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عجمية مها

أبو

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- Dr Alia Shatnawi

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A Skippable Intr0…

• Blood pressure normally decreases during the night. Absence of this phenomenon is called

(nondipping)

• Wikipedia: Circadian rhythm. ... A circadian rhythm is any biological process that displays an

endogenous oscillation of about 24 hours. These 24-hour rhythms are driven by a circadian clock.

Men has no ESTROGEN, normally :P

• In this course, We will cover the drugs that are used in the most common cardiovascular

diseases.

• Dr. Alia encourages you to revise the ANS physiology.

• Piece of Advice: try not to waste lots of time on this sheet.

• SORRY if there was any mistake.

• I’ve tried to include what was mentioned in the slides, sorry again if I missed anything.

BLOOD PRESSURE • Blood pressure is the force that the circulating blood exerts on the walls of the blood

vessels.

o The Numerator =120 mmHg, the systolic pressure, which represents the

contraction of the heart -the ventricles in particular-.

o The Denominator = 80 mmHg, the diastolic pressure, which represents its

relaxation (between beats).

• The blood pressure depends on two variables:

o Cardiac output.

o Peripheral Resistance.

- THE EQUATION:

Mean Arterial Blood Pressure = Cardiac Output * Total Peripheral Resistance,

(physiology note: if Right Atrial Pressure was Zero)

- EXTRA EXPLANATION FOR THE EQUATION how could we increase arterial

pressure? Either by increasing the amount of blood that is pumped by heart per

minute (the cardiac output) or by increasing the resistance offered by the systemic

circulation specifically by arterioles (the TPR).

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How could we lower blood pressure?

- Reduce plasma volume (diuretics)

- Reduce cardiac output (ß-blockers, Ca2+ channel

blockers)

- Reduce peripheral vascular resistance (vasodilators)

HYPERTENSION Definition

The normal mean blood pressure is 120/ 80.

- If the systolic was between from 120 to 139 or if the diastolic was from 80 to 89,

the person would be pre-hypertensive . (you could prevent hypertension in

these people)

- if the systolic was more than 140 or the diastolic was more than 90, the person

would be hypertensive.

- There are two stages of hypertension (slide)

Therefore, hypertension is the elevation of arterial blood pressure above 140/90

mm Hg.

Signs&Complications

why Hypertension is Bad?

- Hypertension is the top deadly cardiovascular disease worldwide.

- HYPERTENSION is a hemodynamic change that will affect your heart, imagine that

it will pump blood against high volume! Heart Failure might develop or infarction.

- Hypertension is a chronic disease, if left untreated, it could cause many other

health problems.

Slide: Hypertension is a common, incurable, persistent, but usually asymptomatic

disease whose treatment provides no obvious benefit.

- 30% people are hypertensive worldwide, 30% out of these 30% don’t know that

they are hypertensive for many years, why? Because of its clinical presenentation,

o It is a silent disease; asymptomatic disease.

o The early sign of hypertension is a mere headache (especially in the

morning), it coincides with morning surge in blood pressure

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There are many hormones that play an important role in the circadian

rhythm sleep-wake cycle, such as melatonin (at night) and cortisol

(early morning), the cortisol can stimulate high blood pressure, this

explains why blood pressure could be higher at mornings, which can

lead to headaches, that will ease up throughout the day.

The upper curve represents the systole, the lower

curve represents the diastole notice the dipping

(the points where pressure has fallen)

- What about those who know that they are hypertensive?

o 11% of them, don’t seek treatment ((special diet or drugs)).

o 25% are on inadequate therapy (although they take medications, their

blood pressure is not controlled) – we should either add another agent or

change the one we are using for these people.

o The lucky 34% are on adequate therapy and everything is controlled.

- Hypertension can become malignant and modulate many organs, (end-organ

damage) o The main organ that is affected by hypertension is the HEART.

o Hypertension can affect the brain (strokes), the blood vessels (aneurysm

and arteriosclerosis), and the kidney (glomerulonephritis?).

- Hypertension Complications could be preventable, even if they started to appear,

but they might be irreversible at late stages, o Chronic hypertension alters blood

vessel/cardiac muscle structure.

o Decreases blood vessel diameter High blood pressure can narrow the

blood vessels’ lumen, and alter their structure, by recruiting more

fibroblasts which will produce more collagen, and make the blood vessels

stiffer, which will reduce their ability to (dilate); there will be less blood

flow.

o Diminishes distribution of oxygenated blood to tissue targets.

o Cardiac hypertrophy, high resistance against the heart, will eventually lead

to hypertrophy (left ventricular hypertrophy) and heart failure.

o High blood pressure ultimately leads to major end-organ damage i.e.,

heart attack, stroke, renal failure Need to diagnose and treat

hypertension early

o Other complications are, edema, papilledema and vascular hyperplasia

(pathology note: onion-skin appearance, in a condition known as

hyperplastic arteriosclerosis.)

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Diagnosis

What if your systolic pressure was higher than 140 AT THIS MOMENT, does that mean that

you are hypertensive? NO, but why?

- because there are many non-pathological conditions that can elevate your blood

pressure, such as :

o Morning surge of BP.

o During Sleep: “Non dipping’ and “extreme dipping” o isolated office

hypertension.

o white coat hypertension: it is syndrome whereby a patient's feeling of

anxiety, stress and fear of doctors results in an abnormally high reading

when their blood pressure is measured. (these poor guys with activated

sympathetic and elevated cortisol levels)

- to diagnose hypertension, you should record 14 blood pressure readings at

different times a day -usually two per session, taken morning and evening- (for

about 7 days), then you see the average, and based on that you can decide

whether you are hypertensive or not.

Categories

• Hypertension can be classified

based on the impact into 2 stages

• Hypertension can be classified

based on its etiology into: primary and secondary

- Primary Hypertension (aka Essential Hypertension) o The cause is

unknown in 90% of the cases. (idiopathic) o It is associated with

increased peripheral vascular resistance.

o Multifactorial, which means that there are many factors that contribute to

the development of the disease:

Genetics, hypertension can run in families. (this is why the

development of hypertension can depend on ethnicity:

African American Men have the highest tendency to

develop hypertension.

White American (Caucasians) Women have the least

tendency.

category Systolic (mmHg) Diastolic (mm Hg)

Normal <120 <80

Prehypertensive 120-139 80-89

Hypertensive Stage 1

140-159 90-99

Hypertensive Stage 2

≥160 ≥100

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Currently, the prevalence of

hypertension in the US age 3545

years is as follows:

Category Percentage

White Women 17%

White Men 26%

African American Women

37%

African American Men

44%

Stress, which is characterized by elevated stress hormones such as

adrenaline, and cortisol. Environment, such as: 1. Smoking: pure nicotine will activate many pathways in the body, such as

binding to nicotinic receptors which can be found in neuromuscular junctions

of skeletal muscles (this is why excessive smoking can lead to muscle

twitching), and in autonomic ganglia (it has two subdivisions: sympathetic and

parasympathetic).

But how could smoking cause hypertension? blood vessels are exclusively

controlled by sympathetic system, they constrict as a result of nicotinic

activation, this vasoconstriction will increase the blood pressure. Extra: there are nicotinic receptors in adrenal medulla too.

2. Diet: high-sodium (salt) diets can cause hypertension.

- Secondary Hypertension o It can be treated, by modifying the

underlying cause, such as:

Congenital conditions: aortic coarctation, or stenosis of renal

arteries. (treatable by surgeries)

Tumors: pheochromocytoma which produces adrenaline.

High Aldosterone Levels.

Cushing’s.

Masked Hypertension

Unlike white coat hypertension, Masked hypertension is defined as a normal blood pressure

in the clinic, but an elevated blood pressure out of the clinic (e.g: at home).

How this condition has been identified? Probably because of the availability of at-home blood

pressure tests and self-checks.

The MOST Susceptible Groups? Smokers.

Why? Unknown, probably because smokers tend not to smoke in the clinic’s waiting room, but

they do smoke at home.

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Any Advice? We, as doctors, should be able to diagnose these people, because if they were left

without treatments, they would suffer from many complications.

Hypertension&Figures

Mortality

• (systolic/ diastolic) Hypertension increases mortality rates.

• Incidence of hypertension and fatal cardiovascular morbidity/ diseases is higher in men,

but lower in women due to hormonal differences, this can be explained by the

vasodilatory effect of estrogen, but postmenopausal women will have as high incidence

rate as men, because their estrogen levels drop.

Coronay Heart DISEASES

• Hypertension increases the risk of heart diseases, hypertensive

people’s risk to develop heart diseases, increases to more than

double (2.3x)

• Other factors:

- Diabetics and those with left ventricle hypertrophy are

about 1.5 times more likely to develop these diseases.

- SMOKERS are 1.4 times more likely to develop them.

- People who follow high cholesterol diets are 4.5x more

likely.

Treatment

• Antihypertensive therapy has been associated with:

- 35% to 40% mean reduction in stroke incidence.

- 20% to 25% reduction in myocardial infarction.

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- More than 50% reduction in heart failure.

• There are many treatment options:

- Lifestyle Modifications (can help in mild cases such as pre-hypertension), o Weight

loss. o physical activity. o High-potassium and calcium diet, but low-sodium diets.

o DASH (Dietary Approaches to Stop Hypertension) eating plan which limits

sodium intake (1600-mg sodium) was found to be as effective as

antihypertensive monotherapy.

- Drugs:

o either monotherapy or commonly used in combination of

drugs. o they can alter glucose levels in a diabetes, or lipid

profile in some patients.

o Tailor treatment according to diagnostic exam, because

there are several factors, such as:

- whether the disease is complicated or uncomplicated.

- Severity of hypertension

- The ethnic group (e.g: African Americans have the tendency to

develop volume-expanded hypertension and low-renin

hypertension!!)

- The presence of other diseases.

- Pregnancy (there are many drugs that are contraindicated during

pregnancy)

- Drug-drug interactions.

- Patient’s Compliance. (instead of prescribing 3-4 combined drugs

to an old patient, we can give him only one or two drugs:/)

• Drugs are categorized based on the organs they target, what can these drugs do to

reduce hypertension?

- Lowering cardiac output (in heart), there are some precautions though.

- Decreasing peripheral resistance (in blood vessels), the dilation of blood

vessels lowers the peripheral pressure

- Modulating kidneys, by increasing kidney’s excretion of sodium which binds

to water, this will decrease the blood volume in vessels, and thus will

contribute to decreasing blood pressure.

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• Homeostasis: (how could the body react to high blood preesure?)

- Renin-Angiotensin, kidney cells (extra: juxtaglomerular cells) secretes renin in

response to the drop in the blood pressure, renin will convert

angiotensinogen into angiotensin I which will be converted to angiotensin II,

angiotensin II has many effects,

o one of which is vasoconstriction when it binds to angiotensin II

receptor on vascular smooth muscle, this will lead to an increase in

the blood pressure.

o the release of aldosterone, which will induce sodium and water

reabsorption.

- ADH, it responds to low blood volume, by inducing H2O reabsorption, to

maintain fluid and pressure of blood.

Extra physiology note: (YOU CAN SKIP) ADH is secreted in response to atrial-

hypothalamic reflex, pulmonary artery is sensitive to changes in volume, when

the pressure is high, ADH will affect the volume through its effect on urine

output and as a result it will change the pressure, ADH is known as

(Vasopressin) because it is a strong vasoconstrictor.

- Baroreceptor-reflex, Baroreceptor-reflex, baroreceptors (they are also

known as stretch receptors), these receptors sense the changes in blood

pressure, when blood pressure falls, these baroreceptors sense this change,

and transmit signals to centers in the brain, then feedback signals are sent via

the autonomic nervous system to the circulation which will result in

vasoconstriction and thus an increase blood pressure back to normal, e.g;

Orthostatic Hypotension, the blood pressure falls when the person (usually

elderly) suddenly stands up from a lying or sitting position (pooling of blood

in veins), this will decrease blood pressure momentarily, baroreceptors will

sense the tone and the volume of the blood vessels, and will eventually result

in an increase the blood pressure again, this response is called the

baroreceptor reflex. this baroreflex-driven change in heart rate, can be

associated with tachycardia (this is why taking some anti-hypertensive drugs

- Modulating autonomic nervous system.

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can lead to tachycardia. (because baroreflex also affects the heart rate, we

will talk about this in more details in the physiology lectures).

Extra physiology note; (YOU CAN SKIP)

- Baroreceptors are very sensitive to high blood pressure.

- how they could they affect heart rate? baroreceptors can be found on the aortic arch -and

carotid-, when baroreceptors sense any change in blood pressure, they will start send their

signals, remember that the heart is supplied by both parasympathetic (through the vagus)

and sympathetic nerves, they send sensory signals to the cardiovascular center in the brain

which is divided into cardio-acceleratory and cardioinhibitory, which are associated with the

sympathetic and vagus respectively, consequently, they will change cardiac output, stroke

volume and heart rate to adjust the pressure to become normal

rNOTE: chronic hypertension can lead to changes in the body, and as a result, the body of the

hypertensive patient will have a different set-point when compared with normal people,

meaning that the person would develop reflexes but at a much higher pressure.

(especially those with kidney diseases)

extra physiology: (YOU CAN SKIP) the different set-point is the reason why baroreceptors only

work for short-term increase in blood pressure, but when it comes to long-term/ chronic

hypertension, there would be other mechanisms to cope with the situation.

CLASSES ANTIHYPERTENSIVE DRUGS:

- Diuretics (they will be covered in detail in the urogenital system)

- Calcium channel blockers

- Beta blockers

- Angiotensin converting enzyme (ACE) inhibitors (ACEI)

- Angiotensin Receptor Blockers (ARBs)

- Central alpha 2-adrenergic receptor agonists

- Adrenergic neuron blocking agents

- Peripheral alpha-1 or (beta) -adrenergic antagonists - Vasodilators.

BEST OF LUCK!!