterone antagonist

a. when BP falls GFR falls as well, thereby promoting retention of

b. the resultant increase in blood volume increases venous return to the heart, causing an increase in____, which in turn increases ____

c.drugs can lower BP by reducing

a. sodium, chloride, and water

b.cardiac output, arterial pressure

c. HR, myocardial contractility, blood volume, venous return, and the tone of arteriolar smooth muscle

a. antihypertensive drugs acting in the brainstem suppress sympathetic outflow to the heart and blood vessels, resultant in

b. Ganglionic blockade reduces sympathetic stimulation of the heart and blood vessles. Antihypertensive effects result primarily from

c. Terminals of Beta-1 adrenergic nerves prevents

d.  Alpha-1 adrenergic receptors on blood vessels promotes dilation of arterioles the veins, which

a. decreased HR, decreased myocardial contractility and vasodilation

b. dialation of arterioles and veins

c. sympathetic stimulation of the heart.

d. reduces peripheral resistance and venous return to the heart

a. Several antihypertensive drugs act directly on vascular smooth muscle to _____

b. Diuretics act on renal tubules to promote

c. Beta-1 receptors on Juxtaglomerular cells suppresses release of renin. The resultant decrease in angiotensin II levels has three effects:

d. Inhibition of renin decreases conversion of angiotensinogen into angiotensin I

a. cause relaxation

b. salt and water excretion

c.peripheral vasodilation, renal vasodilation, and suppression of aldosterone-mediated volume expansion

d. and thereby suppressing the entire RAAS system

a. Inhibitors of ACE supress formation of angiotensin II.  The result is

b. Blockade of angiotensin II receptors prevents

c.Blockade of aldosterone receptors in the kidney promotes

a. peripheral vasodilaiton, renal vasodilation, and suppression of aldosterone-mediated volume expansion

b.the actions of angiotensin II

c. excretion of Na and water, and thereby reduces blood volume

a. It is among the most commonly used antihypertensive drugs.  They reduce PB by two mechanisms: reduction of blood volume and reduction of arterial resistance. 

b. These are reserved for HTN treatment for:

1. patients who need greater diuresis

2. patients with a low GFR

c. Sympatholytic drugs suppress the influence of the sympathetic nervous system on the heart, blood vessels, and other structures.  There are 5 categories:

a. thiazide diuretics: side effects: dehydration, hyperglycemia, hyperuricemia

b. loop diuretics

c. beta blocker, alpha1 blockers, alpha/beta blockers, centrally acting alpha2 agonists, and adrenergic neuron blockers

Beta blockers are among the most widely used antihypertensive drugs.  They have at least four useful actions:

1. blockade of cardiac beta1 receptors:

2. beta blockers can suppress

3. blockade of beta1 receptors on juxtaglomerular cells of the kidney

4. long-term use of beta blockers

5. beta blockers have intrinsic sympathomeimetic activity

1. blockade of cardiac beta1 receptors: decreases heart rate and contractility=cardiac output declines

2.reflex tachycardia caused by vasodilators

3. reduces release of renin, thereby reducing antiotensin II-mediated vasoconstraction and aldosterone-mediated volume expansion

4. reduces peripheral vascular resistance

5. they can produce mild activation of beta receptors while blocking receptor activation by strong antagonists

a. Blockade of cardiac beta 1 receptors (beta blockers) can produce what adverse effects?

b. Blockade of beta 2 receptors (beta blockers) in the lung can promote

c. Beta blockers can mask signs of hypoglycemia, and therefore mus be used with caution

a. bradycardia, decreased atrioventricular conduction, reduced contractility

b. bronchoconstriction (not for pts. with asthma)

c. in pts with diabetes

a. alpha-1 blockers prevent stimulation of alpha-1 receptors on arteries and veins, thereby preventing

b. alpha/beta blockers Carvedilol and Labetalol are unusual in that they block alpha-1 and beta receptors. Blood pressure reduction results from

1. alpha 1 blockade

2. blockade of cardiac beta 1 receptors

3. blockade of beta 1 receptors on juxtaglomerular cells

a. sympathetic vasoconstriction

b.Carvedilol/ Labetalol

1.promotes dilation of arterioles and veins

2. reduces HR and contractility

3. supresses the rlease of renin

a. calcium channel blockers fall into two groups that both promote

b. reflex tachycardia is low with verapamil and diltiazem

c. Since dihydropyridines (nifidipine) do not block cardiac calcium channels

d. The rapid-acting formulation of nifedipine has been associated with increased mortaility with

a. the dialation of arterioles

b. because of cardiosupression

c. reflex tachycardia with these drugs can be substantial

d. patients with MI and unstable angina

 initial drug selection for HTN treatment is determined by the presence or absence of a compelling indication (comorbid condition)

a. without:

b. with compelling indications: htn + comorbid conditions (heart failure, diabetes):

c. after BP has been controlled for 1 year, an attempt should be made to

a. thiazide diuretic for most patients.  Other options include ACE inhibitors, ARBs, DRIs, CCBs, and alpha/beta blockers

b.diuretic, ACE inhibitor, ARB, DRI, beta blocker, CCB, aldosterone antagonist (depends on condition)

c. reduce dosages and number of drugs in regimen, lifestyle modifications considered

a. ways to promote adherence of HTN treatment include

b. chronic HTN occurs in 5% of pregnancies, is described as

c. These drugs are contraindicated during pregnancy to reduce HTN due to risk of fetal harm

a. patient eduction, teach self-monitoring, minimize side effects, establish a collaborative relationship, simplify the regimen, positive reinforcement given

b. HTN that was present prior to pregnancy or before the 20th gestational week of pregnancy

c. ACE inhibitors, ARBs, and DRIs (methyldopa is usually used)

a. Preeclampsia is a multisystem disorder that is characterized by

b. If seizures develop with preeclampsia it is called

c. risk factors for preeclampsia include

a. elevated BP and proteinuria (develop after 20 weeks gestation age)

b.eclampsia

c. obesity, black race, chronic HTN, diabetes, collagen vascular disorders, adn previous preeclampsia