Cvs drugs new

Cardiovascular DrugsCardiovascular Drugs
Dra. Hena W. Alcantara

The Cardiovascular SystemThe Cardiovascular System
• Heart
• Blood
• Blood Vessels
–Arteries
–Veins
–Capillaries

In simple terms…In simple terms…
• The heart is a pump.
• It pumps blood through a system of
blood vessels that has a limited
volume capacity.
• An electric conduction system
maintains regular rate and rhythm.
• Myocardial cells require oxygen.

MalfunctionsMalfunctions
when the heart can
no longer pump
enough blood to
meet the metabolic
demands of the
body
HEART FAILURE
when blood
volume is great
compared to the
space available
inside blood
vessels
HYPERTENSION

when the electrical
conduction
pathways
malfunction
ARRHYTHMIA
the heart’s way of
signaling that
some of the cells
are not getting
enough oxygen
ANGINA

when oxygen-
starved areas of
the heart begin
dying
MYOCARDIAL
INFARCTION
when you broke
with someone…

• Anti-hypertensives
• Drugs for Heart Failure
• Anti-anginal and Drugs for MI
• Anti-arrhythmic Agents

Anti-Hypertensive DrugsAnti-Hypertensive Drugs

Physiology of BP RegulationPhysiology of BP Regulation
• Hydraulic Equation:
BP = CO x TPR

Blood
Pressure
Heart
Rate
Low Blood Pressure
Low Blood Volume
Na+
depletion
Angiotensin I
Sympathetic AdrenergicSympathetic Adrenergic
SystemSystem
Pituitary
Gland
Na+
& H2O
Reabsorption
Aldosterone
Blood
Volume
Rises
Venous
Return
x
Stroke
Volumex
Renin –Renin –
AngiotensinAngiotensin
SystemSystem
Angiotensin II
ACE
vasoconstriction
=
Factors that alter the Blood Pressure EquationFactors that alter the Blood Pressure Equation
Kidney
Renin
Cardiac
Output
Total Peripheral
Arterial Resistance

Determinants of BloodDeterminants of Blood
PressurePressure
• Cardiac Output (CO)
–volume of blood pumped out by the
heart in 1 minute
–approximately 2.2 – 3.5 L / min / m2
BSA
–determined by Stroke Volume (SV) and
Heart Rate (HR)

• Stroke Volume (SV)
–volume of blood pumped out by the
heart in every contraction
–determined by:
• Inotropic activity –strength of cardiac
contraction
• Venous return – cardiac preload; amount of
blood delivered to the heart from the veins;
affected by the tone of the veins
PressurePressure

• Heart Rate (HR)
–speed of heart contraction
–chronotropism
• Fluid Content of the Blood
• Total Peripheral Resistance (TPR)
– resistance or pressure encountered by
the heart as it pumps out blood into the
peripheral circulation (cardiac afterload)
–determined by the arterioles
PressurePressure

Mechanisms of BPMechanisms of BP
RegulationRegulation
• Baroreceptor Reflex Arch Mechanism
–aka: Postural Reflex Mechanism
–moment-to-moment BP regulation
• Baroreceptor – a type of sensory nerve
ending found in the walls of the atria of the
heart, the vena cava, the aortic arch, and
the carotid sinus that is stimulated by
changes in pressure
• Renin Angiotensin Aldosterone

Angiotensinogen (from the liver)
Renin
Angiotensin I (inactive)
Angiotensin Converting Enzyme (ACE)
or
Peptidyl dipeptidase
(majority found in the lungs)
Angiotensin II (active)
-direct vasoconstriction
-stimulates synthesis & release of Epi & NE
-stimulates the synthesis & release of
aldosterone
Renin Angiotensin AldosteroneRenin Angiotensin Aldosterone
System (RAAS)System (RAAS)

HypertensionHypertension
• persistent or recurrent elevation of BP
defined as having a:
–Systolic reading > 140 mmHg
–Diastolic reading > 90 mmHg
–BP > 140/90
• most common cardiovascular
disorder

• Systole
–the period during which the ventricles
are contracting
• Diastole
–the period during which the ventricles
are relaxed and filling with blood

• Essential (Primary, Idiopathic)
– hypertension with no identifiable cause
– accounts for > 90% of HTNsive cases
• Secondary
– resulting from identifiable causes
• kidney diseases
• adrenal cortical disorders
• pheochromocytoma (adrenal medulla tumor)
• coarctation of the aorta
• drugs such as steroids, sympathomimetics, contraceptives
– treat the underlying cause
– accounts for ~ 10% of HTNsive cases

Classification of BP based on the 7Classification of BP based on the 7thth
Report of theReport of the
Joint National Committee on Detection, EvaluationJoint National Committee on Detection, Evaluation
and Treatment of High Blood Pressure (JNC VII)and Treatment of High Blood Pressure (JNC VII)
Classification of Blood Pressure (JNC VII)
Systolic BP, mm Hg Diastolic BP, mm
Hg
Normal <120 and <80
Prehypertension 120-139 or 80-89
Stage 1 hypertension 140-159 or 90-99
Stage 2 hypertension >160 or >100
Adapted from JNC VII

Hypertensive EmergencyHypertensive Emergency
• aka: Hypertensive Crisis
• rare, but life-threatening situation
• systolic pressure > 210 mm Hg
• diastolic pressure > 150 mm Hg

Risk FactorsRisk Factors
• Family history
• Patient history
• Racial predisposition
– More common in blacks
• Obesity
• Smoking
• Stress
• High dietary intake
– Saturated fats and
sodium
• Sedentary lifestyle
• DM
• Hyperlipidemia
• Gender – males
• Age > 60
• Postmenopausal
women

Treatment GoalsTreatment Goals
• Rule out uncommon secondary causes of
hypertension
• Determine the presence and extent of
target organ damage
• Determine the presence of other CV risk
factors
• To lower BP with minimal side effects

ComplicationsComplications
• Cardiac effects
– Increased oxygen requirements  angina pectoris;
because of atherosclerosis  angina, MI, sudden death
• Renal effects
– Increased blood volume; renal parenchymal damage due
to atherosclerosis
• Cerebral effects
– Transient ischemic attacks, cerebral thromboses,
aneurysms with hemorrhage
• Retinal effects
– Visual defects (blurred vision, spots, blindness)

TreatmentTreatment
• First line: diuretics (thiazides) and beta blockers
• Alternatives: ACE inhibitors, ARBs, alpha blockers, calcium-
channel blockers  for px who cannot tolerate first line
agents
• Monitor:
– blood pressure routinely
– observe adverse effects
• Patient Counseling:
– Importance of compliance  make px realize seriousness
of noncompliance

Anti-hypertensivesAnti-hypertensives
• Diuretics
• Sympathoplegics
• Vasodilators
• Calcium Channel Blockers (CCBs)
• ACE Inhibitors
• Angiotensin II Receptor Blockers
(ARBs)

DiureticsDiuretics
• agents that cause urinary loss of Na+
and H2O
• Gen MOA: act on their specific sites
in the renal tubule

Five major classesFive major classes
1. Thiazides and thiazide-like
2. Loop diuretics
3. Potassium-sparing
4. Carbonic anhydrase inhibitors
5. Osmotic diuretics

Carbonic AnhydraseCarbonic Anhydrase
InhibitorsInhibitors
• MOA: inhibit carbonic anhydrase (the
enzyme that catalyzes the reaction of
CO2 and H2O leading to H+
and HCO3
-
)
that can lead to the spillage of Na+
causing diuresis.
• act on the proximal convoluted tubule
(PCT)

• Acetazolamide
• Brinzolamide
• Dorzolamide

• limited diuretic effect (2 to 3 days)
• SE: metabolic acidosis, bone marrow
depression (sulfonamide-like toxicity),
allergic reactions (Stevens-Johnson’s
Syndrome)

Loop DiureticsLoop Diuretics
• aka: High Ceiling Diuretics
• high ceiling (most efficacious) as
compared with other diuretics
• act on the thick ascending Loop of
Henle

• MOA: inhibit the Cl-Na-K-
cotransporter at the thick ascending
LOH
• Furosemide
• Bumetanide
• Torsemide
• Ethacrynic acid

• for px who cannot tolerate thiazides,
have renal impairment, or
ineffectiveness of thiazides
• SE: hypovolemia, ototoxicity, increase
serum creatinine
• DI: their efficacy can be reduced by
NSAIDs

• Side-effects
–Hypokalemia
–Bicarbonate is lost in the urine
–INCREASED calcium excretion
Hypocalcemia
–Ototoxicity
• due to the electrolyte imbalances

Thiazide DiureticsThiazide Diuretics
• MOA: inhibit Na-Cl-cotransporter at
the distal convoluted tubule
• Chlorothiazide
• Hydrochlorothiazide
• Chlorthalidone
• Indapamide

• first-line drug for uncomplicated
hypertension as recommended by
JNC 7
• effective initial therapy together with
beta-blockers
• also used for Nephrogenic Diabetes

• SE: hypokalemia, hyponatremia,
hyperuricemia, hyperglycemia,
hyperlipidemia
• DI: their efficacy can be reduced by
NSAIDs

ThiazideThiazide
• Side effects
–Hypokalemia
–DECREASED calcium
excretion hypercalcemia
–DECREASED uric acid
secretion hyperuricemia
–Hyperglycemia

Potassium-Sparing DiureticsPotassium-Sparing Diuretics
• MOA: act in the collecting tubule by
inhibiting Na+
reabsorption, K+
secretion and H+
secretion
• Spironolactone
• Eprenolone
• Amiloride
• Triamterene

• for patients where potassium loss is
significant and supplementation is not
feasible
• often combined with thiazides 
potentiation
–Amiloride, Spirinolactone, Triamterene
• precautions
–Avoid in px with acute renal failure; use
with caution  px with impaired renal
function

Potassium Rich FoodsPotassium Rich Foods
TOPP PNBB’S

• T- Tomatoes
• O-Oranges
• P- Peaches
• P-potatoes
• P-Prunes
• N-Nuts
• B-Banana
• B-Broccoli
• S-Spinatch

• not associated with hypokalemia
• can be given with other diuretics to
lessen the risk of hypokalemia
• SE: hyperkalemia, gynecomastia,
impotence, sterility

Osmotic DiureticsOsmotic Diuretics
• MOA: increase the osmotic pressure
at the proximal convoluted tubule and
Loop of Henle preventing water
reabsorption
• Mannitol
• Sorbitol
• Urea

Osmotic DiureticsOsmotic Diuretics
• used to induce forced diuresis
• mostly used to reduce intracranial
pressure
• SE: hypernatremia, hypovolemia

Diuretics ComparisonDiuretics Comparison
Diuretic class Major site of action Special Side effect
(s)
1. Carbonic
anhydrase
inhibitor
Proximal tubule Acidosis
2. Thiazide and
thiazide like
Distal tubule Hyperuricemia
Hypokalemia
3. Loop diuretics L p of Henle Hypokalemia
Ototoxicity
4. Potassium
sparing
Distal tubule Hyperkalemia
5. Osmotic
diuretic
Glomerulus Hypovolemia &
hypotension

Diuretics ComparisonDiuretics ComparisonDiuretic class Special Uses
1. Carbonic
anhydrase
inhibitor
Mountain sickness
Meniere’s disease
2. Thiazide and
thiazide like
Nephrolithiasis due to calcium
stones
Hypocalcemia
3. Loop diuretics Hypercalcemia
4. Potassium
sparing
CHF taking digoxin
5. Osmotic
diuretic
Increased ICP
LITHIUM TOXICITY

SympathoplegicsSympathoplegics

• Centrally-acting
• Peripherally-acting
• Alpha-1 blockers
• Beta blockers

Centrally-ActingCentrally-Acting

Centrally-ActingCentrally-Acting
• MOA: act primarily within the CNS on
alpha-2 receptors to decrease
sympathetic outflow to the CVS
• Clonidine
• Methyldopa
• Guanfacine
• Guanabenz

ClonidineClonidine
• MOA: agonist at alpha-2 receptors
(leading to vasodilation)
• effective in patients with renal
impairment
• SE: transient increase in BP,
sedation/depression, rebound

MethyldopaMethyldopa
• reduce TPR with little effect on CO
and blood flow to vital organs (such
as kidneys)
• effective for patients with renal
impairment
• used in the management of HTN in

MethyldopaMethyldopa
• SE: sedation, depression,
hepatotoxicity (at doses >2g / day),
(+) Coomb,s Test*
* Coomb’s Test – indicator of a
possible immune-mediated hemolytic
anemia

Guanfacine, GuanabenzGuanfacine, Guanabenz
• adjunctive therapy to other anti-
HTNsive drugs
• avoided unless necessary to treat
severe refractory HTN that is
unresponsive to other meds

Peripherally-ActingPeripherally-Acting

Peripherally-ActingPeripherally-Acting
• Trimethaphan
• Reserpine
• Guanethidine
• Guanadrel

TrimethaphanTrimethaphan
• ganglionic receptor blocker
• given via IV infusion
• used in hypertensive emergencies
caused by pulmonary edema or aortic
aneurism when other agents cannot
be used

ReserpineReserpine
• plant alkaloid
• inhibits catecholamine (NE, Epi,
Dopamine, Serotonin) storage
• impairs sympathetic function because
of decreased release of
Norepinephrine (NE)

Guanethidine, GuanadrelGuanethidine, Guanadrel
• inhibit the response of the adrenergic
nerve to stimulation or to indirectly-
acting sympathetic amines
• blocks the release of stored
Norepinephrine
• SE: orthostatic hypotension, impaired
male sexual function

Alpha-1 BlockersAlpha-1 Blockers

• MOA: inhibit the alpha-1 receptors,
resulting to vasodilation of arteries
and veins
• Prazosin
• Doxazosin
• Alfazosin
• Terazosin

• alternative drugs for the management
of HTN esp among patients with BPH
• First-Dose Phenomenon:
–orthostatic hypotension
–syncope
–remedy: take the drug at bedtime, slow
increase in dose

Beta BlockersBeta Blockers
• used for the initial therapy of HTN;
effective for patients with rapid resting
HR or concomitant IHD
• MOA
–Block stimulation of renin secretion
–Decrease contractility  decrease CO
–Decrease sympathetic output centrally
–Reduction in HR  reduced CO
–Combination of all

• SE/Precautions/Contraindications:
–can mask hypoglycemia
–CI to patients with bronchospastic
disease: COPD, Bronchial Asthma
–rebound tachycardia and HTN
–easy fatigability
–severe bradycardia and heartblock
(seen esp with concomitant use of
verapamil and diltiazem)

• Selective
B – Betaxolol
B – Bisoprolol
E – Esmolol
A – Acebutolol
A – Atenolol
M – Metoprolol
• Membrane Stabilizing
Activity
– Anesthetic-like effect
– Cannot be given as
ophthalmic drops
P – Propranolol
P – Pindolol
A – Acebutolol
L – Labetalol
M – Metoprolol

• Mixed alpha and
beta blocking
effect
L – Labetalol
C – Carvedilol
• Intrinsic
sympathomimetic
activity
– partial agonist effect
– not usually associated
with rebound
hypertension
A – Acebutolol
B – Bisoprolol
C – Carteolol
P – Pindolol
P - Penbutolol

Nematodes (Roundworms)Nematodes (Roundworms)

VasodilatorsVasodilators
• second-line agents
• directly relax the peripheral vascular
smooth muscles
• not used alone  inc in plasma renin
activity, CO, HR

• common SE: reflex tachycardia,
peripheral edema
• common CI: as single agents, should
be avoided in patients with Ischemic
Heart Disease (IHD)

• Hydralazine
• Diazoxide
• Minoxidil
• Sodium Nitroprusside

HydralazineHydralazine
• used in the management of HTN in
pregnancy
• SE: Lupus-like side effect (drug-
induced SLE or Systemic Lupus
Erythematosus)

DiazoxideDiazoxide
• used in the emergency treatment of
hypertensive crisis

MinoxidilMinoxidil
• most effective arteriolar vasodilator
• SE: hypertrichosis, hirsutism

Sodium NitroprussideSodium Nitroprusside
• metabolized in the body into nitric
oxide (NO) also called EDRF or
Endothelium-Derived Relaxing Factor
• 1st
line drug for almost all types of
HTNsive emergencies

Sodium NitroprussideSodium Nitroprusside
• Caution: use freshly prepared
solutions or admixtures
• protect from light
• SE: thiocyanate or cyanide toxicity,
acute psychosis, severe hypotension,
coma, death

Calcium Channel BlockersCalcium Channel Blockers

(CCBs)(CCBs)
• alternative for the mgt of HTN
• MOA
–Inhibit influx of Ca through the slow
channels in vascular smooth muscle
and cause relaxation

• Dihydropyridine (DHP)
– block Ca channels in the blood vessels
– Nifedipine, Nicardipine, Felodipine,
Amlodipine
• Non-dihydropyridine (Non-DHP)
– block Ca channels both in the heart and blood
vessels
– Verapamil – heart > blood vessels
– Diltiazem – heart = blood vessels
ClassificationClassification

(CCBs)(CCBs)
• SE:
–peripheral edema
–reflex tachycardia (DHP)
–bradycardia (Non-DHP)
–heart block (Non-DHP + Beta Blocker)

Angiotensin Converting EnzymeAngiotensin Converting Enzyme
• MOA: inhibit ACE, thereby preventing the
conversion of angiotensin I into the active
form angiotensin II
• Short-acting
– Captopril
• Long-acting
– Enalapril
– Lisinopril
– Perindopril
Generally, long acting ACE
Inhibitors are prodrugs:
Enalapril Enalaprilat
(prodrug) (active)

• SE:
–idiosyncratic dry cough
ACE
Bradykinin inactive
fragments
(causes cough)
–angioedema
–hyperkalemia
Angiotensin Converting EnzymeAngiotensin Converting Enzyme

Angiotensin II ReceptorAngiotensin II Receptor
BlockersBlockers

Angiotensin II ReceptorAngiotensin II Receptor
Blockers (ARBs)Blockers (ARBs)
• direct inhibitors of angiotensin II receptors
• Losartan, Valdesartan, Candesartan
• clinical use: same as ACE Inhibitors
• Advantage over ACE inhibitors: less
associated with dry cough

1. A friend has very severe hypertension and asks1. A friend has very severe hypertension and asks
about a drugabout a drug her doctor wishes to prescribe. Herher doctor wishes to prescribe. Her
physician has explained that this drug isphysician has explained that this drug is
associated with tachycardia and fluid retention (w/cassociated with tachycardia and fluid retention (w/c
may be marked) and increased hair growth. Whichmay be marked) and increased hair growth. Which
of the following is most likely to produce the effectsof the following is most likely to produce the effects
that your friend has described?that your friend has described?
A. Captopril
B. Guanethidine
C. Minoxidil
D. Prazosin
E. Propanolol

2. A patient is admitted to the emergency2. A patient is admitted to the emergency
department with severe bradycardia following adepartment with severe bradycardia following a
drug overdose. His family reports that he has beendrug overdose. His family reports that he has been
depressed about his hypertension. Each of thedepressed about his hypertension. Each of the
following can slow the heart rate EXCEPTfollowing can slow the heart rate EXCEPT
A. Clonidine
B. Guanethidine
C. Hydralazine
D. Propanolol
E. Reserpine

3. Which one of the following is characteristic of3. Which one of the following is characteristic of
enalapril treatment in patients with essentialenalapril treatment in patients with essential
hypertension?hypertension?
A. Competitively blocks angiotensin II at its
receptor
B. Decreases angiotensin II concentration in the
blood
C. Decreases renin concentration in the blood
D. Increases sodium and decreases potassium in
the blood
E. Decreases sodium and increases potassium in
the urine

4. A pregnant patient is admitted to the4. A pregnant patient is admitted to the
hematology service with moderately severehematology service with moderately severe
hemolytic anemia. After a thorough workup, thehemolytic anemia. After a thorough workup, the
only positive finding is a history of treatment withonly positive finding is a history of treatment with
an antihypertensive drug since 2 months afteran antihypertensive drug since 2 months after
beginning the pregnancy. The most likely cause ofbeginning the pregnancy. The most likely cause of
the patient’s blood disorder isthe patient’s blood disorder is
A. Atenolol
B. Captopril
C. Hydralazine
D. Methyldopa
E. Minoxidil

5. Postural hypotension is a common5. Postural hypotension is a common
adverse effect of which one of theadverse effect of which one of the
following types of drugs?following types of drugs?
A. ACE inhibitors
B. Alpha receptor blockers
C. Arteriolar dilators
D. Beta-selective receptor blockers
E. Nonselective B-blockers

Congestive Heart FailureCongestive Heart Failure

Heart FailureHeart Failure
• is the failure of
the heart as a
pump
• inability of the
heart to pump
sufficient
amount of
blood to the
body

Congestive Heart FailureCongestive Heart Failure
• pumping ability of the heart becomes
impaired
• accompanied by congestion of body
tissues
• etiology
–acute MI, HPN, cardiomyopathies
–excessive work demands on the heart

Forms of CHFForms of CHF
• High-output
– uncommon
– caused by excessive
need for cardiac
output
– high metabolic
demands
• Low-output
– caused by disorders
that impair the
pumping ability of the
heart (IHD)
– normal metabolic
demands, heart
unable to meet them

Forms of CHFForms of CHF
• Right sided
– fatigue
– jugular vein
distension
– liver engorgement
– anorexia, GI distress
– cyanosis
– elevation in
peripheral venous
pressure
– peripheral edema
• Left-sided
– exertional dyspnea
– paroxysmal nocturnal
dyspnea
– cough
– blood-tinged sputum
– cyanosis
– pulmonary edema

Treatment GoalsTreatment Goals
• To remove or mitigate the underlying
cause
• To relieve the symptoms and improve
pump
function by:
– Reducing metabolic demands (rest,
relaxation, pharm’l controls)
– Reduce fluid volume excess (food intake,
meds)
– Administer digitalis and other inotropic
agents
– Promote px compliance and self-regulation
through education

Compensatory MechanismCompensatory Mechanism
• Myocardial Hypertrophy
–long-term compensatory mechanism
–increase in the number of contractile
elements in myocardial cells as a means
of increasing their myocardial
performance
–ventricular remodeling

Compensatory MechanismCompensatory Mechanism
• Frank-Starling Mechanism
–is the intrinsic ability of the heart to
adapt to changing volumes of inflowing
blood
–the greater the heart muscle is stretched
during filling, the greater the force of
contraction and the greater the quantity
of blood pumped into the aorta
–within physiologic limits, the heart
pumps all the blood that comes to it
without allowing excessive damming of

Drugs for CHFDrugs for CHF
• Inotropic Agents
–Cardiac glycosides
–Beta Agonists
–Phosphodiesterase Inhibitors
• Unloaders
–ACE Inhibitors & ARBs
–Beta Blockers
–Diuretics
–Vasodilators

TREATING
CONGESTIVE HEART FAILURE
U
N
L
O
A
D
UPRIGHT POSITION
NITRATES (LOW DOSE)
LASIX
OXYGEN
AMINOPHYLLINE
DIGOXIN
F
A
S
T
FLUIDS (DECREASE)
AFTERLOAD (DECREASE)
SODIUM RESTRICTION
TEST (Dig Level, ABGs, Potassium
Level)

Cardiac GlycosidesCardiac Glycosides
• from Digitalis species
• Digoxin, Digitoxin
• MOA: inhibit the Na-K-ATPase pump
leading to an increase in intracellular
calcium

• Digoxin
– ~75% Bioavailable
– half-life: 36-40
hours
– 20-40% protein
bound
– excreted in the
urine
• Digitoxin
– >90% Bioavailable
– half-life: 168 hours
– >90% protein bound
– excreted in the bile

- have low therapeutic indices
- toxicity can be enhanced by:
- hypokalemia
- hypomagnesemia
- hypercalcemia

ToxicityToxicity
• Cardiac Manifestations
–arrhythmias (ventricular tachycardia)
–cardiac death
• Extra-cardiac Manifestations
–GI disturbances (nausea & vomiting)
–visual disturbances (blurred vision,
alteration of color perception, haloes on
dark objects)

Management of ToxicityManagement of Toxicity
• give potassium supplement
• give digitalis antibodies (FAB
fragments)
• for arrhythmias, give lidocaine or
amiodarone

Beta-1 AgonistsBeta-1 Agonists
• Dopamine
• Dobutamine
• MOA: increase intracellular cAMP,
which results in the activation of
protein kinase, that leads to an
increase in intracellular calcium

DobutamineDobutamine
• given as an IV infusion
• primarily used in the management of
acute heart failure in the hospital
setting

Phosphodiesterase InhibitorsPhosphodiesterase Inhibitors
• MOA: inhibits the enzyme
phosphodiesterase which hydrolyses
cAMP , thereby prolonging the action
of protein kinase
• Amrinone
• Milrinone

UnloadersUnloaders
• ACE Inhibitors & ARBs
– preload and afterload unloaders
– vasodilating effect
– Captopril, Enalapril
• Beta Blockers
– vasodilating effect
– Metoprolol, Misoprolol, Carvedilol
• Diuretics
– preload unloaders
– Spironolactone
• Vasodilators

1. Drugs that have been found to be useful in one1. Drugs that have been found to be useful in one
or more types of heart failure include all of theor more types of heart failure include all of the
following EXCEPTfollowing EXCEPT
A. Na+/K+ ATPase inhibitors
B. Alpha-adrenoceptor agonists
C. Beta-adrenoceptor agonists
D. ACE inhibitors

2. The mechanism of action of digitalis is2. The mechanism of action of digitalis is
associated withassociated with
A. A decrease in calcium uptake by the
sarcoplasmic reticulum
B. An increase in ATP synthesis
C. A modification of the actin molecule
D. An increase in systolic intracellular calcium
levels
E. A block of cardiac B adrenoceptors

4. A 65-year old woman has been admitted to the4. A 65-year old woman has been admitted to the
coronary care unit with a left ventricular myocardialcoronary care unit with a left ventricular myocardial
infarction. If this patient develops acute severeinfarction. If this patient develops acute severe
heart failure with mark pulmonary edema, whichheart failure with mark pulmonary edema, which
one of the following would be most useful?one of the following would be most useful?
A. Digoxin
B. Furosemide
C. Minoxidil
D. Propanolol
E. Spironolactone

6. Drugs associated with clinically useful or6. Drugs associated with clinically useful or
physiologically important positive inotropic effectsphysiologically important positive inotropic effects
include all of the following EXCEPTinclude all of the following EXCEPT
A. Amrinone
B. Captopril
C. Digoxin
D. Dobutamine
E. Norepinphrine

7. Successful therapy of heart failure with digoxin7. Successful therapy of heart failure with digoxin
will result in which one of the following?will result in which one of the following?
A. Decreased heart rate
B. Increased afterload
C. Increased aldosterone
D. Increased renin secretion
E. Increased sympathetic outflow to the heart

8. Which of the following has been shown to8. Which of the following has been shown to
prolong life in patients with chronic congestiveprolong life in patients with chronic congestive
failure but has a negative inotropic effect onfailure but has a negative inotropic effect on
cardiac contractility?cardiac contractility?
A. Carvedilol
B. Digoxin
C. Dobutamine
D. Enalapril
E. Furosemide

10. Which of the following is the drug of choice in10. Which of the following is the drug of choice in
treating suicidal overdose of digitoxin?treating suicidal overdose of digitoxin?
A. Digoxin antibodies
B. Lidocaine
C. Magnesium
D. Phenytoin
E. Potassium

Coronary Artery DiseasesCoronary Artery Diseases
(CAD)(CAD)
oror
Ischemic Heart DiseasesIschemic Heart Diseases
(IHD)(IHD)

• occur when the
coronary arteries
become so
narrowed by
atherosclerosis that
they are unable to
deliver sufficient
blood to the heart
muscle
– Localized areas of
thickened tunica
intima associated
with accumulation of

• Angina Pectoris
– episodic, reversible oxygen insufficiency
– severe chest pains generally radiating to the left
shoulder and down the inner side of the arm
– usually precipitated by physical exertion or emotional
stress
• Myocardial Ischemia
– deprivation of oxygen to a portion of the myocardium
(reversible)
• Myocardial Infarction
– severe, prolonged deprivation of oxygen to a portion

Risks FactorsRisks Factors
• Smoking
• Hypertension
• Diabetes Mellitus
• Males >45 yo; Females >55 yo
• Dyslipidemia
• Obesity
• Family history of CAD
• Others:
– sedentary lifestyle, hx of chronic inflammation

EtiologyEtiology
• Decreased blood flow
– Atherosclerosis – most common cause
– Coronary artery spasm – sustained
contraction of 1 or more coronary arteries 
Prinzmetal’s angina or MI
– Traumatic injury – that interferes with blood
flow in the heart
– Embolic events – can abruptly restrict oxygen
supply
• Increased oxygen demand
– Exertion and emotional stress  sympathetic
stimulation  increase HR
• Reduced blood oxygenation

Angina PectorisAngina Pectoris
• chest pain
• a symptom of myocardial ischemia in
the absence of an infaction

• Types:
– Stable Angina
• aka: Classical Angina
• develops on exertion and lasts for < 5 min
• relieved with rest or drugs
• mechanism: imbalance oxygen supply
– Unstable Angina
• can be experienced at rest, or with increasing
severity for the last 1-2 months or a new chest pain
for < 1 month

• Types:
–Angina Decubitus
• nocturnal angina
• occurs in recumbent position
–Prinzmetal Angina
• aka: Variant Angina
• precipitated by coronary artery spasm

Drugs for Angina PectorisDrugs for Angina Pectoris
• Nitrates
• Beta Blockers
• Calcium Channel Blockers

NitratesNitrates
• MOA: metabolized into NO in the
body, leading to peripheral
vasodilation
• examples
–amyl nitrite
–nitroglycerin
–isosorbide dinitrate (ISDN)
–isosorbide mononitrate (ISMN)
• SE:

• drug of choice for stable angina
• MOA: decreases HR & contractility 
reduce oxygen demand (rest and
during exertion)  reduce arterial BP

CCBsCCBs
• MOA
– inhibits calcium influx into vascular smooth
muscle & heart muscles  increased blood
flow  enhance oxygen supply  prevent
and reverse coronary spasm
– dilates peripheral arterioles & reduce
contractility  reduce total peripheral
vascular resistance  reduced oxygen
demand
• Indications
– Stable angina not controlled by nitrates & beta
blockers; px who could not take beta blockers
– Prinzmetal’s angina (with or without nitrates)

Other AgentsOther Agents
• Morphine
–Unstable angina with no CI; IV doses
given after 3 sublingual nitroglycerin
tabs have failed to relieve pain
• Aspirin
–Indefinite in px with stable or unstable
angina
• Heparin, Enoxaparin, Dalteparin
–Together with aspirin  hospitalized px
with unstable angina until resolved

Myocardial InfarctionMyocardial Infarction

Myocardial Infarction (MI)Myocardial Infarction (MI)
–Results from prolonged myocardial
ischemia, precipitated in most cases by
an occlusive coronary thrombus at the
site of a pre-existing atherosclerotic
plaque
Cellular ischemia
Tissue injury
Tissue necrosis
Note:
Damage on myocardial tissue
is not reversible 
myocardial tissue dies

• persistent, severe chest pain or
pressure  “crushing”, “squeezing” or
heavy “an elephant sitting on the
chest”

Signs and Symptoms of MISigns and Symptoms of MI
• Compared to angina
– Pain persists longer
– Not relieved by rest or nitroglycerin
– Sense of impending doom, sweating, nausea,
vomiting, difficulty in breathing; some px 
fainting and sudden death
– Extreme anxiety, restlessness, ashen pallor
• Some px:
– Mild or indigestion-like pain, manifest in
worsening CHF, loss of consciousness, acute
confusion, dyspnea, sudden drop in BP, lethal
arrhythmia

IMMEDIATE TREATMENT FOR
MYOCARDIAL INFARCTION
M
O
N
MORPHINE
OXYGEN
NITROGLYCERINE
ASA

Drugs for MIDrugs for MI
• Nitrates
• Oxygen
• Morphine
• Thrombolytic Agents

NitratesNitrates
• MOA
– Decrease oxygen demand and facilitate
coronary blood flow
– converted to nitric oxide intracellularly which
activates guanylate cyclase  increase
cGMP  dephosphorylation of myosin
light chain  relaxation of vascular smooth
muscle  vasodilation
• Important SE
– HEADACHE – most common side effect
– Tolerance (“Nitrate-free interval”)
– Postural hypotension, facial flushing, reflex

OxygenOxygen
• for patients who have chest pain and
who may be ischemic
• improve oxygenation of myocardium

MorphineMorphine
• MOA
– causes venous pooling and reduces preload,
cardiac workload, and oxygen consumption
– IV until pain is relieved
• Indication
– DOC for MI pain and anxiety
• Precautions
– can produce orthostatic hypotension and
fainting
– monitor for hypotension & signs of resp
depression

Thrombolytic AgentsThrombolytic Agents
• MOA:
– Lysis of thrombus clot
• The following are given IV within 12 h to
restore normal blood flow in an acute MI:
– Recombinant t-PA (recombinant tissue-type
plasminogen activator alteplase)
– Streptokinase
– Anisoylated plasminogen streptokinase
activator complex (APSAC)
– Reteplase
– Tenecteplase

Post thrombolysis adjunctivePost thrombolysis adjunctive
therapytherapy
• Aspirin
– prevents platelet aggregation; shown to
reduce post-infarct mortality
– also: dipyridamole, ticlopidine, clopidogrel
• Heparin
– prevent re-occlusion once a coronary artery
has been opened
– not used with streptokinase  increased risk
of hemorrhage
• Warfarin
– reduce mortality, prevent recurrent MI

therapytherapy
• Beta Blockers
– if administered early  reduce ischemia,
reduce potential zone of infarction, decrease
oxygen demands, preserve left ventricular
function, decrease cardiac workload
• ACE Inhibitors
– improve exercise capacity and reduce
mortality in px with CHF; aid in the prevention
of progressive ventricular remodelling
• “Statins”
– reduced mortality due to MI when used by px
to aggressively lower cholesterol

therapytherapy
• Lidocaine
–used for px who develop ventricular
arrhythmia
• Calcium Channel Blockers
–decrease incidence of reinfarction in px
with non-Q-wave infarcts; not for acute
mgt.

Items 1-3. Mr. Green, 60 years old, hasItems 1-3. Mr. Green, 60 years old, has
severe chest pain when he attempts to carrysevere chest pain when he attempts to carry
parcels upstairs to his apartment. The painparcels upstairs to his apartment. The pain
rapidly disappears when he rest. A decisionrapidly disappears when he rest. A decision
is made to treat him with nitroglycerin.is made to treat him with nitroglycerin.

2. In advising Mr. Green about the adverse effects2. In advising Mr. Green about the adverse effects
he may notice, you point out that nitroglycerin inhe may notice, you point out that nitroglycerin in
moderate doses often produces certain symptoms.moderate doses often produces certain symptoms.
These toxicities result from all of the followingThese toxicities result from all of the following
EXCEPTEXCEPT
A. Meningeal vasodilation
B. Reflex tachycardia
C. Hypotension
D. Methemoglobinemia

3. 2 years later, Mr. Green returns complaining3. 2 years later, Mr. Green returns complaining
that his nitroglycerin works well when he takes itthat his nitroglycerin works well when he takes it
for an acute attack but that he is having frequentfor an acute attack but that he is having frequent
attacks now and would like something to preventattacks now and would like something to prevent
them. Useful drugs for the prophylaxis of angina ofthem. Useful drugs for the prophylaxis of angina of
effort include which one of the following?effort include which one of the following?
A. Amyl nitrite
B. Diltiazem
C. Sublingual isosorbide dinitrate
D. Sublingual nitroglycerin

4. The antianginal effect of propanolol may be4. The antianginal effect of propanolol may be
attributed to which one of the following?attributed to which one of the following?
A. Block of exercise-induced tachycardia
B. Decreased end-diastolic ventricular volume
C. Dilation of constricted coronary vessels
D. Increased cardiac force
E. Decreases heart rate

5. The major common determinant of myocardial5. The major common determinant of myocardial
oxygen consumption isoxygen consumption is
A. Blood volume
B. Cardiac output
C. Diastolic blood pressure
D. Heart rate
E. Myocardial fiber tension

6. You are considering therapeutic options for a6. You are considering therapeutic options for a
new patient who presents with hypertension andnew patient who presents with hypertension and
angina. In considering adverse effects, you noteangina. In considering adverse effects, you note
that an adverse effect which nitroglycerin,that an adverse effect which nitroglycerin,
prazosin, and ganglion blockers have in commonprazosin, and ganglion blockers have in common
isis
A. Bradycardia
B. Impaired sexual function
C. Lupus erythematosus syndrome
D. Orthostatic hypotension
E. Throbbing headache

7. A patient is admitted to the emergency7. A patient is admitted to the emergency
department following a drug overdose. He is noteddepartment following a drug overdose. He is noted
to have severe tachycardia. He has been receivingto have severe tachycardia. He has been receiving
therapy for hypertension and angina. A drug thattherapy for hypertension and angina. A drug that
often causes tachycardia isoften causes tachycardia is
A. Diltiazem
B. Guanethidine
C. Isosorbide dinitrate
D. Propanolol
E. Verapamil

ArrhythmiasArrhythmias
• deviations from normal heartbeat
pattern
–abnormalities in impulse formation
–conduction disturbances

ArrhythmiasArrhythmias
• The heart is endowed with a
specialized electrogenic system for:
–Generating rhythmical impulses to
cause rhythmical contraction of the
heart muscle
–Conducting these impulses rapidly
throughout the heart

Cardiac Conduction SystemCardiac Conduction System
• Sinoatrial node
– Pacemaker of the heart
– 60 – 100 beats/min
– Location: posterior wall of the right atrium
near the entrance of the superior vena cava
• Atrioventricular node
– Location: posterior septal wall of the right
atrium immediately behind the tricuspid valve
– Connects the atrial and ventricular conduction
systems

• Bundle of His (AV bundle)
–Delayed transmission
• Delays in transmission provide mechanical
advantage  atria complete ejection of
blood before initiating ventricular
contraction• Purkinje system
– Supplies the ventricles
– Has large fibers that allow for rapid conduction and
almost simultaneous excitation of the entire left and
right ventricles
– Rapid rate of ejection is necessary for the swift and
efficient ejection of blood from the heart

Myocardial Action PotentialMyocardial Action Potential
• electric current generated by nerve
and muscle cells
• involve movement or flow of
electrically charged ions at the level
of the cell membrane

Resting Membrane PotentialResting Membrane Potential
• membrane is
relatively permeable
to K+
• charges of opposite
polarity become
aligned along the
membrane
(+)  outside
(-)  inside

DepolarizationDepolarization
• cell membrane
suddenly becomes
selectively
permeable to
current-carrying ions
such as Na+
• Na+
enters cell 
sharp rise of
intracellular potential
to positivity while K+
migrate outside

RepolarizationRepolarization
• re-establishment of
the resting potential
• slower process;
increased
permeability to K+

K+
ions move outward
 removes (+)
charges inside the
cell
– The Na-K pump
helps to preserve
the intracellular
negativity by moving 3

• Five Phases:
Phase 0: Rapid Depolarization
Phase 1: Early Rapid Repolarization
Phase 2: Plateau Phase of
Repolarization
Phase 3: Final Rapid Repolarization
Phase 4: Slow Depolarization

Electrocardiography (ECG)Electrocardiography (ECG)
• A recording of the electrical activity of
the heart during depolarization-
repolarization
–P wave
• SA node and atrial depolarization
–QRS complex
• Ventricular depolarization
–T wave
• Ventricular repolarization

–Isoelectric line between P wave & Q
wave
• Depolarization of the AV node, bundle
branches, Purkinje system
–ST segment
• Absolute refractory period; part of
ventricular repolarization
–Atrial repolarization occurs during
ventricular depolarization and is hidden
in the QRS complex.

Cardiac arrhythmia mayCardiac arrhythmia may
cause the heart tocause the heart to
• To beat too slowly
• To beat too rapidly
• To respond to impulses originating from
sites other than the SA node
• To respond to impulses travelling along
extra pathways

CAUSES OF ARRHYTHMIACAUSES OF ARRHYTHMIA
• Abnormal automaticity
• Effect of drug
• Abnormalities in impulse conduction

Action Potential & ECGAction Potential & ECG

Classification of ArrhythmiasClassification of Arrhythmias
• By origin
–Supraventricular arrhythmia
• Stem from enhanced automaticity of the SA
node or from re-entry conduction
–Ventricular arrhythmia
• Occur when an ectopic pacemaker triggers
a ventricular contraction before the SA
node fires

Normal ECG PatternNormal ECG Pattern

ECG Patterns of ArrhythmiasECG Patterns of Arrhythmias

Anti-arrhythmic AgentsAnti-arrhythmic Agents

AntiarrhythmicsAntiarrhythmics
Sodium Channel Blockers
Class IA
Class IB
Class IC
•Quinidine
•Procainamide
•Disopyramide
•Lidocaine
•Tocainide
•Mexiletine
•Phenytoin
•Flecainide
•Propafenone
•Moricizine
Beta Adrenergic Blockers Class II
•Propranolol
•Esmolol
•Acebutolol
Potassium Channel Blockers Class III
•Amiodarone
•Sotalol
•Bretylium
Calcium Channel Blockers Class IV
•Verapamil
•Diltiazem

CLASS 1ACLASS 1A
• Slows phase 0 depolarization
• Prolong action potential
• Slow conduction

CLASS 1BCLASS 1B
• Shortens phase 3 repolarization
• Decrease duration of action potential

CLASS 1CCLASS 1C
• Markedly slow phase 0 depolarization

CLASS IICLASS II
• Suppresses phase 4 depolarization

CLASS IIICLASS III
• Prolongs phase 3 repolarization

CLASS IVCLASS IV
• Slows phase 4 spontaneous
depolarization
• Shorten action potential

Miscellaneous AgentsMiscellaneous Agents
• Adenosine
• MgSO4

TYPE OF ARRHYTHMIATYPE OF ARRHYTHMIA
AND DRUGSAND DRUGS
• Atrial flutter
• Class 1 – quinidine
• Class II - propranolol
• Class IV – verapamil
• Others - digoxin

• Atrial fibrillation
• 1- quinidine
• 2- propranolol
• 3- amniodarone
• 4 – anticoagulant

• AV –NODAL REENTRY
• PROPRANOLOL
• VERAPAMIL
• DIGOXIN

• ACUTE SUPRAVENTRICULAR
TACHYCARDIA
• Verapamil
• adenosine

• ACUTE VENTRICULAR TACHYCARDIA
• Lidocaine
• Sotalol
• Amniodarone

• VENTRICULAR FIBBRILLATION
• Lidocaine
• Bretylium
• Amnidarone
• epinephrine

ProcainamideProcainamide
• can cause SLE (Systemic Lupus
Erythematosus)

QuinidineQuinidine
• drug interaction with digoxin
• can increase serum levels of digoxin
by at least 2x

LidocaineLidocaine
• anesthetic
• DOC for digitalis-induced arrhythmias

PropafenonePropafenone
• for acute atrial fibrillation

AmiodaroneAmiodarone
• iodine-containing molecule
• first-line treatment for almost all types
of Ventricular Tachycardia and Atrial
Fibrillation

VerapamilVerapamil
• alternative for acute SVT
(Supraventricular Tachycardia)

AdenosineAdenosine
• first-line drug for acute SVT

Drugs for CoagulationDrugs for Coagulation
DisordersDisorders

Clotting MechanismClotting Mechanism
• inciting event: epithelial vascular injury
• followed by:
– migration of platelets to the site of injury
– platelet aggregation
• aka: primary hemostasis
• white thrombus
• platelet plug
• unstable clot
– deposition of fibrin over the plug
– attachment of other blood cells
• aka: secondary hemostasis
• red thrombus
• stable clot

• thrombus
–clot that adheres to a blood vessel wall
• embolus
–detached thrombus

• the coagulation process that
generates thrombin that is essential in
the formation of fibrin used in clot
formation involves coagulation
cascade

Coagulation CascadeCoagulation Cascade

Drugs for CoagulationDrugs for Coagulation
DisordersDisorders
Anticoagulants
Anti-Platelet Drugs
Fibrinolytic Agents
Pro-coagulant Drugs

AnticoagulantsAnticoagulants
• Site of action
– synthesis of or directly against clotting factors
(II, IIa)
• Types:
– Parenteral
• Hirudin, Heparin
– Oral
• Dicumarol, Warfarin

Parenteral AnticoagulantsParenteral Anticoagulants

HirudinHirudin
• obtained from medicinal leeches
(Hirudo medicinalis)
• used in the management of HIT
(Heparin-Induced Thrombocytopenia)
• Lepirudin – produced by recombinant
DNA technology

HeparinHeparin
• heterogeneous mixture of sulfated
mucopolysaccharides
–Regular or Unfractionated heparin
• activates antithrombin III which in turn
inactivates thrombin (IIa); Ixa, Xa, Xia
• SQ/IV
–Low MW Heparin
• Inactivates IIa and Xa
• Enoxaparin,fraxiparin,dalteparin
• SQ

HeparinHeparin
• Clinical use
–initiation of anticoagulant therapy
–mgt of MI or unstable angina
–tx & prevention of pulmonary embolism
& DVT
–anticoagulation in pregnancy (APAS)
• SE:
–hemorrhage (monitor aPTT – activated
partial thromboplastin time) 2-2.5x or
delay of 50 – 80 secs except SQ
–Thrombocytopenia

CONTRAINDICATIONSCONTRAINDICATIONS
• Hypersensitivity
• Active bleeding
• Thrombocytopenia
• Severe HPN
• Active TB

Oral AnticoagulantsOral Anticoagulants

• DICUMAROL
• aka: bis-hydroxycoumarin
• high incidence of GI side-effects
• PHENPROCOUMON
• INDANEDIONES ex:
anisindione,phenindione
• WARFARIN

• MOA: blocks carboxylation of X, IX,VII,II
• ONSET: 8 – 12 hrs maximum after 1 to
3days

• delay in the anticoagulant effect
• Clinical use
– Chronic anticoagulation (DVT prophylaxis,
cardiac thrombus, prosthetic heart valves)
• SE:
– Hemorrhage
• Monitor PT (Prothrombin Time) and INR
(International Normalized Ratio)
• Goal for INR = 2-3
• <2  insufficient dose
• >3  x’sive dose
• With prosthetic heart valves INR goal = 3-4

SE:SE:
• Hemorrhagic dse of the newborn
• Teratogenic: abnormal bone formation
• Cutaneous necrosis
• Purple toe syndrome
• Alopecia, urticaria,dermatitis

Anti-Platelet DrugsAnti-Platelet Drugs

Anti-Platelet DrugsAnti-Platelet Drugs
• Thromboxane Synthesis Inhibitors
• Phosphodiesterase Inhibitors
• ADP Inhibitors
• Glycoprotein IIb/IIIa Inhibitors

Thromboxane SynthesisThromboxane Synthesis
• Irreversibly acetylates COX- inhibition
of TXA2 synthesis, lasts for 8 – 10
days
• Aspirin
–primary prophylaxis for MI
–secondary prophylaxis for MI and stroke

Phosphodiesterase InhibitorsPhosphodiesterase Inhibitors
• Dypiridamole
–given together with antiplatelet;
ineffective when alone
–Inc CAMP
–SE: coronary steal phenomenon

ADP Inhibitors -ADP Inhibitors -
ThienopyridinesThienopyridines
• Ticlopidine
–SE: thrombocytopenia
purpura,neutropenia,
–n/v,diarrhea
• Clopidogrel
–safer than ticlopidine

Glycoprotein InhibitorsGlycoprotein Inhibitors
• Abciximab
• Eptifibatide
• Tirofiban

Fibrinolytic AgentsFibrinolytic Agents

Fibrinolytic Agents /Fibrinolytic Agents /
ThrombolyticsThrombolytics
• MOA
– catalyse activation of plasminogen to
plasmin(serine protease)
• Use
– mgt of severe pulmonary embolism
– heart attack, acute MI,DVT
• Ex
– Streptokinase – destroy fibrin that is either
bound to clots or is in the unbound form
– Tissue plasminogen activator – binds to fibrin
bound to a clot
– Anistreplase (APSAC)

Pro-coagulant DrugsPro-coagulant Drugs

Pro-coagulant DrugsPro-coagulant Drugs
• Mgt of bleeding disorders
–Vitamin K
• K1 – phytonadione (in plants, useful
clinically)
• K2 – menaquinone (intestinal bacteria)
• K3 – menadione (synthetic)
• used for Vit. K deficiency; hemorrhagic
disorders in newborns
–Aminocaproic Acid
• prevents activation of plasminogen
– Tranexamic Acid (analogue)

Drugs for DyslipidemiaDrugs for Dyslipidemia

DyslipidemiaDyslipidemia
• Hypercholesterolemia (inc LDL, dec
HDL)
• Hypertriglyceridemia (inc TG, ~ inc
VLDL, chylomicrons)
• Liver
–Only organ in the body that efficiently
uses cholesterol
• Converts it to bile salts

Cholesterol SynthesisCholesterol Synthesis
HMG-CoA Mevalonat
e
Cholesterol
HMG-CoA
Reductase
Cholesterol Source
–Diet (exogenous)
–Endogenous
hydroxymethylglutaryl-
Coenzyme A (HMG-CoA)

AtherosclerosisAtherosclerosis
Condition
associated with
cholesterol
deposition in
vascular smooth
muscles
(arthroma) with
consequent
narrowing of the
lumen of the

• Could lead to…
–CAD
–Cerebrovascular disease
–Aortic disease
–Renal artery disease

• Major Risk factors
– Age (males: > 45;
females: > 55)
– Smoking
– DM
– HPN
– Dyslipidemia
– Obesity
– Family history of
premature heart
• Minor Risk Factors
– Chronic infection
– Sedentary lifestyle
• Modifiable Risk
Factors
– By therapy
– By lifestyle change

Drugs for DyslipidemiaDrugs for Dyslipidemia
• HMG-CoA Reductase Inhibitors
• Nicotinic Acid
• Bile Acid Sequesterants
• Fibric Acid Derivatives
• Probucol

HMG-CoA ReductaseHMG-CoA Reductase
• “-statins”
• MOA: inhibit the enzyme HMG-CoA
Reductase, thereby inhibiting the first
step (rate-limiting step) in cholesterol
synthesis
• first-line drugs for dyslipidemia

• Diurnal Pattern of Cholesterol
Synthesis
–means that the biosynthesis of
cholesterol in the body occurs at night
–thus most statins are given at bedtime
(esp the short-acting ones)

• Short-acting
– simvastatin
– lovastatin
– fluvastatin
• Long-acting
– atorvastatin
– rosuvastatin Long-acting statins can
be given any time of
the day.

• SE:
–hepatotoxicity
–myositis
–rhabdomyolysis (muscle wasting)

Nicotinic AcidNicotinic Acid
• unknown MOA
• used in the management of
hypertriglyceridemia
• SE: flushing (due to percutaneous
vasodilation), myositis

Bile Acid SequesterantsBile Acid Sequesterants
• aka: Bile Acid – Binding Resins
• MOA: Inhibit reabsorption of bile acid
• since liver must maintain a certain
amount of bile, it will synthesize bile
from endogenous cholesterol when
bile levels go low

Bile Acid SequesterantsBile Acid Sequesterants
• Cholestyramine
• Colestipol
• SE:
–constipation
–impaired absorption of certain drugs
–may increase incidence / risk of biliary
stone formation

Fibric Acid DerivativesFibric Acid Derivatives
• MOA: stimulate lipoprotein lipase
which decreases triglycerides
• first-line drug in hypertriglyceridemia
• Gemfibrozil
• Fenofibrate
• Clofibrate (withdrawn)

Fibric Acid DerivativesFibric Acid Derivatives
• SE:
–myositis
–rhabdomyolysis
–increase risk of bile stone formation
–hepatobiliary cancer (Clofibrate)

ProbucolProbucol
• MOA: anti-oxidant
• SE:
–increase risk of arrhythmia
–produces fetid odor

Ok, before we end ourOk, before we end our
lecture, quiz muna tayo…lecture, quiz muna tayo… 

Question 1:Question 1:
• Which enzyme is responsible for the
conversion of Angiotensin I into the
active form Angiotensin II?
A. Renin
B. ACE
C. HMG-CoA
D. Streptokinase B

• A 55 y/o male patient was
diagnosed to have uncomplicated
HTN. Which of the following drugs
would most likely be given to him?
A. Thiazide diuretic + Beta Blocker
B. ACE Inhibitor
C. CCB + ACE Inhibitor
D. ACEi + ARB A

• From the list of anti-hypertensive
drugs below, select the one most
likely to lower blood sugar:
A. Prazosin
B. Nifedipine
C. Propranolol
D. Hydralazine
E. Labetalol
C

• Which of the following conditions
predisposes a patient taking digitalis
into arrhythmia?
A. hypocalcemia
B. decreased heart rate
C. hyponatremia
D. hypokalemia D

• All of the following mechanisms of
action correctly match a drug,
EXCEPT:
A. Quinidine: blocks Na+
channels
B. Bretylium: blocks K+
channels
C. Propranolol: blocks β-receptors
D. Procainamide: blocks K+
channelsD

• Which of the following adverse
effects is associated with nitrates?
A. nausea
B. throbbing headache
C. sexual dysfunction
D. anemia
B

• A patient experienced orthostatic
hypotension after taking the first
dose of her drug. She most likely
took:
A. Labetalol
B. Valdesartan
C. Prazosin
D. Digoxin
C

• Mrs. G. R. is a hypertensive patient
under therapy. After some time, she
developed Lupus-like symptoms.
Which of the ff drugs may have
cause this?
A. Hydralazine
B. Losartan
C. Furosemide A

• Which of the following antagonizes
the co-factor functions of Vitamin K?
A. Tranexamic acid
B. Heparin
C. Warfarin
D. Hirudin
C

• The following drugs for dyslipidemia
can cause rhabdomyolysis,
EXCEPT:
A. simvastatin
B. atorvastatin
C. colestipol
D. fenofibrate
C

““The only thing greater than the powerThe only thing greater than the power
of the mind is the courage of theof the mind is the courage of the
heart.”heart.”
- from the movie,- from the movie, A Beautiful MindA Beautiful Mind

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