Pharmacotherapy of heart failure

Abera J. (BPharm., MSc in Clinical Pharmacy)

School of Pharmacy, CHMS, HU.

07/08/2022 By; Abera J 1

 Introduction
• Heart failure (HF)
– a clinical syndrome caused by the inability of the heart to pump
sufficient blood to meet the metabolic demands of the body

• Result from any abnormality in cardiac structure or function that

reduces
– Ventricular filling (diastolic dysfunction) and/or

– Myocardial contractility (systolic dysfunction)

 Introduction…
Systolic dysfuncton
– When the pumping action of the heart is reduced or weakened
 As a result of an increase in wall stress
– EF is a common clinical measurement
• Calculated as stroke volume divided by maximum
volume remaining in LV after diastole
» Normal ≥ 40-50%
• HF < 40%
– In Systolic HF, decrease in EF results in decrease in SV and
CO.
 Introduction…
Diastolic dysfunction
– HF with preserved LVEF (HFpEF)
– EF is normal or slightly abnormal
– Results from disturbances in relaxation properties of the
heart
 Decreases proper filling of blood in the heart causing it
to back up in the lungs
– Accounts for 50% of patients with HF
 The underlying pathophysiologic process and principal
clinical manifestations
– Similar for both systolic and diastolic dysfunction
 Introduction…
• HF can be right sided or left sided
– When the left side of the heart fails, then fluid collects
in the lungs (pulmonary edema)
• Difficult for airways to expand
• Breathing difficulty
• SOB( with activity or lying down)
– When the right side of the heart fails, the fluid collects
in the feet and lower legs;
– May also progress to abdomen causing ascites
 Introduction...
• HF can be low output or high output failure

– low output HF
• Accounts for >90% of cases

• Results in a diminished volume of blood being

pumped by a weakened heart in patients who have
otherwise normal metabolic needs
 Introduction…
– High-output HF
• the heart is healthy and pumps a normal or even higher
than normal volume of blood
• Discrepancy in supply and demand results from high
metabolic demands caused by other underlying medical
disorders
– e.g., hyperthyroidism, anemia
• Primary treatment is amelioration of the underlying
disease
 Epidemiology
• Affects about 5 million people
 550,000 new cases each year

• After diagnosis 30-50% die within 1 year, 80% within 5 years

• CHF is the leading cause of hospitalization in elderly patients

• Responsible for >11 million visits to a physician's office and

result in 3.5 million hospitalizations per year
• Each year, 250,000 people die from CHF
 Etiology
• Systolic dysfunction (decreased contractility)
– CAD (70%)
– Reduction in muscle mass (e.g. myocardial infarction)
– DCM
– VH
• Pressure overload (e.g. systemic or pulmonary
hypertension, and aortic or pulmonic valve stenosis)
• Volume overload (e.g. valvular regurgitation, shunts,
and high-output states)
 Etiology…
• Diastolic dysfunction (restriction in ventricular filling)

– Increased ventricular stiffness

 VH (e.g., hypertrophic cardiomyopathy; pressure overload,
volume overload)
 Myocardial ischemia and infarction

– Mitral or tricuspid valve stenosis

– Pericardial disease (e.g. pericarditis)

 Etiology…

• Modifiable risk factors for HF

 Uncontrolled HTN

 CHD

 Smoking and

 CKD
 Pathophysiology of HF
• When heart fails CO is reduced

CO = HR x SV
 HR
 Controlled by the ANS

 Stroke volume: depends on

 Preload

 Afterload, and

 Contractility
 Pathophysiology…
 Preload
 Determined by left ventricular end-diastolic volume
(LVEDV)
 The ability of the heart to alter the force of contraction
depends on changes in preload
 LVED pressure - used in the clinical setting to estimate
preload
 Frank-Starling mechanism
in preload-----myocardial sarcomere length-----
number of cross-bridges between thick and thin
myofilaments-----force of contraction-----SV-----
CO
 Pathophysiology…
Afterload
– The sum of forces preventing active forward ejection of
blood by the ventricle
– Major components include;
• Ejection impedance
• Wall tension and
• Regional wall geometry
• Contractility
– The intrinsic property of cardiac muscle
– Describes fiber shortening and tension dev’t
 Pathophysiology…
• As a result of decrease in CO in HF

– The heart will rely on compensatory responses to maintain an

adequate CO
– These compensatory responses include;

• Activation of SNS
• Activation of RAAS

– Increased preload
– Vasoconstriction

– VH and remodeling
 Pathophysiology…
• Compensatory responses
– Intended to provide short-term support to maintain
circulatory homeostasis
– However, long-term activation
• Results in complex functional, structural,
biochemical, and molecular changes that leads to
HF
Beneficial and Detrimental Effects of the
Compensatory Responses in HF
 Signs and symptoms
• Symptoms • Abdominal pain
– DOE • Anorexia
– Orthopnea • Bloating
– PND • Poor appetite, early satiety
– Exercise intolerance • Ascites
– Tachypnea • Mental status changes
– Cough
– Fatigue
– Hemoptysis
 Signs and symptoms…
• Signs
• Cardiomegally
– Pulmonary edema
• Peripheral edema
– Cool extremities • JVD
• Hepatojugular reflux
– Pleural effusion
• Hepatomegaly
– Tachycardia
 Signs and symptoms…
• Laboratory Tests
– BNP >100 pg/mL
– Electrocardiogram
• May be normal, or acute ST-T wave changes
– Elevated SCr
– Complete blood count (CBC)…….Anemia
– Chest x-ray: useful for detecting
Cardiac enlargement
Pulmonary edema, and
Pleural effusions
 Signs and symptoms…
 Echocardiogram: used to assess
– The size of the LV
– Valve function
– pericardial effusion
– Wall motion abnormalities, and
– EF
 Hyponatremia…...associated with reduced survival and
may indicate worsening volume overload and/or disease
progression
 Diagnosis
 A complete history and physical examination targeted
at identifying cardiac or noncardiac disorders
 A careful medication history
 Laboratory testing
– BNP
– CBC
– Electrolytes (including calcium and magnesium)
– Thyroid function tests
– Chest x-ray
– ECG
 Classification…ACC/AHA
ACC/AHA Description
stage
A Pts at high risk for developing HF e.g. HTN, CAD,
DM, dyslipidemia, obesity
B Pts with structural heart disease but no HF sign or
symptoms e.g. previous MI, left ventricular
dysfunction, left ventricular hypertrophy

C Pts with structural heart disease but previous or

current HF sign or symptoms
e.g. LV systolic dysfunction and symptoms such as
dyspnea, fatigue
D Refractory HF requiring specialized intervention

07/08/2022 By; Abera J 23

 Classification…NYHA
NYHA Description
class
I Pts with cardiac disease but without limitations of physical
activity. Ordinary physical activity does not cause undue
fatigue, dyspnea, or palpitation
II Pts with cardiac disease that results in slight limitations of
physical activity. Ordinary physical activity results in
fatigue, palpitation, dyspnea, or angina.
III Pts with cardiac disease that results in marked limitation of
physical activity. Although patients are comfortable at rest,
less than ordinary activity will lead to symptoms

IV Pts with cardiac disease that results in an inability to carry on

physical activity without discomfort. Symptoms of CHF are
present even at rest. With any physical activity, increased
discomfort is experienced.
 Treatment of HF
Goal of therapy
– To improve the patient's QoL
– To relieve or reduce symptoms
– To prevent or minimize hospitalizations for
exacerbations of HF
– To slow progression of the disease process
– To prolong survival
 Non-pharmacologic Therapy
• Restriction of physical activity
– For Pt’s with acute congestive symptoms
• Encourage physical activity
– Once the Pt's symptoms have stabilized and excess
fluid is removed
• Restriction of dietary sodium and fluid intake
– Mild (<3 g per day)
– Moderate (<2 g per day) sodium restriction
 Non-pharmacologic treatment…
• Restriction of fluid intake
– In Pts with hyponatremia (serum Na <130 mEq/L) or
– In those with persistent volume retention despite high
diuretic doses and sodium restriction,
• fluid intake- 2 L per day from all sources
• Immunization against influenza and pneumococcus
– Reduce the risk of respiratory infections
• Avoidance of medications that can exacerbate HF
 Treatment of HF
• Treatment of Stage A HF
– Identification and modification of risk factors
– Treat according to current guidelines;
• HTN, Dyslipidemia, DM, CAD, and metabolic
syndrome
Additional risk factors that require modifications
includes;
• Obesity
• Smoking
 Treatment of HF…
• Treatment of Stage B HF
– Treatment is targeted at minimizing additional injury and
– Preventing or slowing the remodeling process
• In addition to the treatment measures outlined in stage A
– ACEIs and BBs are important components of therapy
• Pts with a previous MI, reduced LVEF (<40%)
– ACEIs+ BBs
– Alternative: ARBs in Pts intolerant to ACEI
 Treatment of HFrEF
Treatment of Stage C HF
• Continue the treatments in Stages A and B
• In stage C, HF Pts should be treated with three
medications
 An ACEIs and
 A β-blocker
 A diuretic (if there is evidence of fluid retention)
• These medications are effective in
 Slowing HF progression
 Reducing morbidity and mortality
 Improving symptoms
 Treatment of HFrEF…
Treatment of Stage C HF
• An aldosterone receptor antagonist should also be
considered in selected Pt’s
• Digoxin therapy
 For symptom reduction
 To decrease hospitalizations, or
 Slow ventricular response in Pts with concomitant
AF
 Treatment of HFrEF…
Diuretics
 Sodium and water retention
result from activation of the compensatory mechanisms
lead to pulmonary and systemic congestion
 Diuretic therapy
Recommended in all Pts with clinical evidence of fluid
retention
Produces symptomatic benefits
Improve exercise tolerance and QoL, and
Reduce hospitalizations from HF
 Treatment of HFrEF…

 Diuretics do not

Prolong survival or

Alter disease progression (with the possible exception

of torsemide)
 Chronic diuretic therapy to maintain euvolemia
 Treatment of HFrEF…
 Includes
 Furosemide: 20-160 mg QD or BID
 CrCl 20-50 ml/min: 160 mg QD or BID
 CrCl <20 ml/min: 400 mg QD
 Bumetanide: 0.5-2 mg QD or BID
 CrCl 20-50 ml/min: 2 mg QD or BID
 CrCl <20 ml/min: 8-10 mg QD
 Torsemide: 10-80 mg QD
 CrCl 20-50 ml/min: 40 mg QD
 CrCl <20 ml/min: 200 mg QD
 Treatment of HFrEF…
Diuretic therapy
• Change in body weight: a sensitive marker of fluid
retention or loss
– Monitor daily morning body weights
 Gain of 1.4 to 2.3 kg in a week: increase dose
of diuretic
• Monitor for volume depletion: Hypotension or
worsening renal function (e.g., increases in SCr)
 Treatment of HFrEF…
Diuretic therapy
• SEs
– Hypovolemia, thirst, hypotension, hyponatremia,
hypokalemia, hypomagnesemia, renal
dysfunction,
• Monitor
– BP, electrolytes, BUN, SCr, glucose, change in
body weight, JVD- reassess after 1-2 weeks of
treatment initiation or dose change
 Diuretic resistance
• The maximal response to diuretics is reduced in HF,
– creating a “ceiling dose” above which there is limited added
benefit
- Compensatory increase in sodium reabsorption in the distal
tubules, which decreases the effect of blocking sodium
reabsorption in the loop of henle
- Simultaneous increase in the reabsorption of sodium from
the proximal tubule, allowing less to reach the site of action
for loop diuretics
07/08/2022 By; Abera J 37
 Diuretic resistance…
• Mechanism /options to overcome diuretic resistance;
- Frequency of dosing to two or three times daily
- Utilizing a continuous infusion of a loop diuretic,
and/or ( not yet proven)
- Combining a loop diuretic with a thiazide diuretic
(Metolazone)
– While metolazone is more commonly used in
combination with loop diuretics, there is no
evidence to support its superiority over other
thiazide diuretics

07/08/2022 By; Abera J 38

 Treatment of HFrEF…
ACE Inhibitors
• Decrease the production of angiotensin II and in turn
aldosterone
• Reduce HF progression including;
 Ventricular remodeling
 Myocardial fibrosis
 Cardiac hypertrophy
 NE release
 Vasoconstriction and
 Sodium and water retention
 Treatment of HFrEF…
ACE Inhibitors
– Improve survival by 20% to 30%
– Reduce the risk of death or hospitalization
– Slow the progression of HF, and
– Reduce the rate of reinfarction (Post-MI)
• Includes;
 Captopril: 6.25-50 mg TID
 Enalapril: 2.5-20 mg BID
 Lisinopril: 2.5- 40 gm QD
 Fosinopril: 5-40 mg QD
 Ramipril: 1.25 mg-5 mg BID
 Start with low dose and titrate to tolerable dose
 Treatment of HFrEF…
ACE Inhibitors
• Contraindication
 Bilateral renal artery stenosis
 Unilateral renal artery stenosis in a single functioning kidney
 Pregnancy
 History of angioedema
• SEs
 Angioedema, cough, hyperkalemia, hypotension, renal
dysfunction
• Monitor
 BP, electrolytes, BUN, Cr: at baseline and 1-2 weeks after
initiation and dose titration
 Treatment of (HFrEF…

β-Blockers

• should be used in all stable patients with HFrEF

 In the absence of contraindications or a clear history of

β-blocker intolerance

 Antagonize the detrimental effects of the SNS

 Treatment of HFrEF…
• β-Blockers
– Reduce morbidity and mortality
o Decrease ventricular mass
o Improve the sphericity of the ventricle Reverse remodeling
o Reduce systolic and diastolic volumes

– Decrease myocyte death from catecholamine-induced necrosis or

apoptosis
– Decrease HR and ventricular wall stress
– Inhibit plasma renin release
 Treatment of HFrEF…
β-Blockers
• Can be initiated before optimizing ACE inhibitor doses
• Recommended for asymptomatic patients with a reduced left ventricular
EF (Stage B) to decrease the risk of progression to HF
• Three β-blockers have been shown to significantly reduce mortality in
RCT
 Carvedilol: 10-80 mg QD
 Metoprolol succinate (CR/XL): 12.5-200 mg QD
 Bisoprolol: 1.25-10 mg QD
 Treatment of HFrEF…
β-Blockers
• Should be initiated in stable patients who have no or
minimal evidence of fluid overload
• Greater magnitude of HR reduction was significantly
associated with greater improvement in survival.
• To minimize acute decompensation
 Start at a very low doses with slow upward dose
titration
 Titrate dose at no more often than every 2 weeks
 Treatment of HFrEF…
β-Blockers
• Side effects
 Bradycardia, heart block, bronchospasm,
hypotension, worsening of HF
• Monitor
 BP, HR, ECG, signs ad symptoms of worsening of
HF blood glucose
 Treatment of HFrEF….
• Treatment of Stage C Heart Failure
– According to the 2016 ACC/AHA/HFSA Focused Update
on New Pharmacological Therapy for Heart Failure
• For patients with stage C HF
– inhibition of the RAAS with
 ACE inhibitors or
 ARBs or
 Angiotensin receptor neprilysin inhibitor (ARNI)
– with beta blockers and aldosterone antagonists is
recommended
 Treatment of HFrEF…
• In patients with chronic symptomatic HFrEF NYHA class II or III who
tolerate an ACE inhibitor or ARB
 replacement by an ARNI is recommended to further reduce morbidity
and mortality
• In ARNI
– an ARB is combined with an inhibitor of neprilysin
 an enzyme that degrades natriuretic peptides, bradykinin,
adrenomedullin, and other vasoactive peptides
 Includes
 valsartan/sacubitril: 160/40 mg BID
 Side effect of ARNI includes
 Hypotension, renal insufficiency and angioedema
 Treatment of HFrEF…

• ARNI should not be administered concomitantly with ACE

inhibitors or within 36 hours of the last dose of an ACE inhibitor

• ARNI should not be administered to patients with a history of

angioedema
 Treatment of HFrEF…
Treatment of Stage D HF
• Includes patients
 With refractory symptoms at rest despite maximal medical
therapy and
 Who undergo recurrent hospitalizations or cannot be discharged
from the hospital without special interventions
 In addition to standard treatments outlined in Stages A to C
– Specialized therapies
– mechanical circulatory support
– continuous IV positive inotropic therapy, and
– cardiac transplantation
 Treatment of HFrEF…
Treatment of Stage D Heart Failure
• Less tolerant to ACE inhibitors (hypotension, worsening renal
insufficiency) and β- blockers (worsening HF)
 Use low doses, slow upward dose titration, and close
monitoring for signs and symptoms
• High doses of diuretics
• Combination therapy with a loop and thiazide diuretic
• Restriction of sodium and fluid intake
• Mechanical methods of fluid removal
 Ultrafiltration
 Drug Therapies in Selected Patients
Angiotensin II Receptor Blockers
• Used in patients intolerant to ACEIs (cough)
• Includes
 Valsartan: 20-160 mg BID
 Candesartan: 4-32 mg QD
 Losartan: 25-150 mg QD
• Should not be used in combination with ACEIs (hyperkalemia)
• Use with caution in patients with a history of ACEIs associated angioedema
 Drug Therapies in Selected Patients…
Angiotensin II Receptor Blockers
• Side effect
 Hyperkalemia, Hypotension, Renal dysfunction
• Monitor

 BP, electrolytes, BUN, and Scr: Assess at baseline and1- 2 weeks

after initiation or dose titration
 Drug Therapies in Selected Patients…
Aldosterone Antagonists
• Aldosterone antagonists attenuate
 Cardiac extracellular matrix and collagen deposition
 Cardiac fibrosis and ventricular remodeling

 The systemic proinflammatory state, atherogenesis, and oxidative

stress caused by aldosterone
 Aldosterone-induced calcium excretion and reductions in bone
mineral density
 Drug Therapies in Selected Patients…
Aldosterone Antagonists
• Adding a low-dose aldosterone antagonist to standard therapy
 Improve symptoms
 Reduce the risk of HF hospitalization, and
 Increase survival

• low-dose aldosterone antagonists are appropriate for patients

 With mild to moderately severe SHF (NYHA class II to IV)
 Post MI with left ventricular dysfunction and either acute HF or DM
• Includes;
 Spironolactone: 12.5-50 mg QD
 Eplerenone: 25-50 mg QD
 Drug Therapies in Selected Patients..
Aldosterone Antagonists
Side effects
 Gynecomastia, menstrual irregularities: spironolactone
 Hyperkalemia

Monitor
 BP, electrolyte, BUN, Cr
 Check potassium 3 days and 1 week after initiation and then monthly
for the first three months and every three months thereafter
 Drug Therapies in Selected Patients…
• Hyperkalemia is common in HF patients receiving aldosterone antagonists
• To reduce incidence of hyperkalemia
– Avoid aldosterone antagonists in patients with
 SCr> 2 mg/dl in women or >2.5 mg/dl in men or a CrCl< 30
ml/min
 Recent worsening of renal function
 Serum potassium concentration ≥5 Meq/l
 History of severe hyperkalemia

– Start with low dose (12.5 mg spironolactone and 25 mg eplerenone)

 Drug Therapies in Selected Patients…
To reduce incidence of hyperkalemia
– Avoid concomitant use of high dose ACEIs, and ARBs with aldosterone
antagonists
– Avoid triple therapy with ACEI, ARB and aldosterone antagonists

• Monitor serum K+ concentration and renal function 3 days and 1 week after
initiation and then monthly for the first three months and every three months
thereafter
– If serum K+ conc.> 5.5 at any point during therapy, discontinue any K+
supplement or reduce dose of aldosterone antagonist therapy
 Drug Therapies in Selected Patients…
Digoxin
 MOA: exerts its positive inotropic effect by inhibiting Na+ K+ATPase which
facilitates Ca2+ entry into the cell
 attenuates the excessive SNS activation present in HF patients
 Cause an increase in parasympathetic activity: HR
 Enhancing diastolic filling
 Result in slowed conduction and prolongation of AV node refractoriness
 Slow the ventricular response in patients with AF
• Benefits in HF are related to its neurohormonal modulating activity
 Drug Therapies in Selected Patients…
Digoxin
• digoxin improves
 cardiac function
 quality of life
 exercise tolerance, and
 HF symptoms in patients with SHF

• Unknown effect on mortality

 Drug Therapies in Selected Patients…
Digoxin
• Place in therapy of HF

– Early: in patients with HF and supraventricular tachyarrhythmias

such as atrial fibrillation
– To control ventricular response rate

– To reduce symptoms: In patients with normal sinus rhythm

– should be used in conjunction with other standard HF
therapies including diuretics, ACE inhibitors, and β-blockers
 Drug Therapies in Selected Patients…
Digoxin
• Dose: 0.125-0.25 mg QD
• Target plasma concentration: 0.5-1 ng/ml (0.6 to 1.3 nmol/L)
• Reduce dose:
 Decreased renal function, the elderly, or those receiving interacting
drugs (e.g., amiodarone)
 Should receive 0.125 mg daily or every other day
• Digoxin withdrawal results in
 Worsening of HF
 Decreased exercise capacity, and
 Reduction in ejection fraction
 Drug Therapies in Selected Patients…
Digoxin
• Side effects
 GI and CNS side effects
 Bradyarrhythmia

 Tachyarrhythmia
• Monitor
 Electrolytes, BUN, Cr, ECG, serum digoxin concentration
 Drug Therapies in Selected Patients…
Nitrates and Hydralazine
• Complementary hemodynamic actions
 Isosorbide dinitrate: Venodilation, decrease preload

 Hydralazine: arterial vasodilator, decrease SVR and increases SV

and CO
• Dose:
 Hydralazine: 37.5-75 mg TID

 ISDN: 20-40 mg TID

 Drug Therapies in Selected Patients…
Nitrates and Hydralazine
• Particularly effective in African Americans
– Added to the standard three drug regimen
• Recommended for patients unable to tolerate either an ACE inhibitor or ARB
• Reduce mortality, hospitalizations for HF and improve quality of life
• Side effects
 Hypotension, headache, rash, arthralgia, lupus (hydralazine) tachycardia, light
headedness
• Monitor
 BP, HR
 Treatment of Concomitant Disorders
HTN
• Treat both disorders by using
 ACE inhibitors, β-blockers, and diuretics
• Target BP < 130/80
• If control of HTN is not achieved add
 aldosterone antagonist, ISDN/hydralazine, or amlodipine (or
possibly felodipine)
• Avoid the following medications in patients with SHF
– verapamil, diltiazem and direct acting vasodilators (e.g.,
minoxidil)
 sodium retention
• In patients with HFpEF, both verapamil and diltiazem can be safely
used
 Treatment of Concomitant Disorders...
Angina
• Nitrates and β-blockers are effective antianginals and are
the preferred agents for patients with both disorders
 Improve hemodynamics and clinical outcomes

• Control fluid retention with diuretics

• Alternatives: amlodipine and felodipine
 Treatment of Concomitant Disorders…
Atrial Fibrillation
 Digoxin: used to slow ventricular response in patients with
HF and atrial fibrillation
 β-Blockers are more effective than digoxin
 Improve morbidity and mortality in patients with SHF
 Combination therapy with digoxin and a β-blocker: more
effective
 Alternative; Amiodarone
 Non-dihydroyridine CCBs such as verapamil or diltiazem
should be avoided
 Antithrombotic therapy for stroke prevention
 Treatment of Concomitant Disorders..
DM
• Avoid the TZDs (pioglitazone and rosiglitazone) in
patients with DM and HF
 Fluid retention
• Absolute CI: NYHA class III or IV HF
• Relative CI: NYHA class I or II
 Treatment of HFpEF
• Relative paucity of evidence

• Many guidelines recommend

– Treating comorbid conditions by controlling
– HR and BP,
– Alleviating causes of myocardial ischemia
– Reducing volume overload and

– Restoring and maintaining sinus rhythm

 Treatment of HFpEF…
• With a few notable exceptions, many of the drugs used to
treat SHF are the same as those for treatment of HFpEF
• Difference
 The rationale for their use
 The pathophysiologic process that is being altered by
the drug, and
 The dosing regimen
 Treatment of HFpEF…
• For example
– β-blockers
• In HFpEF, used to
 decrease HR
 increase diastolic duration, and
 modify the hemodynamic response to exercise
– Diuretics
 The doses in HFpEF smaller than those used to treat
SHF
 Treatment of HFpEF…
• Antagonists of the RAAS: useful to
 Lower BP and

 Reducing LVH

• CCBs: diltiazem, nifedipine, and verapamil

– Little use in the treatment of SHF but useful in the
treatment of HFpEF
 Treatment of HFpEF…
CCBs
• Used in HFpEF
– Decrease HR and increase exercise tolerance
• Important for patients with HTN and coronary artery disease
• Nondihydropyridines:
 Verapamil: 20 to 240 mg/day
 Diltiazem:90 to 120 mg/day
• Dihydropyridines:
 Amlodipine: 2.5 mg/day
 Treatment of HFpEF…
CCBs
 Drug interaction
 Verapamil raises digoxin serum concentrations by 70%
 Diltiazem increases cyclosporine, tacrolimus, and
sirolimus serum concentrations
• Contraindication: Heart block for the non-dihydropyridines
• Side effects:
 Bradycardia and heart block (for the non-dihydropyridines)
 Peripheral edema and headache
 Drug Monitoring

07/08/2022 By; Abera J 78

 Reading Assignment

 Acute heart failure

07/08/2022 By; Abera J 79