Cardiovascular

What is Heart Failure?
A symptom complex due to
the inability of the heart to
function efficiently as a
pump - there is a
disproportion between the
hemodynamic demand and
the capacity of the heart to
handle the demand
( Supply ≠ Demand)

Heart Failure
• Heart failure occurs when cardiac
output is inadequate to provide the
oxygen needed by the body.
• It is a highly lethal condition, with a 5-
year mortality rate conventionally said to
be about 50%.
• The most common cause of heart
failure is coronary artery disease.

If Heart does not contract well (systolic
HF) traffic (blood) piles up before the
heart (lungs and periphery).

Role of physiologic compensatory
mechanisms in the progression of HF
• Chronic activation of the sympathetic
nervous system and the renin-
angiotensin-aldosterone axis is
associated with remodeling of cardiac
tissue, characterized by:
• loss of myocytes.
• Hypertrophy.
• fibrosis.

Sequelae of Heart Failure
Right Heart Failure
Systemic venous
congestion:
1. distended neck
veins.
2. enlarged liver.
3. peripheral
edema.
4. ascites.
Left Heart Failure
• Pulmonary
edema
(Dyspnea)

Symptoms of Heart Failure
Compensated (Asymptomatic)
Uncompensated (Symptomatic)
• Fatigue
• Dyspnea
• Orthopnea
(shortness of breath (dyspnea) which occurs when lying flat)
• Paroxysmal Nocturnal Dyspnea
• Ankle Edema
• Weight Gain

Adaptive mechanisms in heart failure
Compensated

Goals of pharmacologic intervention in HF
1. To alleviate symptoms.
2. Slow disease progression.
3. Improve survival.

Summary of drugs used to treat
heart failure.

ACE inhibitors (ACEI) - (Oral Meds)
The ACE inhibitor are the agents
of choice in HF
• Benazepril - Lotensin
• Captopril - Capoten
• Enalapril - Vasotec
• Fosinopril - Monopril
• Lisinopril – Prinivil

Angiotensin - converting enzyme inhibitors
Mechansim of action:

Angiotensin - converting enzyme inhibitors
Actions on the heart:
ACE inhibitors decrease:
1. Vascular resistance.
2. Venous tone.
3. Blood pressure.
preload andafterload
.
ACE inhibitors also blunt the usual
angiotensin II mediated increase in
epinephrine and aldosterone seen in HF.

Angiotensin - converting enzyme
inhibitors,
• Indications:
1. Single-agent therapy in patients who present with mild
dyspnea on exertion and do not show signs or symptoms
of volume overload.
2. In asymptomatic patients with an ejection fraction of
less than 35 % (left ventricular dysfunction).
(The term "ejection fraction" refers to the percentage of blood that's pumped out of a filled
ventricle with each heartbeat.)
1. Recent myocardial infarction also benefit from long-
term ACE inhibitor therapy.
2. In patients with all stages of left ventricular failure,
with and without symptoms, and therapy should be
initiated immediately after myocardial infarction.

• ACE inhibitors improve clinical signs and
symptoms in patients also receiving
thiazide or loop diuretics and/or digoxin.
• The use of ACE inhibitors in the treatment
of HF has significantly decreased both
morbidity and mortality.

inhibitors,
• Pharmacokinetics:
• Adequately but incompletely absorbed following oral
administration.
• The presence of food may decrease absorption, so they should be
taken on an empty stomach.
• ACE inhibitors are prodrugs that require activation by hydrolysis
via hepatic enzymes (Except for captopril ).
• Renal elimination of the active moiety is important (Except for
fosinopril) .
• t½ 2 to 12 hours.

inhibitors,
• Adverse effects:
• postural hypotension,
• renal insufficiency,
• hyperkalemia,
• Angioedema.
• persistent dry cough.
• ACE inhibitors should not be used in pregnant women,
because they are fetotoxic

Angiotensin receptor blockers, &
related agents
• losartan (AT1 receptor-blockers) appear to
have similar but more limited beneficial
effects.
• Angiotensin receptor blockers should be
considered in patients intolerant of ACE
inhibitors.

related agents (ARBs)
• extremely potent competitive antagonists of the angiotensin type
1 (AT1)receptor.
• ARBs have the advantage of more complete blockade of
angiotensin action, because ACE inhibitors inhibit only one
enzyme responsible for the production of angiotensin II.
• ARBs do not affect bradykinin levels.

• All the ARBs are approved for treatment of
hypertension based on their clinical efficacy in
lowering blood pressure and reducing the
morbidity and mortality associated with
hypertension.
• Their use in HF is as a substitute for ACE
inhibitors in those patients with severe cough
or angioedema.

• Pharmacokinetics:
• orally active.
• require only once-a-day dosing.
• Losartan, the first approved member of the class,
differs from the others in that it undergoes extensive
first-pass hepatic metabolism, including conversion to
its active metabolite. The other drugs have inactive
metabolites.
• Elimination in the urine and feces
• All are highly plasma protein bound (greater than 90
percent)

• Adverse effects:
• ARBs have an adverse effect profile similar to
that of ACE inhibitors.
• However, ARBs do not produce cough.
• ARBs are contraindicated in pregnancy.

β -adrenoceptor blockers
• Most patients with chronic heart failure respond
favorably to certain β blockers in spite of the fact
that these drugs can precipitate acute
decompensation of cardiac function.
• Studies with bisoprolol, carvedilol, and
metoprolol showed a reduction in mortality in
patients with stable severe heart failure.
• Suggested mechanisms include attenuation of
the adverse effects of high concentrations of
catecholamines.

β -adrenoceptor blockers
• Most patients with chronic heart failure respond
favorably to certain β blockers in spite of the fact
that these drugs can precipitate acute
decompensation of cardiac function. Studies with
bisoprolol, carvedilol, and metoprolol showed a
reduction in mortality in patients with stable
severe heart failure.
• Suggested mechanisms include attenuation of
the adverse effects of high concentrations of
catecholamines.

Diuretics
• Common thiazide diuretics
– Chlorothiazide (Diuril)
– Indapamide (Lozol)
– Metolazone (Zaroxolyn)
• Common loop diuretics
– Bumetanide (Bumex)
– Ethacrynic acid (Edecrin)
– Furosemide (Lasix)
• Common potassium-sparing diuretics
– Amiloride (Midamor)
– Eplerenone (Inspra)
– Spironolactone (Aldactone

Diuretics
• Their major mechanism of action in heart failure is to
reduce venous pressure and ventricular preload. This
results in reduction of edema and its symptoms, and
reduction of cardiac size, which leads to improved pump
efficiency.
• Loop diuretics, such as furosemide (Lasix), block the Na+-
K+ - 2Cl
_
in the ascending limb of the loop of Henle. loop diuretics are
still part of the mainstay of therapy for CHF despite these
potential problems
• Spironolactone and eplerenone, the aldosterone antagonist
diuretics have the additional benefit of decreasing
morbidity and mortality in patients with severe heart
failure.

Vasodilators
• The vasodilators are effective in acute
heart failure because they provide a
reduction in preload (through
venodilation), or reduction in afterload
(through arteriolar dilation), or both.
Some evidence suggests that long-term
use of hydralazine and isosorbide
dinitrate can also reduce damaging
remodeling of the heart.

Drug Therapy - Digitalis
Glycosides
Action: Increases the
force and velocity of
myocardial
contraction
Digoxin (Lanoxin)
Digitoxin
(Crystodigin)
Purple foxglove - digitalis

Drug Considerations - Digitalis
Glycosides
• Vasoconstrictor Interaction: concurrent
use may increase the risk of cardiac
arrhythmias – avoid if possible
• Oral Manifestations: increased gag reflex,
nausea/vomiting
• Other Considerations:
– macrolide antibiotics (erythromycin) can
increase bioavailability of DG resulting in
toxicity; avoid these drugs
– watch for DG toxicity (tachycardia, N/V,
hypersalivation, vision changes, fatigue, HA)

DIGITALIS
• Introduction
• Digitalis is the genus name for the family of
plants that provide most of the medically useful
cardiac glycosides, eg, digoxin.

Inotropic Definition
• Force of myocardial contraction
• Positive inotropic drug: increases force
of contractions
• Negative inotropic drug: decreases
force of contraction

Digitalis Glycosides
• Increase force of myocardial
contraction.
• Increase myocardial contractility
causing more complete emptying.
• Causes improved heart’s pumping
ability

Pharmacokinetics
A. Absorption:
• 65-80% absorbed after oral administration.
B. Distribution:
• widely distributed to tissues, including the
central nervous system.
C. Metabolism:
• Small amount in liver & GI flora.
D. Excretion:
• Unchanged drug from kidneys

Pharmacodynamics
• At the molecular level, all therapeutically useful
cardiac glycosides inhibit Na+/K+ ATPase, the
membrane-bound transporter often called the
sodium pump.

Pharmacodynamics
• Cardiac glycosides increase contraction
of the cardiac sarcomere , by increasing
the free calcium concentration in the
vicinity of the contractile proteins during
systole.
1. An increase of intracellular sodium
concentration because of Na+/K+ ATPase
inhibition.
2. Relative reduction of calcium expulsion
from the cell by the sodium-calcium
exchanger caused by the increase in
intracellular sodium, ( contractile force,

Clinical Use
1. Congestive heart failure:
2. Cardiac arrhythmias: ( atrial
fibrillation )

Toxicity
1. Gastrointestinal
– Salivation
– Anorexia
– Nausea
– Vomiting
– Diarrhea
2. CNS
– Headache
– Visual disturbances
characteristic (green
yellow halos around
bright objects).
– Fatigue
– Drowsiness
• Digitalis is a fat-soluble steroid that
crosses the blood-brain barrier and
enhances vagal tone
• This action involves:
• sensitization of the baroreceptors.
• central vagal stimulation.

Toxicity
3. Cardiac
• Atrioventricular (AV) block.
• Excessive slowing of the
heart
• supraventricular and
ventricular tachycardia.
4. Miscellaneous
• Excessive urination
• Because cholinergic
innervation is much richer
in the atria.
• Enhanced vagal nerve
activity causes a decrease
in sinoatrial beating rate
and velocity of
atrioventricular
conduction.
• facilitation of muscarinic
transmission at the cardiac
muscle cell

Treatment for digitalis toxicity:
• Mild cases that respond to simply
stopping the drug temporarily.
• In severe cases the use of
antidigoxin drug, antidote is given
intravenously and inactivates
digoxin in life-threatening situations.

Other positive inotropic drugs

Dobutamine.
• The selective β1 agonist that has been most
widely used in patients with heart failure.
• Tachycardia and an increase in myocardial
oxygen consumption have been reported.
Therefore, the potential for producing angina or
arrhythmias in patients with coronary artery
disease must be considered.
• Dopamine has also been used in acute heart
failure and may be particularly helpful if there is a
need to raise blood pressure.

Drugs without positive inotropic effects
• Paradoxically, these agents-not positive
inotropic drugs-are the first-line
therapies for chronic heart failure.
• In acute failure, diuretics and
vasodilators play important roles.

Beneficial effects of pharmacologic intervention in
HF
1. Reduction of the load on the
myocardium.
2. Decreased extracellular fluid volume.
3. Improved cardiac contractility.
4. Slowing of the rate of cardiac
remodeling.

•
IMPLICATIONS FOR
DENTISTRY

Stress Factors
 -Eliminate needless stress for cardiac patients, especially
anxiety or pain associated with dental procedures. Patients
being treated for heart failure possess limited cardiac function.
 -These patients are at special risk in stressful situations
because stress puts a greater workload on the heart and
stimulates the release of endogenous catecholamines.
 -catecholamines increase the risk of digoxin-induced
arrhythmias.
 -Fear and apprehension may also increase the likelihood of
adverse CNS reactions to digoxin.
 -One practical conclusion is that antianxiety therapy or
analgesics should be used preemptively if emotional stress or
pain is likely.

Drug Interactions
 The use of catecholamines in local anesthetic injections for
patients taking digoxin is not contraindicated but should be
approached with special caution.
 Proper injection technique to avoid intravascular injection
should be followed.
 Many factors influence the decision to use vasoconstrictors in
local anesthetic solutions, including the ability to achieve
adequate anesthesia without vasoconstrictors and the volume
of anesthetic solution required.
 The chief danger of sympathomimetic vasoconstrictors for
patients taking digoxin is that the combination of drugs
increases the risk of cardiac arrhythmias if significant amounts
of vasoconstrictor enter the vascular space

- The use of gingival retraction cords impregnated with
epinephrine is not recommended in patients taking digoxin.
Cardiac disease in general is a contraindication for their use.
Considerable amounts of vasoconstrictor may be absorbed
systemically from these retraction cords, and the possibility of
cardiac arrhythmias developing is significant. If hemostatic
retraction cords are to be used in patients who are on digoxin,
the cords should be impregnated with an astringent in place
of a vasoconstrictor.

• Antisialagogues such as atropine and
methantheline should not be used in patients
taking digoxin because they tend to reduce
the effects of digoxin.
• Muscarinic receptor agonists such as
pilocarpine enhance the effect of digoxin on
the SA node, the atria, and the AV node.
• Excessive salivation may be a sign of toxicity
owing to digoxin.

Antibiotic therapy may alter the intestinal flora
and, in so doing, increase the absorption of
digoxin in patients whose gastrointestinal flora
metabolizes digoxin.
Erythromycin, and presumably other macrolides,
has been shown to have this effect.
Tetracyclines also seem to interact through this
mechanism.

Cardiovascular

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