Hypertension and Diseases of Peripheral Vasculature

Question 1

What are the three layers of aorta?

Answer 1

• luminal surface - intima (endothelial cells)
• middle - media (smooth muscle cells, collagen, elastic fibers)
  
  • collagen - tensile strength to deal with high pressure
  • elastin - stretching up to 250%, ability to recoil under pressure
• outer - adventitia (collagen, perivascular nerves, vasa vasorum = network that supplies O2 blood to aorta itself

Question 2

What happens to aortic layers as you age?

Why does systolic pressure tend to rise with age?

Answer 2

Media layer of the aorta in young age has 1collagen (tensile) :2 elastin (stretch and recoil). With age, elastin wears off and collagen become predominant - arteries stiffen.

With less elastin, aorta is not stretching as much during systole and most energy from myocardial contraction is spent pushing blood through stiffer aortic walls.

Question 3

What is an aneurysm?

Answer 3

An aneurysm is an abnormal localized dilatation of an artery.

Question 4

What is an aortic aneurysm? How is it different from diffuse ectasia?

Answer 4

aortic aneurism - dilatation of a portion of the aorta by at least 50%. true aneurysm - dilatation of all three layers of the aorta - large bulge.

diffuse ectasia - generalized (vs localized) dilatation of the aortic diameter, tends to be lesser than aneurism.

Question 5

What are the two types of true aortic aneurisms?

Answer 5

a fusiform aneurysm - symmetrical dilation of the entire circumference of a segment of the aorta, more common

a saccular aneurysm is a localized outpouching involving only a portion of a circumference

memory aid : think “fuse” for double sided and “sac (bag)” for one sided

Question 6

What is the difference between true and false aneurysm?

Answer 6

true aneurysm - dilation of all three layers of the aorta (intima, media and adventitia), caused by degenerative changes in the aortic wall.

false aneurysm or pseudoaneurysm - contained hole (rupture) of the vessel wall that develops when blood leaks out of intimal and medial layers, but is contained by adventitia or perivascular clot (not all of 3 layers are affected). false anneurysms are unstable and can rupture completely.

Question 7

What is cystic medial degeneration or cystic medial necrosis?

Answer 7

cystic medial degeneration = cystic medial necrosis

degeneration changes in media with destruction of elastic and muscular tissues. associated with aging, genetic conditions (like Marfan syndrome) and hypertension. cystic b/c sometimes can form cyst-like shapes. characteristic of an aneurysms.

Question 8

What conditionals are associated with true aortic aneurysms?

Answer 8

1. cystic medial necrosis (usually for ascending aortic aneurysms)
2. atherosclerosis (usually for descending and abdo aneurysms)
3. infection of the arterial wall
4. vasculitis

Question 9

What is atherosclerosis?

Answer 9

condition in which an artery wall thickens as a result of the accumulation of calcium and fatty materials such as cholesterol and triglyceride -> reduced elasticity, less blood flow, higher bp.

Question 10

How is atherosclerosis different from arterosclerosis and arteriolosclerosis?

Answer 10

arteriosclerosis is a general term describing any hardening (and loss of elasticity) of medium or large arteries (from Greek ἀρτηρία (artēria), meaning “artery”, and σκλήρωσις (sklerosis), meaning “hardening”); arteriolosclerosis is any hardening (and loss of elasticity) of arterioles (small arteries); atherosclerosis is a hardening of an artery specifically due to an atheromatous plaque.

Question 11

What are risk factors for atherosclerosis?

Answer 11

• smoking
• hypertension
• dyslipidemia (abnormal amount of lipids = cholesterol and fats in the blood)
• male gender
• advanced age
  *

Question 12

Clinical presentation of aortic aneurysms?

Answer 12

Most aneurysms are asymptomatic

Symptoms may be related to compression of nearby-structures. Thoracic aortic aneurysms may compress the trachea or bronchus = cough, dyspnea (shortness of breath), pneumonia

compression of the esophagus can lead to dysphagia (difficulty swallowing), involvement of recurrent laryngeal nerve - voice hoarseness.

abdominal aortic aneurysms can cause abdo or back pain or non-specific GI symptoms.

most worried about rupture (risk related to size), which can be fatal.

Question 13

Optional: aortic aneurysm

risk of rupture vs surgical risk

Answer 13

thoracic aneurysms rupture (annual rates)

2% for

3% for 5-5.9 cm

7% for > 6 cm

mortality due to surgical repair = 3-5%

abdo aneurysm rupture (annual risk)

0. 3% for < 4 cm
1. 5% for 4-4.9 cm
2. 5% for 5-5.9 cm

mortality due to surgical removal of abdo eneurysms = 1-2%

Question 14

What is the management of aortic aneurysms?

Answer 14

Repeated imaging every 6-12 months

surgical treatment for ascending aneurysms >5.5-6 cm, less if Marfan

surgical treatment for descending aneurysms >6.5-7 cm,

abdo > 5.5 or those that enlarge at >1.0 cm/year

FYI:

thoracic aneurysms rupture (annual rates)

2% for

3% for 5-5.9 cm

7% for > 6 cm

mortality due to surgical repair = 3-5%

abdo aneurysm rupture (annual risk)

0. 3% for < 4 cm
1. 5% for 4-4.9 cm
2. 5% for 5-5.9 cm

mortality due to surgical removal of abdo eneurysms = 1-2%

Question 15

How are aortic aneurysms surgically repaired?

Answer 15

thoracic: bypass -> aneurysm resected -> replaced with a prosthetic Dacron graft

multiple segments done in stages if necessary

in some cases, endovascular stent is possible across aneurysm via transluminal placement

abdo: prosthetic graft

Question 16

What are some steps towards management of aortic aneurysms?

Answer 16

medical management: lifestyle (smoking reduction, diet, exercise)

beta-blockers for Marfan syndrome

surgery considered

Question 17

What is aortic dissection?

Answer 17

blood from the aortic lumen goes through a tear in the intima and spreads in medial layer. can be due to advanced age, hypertension, other causes (cystic medial necrosis,…)

Question 18

What are the two types of aortic dissection?

Answer 18

Stanford type A - ascending aorta is involved, regardless of site of primary tear

Stanford type B - does not involve ascending aorta or arch, only descending thoracic and abdo aorta

ascending thoracic aorta (65%)

descending thoracic aorta (20%)

aortic arch (10%)

abdo (5%)

Question 19

What is the treatment for Stanford Type A aortic dissection and Stanford Type B aortic dissection?

Answer 19

reduce systolic blood pressure -> 100-120 mm Hg

decrease force of ventricular contraction to minimize aortic wall stress -> beta blockers (to reduce force of contraction and heart rate), vasodilators (sodium nitroprusside, etc)

Type A dissection - more serious because of risk of spread to coronary and arch vessels (2/3 or all dissections). In this type, early surgical intervention is shown to improve outcomes (repairing tear, suturing the edges +/- insrting a synthetic aortic graft)

Type B dissection - if uncomplicated, can be managed with meds alone. Surgery is indicated in rare cases (if spreading, compromises major branches of aorta, etc)

Question 20

What do grafts do in aortic dissection?

Answer 20

they “seal” the entry site of dissection, so that false lumen can thrombose and close

Question 21

What is the clinical presentation of aortic dissections?

Answer 21

sudden, severe pain with “rearing” or “ripping” quality in the anterior chest (typical type A dissection) or between the scapulae (type B dissections). the pain travels as dissection spreads and can radiate anywhere in thorax and abdomen. painless dissections rare (6.4%)

some physical findings:

hypertension (either as cause or secondary to severe pain (sympa response) or decreased renal vascular flow (renin-angiotensin activated)

if dissection occludes one of the subclavian arteries, there may be a difference in systolic bp between arms

neurologic deficits may accompany dissection into the carotid vessels.

IMAGE right away!

Question 22

What is peripheral artery disease (PAD)?

Answer 22

Peripheral artery disease (PAD) is an occlusion or stenosis (narrowing) of an artery that provides blood to the limbs.

Question 23

List causes of peripheral artery disease (PAD)?

Answer 23

atherosclerosis

thromboembolism

vasculitis

Question 24

What is the most common cause of PAD?

Answer 24

atherosclerosis

Question 25

What are major risk factors for atherosclerotic PAD?

Answer 25

smoking

diabetes mellitus

dyslipidemia

hypertension

about 40% of PAD patients also have CAD

=> 2x increase in cardiovascular death if diagnosed with PAD

Question 26

What is the relationship between blood flow, vessel radius and length?

Answer 26

Poiseuille’s equation:

delta P = pressure drop across stenosis

r = vessel radius

n = blood viscosity

L= length of stenosis

the degree of vessel narrowing by the stenosis (change in r) has the gratest impact on flow

also for stenoses of same radius and legth, the greater the pressure drop, the greater the flow

Question 27

Compare normal physiology of arteries during exercise to that of peripheral artery disease due to atherosclerosis?

Answer 27

exercise -> muscle metabolism -> adenosine, etc released -> act locally to dilate arterioles -> decrease in vascular resistance -> increase in blood flow to active muscle -> increased flow stimulates healthy arterial endothelium to release more vasodilating factors (ex. NO) -> increased radii of upstream vessels

PAD -> obstructed artery -> cannot respond to vasodilating muscle stimuli -> flow does not increase accordingly + atherosclerotic endothelium does not release normal amounts of vasodilating substances -> lack of adequate blood flow to distal tissues -> ischemia

Question 28

What are characteristics of peripheral artery disease due to atherosclerosis?

Answer 28

reduced blood flow to extremities

=> changes in muscle fiber metabolism + atrophy to adapt to intermittent ischemia -> changes in muscle structure and function (weak limbs)

dramatic reduction in exercise capacity

severe peripheral atherosclerosis may reduce limb flow so that it cannot even provide enough blood for resting state -> worry about tissue necrosis and gangrene -> risk of limb amputation

Question 29

What is the clinical presentation of PAD?

Answer 29

most frequently affects lower limbs

starts with buttock, thigh or calf discomfort after exercise/walking, disappears after rest

exertional limb fatigue and pain is called claudication

location of claudication is the location of diseased artery

in severe PAD, patients may experience pain at rest, usually of feet and toes.

lack of blood flow increaes chances of ulcers, infection and skin necrosis, especially for patients who smoke or who have diabetes mellitus

physical exam generally shows loss of pulse below arterial obsturction. bruits (swishing soungs auscultaged over a region of turbulent blood flow) may be heard

in patients with chronic severe ischemia, lack of blood flow -> muscle atrophy, pallor, cyanotic discoloration, hair loss at site, occasionally gangrene and necrosis of foot and digits

ischemic ulcers possible - small wounds in areas of increased pressure or regions prone to injury, especially in diabetic patients

Question 30

What do you look for on a physical if peripheral artery disease is suspected?

Answer 30

measure ratio of blood pressure in the ankles to that in the arms (ankle-brachial index (ABI); normal ABI >=1.0 (ankle pressure is equal to or slightly greater than, that in the arms). An index

lack of blood flow increaes chances of ulcers, infection and skin necrosis, especially for patients who smoke or who have diabetes mellitus => this is why we look at feet during cardiac exam

physical exam generally shows loss of pulse below arterial obsturction. bruits (swishing soungs auscultaged over a region of turbulent blood flow) may be heard

in patients with chronic severe ischemia, lack of blood flow -> muscle atrophy, pallor, cyanotic discoloration, hair loss at site, occasionally gangrene and necrosis of foot and digits

ischemic ulcers possible - small wounds in areas of increased pressure or regions prone to injury, especially in diabetic patients

Question 31

What is ankle-brachial index (ABI)?

Answer 31

used in the evaluation of peripheral artery disease

measure ratio of blood pressure in the ankles to that in the arms (ankle-brachial index (ABI); normal ABI >=1.0 (ankle pressure is equal to or slightly greater than, that in the arms). An index

Question 32

what is claudication?

Answer 32

claudication = pain and discomfort that happens during exercise/walking, which disappears at rest

suspect peripheral artery disease

Question 33

What are treatment options for peripheral artery disease?

Answer 33

• antiplatelet therapy (Aspirin have been shown to reduce CV morbidity and mortality in patients with PAD)
• risk factor modification (smoking cessation, lipid lowering, control of diabetes and hypertension)
• supportive care of the feet to prevent trauma or restriction of blood flow - exercise, esp walking is recommended: formal exercise program is considered first-line therapy
• cilostazol is drug that increases cyclic adenosine monophosphate and has vasolidating and platelet inhibiting proerties, also shown to increase exercise capacity for patients with PAD
• most vasodilator drugs not helpful in relieving claudication
• mechanical revascularization is indicated when conventional therapy failed in patients with disabling claudication and as first-line therapy in cases of severe limb ischemia
• stents and bypass operations to bypass occluded arteries are also possibilities
• amputations may be necessary if blood flow cannot be reestablished

-

Question 34

What is essential hypertension?

Answer 34

essential hypertension - cause of high bp unknown, 90% of patients

Question 35

What is secondary hypertension?

Answer 35

secondary hypertension - high bp attributed to a specific cause - treat cause

Question 36

What is hypertension?

Answer 36

definitions vary, Lilly uses

diastolic >= 90 mm Hg consistently

or

systolic >= 140 mm Hg consistently

Question 37

What is prehypertension?

Answer 37

systolic pressure of 120-139 mm Hg

diastolic of 80-99 mm Hg

Question 38

What are the formulas for BP and CO?

Answer 38

BP = CO x TPR

where CO - cardiac output

TPR - total peripheral resistance

CO = SV x HR

SV - stroke volume

HR - heart rate

Question 39

What systems are responsible for blood pressure regulation?

Answer 39

the heart, which supplies the pumping pressure

blood vessel tone - systematic resistance

kidney* - regulates intravascular volume of blood

hormones - regulate the function of the three above

* high BP is not just cardiovascular problem. no matter how high BP is, kidneys can return blood pressure to normal by reducing intravascular volume. kidney implant from normotensive to hypertensive typically improves bp.

Question 40

What is a baroreceptor reflex?

Answer 40

The baroreflex or baroreceptor reflex is one of the body’s homeostatic mechanisms for maintaining blood pressure.

System relies on specialized neurons, known as baroreceptors, located primarily in the aortic arch and carotid sinuses. Baroreceptors monitor changes in bp by sensing the stretch and deformation of repsective arteries. If bp rises, the baroreceptors are stimulated, they increase transmission of nerve impulses to medulla (CNS).

Question 41

How do baroreceptors regulate BP?

Answer 41

The higher the rise in bp, the more baroreceptors are engaged in firing, the greater the impulse transmission rate to medulla. Carotid sinus sends signals via glossopharyngeal nerve (cranial nerve IX), aortic arch receptors communicate thorugh vagus nerve (cranial nerve X). Glossopharyngeal and vagus meet at tractus solitarius int eh medulla, where the baroreceptor impusles inhibit sympathetic nervous system and excite parasympathetic nervous system. Net result is:

1) decline in peripheral vascular resistance (vasodilation)
2) reduction in CO (because of lower HR and reduced force of cardiac contraction)

if fall in bp is sensed, fever impulses sent ot medulla, leading to increase in bp.

baroreceptors only regulate short-term bp, as they constantly reset themselves to new values.

Question 42

What are some clues that hypertension is secondary (non-essential)? Why should we care?

Answer 42

Secondary hypertension is often curable and may require different therapy from EH.

Clues:

• if patient develops hypertension btwn ages 20 and 50
• secondary hypertension often causes bp to rise dramatically, EH tends to be mild to moderate
• often presents abruptly in a patient who was previously normotensive
• process that leads to secondary hypertension may lead to other symptoms that can be seen on physical exam
• lack of family history of hypertension more likely

Question 43

Optional: hypertension during pregnancy

difference between gestational hypertension and pre-eclampsia

Answer 43

Table 34-1. Diagnosis of Hypertensive Disorders Complicating Pregnancy
Gestational Hypertension:

Systolic BP ≥140 or diastolic BP ≥90 mm Hg for first time during pregnancy
No proteinuria
BP returns to normal before 12 weeks postpartum
Final diagnosis made only postpartum
May have other signs or symptoms of preeclampsia, for example, epigastric discomfort or thrombocytopenia
Preeclampsia:

Minimum criteria:

BP ≥140/90 mm Hg after 20 weeks’ gestation
Proteinuria ≥300 mg/24 hours or ≥ 1+ dipstick
Increased certainty of preeclampsia:

BP ≥160/110 mm Hg
Proteinuria 2.0 g/24 hours or ≥ 2+ dipstick
Serum creatinine >1.2 mg/dL unless known to be previously elevated
Platelets < 100,000/μL
Microangiopathic hemolysis—increased LDH
Elevated serum transaminase levels—ALT or AST
Persistent headache or other cerebral or visual disturbance
Persistent epigastric pain
Eclampsia:

Seizures that cannot be attributed to other causes in a woman with preeclampsia
Superimposed Preeclampsia On Chronic Hypertension:

New-onset proteinuria ≥ 300 mg/24 hours in hypertensive women but no proteinuria before 20 weeks’ gestation
A sudden increase in proteinuria or blood pressure or platelet count < 100,000/μL in women with hypertension and proteinuria before 20 weeks’ gestation
Chronic Hypertension:

BP ≥ 140/90 mm Hg before pregnancy or diagnosed before 20 weeks’ gestation not attributable to gestational trophoblastic disease
or

Hypertension first diagnosed after 20 weeks’ gestation and persistent after 12 weeks postpartum

ALT = alanine aminotransferase; AST = aspartate aminotransferase; BP = blood pressure; LDH = lactate dehydrogenase.

National High Blood Pressure Education Program Working Group Report on High Blood Pressure in Pregnancy (2000).

Question 44

OPTIONAL: gestational hypertension and pre-eclampsia : more info

Answer 44

Gestational Hypertension
The diagnosis of gestational hypertension is made in women whose blood pressure reaches 140/90 mm Hg or greater for the first time after midpregnancy, but in whom proteinuria is not identified. Almost half of these women subsequently develop preeclampsia syndrome, which includes signs such as proteinuria and thrombocytopenia or symptoms such as headaches or epigastric pain. Gestational hypertension is reclassified as transient hypertension if evidence for preeclampsia does not develop, and the blood pressure returns to normal by 12 weeks postpartum.

Proteinuria is the surrogate objective marker that defines the system wide endothelial leak, which characterizes the preeclampsia syndrome. Even so, when blood pressure increases appreciably, it is dangerous to both mother and fetus to ignore this rise because proteinuria has not yet developed. As Chesley (1985) emphasized, 10 percent of eclamptic seizures develop before overt proteinuria is identified.

Preeclampsia
As shown throughout this chapter, preeclampsia is best described as a pregnancy-specific syndrome that can affect virtually every organ system. As discussed, although preeclampsia is much more than simply gestational hypertension with proteinuria, appearance of proteinuria remains an important objective diagnostic criterion. Proteinuria is defined by 24-hour urinary protein excretion exceeding 300 mg, a urine protein:creatinine ratio of ≥ 0.3, or persistent 30 mg/dL (1+ dipstick) protein in random urine samples (Lindheimer and colleagues, 2008a). None of these values are sacrosanct.

Abnormal laboratory findings in tests of renal, hepatic, and hematological function increase the certainty of preeclampsia. Persistent premonitory symptoms of eclampsia, such as headache and epigastric pain, also increase the certainty. That said, some women may have atypical preeclampsia with all aspects of the syndrome, but without hypertension or proteinuria, or both (Sibai and Stella, 2009).

Headaches or visual disturbances such as scotomata can be premonitory symptoms of eclampsia. Epigastric or right upper quadrant pain frequently accompanies hepatocellular necrosis, ischemia, and edema that stretch Glisson capsule. This characteristic pain is frequently accompanied by elevated serum hepatic transaminase levels. Thrombocytopenia is also characteristic of worsening preeclampsia. It probably is caused by platelet activation and aggregation as well as microangiopathic hemolysis induced by severe vasospasm. Other factors indicative of severe preeclampsia include renal or cardiac involvement as well as obvious fetal-growth restriction, which attest to its duration.

The more profound these signs and symptoms, the less likely it is that they can be temporized, and the more likely it is that delivery will be indicated. The differentiation between nonsevere and severe gestational hypertension or preeclampsia can be misleading because what might be apparently mild disease may progress rapidly to severe disease.

Eclampsia
The onset of convulsions in a woman with preeclampsia that cannot be attributed to other causes is termed eclampsia. The seizures are generalized and may appear before, during, or after labor. In older reports, up to 10 percent of eclamptic women, especially nulliparas, did not develop seizures until after 48 hours postpartum (Sibai, 2005). Others have reported that up to a fourth of eclamptic seizures developed beyond 48 hours postpartum (Chames and co-workers, 2002).

Question 45

What tests should be ordered to investigate cause of hypertension?

Answer 45

screen for secondary causes:

1) urinalysis and measurement of serum concentration of creatinine and blood urea nitrogen to evaluate for renal abnormalities
2) serum potassium level (abnormlaly low in renovascular hypertension or aldosteronism)
3) blood glucose level (elevated in diabetes, which is strongly associated with hypertension and renal disease)
4) serum cholesterol, HDL cholesterol, and triglyceride levels, as part of the global vascular risk screen
5) electrocardiogram (for evidence of left ventricular hypertrophy caused by chronic hypertension)

Question 46

What organs are damaged by hypertension?

Answer 46

Heart Cerebrovascular system Kidney Retina

Question 47

What are examples of nonpharmacologic treatment in hypertension?

Answer 47

weight reduction exercise diet sodium levels potassium levels alcohol other smoking cessation relaxation therapy

Question 48

Why should weight loss be considered during hypertension?

Answer 48

obesity and hypertension correlated, especially if fat is of central (belly) distribution. blood pressure reduction follows weight loss in a large portion of hypertensive patients who are more than 10% above their ideal weights. Each 10 kg weight loss - 5-20 mm Hg fall in systolic pressure.

Question 49

Why should exercise be considered in treatment of hypertension?

Answer 49

sedentary people have a 20-50% higher risk of developing hypertension

Question 50

What are dietary considerations in hypertension?

Answer 50

salt restriction - sodium controversial issue, as salt should be simply excreted by kidneys, but in 50% of patients with essential hypertension, BP varies with sodium intake sensitivity to salt is more common in African Americans and elderly patients. low-salt diets tend to increase the effectiveness of antihypertensive meds in general, current recommendation is to limit salt to

Question 51

What is the effect of smoking on hypertension?

Answer 51

smoking transiently increases BP, likely because nicotine stimulates autonomic NS smoking also a risk factor for sustained hypertension atherogenic effect of smoking may contribute to the development of renovascular hypertension

Question 52

What is the effect of relaxation therapy on hypertension?

Answer 52

BP often rises under conditions of stress essential hypertensive patients and their relatives show higher than normal basal sympathetic tone and exaggerated autonomic response to mental stress.

Question 53

What are the main classes of antihypertensive drugs?

Answer 53

• diuretics
• sympatholytic agents (alpha and beta blockers)
• vasodilators: Calcium channel blockers, direct vasodilators
• renin-angiotensin-aldosterone system antagonists (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, direct renin inhibitors)

Question 54

What drugs are commonly linked to hypertension?

Answer 54

Question 55

What drugs are commonly linked to hypertension?

Answer 55

Question 56

What are diuretics? How do they treat hypertension?

Answer 56

Diuretics reduce circulatory volume, CO, and mean arterial pressure and are most effective in patients with mild to moderate hypertension who have normal renal function.

Question 57

What are thiazide diuretics. When should they be used?

Answer 57

Thiazide diuretics (hydrochlorothiazide) and potassium-sparing diuretics (eg. spironolactone) promote Na+ excretion in the distal nephron, with water following it, reducing circulatory volume -> reducing CO

best used in patients with normal kidney function

Question 58

What are potassium-sparing diuretics?

Answer 58

Similarly to thiazide diuretics, potassium-sparing diuretics promote Na+ excretion in the distal nephron, with water following it, reducing circulatory volume -> reducing CO (ex. spironolactone), but spare potassium to prevent hypokalemia (common with loop diuretics)

Question 59

What are loop diuretics? When should they be used?

Answer 59

Loop diuretics are drugs that act on ascending loop of Henle (ex. furosemide), leading to Na+ excretion -> water follows -> urine production increases while circulatory volume decreases. They are generally too strong and their effect too short to be used in otherwise healthy hypertensive patients, but are used to lower BP in patients with renal disease, who usually do not respond to other diuretics.

they act on Na+/K+/Cl- symporter and may lead to K+ deficiency, so that is why sometimes K+ sparing diuretics are used in combo with loops.

Question 60

What are sympatholytic agents?

Describe function of beta blockers and alpha agonists?

Answer 60

Sympatholytic agents include

1) beta blockers

2) central alpha-adrenergic agonists

3) systemic alpha-adrenergic-blocking drugs (alpha 1 antagonists)

beta blockers lower BP by:

decreased HR -> reduction in CO (CO = HR+SV) & mild decrease in contractility

decreasing secretion of renin -> angiotensin II decreases -> decrease in total peripheral resistance

less effective then diuretics in elderly and African-American

worry about bronchospasms (since beta 2 receptors blocked, which cause bronchodilation), fatigue, impotence and hyperglycemia.

centrally acting alpha 2 adrenergic agonists lower BP by:

reducing sympathetic stimulation to heart, blood vessels and kidneys

but not well liked because of sedation (think blocked sympathetic - really parasympathetic) - dry mouth, sedation, etc

_systemic alpha 1- antagonists _

cause a decrease in TPR thorugh relaxation of vascular smooth muscle, useful in older men also because they also improve symptoms of prosthetic enlargement in men (alpha 1 vasoconstricts sphincters and makes it more difficult to pee, antagonist reverses it)

not greatly recommended in general population as a big trial showed that they are more risky then diuretics (more cardiovascular events)

Question 61

What are vasodilators? How do they reduce hypertension?

Answer 61

Vasodilators consist of direct vasodilators (hydralazine, minoxidil) and calcium channel blockers. Both reduce BP by decreasing peripheral vascular resistance.

Ca ++ blockers reduce influx of calcium, cardiac and vascular smooth muscles require Ca for contraction, so Ca++ blockers reduce cardiac contractility and TPR.

Studies show that Ca++ blockers reduce the chance of myocardial infarction and stroke.

Direct vasodilators (hydralazine, minoxidil) reduce BP by directly relaxing vascular smooth muscle of pre-capillaries, but it can result in reflex increase in HR, so beta blockers are often necessary in combo.

Question 62

What are ACE inhibitors? How do they reduce blood pressure?

Answer 62

renin-angiotensin-aldosterone system antagonists

ACE inhibitors decrease BP by blocking the conversion of angiotensin I to angiotensin II, reducing the vasoconstricting effect that angiotensin II would have had, as well as reducing production of aldosterone angiotensin II would have stimulated.

ACE inhibitors -> peripheral vascular resistance decreases & sodium retention by kidney declines (aldosterone decreased)

ACE inhibitor also increases the concentration of vasodilator bradykinin.

Question 63

What do Angiotensin II receptor blockers do? (dah!)

Answer 63

renin-angiotensin-aldosterone system antagonists

block binding of angiotensin II to its receptors -> vasodilation and reduced secretion of aldosterone -> BP falls

efficacy similar to ACE inhibitors, but generally better tolerated

Question 64

What do direct renin inhibitors do?

Answer 64

renin-angiotensin-aldosterone system antagonists

“newly introduced class of anti-hypertensive drugs. It reduces levels of angiotensin I and II by binding to the proteolytic site of renin, thus inhibiting cleavage of angiotensinogen. Antihypertensive effectiveness is no greater than other drugs from renin-angiotensin family”

Question 65

What effect do birth control pills have on blood pressure?

Answer 65

Estrogen in birth control pills can lead to secondary hypertension in some women. This is because estrogen stimulates liver to produce angiotensinogen, which later gets cleaved into angiotensin I (via renin) and angiotensin II (via ACE). Angiotensin II, in turn, causes vascular constriction and production of aldosterone, which causes water reabsorption in kidneys and increase in circulation volume.