CARDIOVASCULAR DISEASE

AND
HYPERTENSION
Report by: Crystal Ann del Castillo
 CASE STUDY

A 35-year old man presents with a blood pressure

of 150/95 mmHg. He has been generally healthy,
is sedentary, drinks several cocktails per day, and
does not smoke cigarettes. He has a family history
of hypertension, and his father died of a
myocardial infarction at age 55. Physical
examination is remarkable only for moderate
obesity. Total cholesterol is 220, and high-density
lipoprotein (HDL) cholesterol level is 40 mg/dL.
Chest x-ray is normal. Electrocardiogram shows
left ventricular enlargement.
 CARDIOVASCULAR DISEASE
AND
HYPERTENSION

1. HTN is the most common cardiovascular disease.

- abnormal elevation of blood pressure in a
given individual
- usually asymptomatic initially
- can lead to myocardial infarction, heart
failure, stroke,
kidney disease.
2. HEART FAILURE
3. CARDIAC ARRYTHMIA
4. ANGINA PECTORIS
 HYPERTENSION

Classification Systolic Diastolic

NORMAL < 120 < 80

PRE-
HYPERTENSION
120 139 80 89
STAGE 1 140 159 90 99
STAGE 2 > 160 > 100
 HYPERTENSION

Blood Pressure BP = CO x TPR

Cardiac Output (CO)

= SV x HR
- determines your systolic pressure
- amount of blood pump from heart/min
- influenced by HR, contractility, and blood volume
- Stroke volume is a volume of blood ejected by the
ventricle during each contraction (70mL/beat)
- Heart Rate is the number of heartbeats per minute
(75 beats/min)
 HYPERTENSION

Blood Pressure BP = CO x TPR

Total Peripheral Resistance (TPR)

- determines your diastolic pressure
- determined by vasoconstriction

STRATEGY:
CO or TPR

TARGET:
<140/90 (<120/<80)
130/80 (with diabetes or renal disease)
 HYPERTENSION

Etiology:
90% have an unknown origin affecting the blood
pressure regulating mechanism.

Risk factors for HTN:

- Family history
- blacks > whites
- middle-age males > middle-age females
- age

Environmental factor:
- stressful &/or sedentary lifestyle
- smoking
- high intake of sodium
 HYPERTENSION

Treatments:

Diuretics
Blockers
Angiotensin-Converting Enzyme inhibitors
Angiotensin 2-Receptor Antagonists
Renin Inhibitors
Ca++ Channel Blockers
Blockers
Others
 HYPERTENSION

DIURETICS
Subtypes:
o Thiazide Diuretics
eg. Hydrochlorothiazide (prototype) MOA: Blocks Na/Cl transporter in renal
distal convoluted tubule
- Effects: Reduce blood volume and
poorly
understood vascular effects
- Clinical Applications: HTN, mild heart
failure
o Loop Diuretics
eg. Furosemide (prototype) MOA: Blocks Na/K/Cl++ transporter in renal
loop of Henle
- Effects: Reduce blood volume and poorly
understood vascular effects (greater efficacy)
- Clinical Applications: Severe HTN, heart
failure
 HYPERTENSION

o Potassium-Sparing Diuretics
eg. Spironolactone (prototype) MOA: Blocks aldosterone receptor in renal collecting
tubule
- Effects: Increase Na and decrease K excretion (poorly

understood reduction in heart failure mortality)

- Clinical Applications: Aldosteronism, heart failure,
HTN
o Osmotic Diuretics MOA: Osmotic effect in proximal convoluted tubule & thin
descending limb of loop of Henle, oppose the action of ADH
(Anti-diuretic Hormone) in the collecting tubule. There is
inhibition of water and Na reabsorption
- Clinical Applications: Acute renal failure, glaucoma, cerebral
edema
- Prototype: Mannitol
o Carbonic Anhydrase Inhibitors MOA: Prevent carbonic acid reabsorption by inhibition
of carbonic anhydrase activity
- Clinical Applications: Glaucoma
- Prototype: Acetazolamide
 HYPERTENSION

Diuretics

Actions
increases sodium & water excretion
Therapeutic uses
useful in combination with other antihypertensive drugs
Pharmacokinetics
orally active
can be given IV
Adverse effects
hypokalemia (thiazide, loop)
hyperkalemia (K+ sparing)
hypotension (common w/ IV use)
 HYPERTENSION
Blockers

Actions
decrease heart rate, contractility, decreases cardiac output
inhibit renin release (block stimulation of renin secretion)

* Selectivity (cardioselectivity) refers to the ability of a drug to preferentially block

the beta-1.

Therapeutic uses
more effective in the young compared to older pxs
useful in treating conditions that co-exists w/ HTN

Pharmacokinetics
orally active, take several weeks to develop full effects
Adverse effects
bradycardia, hypotension
fatigue & insomnia
decrease libido & cause impotence
 HYPERTENSION

Nonselective
Propranolol (prototype)
Nadolol
Timolol
Penbutolol
Carteolol
Carvedilol
Labetalol

Note: Nonselective cant be given in px with asthma

Selective
Bisoprolol
Esmolol
Atenolol
Metoprolol
Betaxolol

Note: Cardioselective Beta-blockers is NOT preferred for use by hypoglycemic agents.

This acts on Beta-1 receptors.
 HYPERTENSION

ACE Inhibitors

Actions
reducing peripheral vascular resistance, w/o increasing cardiac output,
rate or contractility
decrease the secretion of aldosterone
Therapeutic uses
more effective in whites & young patients
slow progression of DM nephropathy
also used in HF, MI

Adverse effects
dry cough, rash & fever
hyperkalemia
hypotension
fetotoxic
 HYPERTENSION

Prototype Drug: Captopril (Capoten)

ACE inhibitors main mechanism is to block the

conversion of angiotensin I to angiotensin II. They
thereby lowerarteriolarresistance and increase
venous capacity; decreasecardiac output,
cardiac index, stroke work, andvolume; lower
resistance in blood vessels in the kidneys; and lead
to increasednatriuresis(excretion of sodium in the
urine). Renin increases in concentration in the
blood as a result of negative feedback of conversion
of Angiotensin I to Angiotensin II. Angiotensin I
increases for the same reason; Angiotensin II and
aldosterone decreases. Bradykinin levels increase
because of less inactivation by ACE.
 HYPERTENSION

Angiotensin II Receptor Antagonist

Actions
blocks the AT1 receptors
causes arteriolar & venous dilatation, blocks
aldosterone
Therapeutic uses
decreases nephrotoxicity of DM
ARBs do not increase bradykinin levels
Adverse effects
fetotoxic
hypotension
lesser angioedema
 HYPERTENSION

Prototype Drug: Losartan (Cozaar)

ARBs main mechanism of action: selective inhibition

of angiotensin II by competitive antagonism of the
angiotensin II receptors, has been speculated to
reduce adverse effects and possibly improve clinical
efficacy. ARBs displace angiotensin II from the
angiotensin I receptor and produce their blood
pressure lowering effects by antagonizing angiotensin
II - induced vasoconstriction, aldosterone release,
catecholamine release, arginine vasopressin release ,
water intake, and hypertrophic response.
 HYPERTENSION

Renin Inhibitors
ALISKERIN
Actions
directly inhibits renin
Therapeutic uses
can be used in combination with other antihypertensives
Adverse effects
diarrhea
less cough & angioedema
contraindicated with pregnancy
hyperkalemia
 HYPERTENSION

Calcium-Channel Blockers

MOA: vasodilation decrease TPR

Negative inotropic/chronotropic effect decrease CO by blocking
calcium influx.
S/E: headache, flushing, dizziness, peripheral edema (Nifedipine),
constipation (Verapamil).

Diphenylalkylamines
VERAPAMIL
Benzothiazepines
DILTIAZEM
Dihydropyridines
NIFEDIPINE
AMLODIPINE
FLODIPINE
NICARDEPINE
 HYPERTENSION

Calcium-Channel Blockers

Actions
blocks the inward movement of calcium in the heart & coronary
& peripheral blood vessels
Therapeutic uses
have an intrinsic natriuretic effect
for HTN patients who have asthma, diabetes, angina
Pharmacokinetics
short half-lives after oral dose

Adverse effects
constipation, should be avoided in patients with CHF & AV
blocks (verapamil)
dizziness, headache, fatigue (dihydropyridines)
 HYPERTENSION

Centrally-Acting Agents
CLONIDINE
Actions
diminishes central adrenergic outflow
Therapeutic uses
used primarily for the treatment of HTN that has not
responded adequately with 2 or more drugs
useful in the treatment of HTN complicated by renal disease
Therapeutics
absorbed well after oral administration and excreted by the
kidneys
Adverse effects
may cause sodium & water retention
sedation & drying of the nasal mucosa
 HYPERTENSION

-Adrenergic Blockers
TERAZOCIN
Actions
relaxation of both arterial & venous smooth
muscle
Therapeutic uses
used to treat mild moderate HTN
Adverse effects
postural HTN
reflex tachycardia & first-dose syncope
 HYPERTENSION

Centrally-Acting Agents
METHYLDOPA
Actions
converted to methylnorepinephrine centrally to
diminish the adrenergic outflow from the CNS
Therapeutic uses
useful in the treatment of hypertensive patients
with renal insufficiency
used in hypertensive pregnant patients
Adverse effects
sedation & drowsiness
 CARDIOVASCULAR DISEASE
AND
HYPERTENSION

1. HYPERTENSION
2. HEART FAILURE
- complex clinical syndrome that can result from any
cardiac disorder that
impairs the ability of the ventricle to deliver adequate
quantities of blood to
the metabolizing tissues during normal activity or at
rest.
3. CARDIAC ARRYTHMIA
4. ANGINA PECTORIS
 HEART FAILURE

- heart is unable to pump sufficient blood

- sign & symptoms are dyspnea, fatigue & fluid retention

- accompanied by abnormal increases in blood volume &

interstitial fluid

- Usual causes are arteriosclerosis, MI, HTN, VHD, CHD

and dilated cardiomyopathy

Causes:
1. Impaired contraction < MI, arrhythmia
2. Increased work load <- HTN
 HEART FAILURE

MOA:

physiologic compensatory mechanism by

activation of the sympathetic nervous
system & the renin- angiotensin-
aldosterone axis
this mechanisms are associated with
remodelling of the cardiac tissue (loss of
myocytes, hypertrophy and fibrosis)
heart becomes less elliptical and more
spherical
 HEART FAILURE

beneficial effects on treatment:

Reduction of the myocardial load

Decreased extracellular fluid volume
Improved cardiac contractility
Slowing the rate of cardiac
remodelling

treatment goals are to alleviate symptoms,

slow disease progression and improve
survival
 HEART FAILURE

Treatments:

1. Inhibitors of the Renin-Angiotensin

system
2. -adrenoreceptor blockers
3. Diuretics
4. Inotropic agents
5. Direct vasodilators
6. Aldosterone antagonists
HEART FAILURE
HEART FAILURE
 HEART FAILURE

ACE Inhibitors
- Agents of choice in HF (with diuretics and digitalis)
- Blocks ACE, Increased bradykinin levels
vasodilation
- Suppress aldosterone diuresis
- Should be taken on an empty stomach

ARBs
- Similar actions with ACEIs but NOT therapeutically
identical
- Do not affect bradykinin levels
- Alternative to ACEIs
 HEART FAILURE

Beta-Blockers
- Tx should be started at low doses and gradually
titrated
- Additional benefit of antihypertensive action
- Metoprolol: long acting, B1 selective antagonist,
management of HF
- Carvedilol: Management of chronic HF
(nonselective)

Diuretics
- Loop Diuretics: most commonly used in HF
 HEART FAILURE

Direct Vasodilators
- Dilation of venous blood vessels leads to a decrease in
cardiac preload
- Agents: NITRATES (Isosorbide dinitrate, Isosorbide
mononitrate, Sodium nitroprusside) which is commonly
used venous dilators for px with congestive heart failure
- Hydralazine, Prazosin

Inotropic Agents
- Increase force of contraction, increase CO due to
increased cytoplasmic Ca2+ concentration that
enhances the contractility of cardiac muscle
- Agents: Digoxin, Dobutamine (Beta-adrenergic agonist),
Inamrinone (Phosphodiesterase inhibitors), Milrinone
 CARDIOVASCULAR DISEASE
AND
HYPERTENSION

1. HYPERTENSION
2. HEART FAILURE
3. CARDIAC ARRHYTHMIA
- irregular heart beat rhythm
- deviations from the normal heartbeat pattern
4. ANGINA PECTORIS
 CARDIAC ARRHYTHMIA

normal HR is between 60 100 beats per minute

heart beats regularly but may be too slow (bradycardia), too

rapid (tachycardia)

may be irregularly (atrial fibrillation), if too slow

(bradyarrythmia), or too rapid (tachyarrythmia)

location may be in the atrium (atrial tachycardia), ventricles

(supraventricular tachycardias)

They include:

Abnormalities of impulse formation

Abnormalities in impulse conduction
 CARDIAC ARRHYTHMIA

ELECTROPHYSIOLOGY (CONDUCTION SYSTEM OF THE

HEART)

o Small electric current starts from the SA node

o Atria contract and pump blood to the ventricles
o Current travels to the AV node (behind the tricuspid
valve)
o Current spreads to the bundle of His and Purkinje fibers
o Ventricles contract and pump blood out of the heart
 CARDIAC ARRHYTHMIA

MYOCARDIAL ACTION POTENTIAL

cardiac cells must depolarize and repolarize before contraction
can take place

the electric currents that make up the cardiac potentials are due
to the flow of ions across cell membrane

Phase 0: sodium influx

Phase 1: potassium efflux
Phase 2: calcium influx balanced with potassium efflux
Phase 3: potassium efflux
Phase 4: returns to resting membrane potential (potassium in,
sodium out)
CARDIAC ARRHYTHMIA

DRUG
MECHANISM OF
CLASS COMMENT
ACTION
ES
Na+ channel
Slows Phase 0 depolarization in the
IA blocker
ventricles
(moderate)
Na+ channel Shortens Phase 3 repolarization in the
IB blocker (weak) ventricles
Na+ channel Markedly slows Phase 0 depolarization
IC blocker (strong) in the ventricles
-Adrenergic Inhibits Phase 4 depolarization in SA &
II blockers AV nodes
K+ channel Prolongs Phase 3 repolarization in the
III blocker ventricles
Ca++ channel Inhibits action potential in SA & AV
IV
CARDIAC ARRHYTHMIA
 CARDIOVASCULAR DISEASE
AND
HYPERTENSION

1.HYPERTENSION
2.HEART FAILURE
3.CARDIAC ARRHYTHMIA
4.ANGINA PECTORIS
- one of the types (CAD) of an ischemic heart disease
- most common form of IHD
- applied to varying forms of transient chest discomfort
that are
attributable to insufficient myocardial oxygen
- chest pain
 ANGINA PECTORIS

sudden, severe, pressing chest pain radiating

to the neck, jaw, back and arms

caused by a coronary blood flow that is

insufficient to meet the oxygen demands of the
heart, leading to ischemia

may result during exertion, vascular spasm &

obstruction of blood flow

transient & does not cause cell death

 ANGINA PECTORIS

lifestyle changes & risk factors modification

are important in its management

options: other than medications include

angioplasty or coronary artery bypass surgery
 ANGINA PECTORIS

Types:
Stable angina

Unstable angina

Prinzmetals or variant or vasospastic angina

Mixed form of angina

ANGINA PECTORIS

Types:
Stable angina
- most common form
- burning, heavy or squeezing feeling
in the chest
- caused by reduced myocardial
perfusion due to a fixed
obstruction
- promptly relieved by rest or nitrates

Unstable angina
Prinzmetals or variant or
vasospastic angina
Mixed form of angina
ANGINA PECTORIS

Types:
Stable angina

Unstable angina
- increasing frequency of chest pain
- precipitated by progressively less
effort
- symptoms not relieved by rest or
nitrates

Prinzmetals or variant or
vasospastic angina
Mixed form of angina
ANGINA PECTORIS

Types:
Stable angina
Unstable angina

Prinzmetals or variant or
vasospastic angina
- uncommon pattern of episodic angina
that occurs
at rest
- due to coronary spasm
- attacks are unrelated to physical
activity, HR or BP
- responds to nitrates & Calcium-
channel blockers
ANGINA PECTORIS

Types:
Stable angina
Unstable angina
Prinzmetals or variant or
vasospastic angina

Mixed form of angina

- seen in advanced coronary artery
disease
- episodes occur during effort & at rest
ANGINA PECTORIS
 CASE STUDY

A 35-year old man presents with a blood pressure of

150/95 mmHg. He has been generally healthy, is
sedentary, drinks several cocktails per day, and does
not smoke cigarettes. He has a family history of
hypertension, and his father died of a myocardial
infarction at age 55. Physical examination is
remarkable only for moderate obesity. Total
cholesterol is 220, and high-density lipoprotein (HDL)
cholesterol level is 40 mg/dL. Chest x-ray is normal.
Electrocardiogram shows left ventricular enlargement.
 CASE STUDY

Subjective Data:

Generally healthy
Sedentary
Drinks several cocktails per day
Does not smoke cigarettes
He has a family history of hypertension
His father died of a myocardial infarction at age
55
 CASE STUDY

Objective Data:

Physical Examination
Diagnostic Laboratory Results
Total cholesterol is 220
High-density lipoprotein (HDL) cholesterol level
is 40 mg/dL.
Chest x-ray is normal.
Electrocardiogram shows left ventricular
enlargement
 CASE STUDY

BLOOD CHEMISTRY NORMAL VALUES

Cholesterol 4.2 5.2 mmol/L
LDL 1.1 5.8 mmol/L
(Low-Density
Lipoprotein)
HDL 0.830 2.490 mmol/L
(High-Density
Lipoprotein)
 Total Cholesterol Level
Category
(Normal Value Reference)
Less than 200mg/dL Desirable
200-239 mg/dL Borderline high
240mg/dL and above High

LDL (Bad) Cholesterol Level LDL Cholesterol Category
Less than 100mg/dL Optimal
100-129mg/dL Near optimal/above optimal
130-159 mg/dL Borderline high
160-189 mg/dL High
190 mg/dL and above Very High

HDL (Good) Cholesterol Level HDL Cholesterol Category
A major risk factor for heart
Less than 40 mg/dL
disease
4059 mg/dL The higher, the better
Considered protective against
60 mg/dL and higher
 CASE STUDY

The patient has stage I hypertension. Cardiovascular risk

factors in this man include family history of early
coronary disease and elevated cholesterol. Evidence of
end-organ impact includes left ventricular enlargement
on EKG. The strong family history suggests that this
patient has essential hypertension. However, the patient
should undergo the usual screening tests including renal
function, thyroid function, and serum electrolyte
measurements. An echocardiogram should also be
considered to determine whether the patient has left
ventricular hypertrophy secondary to valvular or other
structural heart disease as opposed to hypertension.
 CASE STUDY

Initial management in this px can be bahavioral, includig dietary changes

and aerobic exercise. However, most pxs like this will require medication.

Thiazide diuretics in low doses, inexpensive, few side effects,

effective in many px with mild HTN
Other first-line agents (ACE Inhibitors and Calcium channel blockers).
Beta-blockers might considered if px had coronary disease/labile HTN

A single agent should be prescibed and the px reassesed in a month. If a

second agent is needed, one of the two agents should be a thiazide
diuretic. Once bp is controlled, px should be followed periodically to
reinforce the need for compliance with both lifestyle changes and
medications.
 THE END

GODBLESS AND THANK YOU!

 QUIZ

1-4. What are some of the cardiovascular disorders?

5. What is the normal BP of a px?
6. This is an asymptomatic type of a cardiovascular
disorder.
7. T/F. One of the major side effect of ARBs is dry cough.
8. Drug of choice for Prinzmetal type of angina.
9. Also known as chest pain.
10-13. What are the types of angina pectoris?
14. Symptoms by this type of angina are not relieved by
nitrates?
15. Explain the differences between ACE Inhibitors and
ARBs according to their mechanism of action.
 ANSWERS

1-4. HTN, Arrhythmia, Angina, Heart Failure

5. <120/<80 mmHg
6. HTN
7. F
8. Ca++ channel blockers
9. Angina pectoris
10-13. Stable, Unstable, Prinzmetals, Mixed form of Angina
14. Unstable Angina
15. They have the same clinical applications/action but their MOA and effects are different.
ACE Inhibitors inhibit angiotensin converting enzyme thus as an effect, reducing angiotensin
II levels, reduce vasoconstriction and aldosterone secretion, increasing resulting to a decrease
in Na and H20 retention thereby reducing bp and CO. There is an increase in bradykinin
levels. Whereas ARBs, inhibit the AT1 receptors thus as an effect, reducing angiotensin II
levels, reduce vasoconstriction and aldosterone secretion, increasing resulting to a decrease
in Na and H20 retention thereby reducing bp and CO. There is NO decrease in bradykinin
levels.