Transcript Chapter 15 outline

Chapter 15:
Cardiovascular Drugs
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Chapter 15 Outline

Cardiovascular Drugs

Dental implications of cardiovascular disease
 Cardiac glycosides
 Antiarrhythmic agents
 Antianginal drugs
 Antihypertensive agents
 Antihyperlipidemic agents
 Drugs that affect blood coagulation
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2
Cardiovascular Drugs




Haveles (p. 186)
Cardiovascular disease refers to diseases of
the heart and blood vessels
Includes hypertension, angina pectoris,
coronary artery disease, cerebrovascular
accident, and congestive heart failure (CHF)
A leading cause of death in the United States

25% of the top 200 drugs are in this group
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3
Dental Implications of
Cardiovascular Disease






Haveles (p. 187)
Contraindications to treatment
Vasoconstrictor limit
Infective endocarditis
Cardiac pacemakers
Periodontal disease and cardiovascular disease
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4
Contraindications to Treatment






Haveles (p. 187) (Box 15-1)
Acute or recent myocardial infarction (MI)
(within the preceding 3 to 6 months)
Unstable or recent onset of angina pectoris
Uncontrolled CHF
Uncontrolled arrhythmias
Significant, uncontrolled hypertension
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5
Vasoconstrictor Limit


Haveles (p. 187)
The majority of cardiovascular patients should
benefit from the use of epinephrine in the local
anesthetic agent


The amount and effect of epinephrine administered
must be weighed against the fact that discomfort
can cause the release of endogenous epinephrine
Limiting the dose to the cardiac dose (0.04 mg) may
be warranted in a few severely affected patients
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6
Infective Endocarditis


Haveles (p. 187)
When a risk of producing infective endocarditis
exists, prophylactic antibiotics should be
prescribed, if warranted by the dental
procedure being performed
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7
Cardiac Pacemakers


Haveles (p. 187)
A cardiac pacemaker is an electrical device
implanted in a patient’s chest to regulate the
heart rhythm


If not appropriately shielded, some electrical devices
used in dentistry may interfere with pacemaker
activity
Consult with physician may be appropriate before
treatment
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8
Periodontal Disease and
Cardiovascular Disease


Haveles (p. 187)
Research has found a relationship between
periodontal disease and both cardiovascular
disease and stroke

An inherited phenotype, MO, is under both genetic
and environmental influences, placing the patient
at increased risk for severe periodontal disease,
insulin-dependent diabetes mellitus,
atherosclerosis, and emboli production
cont’d…
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9
Periodontal Disease and
Cardiovascular Disease


Monocytes in these patients secrete
abnormally high levels of cytokines, including
prostaglandin (PG)E2, interleukin (IL)-1β, and
tumor necrosis factor (TNF)-α, all of which
are associated with both periodontal and
cardiovascular disease
An increase in dietary intake of fat leads to an
increase in low-density lipoproteins (LDL, bad
cholesterol), which are known to upregulate
the destructive monocyte response
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10
Cardiac Glycosides



Haveles (pp. 187-189)
CHF
Digitalis glycosides
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11
Heart Failure


Haveles (pp. 187-188) (Fig. 15-1)
In CHF, the heart does not provide adequate
cardiac output

Blood accumulates in the failing ventricle(s), the
ventricle(s) enlarges and finally becomes
ineffective as a pump
• Left side failure backs into pulmonary circulation (lungs)
leading to edema, dyspnea and orthopnea
• Right side failure causes systemic congestion, leading to
peripheral edema with fluid accumulation evidenced by
pitting edema (pedal edema)
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12
Digitalis Glycosides






Haveles (pp. 188-189)
Pharmacologic effects
Uses
Adverse reactions
Management of the dental patient taking
digoxin
Other drugs
cont’d…
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13
Digitalis Glycosides


The most common type of drug used in the
treatment of CHF


Haveles (p. 188)
Not considered first-line therapy
digoxin (Lanoxin) is used as the prototype
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14
Pharmacologic Effects of Digitalis
Glycosides


Haveles (p. 188)
Increases force and strength of contraction of
the myocardium (positive inotropic effect)


Allows the heart to do more work without
increasing the use of oxygen
The heart becomes more efficient, and cardiac
output increases
cont’d…
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15
Pharmacologic Effects of Digitalis
Glycosides

In CHF, the heart rate is increased due to
increased sympathetic action resulting from
decreased carbon monoxide (CO)




As digoxin increases CO, sympathetic tone is
decreased, with a decrease in heart rate
Digoxin also reduces edema that occurs with CHF
The size of the heart is reduced as excess blood
volume is removed via the kidneys
Digoxin can affect automaticity, conduction
velocity, and refractory periods of different parts
of the heart in different ways
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16
Uses of Digitalis Glycosides


Most common usage is treatment of CHF


Haveles (p. 188)
Also used for atrial arrhythmias, including atrial
fibrillation (AF) and paroxysmal atrial tachycardia
(PAT)
A recent trial found digoxin did not reduce
mortality; for this reason use of digoxin is
decreasing

Angiotensin-converting enzyme inhibitors (ACEIs),
angiotensin receptor blockers (ARBs) and βadrenergic blockers are used more often
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17
Adverse Reactions of Digitalis
Glycosides





Haveles (pp. 188-189)
Narrow therapeutic index: slight changes in
dose, absorption, or metabolism can trigger toxic
symptoms
Gastrointestinal (GI): signs of toxicity include
anorexia, nausea, vomiting, copious salivation
Arrhythmias: if sufficient overdose is given (note:
digitalis is used to treat arrhythmias, its toxicity
can cause them)
Neurologic: signs of toxicity include headache,
drowsiness, and visual disturbances
cont’d…
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18
Adverse Reactions of Digitalis
Glycosides


Oral: increased salivation is associated with
digoxin toxicity
Dental drug interactions: interaction with
sympathomimetics can increase chances of
arrhythmias; in severe cardiac disease, the
epinephrine dose may be limited to the
cardiac dose (0.04 mg)

Erythromycin and tetracycline can increase toxicity
of digoxin in some patients
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19
Management of the Dental
Patient Taking Digoxin





Haveles (p. 189) (Box 15-2)
Watch for overdose side effects such as
nausea, vision changes, and copious salivation
Use epinephrine with caution to minimize
arrhythmias
Monitor pulse to check for bradycardia
Tetracycline and erythromycin can increase
digoxin levels (in approximately 10% of
patients)
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20
Other Drugs







Haveles (p. 189) (Note: these are not cardiac
glycosides)
ACEIs: now first-line therapy for CHF
ARBs: for patients who cannot tolerate ACEIs;
also first-line therapy
β-Adrenergic blockers
Vasodilators: hydralazine and isosorbide
dinitrate
Diuretics: to relieve edema
Aldosterone antagonists
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21
Antiarrhythmic Agents
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





Haveles (pp. 189-191)
Automaticity
Action potential
Arrhythmias
Antiarrhythmic agents
Adverse reactions
Dental implications
cont’d…
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22
Antiarrhythmic Agents


Arrhythmias may result from abnormal
impulse generation or abnormal impulse
conduction


Haveles (p. 189)
Cardiac diseases such as myocardial anorexia,
arteriosclerosis, and heart block can produce
arrhythmias
Antiarrhythmic agents are used to prevent
arrhythmias
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23
Automaticity


Haveles (pp. 189-190) (Fig. 15-2)
Cells of cardiac muscles have an intrinsic
rhythm called automaticity

The sinoatrial (SA) node in right atrium has the
fastest rate of depolarization and directs other cells
of the heart
• It is innervated by both the parasympathetic and
sympathetic nervous system

It signals the atrioventricular (AV) node, which
sends signals through the bundle of His to Purkinje
fibers and ventricles
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24
Action Potential


Electrical excitation from the nerve produces
movement of ions across the membrane,
generating an action potential


Haveles (p. 190) (Fig. 15-2)
Visualized as an electrocardiogram (ECG)
A relationship exists between the action
potential and the ECG tracing
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25
Arrhythmias


Arrhythmias are divided into supraventricular
(atrial) and ventricular types


Haveles (p. 190)
May result in tachycardia or bradycardia of
supraventricular or ventricular parts of the heart
May result from ectopic foci “emergent
leaders” that preempt the SA or AV nodal rate
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26
Antiarrhythmic Agents


Haveles (pp. 190-191) (Tables 15-1, 15-2)
Placed in four groups designated by numeral
I through IV according to mechanism of action

Subsets of these Roman numerals use capital
letters (A, B, C)
cont’d…
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27
Antiarrhythmic Agents

Antiarrhythmic agents work by depressing
parts of the heart that are beating abnormally

They may decrease the velocity of depolarization,
decrease impulse propagation, and inhibit
aberrant impulse propagation
cont’d…
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28
Antiarrhythmic Agents


Haveles (p. 191)
Digoxin: although digoxin is not included in
the other groups of antiarrhythmics, it is used
to treat some arrhythmias

Shortens the refractory period of atrial and
ventricular tissues while prolonging the refractory
period and diminishing the conduction velocity in
the Purkinje fibers
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29
Adverse Reactions of
Antiarrhythmic Agents


Haveles (p. 191)
Antiarrhythmic agents have a narrow
therapeutic index and are difficult to manage

Only used for patients with arrhythmias that
prevent the proper functioning of the heart
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30
Classification and Mechanism of
Action of the Antiarrhythmic Agents


Class IA sodium (Na+) channel blocker
(medium)


Quinidine, procainamide, disopyramide
Class IB Na+ channel blocker (fast)


Haveles (p. 191) (Table 15-1)
lidocaine
Class IC Na+ channel blocker (slow)

Flecainide, encainide, propafenone
cont’d…
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31
Classification and Mechanism of
Action of Antiarrhythmic Agents

Class II β-blockers


Class III potassium (K+) channel blockers


Propranolol, esmolol, acebutolol, sotalol
Bretylium and d-sotalol (non–β-blocking
enantiomer)
Class IV calcium channel blockers (CCBs)

Verapamil, diltiazem
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32
Management of Dental Patients
Taking Antiarrhythmic Agents










Haveles (p. 191) (Table 15-2)
All: Check for abnormal or extra beats when taking blood
pressure and pulse
AF: pt. on warfarin-check international normalized ratio
(INR)
Amiodarone: liver toxicity, blue skin, photosensitivity
CCBs: gingival enlargement
Disopyramide: anticholinergic xerostomia
Procainamide: reversible lupus-like syndrome, 25%-30%,
central nervous system (CNS) depression xerostomia
Quinidine: nausea, vomiting, diarrhea; cinchonism with large
doses; atropine-like effect, xerostomia
Phenytoin: gingival enlargement
β-Blockers, nonspecific: interaction with epinephrine
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33
Antianginal Drugs









Haveles (pp. 191-194)
Angina pectoris
Nitroglycerin (NTG)-like compounds
CCBs
β-Adrenergic blocking agents
Ranolazine
Dental implications
Prevention of an anginal attack
MI
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34
Angina Pectoris


Characterized by pain or discomfort in the
chest radiating to the left arm and shoulder



Haveles (pp. 191-192)
Pain can also radiate to neck, back, and lower jaw
Jaw pain may be confused with a toothache
Occurs when coronary arteries do not supply
enough oxygen to the myocardium
cont’d…
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35
Angina Pectoris


At one time, NTG-like compounds were the
only drugs that could relieve the symptoms


Haveles (pp. 191-192) (Table 15-3)
Today, β-adrenergic blockers and CCBs have
added a new dimension
The effect of these drugs is to reduce the
workload of the heart

Oxygen requirement of myocardium is reduced,
relieving painful symptoms
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36
Nitroglycerin-Like Compounds


Haveles (pp. 191-192) (Box 15-3)
NTG is by far the most often used nitrate for
management of acute anginal episodes

Also to prevent anginal attacks induced by stress
or exercise
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37
Mechanism of Nitroglycerin-Like
Compounds


Haveles (p. 192)
NTG is a vasodilator

Releases free nitrite ion and nitric oxide
• Nitric oxide activates guanylyl cyclase and increases
cyclic guanosine monophosphate (cGMP), producing
relaxation of vascular smooth muscle throughout the
body

By reducing workload on the heart, NTG
decreases the oxygen demand
cont’d…
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38
Mechanism of Nitroglycerin-Like
Compounds

Amyl nitrite is a volatile agent in a closed
container


Sublingual (SL) NTG is available as an SL
tablet (Nitrostat) or spray used sublingually
(Nitroingual)


It is administered by crushing the container and
inhaling the fumes
SL isosorbide dinitrate is also effective for an acute
anginal attack
One of the NTG products should be in the
dental office emergency kit; the patient should
bring their NTG to each appointment
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39
Adverse Reactions of
Nitroglycerin-Like Compounds


Most reactions are caused its effect on
vascular smooth muscle



Haveles (p. 193)
Severe headaches are often reported
Flushing, hypotension, light-headedness, and
syncope can also result
SL NTG can produce a localized burning or
tingling
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40
Significant Drug Interactions and
Contraindications


Haveles (p. 193)
Phosphodiesterase 5 (PDE5) inhibitors
include sildenafil (Viagra), vardenafil (Levitra),
and tadalafil (Cialis)

The administration of any of these drugs with
doses of any nitrate is contraindicated
 The combination can cause dangerously low
blood pressure
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41
Storage of Nitroglycerin-Like
Compounds


NTG is degraded by heat and moisture but
not by light



Haveles (p. 193)
Tablets should be stored in the original dark-brown
glass container
• If opened it should be discarded between 3 and 6 months
NTG spray is effective until its expiration date
Long-acting NTG-like products are available
for long-term prophylaxis of anginal attacks

Dose forms include tablets and topical products
cont’d…
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42
Storage of Nitroglycerin-Like
Compounds

With long-term regular use, tolerance develops


Prophylactic nitrates should be given with an 8- to
12- hour “vacation” every day
The mononitrate dose form requires a 7-hour
“vacation” daily
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43
Examples of Antianginal
Preparations


Haveles (pp. 192-193) (Table 15-3)
Acute attacks


Nitrites
• Amyl nitrite
Short-acting nitrates
• NTG (Nitrostat) (Nitrolingual)
• isosorbide dinitrate
cont’d…
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44
Examples of Antianginal
Preparations

Prophylactic use



Long-acting nitrates
• NTG (Nitro-Bid) (Nitro Dur, Minitran)
• isosorbide dinitrate (Isordil, Sorbitrate-DSC)
• isosorbide mononitrate (Imdur, Ismo, Monoket)
• pentaerythritol tetranitrate (Peritrate)
β-Blockers
• Propranolol
CCBs* (See Box 15-4)
• verapamil (Calan, Isoptin)
• nifedipine (Procardia)
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45
Calcium Channel Blocking
Agents


Mechanism of action of CCBs for treatment of
angina is related to inhibition of movement of
calcium during the contraction of cardiac and
vascular smooth muscle



Haveles (pp. 193-194) (Table 15-4)
Vasodilation and a decrease in peripheral resistance
results, decreasing the work of the heart
CCBs are also used in treatment of cardiac
arrhythmias and hypertension
Adverse effects include dizziness, weakness,
constipation, and hypotension

Nifedipine is associated with gingival enlargement and
dysgeusia
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46
β-Adrenergic Blocking Agents


Used in the treatment of angina (as well as
hypertension)



Haveles (p. 194)
Block the beta response to catecholamine
stimulation reducing both chronotropic and inotropic
effects
Net result is a reduced myocardial oxygen demand
Adverse effects include bradycardia, CHF,
headache, dry mouth, blurred vision, and
unpleasant dreams
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47
ranolazine
(Ranexa)


Haveles (p. 194)
A new drug for treatment of chronic angina


Exact mechanism of action is unknown
Should only be used in patients that have not
responded to long-acting nitrates, CCBs, and βblockers
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48
Dental Implications




Haveles (p. 194)
Treatment of an acute anginal attack
Prevention of anginal attack
MI
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49
Treatment of an Acute Anginal
Attack


Before administering NTG, the dental team
should make sure the patient has not used a
PDE5 inhibitor within the past 24 hours; if
such is the case, call 911
The patient’s personal NTG tablets or spray
should be available

Long-acting nitrates and topical products are not
useful for the treatment of an acute anginal attack
cont’d…
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50
Treatment of an Acute Anginal
Attack

For acute emergencies, the office should
have a supply of SL NTG


The patient should be seated
Three tablets or doses of spray, each 5 minutes
apart
• If the anginal attack is not stopped, the patient should be
taken to the emergency room
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51
Prevention of Anginal Attack


Haveles (p. 194)
Two methods to prevent an acute anginal
attack include pretreatment with either an
anxiolytic agent or SL NTG


Anxiolytics: an antianxiety agent, or anxiolytic
(benzodiazepine) may be prescribed to allay
anxiety and prevent an acute anginal attack
NTG: premedicating an anxious patient with SL
NTG can reduce the chance of an attack
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52
Myocardial Infarction


Haveles (p. 194)
An anginal attack not relieved by three doses
of SL NTG may be experiencing an MI


If the patient who has not been previously
diagnosed as having angina experiences chest
pain, he or she should be taken to an emergency
room for diagnosis
Any patient with an anginal attack not relieved by
NTG should go to the hospital emergency room
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53
Antihypertensive Agents











Haveles (pp. 194-205)
Patient evaluation
Treatment of hypertension
Diuretic agents
β-Adrenergic blocking agents
CCBs
Angiotensin-related agents
Renin inhibitors
α1-Adrenergic blocking agents
Other antihypertensive agents
Management of the dental patient taking
antihypertensive agents
cont’d…
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54
Antihypertensive Agents


Haveles (pp. 194-196) (Box 15-4)
Hypertension is the most common
cardiovascular disease (28.6% of Americans)



Even blood pressure within the formerly “normal”
range is associated with an increase in morbidity
and mortality
Eventually, elevated blood pressure damages
internal organs
More likely to have kidney and heart disease and
cardiovascular problems
cont’d…
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55
Antihypertensive Agents


Haveles (pp. 195, 197) (Table 15-5)
Hypertension is divided into categories based
on the cause or progression of the disease



Essential (idiopathic, primary): from an unknown
cause, 85% to 90% of patients
Secondary: cause can be identified and
associated to a disease process of endocrine or
renal system (10% of patients)
Malignant: high or rapidly rising blood pressure,
develops in about 5% of patients with primary or
secondary hypertension
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56
Patient Evaluation


Haveles (p. 195)
Three objectives



To assess lifestyle and identify other
cardiovascular risk factors or concomitant
disorders that may affect prognosis and treatment
To reveal identifiable causes of hypertension
To assess for the presence or absence of targetorgan damage or cardiovascular disease
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57
Treatment of Hypertension



A stepped-care approach as blood pressures
become greater than 140/90 or less than
130/80 mm Hg in patients with diabetes or
chronic kidney disease
Lifestyle modification: stage 1 or stage 2 and
everyone


Haveles (pp. 195, 197) (Fig. 15-4; Table 15-6)
Weight reduction, physical activity, a diet rich in
fruits and vegetables, reduced contents of
saturated and total fats, sodium restriction
Initial drug choices: once diagnosed with
stage 1 or stage 2 hypertension

Sex, race, presence of diabetes or hyperlipidemia,
and renin activity are taken into consideration
cont’d…
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58
Treatment of Hypertension


Haveles (pp. 195, 199) (Box 15-5)
The Big Five antihypertensive groups

Diuretics
 β-Blockers
 CCBs
 ACEIs
 ARBs
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59
Diuretic Agents for Hypertension


Haveles (pp. 197-200) (Fig. 15-6)
The three major types of diuretics are found



Thiazides (-like) diuretics
Loop diuretics
Potassium-sparing diuretics
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60
Thiazide Diuretics


Haveles (pp. 197, 199-200)
Among the most common agents for
treatment of hypertension


hydrochlorothiazide (HCTZ) is the most commonly
used thiazide
Many patients with stage 1 hypertension are
treated solely with HCTZ
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61
Mechanism of Action of Thiazide
Diuretics


Haveles (pp. 197, 199) (Table 15-8)
The exact mechanism by which thiazide
diuretics lower blood pressure has not been
determined



Initially inhibit sodium reabsorption from the distal
convoluted tubule and part of the ascending loop
of Henle of the kidney
Water and chloride ions passively accompany the
sodium, producing diuresis
Potassium excretion is also increased
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62
Adverse Reactions of Thiazide
Diuretics


Haveles (pp. 199-200) (Table 15-9)
Common adverse reactions include
hypokalemia (secondary to sodiumpotassium exchange) and hyperuricemia
(inhibits uric acid secretion)


Hyperglycemia, hyperlipidemia, hypercalcemia,
and anorexia are other side effects
Hyperuricemia is of special concern if the patient
has gout
cont’d…
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63
Adverse Reactions of Thiazide
Diuretics



Oral adverse reactions include xerostomia and,
rarely, oral lichenoid eruptions indistinguishable
from lichen planus
Nonsteroidal antiinflammatory drugs (NSAIDs) can
reduce the antihypertensive effect of the thiazide
diuretics
Thiazides can cause hypokalemia and can
sensitize the myocardium to developing
arrhythmias

The potential for arrhythmias is exacerbated in patients
taking digoxin, especially if digitalis toxicity is present
 Epinephrine also has arrhythmic potential; limit to
cardiac dose when patient is taking thiazide diuretics
and digitalis toxicity may be present
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64
Examples of Thiazide Diuretics



Haveles (p. 196) (Box 15-4)
chlorothiazide (Diuril)
hydrochlorothiazide (HCTZ, Esidrix)
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65
Loop Diuretics



Haveles (p. 200)
The “strong cousins of thiazides”
furosemide (Lasix) is the most commonly
used loop diuretic

Acts on the ascending limb of the loop of Henle
and has some effect on the distal tubule
 Inhibits reabsorption of sodium with concurrent
loss of fluids
cont’d…
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66
Loop Diuretics


Side effects include hypokalemia and
hyperuricemia
Used in management of hypertensive patients
with CHF

Can be used when rapid diuresis is desired
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67
Examples of Loop Diuretics




Haveles (p. 196) (Box 15-4)
bumetanide (Bumex)
furosemide (Lasix)
torsemide (Demadex)
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68
Potassium-Sparing Diuretics


Haveles (p. 200)
“Puny” diuretics with “potassium-catching”
ability (weak diuretic action)

Spironolactone: competitively antagonizes the
action of aldosterone
• Result is sodium excretion through diuresis and loss of
fluid volume

Triamterene: interferes with potassium-sodium
exchange in the distal and cortical collecting
tubules and the collecting duct by inhibiting sodiumpotassium adenosine triphosphate (ATPase)
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69
Examples of Potassium-Sparing
Diuretics





Haveles (p. 196) (Box 15-4)
amiloride (Midamor)
spironolactone (Aldactone)
triamterene (Dyrenium)
eplerenone (Inspra)
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70
Potassium Salts


Potassium salts are not cardiac drugs



Haveles (p. 200)
Lack of potassium caused by diuretics must be
managed, often with potassium supplementation
The most common adverse reaction relates to
the GI tract; includes nausea and abdominal
discomfort
Patients taking calcium salts should be
questioned about their use of diuretics
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71
β-Adrenergic Blocking Agents for
Hypertension


β-Adrenergic blockers are frequently used to
treat hypertension



Haveles (pp. 200-201)
β1-receptor stimulation is associated with increased
heart rate, cardiac contractility, and AV conduction
β2-receptor stimulation causes vasodilation of
skeletal muscle and bronchodilation in pulmonary
tissues
β-Adrenergic blockers inhibit these actions
cont’d…
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72
β-Adrenergic Blocking Agents for
Hypertension



Haveles (pp. 196, 201) (Box 15-4)
Nonselective β-adrenergic blocking drugs such
as propranolol, block both β1- and β2-receptors
In usual doses selective β-adrenergic blocking
drugs such as metoprolol, block β1-receptors
more than β2-receptors (β1 > β2 )

At larger doses, the selectivity disappears
• Pindolol and acebutolol have partial agonist
activity and cause some beta stimulation while
blocking catecholamine action
cont’d…
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73
β-Adrenergic Blocking Agents for
Hypertension


Haveles (pp. 200-201)
β-Adrenergic blockers lower blood pressure
by decreasing cardiac output

Side effects: bradycardia, mental depression, and
decreased sexual ability
 CNS effects: confusion, hallucinations, dizziness,
and fatigue have been reported
 GI tract effects: diarrhea, nausea, and vomiting
 Can produce xerostomia (very mild) or worsen a
patient’s lipid profile
 May exacerbate asthma, angina, or peripheral
vascular disease
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74
Dental Drug Interactions of βAdrenergic Blocking Agents


Nonselective β-blockers can have a drug
interaction with epinephrine


Haveles (p. 201)
May have a two- to fourfold increase in vasopressor
response resulting in hypertension
In patients with cardiovascular disease or higher
blood pressure, the amount of epinephrine given
to patients taking nonspecific β-blockers should
be limited to the cardiac dose unless blood
pressure monitoring accompanies the use of
larger doses

Usual doses can be given to patients taking specific
β-blockers or α- and β-blockers
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75
α- and β-Adrenergic Blocking
Drug for Hypertension


Haveles (p. 201)
Labetalol is a nonselective β-adrenergic
receptor blocking drug that also has αreceptor blocking activity

Reduces peripheral resistance through its αblocking action
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76
Examples of β-Adrenergic
Blocking Agents for Hypertension


Haveles (p. 196) (Box 15-4)
β-Adrenergic blockers

atenolol (Tenormin)
 betaxolol (Kerlone)
 bisoprolol (Zebeta)
 metoprolol (Lopressor) (Toprol-XL)
 nadolol (Corgard)
 propranolol (Inderal [LA])
 timolol (Blocadren)
cont’d…
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77
Examples of β-Adrenergic
Blocking Agents for Hypertension

β-Blockers with intrinsic sympathomimetic
activity




acebutolol (Sectral)
penbutolol (Levatol)
pindolol (Visken)
β-Blockers with α-blocking activity


carvedilol (Coreg)
labetalol (Normodyne, Trandate)
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78
Calcium Channel Blocking
Agents for Hypertension


Haveles (pp. 201-202)
Many CCBs end in the suffix -dipine

Used to treat hypertension and other cardiac
conditions such as arrhythmias and angina
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79
Mechanism of Calcium Channel
Blocking Agents


Haveles (p. 201)
Inhibit the movement of extracellular calcium
ions into cells, including vascular smoothmuscle and cardiac cells

Produces vasodilation, which produces coronary
vasodilation and reverses vasospasms
 By producing systemic vasodilation CCBs reduce
the afterload on the heart

Useful in treatment of both angina pectoris
and hypertension
cont’d…
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80
Mechanism of Calcium Channel
Blocking Agents

At least four types of calcium channels (L, T,
N, and P) have been discovered


Current CCBs are all of the L type
The decrease in transmembrane calcium
current results in relaxation of vascular
smooth-muscle cells and a reduction in
cardiac contractility and conduction
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81
Pharmacologic Effects of Calcium
Channel Blocking Agents for
Hypertension



Haveles (p. 201)
Smooth muscle: vascular smooth muscle is
relaxed and dilation of coronary and peripheral
arteries and arterioles occur, reducing preload
Cardiac muscle: may reduce heart rate,
decrease myocardial contractility (negative
inotropic effect), and slow AV nodal conduction
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82
Adverse Reactions of Calcium
Channel Blocking Agents


Haveles (pp. 201-202)
Extensions of pharmacologic effects




CNS: can produce excessive hypotension, which
can cause dizziness and lightheadedness,
headache
GI: nausea, vomiting, and constipation
Cardiovascular: bradycardia and edema
Other: shortness of breath due to pulmonary
edema has been reported
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83
Oral Manifestations of Calcium
Channel Blocking Agents


Haveles (p. 202)
Include xerostomia, dysgeusia, gingival
enlargement


On discontinuation of the CCB, the gingival
enlargement usually reverts to normal tissue and
does not reappear
If not, gingivectomy or gingivoplasty may be
required
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84
Dental Drug Interactions of Calcium
Channel Blocking Agents


carbamazepine (Tegretol) is used for
trigeminal neuralgia


Haveles (p. 202)
Diltiazem and verapamil may increase serum
levels of carbamazepine, resulting in toxicity
Both nausea and constipation, side effects of
CCBs, could be additive with side effects
produced by NSAIDs (nausea) and opioids
(constipation)
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85
Examples of Calcium Channel
Blocking Agents


CCBs



Haveles (p. 196) (Box 15-4)
diltiazem (Cardizem [SR], Dilacor [XR])
verapamil (Isoptin [SR], Calan [SR])
Dihydropyridines

amlodipine (Norvasc)
 felodipine (Plendil)
 isradipine (DynaCirc)
 nicardipine (Cardene [SR])
 nifedipine (Procardia [XL], Adalat [CC])
 nisoldipine (Sular)
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86
Angiotensin-Related Agents


Haveles (pp. 202-203)
Two types of drugs whose mechanism involves
angiotensin


ACEIs
ARBs
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87
Angiotensin-Converting Enzyme
Inhibitors


Haveles (pp. 202-203)
ACEIs prevent the conversion of angiotensin I
to angiotensin II


ACEI drugs are commonly used as
antihypertensives
Many ACEIs end in -pril
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88
Mechanism of AngiotensinConverting Enzyme Inhibitors


The renin-angiotensin-aldosterone system
adjusts the quantity of sodium and water
retained (circulatory volume) and the peripheral
resistance (blood vessels)




Haveles (p. 202) (Fig. 15-7)
When the kidney senses a decrease in blood
pressure or flow it releases renin
Renin catalyzes the conversion of angiotensinogen
(inactive precursor) to angiotensin I
ACE converts angiotensin I to angiotensin II
ACE is the enzyme blocked by ACEIs
cont’d…
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89
Mechanism of AngiotensinConverting Enzyme Inhibitors

Angiotensin II produces vasoconstriction and
stimulates the adrenal cortex to release
aldosterone, facilitating water retention

By blocking these events, blood pressure is
lowered
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90
Adverse Reactions of AngiotensinConverting Enzyme Inhibitors


Haveles (pp. 202-203) (Box 15-6)
The most common adverse reactions are related
to the cardiovascular system and the CNS


Cardiovascular: hypotension has produced dizziness,
lightheadedness, and fainting
• Tachycardia and chest pain have been noted
CNS: side effects may include dizziness, insomnia,
fatigue, and headache
cont’d…
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91
Adverse Reactions of AngiotensinConverting Enzyme Inhibitors



Haveles (pp. 202-203) (Box 15-6)
GI: nausea, vomiting, and diarrhea can occur
Respiratory: an increase in upper respiratory
symptoms, including a dry, hacking cough
can occur

It occurs because the ACE also inactivates
bradykinin, a potent stimulator of allergic reactions
cont’d…
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92
Adverse Reactions of AngiotensinConverting Enzyme Inhibitors

Allergic-like reactions



Angioedema: swelling of the extremities, face, lips,
mucous membranes, tongue, glottis, or larynx can
occur
Rash
Other: because teratogenicity can cause fetal
and neonatal morbidity and mortality, ACEIs
should not be given to women who could be or
become pregnant
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93
Oral Adverse Reactions of
Angiotensin-Converting Enzyme
Inhibitors


Dysgeusia: an altered sense of taste is reported
in about 6% of patients taking captopril


Haveles (pp. 202-203)
Usually reversible after a few months, even with
continued drug treatment
Autoimmune oral lesions: lichenoid or
pemphigoid reactions may produce oral
manifestations

May have a photosensitivity factor
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94
Dental Drug Interactions of
Angiotensin-Converting Enzyme
Inhibitors


The antihypertensive effectiveness of ACEIs is
reduced by administration of the NSAIDs


Haveles (p. 203)
Chronic administration for several days may result in
an increase in the patient’s blood pressure
ACEIs may be used alone or in combination with
a β-blocker, thiazide diuretic, or CCB
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95
Examples of Angiotensin-Converting
Enzyme Inhibitors for Hypertension











Haveles (p. 196) (Box 15-4)
benazepril (Lotensin)
captopril (Capoten)
enalapril (Vasotec)
fosinopril (Monopril)
lisinopril (Zestril, Prinivil)
moexipril (Univasc)
perindopril (Aceon)
quinapril (Accupril)
ramipril (Altace)
trandolapril (Mavik)
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96
Angiotensin Receptor Blockers



Haveles (p. 203)
ARBs attach to the angiotensin II receptor
and block the effect of angiotensin II
losartan (Cozaar) is the prototype

losartan a high affinity and selectivity for the AT1receptor
 It blocks the vasoconstrictor and aldosteronesecreting effects of angiotensin II
 An increase in plasma renin level follows
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97
Adverse Reactions of
Angiotensin Receptor Blockers


Haveles (p. 203)
ARBs are more specific than ACEIs and may
be expected to have fewer adverse reactions

CNS: effects can include dizziness, fatigue,
insomnia, and headache
 Upper respiratory infections occur more often in
patients taking losartan
 GI: losartan can produce diarrhea
 Pain: both muscle cramps and leg and back pain
have been reported with losartan
 Angioedema can occur, rarely
 Teratogenicity can occur if losartan is administered
to pregnant women
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98
Dental Drug Interactions of
Angiotensin Receptor Blockers


Haveles (p. 203)
NSAIDs may antagonize the antihypertensive
effect of losartan by inhibiting renal
prostaglandin synthesis or causing sodium
and fluid retention
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99
Examples of Angiotensin
Receptor Blockers








Haveles (p. 196) (Box 15-4)
candesartan (Atacand)
eprosartan (Tevetan)
irbesartan (Avapro)
losartan (Cozaar)
olmesartan (Benicar)
telmisartan (Micardis)
valsartan (Diovan)
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100
Renin Inhibitors


Haveles (p. 203)
aliskiren (Tekturna): the first of a new class of
drugs approved by the U.S Food and Drug
Administration for treatment of hypertension

Works by binding to renin which then reduces the
levels of angiotensin I, angiotensin II, and
aldosterone
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101
α1-Adrenergic Blocking Agents
for Hypertension


Haveles (p. 204)
The adrenergic blockers include the αblockers and β-blockers previously described

Two α-receptor subtypes have been identified, α1
and α2
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102
Mechanism of α1-Adrenergic
Blocking Agents for Hypertension

α1-Receptors, located on postsynaptic
receptor tissues, produce vasoconstriction and
increase peripheral resistance when
stimulated



α1-Blocking agents produce peripheral vasodilation
in the arterioles and venules that decreases
peripheral vascular resistance
α1-Adrenergic blockers result in a reduction in
urethral resistance and pressure, bladder outlet
resistance, and urinary symptoms
Used in management of older men who have
an enlarged prostate gland
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103
Adverse Reactions of α1-Adrenergic
Blocking Agents for Hypertension




Haveles (p. 204)
Orthostatic hypotension: can result in
dizziness or syncope
CNS: α1-adrenergic blockers can cause CNS
depression, producing either drowsiness or
excitation and headache
Cardiovascular: tachycardia, arrhythmias,
and palpitations can occur

Peripheral edema is another side effect
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104
Dental Drug Interactions of α1Adrenergic Blocking Agents for
Hypertension


Haveles (p. 204) (Box 15-7)
NSAIDs, especially indomethacin, can reduce
antihypertensive effect of the α1-blockers

Inhibit renal prostaglandin synthesis or cause sodium
and fluid retention
cont’d…
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105
Dental Drug Interactions of α1Adrenergic Blocking Agents for
Hypertension


Haveles (p. 204) (Box 15-7)
Epinephrine: sympathomimetics can increase
the antihypertensive effect of doxazosin


α1-Blockers prevent α1-agonist effects
(vasoconstriction) of epinephrine, leaving the β1agonist and β2-agonist effects (vasodilation) to
predominate
Can result in severe hypotension and reflex
tachycardia
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106
Uses of α1-Adrenergic Blocking
Agents for Hypertension


Haveles (p. 204)
Both doxazosin and terazosin are indicated
for the management of benign prostatic
hypertrophy (BPH) in addition to the
treatment of hypertension
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107
Examples of α1-Receptor Antagonists
(Blockers) for Hypertension




Haveles (p. 196) (Box 15-4)
doxazosin (Cardura)
prazosin (Minipress)
terazosin (Hytrin)
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108
Other Antihypertensive Agents


Haveles (p. 204)
These antihypertensive agents are used less
often than those previously described
because they generally have more or less
tolerated adverse reactions

Clonidine
 Other centrally acting antihypertensive agents
• Guanethidine
• Reserpine
• Hydralazine
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109
clonidine
(Catapres)


A CNS-mediated (centrally acting)
antihypertensive drug that reduces peripheral
resistance through a CNS-mediated action on
the α-receptor



Haveles (p. 204)
Stimulation of presynaptic central α2-adrenergic
receptors results in decreased sympathetic outflow
Reduces heart rate, cardiac output, and total
peripheral resistance
May be administered orally or by transdermal
patch
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110
Adverse Reactions of Clonidine


Include a high incidence of sedation and
dizziness


Haveles (p. 204)
Rapid elevation of blood pressure has occurred
with abrupt discontinuation
CNS depressants employed in dental
conscious-sedation techniques may
contribute to postural hypotension when used
in a patient taking clonidine
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111
Oral Effects of Clonidine


Haveles (p. 204)
A high incidence of xerostomia (40%), parotid
gland swelling, and pain

Another side effect is dysgeusia
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112
Other Centrally Acting
Antihypertensive Agents


Two other centrally acting antihypertensive
agents are also available


Haveles (pp. 204-205)
methyldopa (Aldomet) and guanabenz (Wytensin)
Adverse effects and indications are similar to
clonidine

May be combined with diuretics in essential
hypertension management
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113
guanethidine
(Ismelin)



Severe adverse reactions severely limits its use
Blocks the release of norepinephrine from the
sympathetic nerve endings



Haveles (pp. 198, 204-205) (Fig. 15-5)
Also depletes the amount of norepinephrine stored in
synaptic vesicles
Reduces sympathetic nervous system tone and
decreases blood pressure
Causes severe postural and exertional
hypotension
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114
Reserpine




Haveles (p. 205)
Depletes norepinephrine from the sympathetic
nerve endings
Adverse effects include diarrhea, bad dreams,
sedation, and even psychic depression leading
to suicide
Aggravates peptic ulcers
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115
hydralazine
(Apresoline)



Acts directly on arterioles to reduce peripheral
resistance (vasodilation)
At the same time a rise in heart rate and output
occurs



Haveles (p. 205)
Propranolol is often administered concurrently to
reduce the tachycardia and increased cardiac output
Side effects include cardiac arrhythmias,
angina, headache, and dizziness
The drug of choice for treatment of a pregnant
hypertensive woman
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116
Management of the Dental Patient
Taking Antihypertensive Agents







Haveles (p. 205) (Box 15-8)
Check for xerostomia and its management
If taking a CCB, check for gingival enlargement
Check blood pressure before each appointment
Avoid dental agents that add to side effects
such as opioids
If on diuretics, check for symptoms of
hypokalemia, which may exacerbate
arrhythmias from epinephrine
If taking an ACEI, check for symptoms of
neutropenia
cont’d…
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117
Management of the Dental Patient
Taking Antihypertensive Agents


Haveles (p. 205)
Adverse reactions

Xerostomia
 Dysgeusia
 Gingival enlargement
 Orthostatic hypotension
 Constipation
 Central nervous system sedation
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118
Antihyperlipidemic Agents






Haveles (pp. 205-207)
3-Hydroxy-3-methylglutaryl coenzyme A (HMG
CoA) reductase inhibitors
Niacin
Cholestyramine
Gemfibrozil
Dental Implications
cont’d…
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119
Antihyperlipidemic Agents


Haveles (p. 205)
Hyperlipidemia and hyperlipoproteinemia are
elevations of plasma lipid concentrations above
accepted normal values


These metabolic distortions include elevations in
cholesterol and/or triglycerides and are associated
with the development of arteriosclerosis
Many different types of hyperlipoproteinemias may
result in elevations of chylomicrons, very-low-density
lipoproteins (VLDLs), low-density lipoproteins (LDLs),
or combinations of these
cont’d…
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120
Antihyperlipidemic Agents

Foam cells, more prevalent in uncontrolled
diabetes, become filled with cholesterol esters



Accumulation of esters leads to deposition of lipids in
arteries
Collagen and fibrin also accumulate, occluding the
vessels
Atherosclerosis can lead to coronary artery
disease, myocardial infarction, and cerebral
artery disease

Endothelium over the plaques activates platelets
leading to formation of thrombi and clinical symptoms
cont’d…
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121
Antihyperlipidemic Agents


Haveles (p. 205)
Cholesterol and other plasma lipids are
carried in the blood as protein complexes to
make them more soluble in plasma


LDLs carry the greatest concentration of
cholesterol and are considered to be the most
dangerous
High-density lipoproteins (HDLs) carry the least
cholesterol and are considered to be beneficial
cont’d…
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122
Antihyperlipidemic Agents


The first line of treatment is increasing
exercise and decreasing saturated fat and
cholesterol from the diet



Haveles (pp. 205-206) (Table 15-12)
Drug therapy of hyperlipoproteinemia is directed at
lowering the level of LDL cholesterol
Some are more specific for cholesterol and some
are more specific for triglycerides
Drugs include bile acid-binding resins, niacin,
gemfibrozil, and HMG CoA reductase
inhibitors
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123
3-Hydroxy-3-Methylglutaryl
Coenzyme A Reductase Inhibitors


Often called “statins” because generic names
end in that suffix


Haveles (p. 206)
lovastatin (Mevacor) is an example
They lower cholesterol levels by inhibiting
HMG-CoA reductase, the rate-limiting enzyme
in cholesterol synthesis
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124
Adverse Effects of 3-Hydroxy-3Methylglutaryl Coenzyme A
Reductase Inhibitors


Haveles (p. 206)
GI complaints, myositis, skin rash, impotence,
hepatotoxicity, blurred vision, and lens opacities


Myositis results in complaints of muscle pain
Can increase anticoagulant effect of warfarin
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125
Inhibitors of Intestinal Absorption
of Cholesterol


Haveles (pp. 206-207)
ezetimibe (Zetia): works by inhibiting
intestinal absorption of cholesterol


Currently comes in combination with simsvastin to
treat cholesterol from two different mechanisms of
action
Side effects include fatigue, abdominal pain, and
diarrhea
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126
Niacin


Haveles (p. 207)
Overview



A B vitamin: in large doses, lowers cholesterol
levels by inhibiting the secretion of VLDLs without
accumulation of triglycerides in the liver
At larger doses, commonly produces cutaneous
flushing and a sensation of warmth after each
dose
• This is blocked by pretreatment with aspirin or ibuprofen
Hyperuricemia, allergic reactions, cholestasis, and
hepatotoxicity have been reported
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127
Dental Implications of Niacin


Haveles (p. 207)
Hypotension may occur as a result of
vasodilation
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128
Cholestyramine


Haveles (p. 207)
Bile acid–binding resins lower cholesterol
because cholesterol is a precursor required
for the synthesis of new bile acids

When the resins bind with bile acids, they produce
an insoluble product lost through the GI tract
 Bile acids use up cholesterol, thereby reducing
cholesterol levels
cont’d…
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129
Cholestyramine

Adverse reactions relate to the GI tract and
include constipation and bloating

Patients often abandon their use
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130
gemfibrozil
(Lopid)


Haveles (p. 207)
Used to treat hyperlipidemias, especially
when triglycerides are elevated

Increases lipolysis of triglycerides, decreasing
lipolysis in adipose tissue, and inhibiting secretion
of VLDLs from the liver
cont’d…
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131
Gemfibrozil

Adverse reactions


Can promote gallstone formation (cholelithiasis)
Taste perversion and hyperglycemia have been
reported
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132
Dental Implications of
Antihyperlipidemic Agents


Haveles (p. 207)
Patients who take antihyperlipidemic agents
have a higher risk of atherosclerosis and are
at increased risk for cardiovascular
emergencies (not because of the drug but
because of the condition for which the drug is
prescribed)

GI and liver abnormalities are side effects
associated with many of these drugs
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133
Examples of Antihyperlipidemic
Agents


HMG-CoA reductase inhibitors (statins)






Haveles (p. 206) (Table 15-10)
atorvastatin (Lipitor)
fluvastatin (Lescol)
lovastatin (Mevacor)
pravastatin (Pravachol)
simvastatin (Zocor)
Bile acid sequestrants


cholestyramine (Questran, Prevalite)
colestipol (Colestid)
cont’d…
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134
Examples of Antihyperlipidemic
Agents


Miscellaneous





Haveles (p. 206) (Table 15-10)
clofibrate (Atromid-S)
ezetimibe (Zetia)
ezetimibe/simvastin (Vytorin)
nicotinic acid (Niacin)
fibrates


fenofibrate (Lipidil-DSC, Tricor)
gemfibrozil (Lopid)
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135
Drugs that Affect Blood
Coagulation


Anticoagulants









Haveles (pp. 207-211)
Hemostasis
Warfarin
Heparin
Clopidogrel
Ticlopidine
Streptokinase and alteplase
Dipyridamole
Pentoxifylline
Drugs that increase blood clotting
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136
Anticoagulants


Haveles (p. 207)
Drugs that interfere with coagulation


Administered in an attempt to prevent clotting
Examples of indications for warfarin (Coumadin)
are after a MI or thrombophlebitis
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137
Hemostasis


Haveles (pp. 207-208) (Fig. 15-8)
Designed to prevent loss of blood after injury
to a blood vessel


Thromboplastin; factors V, VII, and X; and calcium
ions form prothrombin, thrombin, and finally
fibrinogen and fibrin
Fibrin, along with vascular spasms, platelets, and
red blood cells quickly forms the clot
cont’d…
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138
Hemostasis

If the blood vessel’s interior remains smooth,
circulating blood does not clot


If internal injury to the vessel occurs and a
roughened surface develops, intravascular clotting
will take place
Many factors required in the clotting process
are synthesized in the liver


Prothrombin (II) and factors VII, IX, and X require
vitamin K for synthesis
Warfarin antagonizes vitamin K and interferes with
the synthesis of four clotting factors to produce an
anticoagulant effect
cont’d…
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139
Hemostasis

Intravascular clots can form in certain
diseases


Clots or thrombi may break off, forming emboli that
lodge in the smaller vessels of major organs such
as the heart, brain, and lungs
Anticoagulant therapy attempts to reduce
intravascular clotting


If the dose is too large, hemorrhage may occur
If the dose is too small, the danger of embolism
remains
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140
Warfarin
(Coumadin)


An oral anticoagulant that blocks the γcarboxylation of glutamate residues in the
synthesis of factors VII, IX, and X,
prothrombin (II), and endogenous
anticoagulant protein C


Haveles (pp. 208-209)
Prevents the metabolism of the inactive vitamin K
epoxide back to its active form
The pharmacologic effect is delayed when
therapy begins and ends
cont’d…
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141
Warfarin
(Coumadin)


Haveles (p. 208) (Fig. 15-9)
Monitoring: the effect of warfarin is monitored
using the INR


A function of the prothrombin time (PT) of the
patient, PT of control, and the international
sensitivity index (ISI)
The target INR for most indications is between 2
and 3, it can range from 1 to 4
cont’d…
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142
Warfarin
(Coumadin)


Haveles (p. 208)
Adverse reactions: the most common adverse
effects are various forms of bleeding


Look for petechial hemorrhages on the hard palate
Ecchymoses can occur, even without trauma
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143
Warfarin-Aspirin Interaction


Haveles (p. 208) (Table 15-11)
Patients taking warfarin should not be given
aspirin or aspirin-containing products,
bleeding episodes or fatal hemorrhages can
result


Aspirin causes hypoprothrombinemia and alters
platelet adhesiveness
• Can irritate the gastrointestinal tract
Aspirin and warfarin compete for the same plasma
protein-binding site
• Increases the proportion of free (unbound) warfarin in the
blood
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144
Warfarin-Acetaminophen
Interaction


Haveles (p. 209)
A statistically significant association was
found between acetaminophen use and the
abnormal elevation of the INR

Toxicity has not been proved
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145
Warfarin-Antibiotics Interaction


Haveles (p. 209) (Table 15-12)
Antibiotics can potentiate the effect of warfarin

Antibiotics reduce the bacterial flora in the GI tract
that normally synthesize vitamin K
 This results in a decrease in vitamin K absorbed
 Because warfarin also inhibits vitamin K–dependent
factors, an added anticoagulant effect occurs

This interaction does not have a chance to
develop when antibiotics are used before a
dental procedure
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146
Management of the Dental
Patient Taking Warfarin



Haveles (p. 209) (Box 15-9)
Bleeding: consult with physician regarding PT
or INR
Analgesics: aspirin is contraindicated unless
the patient is taking one aspirin daily for its
anticoagulant effect
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147
Heparin


One of the most commonly used
anticoagulant agents for hospitalized patients




Haveles (pp. 209-210)
Administered by injection; not used orally
Used after MI, stroke (embolism), or
thrombophlebitis
When heparin is started, warfarin is also
begun
An overdose of heparin is antagonized by
protamine sulfate
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148
clopidogrel
(Plavix)


Haveles (p. 210)
An inhibitor of adenosine diphosphate (ADP)induced platelet aggregation


Indicated for patients with recent history of MI or
stroke, established peripheral arterial disease, and
for patients with acute coronary artery syndrome
Side effects include thrombotic thrombocytopenia
purpura (TTP) and increased bleeding
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149
ticlopidine
(Ticlid)


Haveles (p. 211)
An irreversible inhibitor of ADP-induced
platelet aggregation, which results in
increased bleeding time

Indicated to decrease thrombotic stroke in patients
with previous stroke
 Used in patients who are intolerant of aspirin
 Major side effect is neutropenia
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150
streptokinase (Streptase,
Kabikinase) and alteplase (tPA,
Activase)


Haveles (p. 211)
Enzymes, called “clotbusters” are sometimes
used in the therapy of deep vein thrombosis,
arterial thrombosis, pulmonary embolism, and
acute coronary artery thrombosis associated
with myocardial infarction

Called thrombolytic drugs because they promote
conversion of plasminogen to plasmin, the natural
clot-resolving enzyme
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151
dipyridamole
(Persantine)


Haveles (p. 211)
Used to prolong the life of platelets in patients
with prosthetic heart valves

Artificial valves cause premature death of platelets
due to their mechanical effect (trauma) on blood
cells passing through the valves
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152
pentoxifylline
(Trental)


Haveles (p. 211)
Improves blood flow by its hemorheologic
effect



Lowers blood viscosity and improves flexibility of
red blood cells
Indicated for claudication (limping) produced by
chronic occlusive artery disease of the limbs
Side effects include cardiovascular and gastric
symptoms
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153
Drugs that Increase Blood
Clotting


Haveles (p. 211)
Hemostatic Agents (fibrinolytic inhibitors)


Aminocaproic acid (EACA) and tranexamic acid
(Cyklokapron) are similar to the amino acid lysine,
and they inhibit plasminogen activation
Adverse effects include intravascular thrombosis,
hypotension, and abdominal discomfort
• Used in the treatment of hemorrhage after surgery
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154