CARDIOVASCULAR PHARMACOLOGY (HEART FAILURE).pdf

Heart failure drugs

1. Cardiovascular
Pharmacology
By: Alemayehu Megersa
Dire DawaUniversity
College of Medicine and Health Sciences
School of Medicine
Email: [email protected]

2. Learningobjectives
In this section you will learn
✓Classes of drugs used for treatment of CVS
disorders
✓Pharmacokinetic properties of CVS drugs
✓Mechanism of action, indication (clinical use)
✓Drug interactions and adverse effects to CVS
drugs
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3. ❖Cardiovascularpharmacologyconcerns
theeffectsofdrugsontheheart,the
vascularsystemandthosepartsofthe
nervoussysteminvolvedinregulating
cardiovascularfunction.
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4. Introduction
❖The heart is the powerhouse of the body,
providing oxygenated blood to organs so
that they can conduct the vital processes
needed to keep the body functioning.
❖Without a properly functioning heart to
ensure blood flow, cells are in jeopardy of
oxygenation starvation, impairment, and
subsequent death.
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5. Nursing Process Related to Cardiovascular
Medications
❖Understanding the MoAof a cardiac medication
will help a nurse choose the proper assessments
to perform on a patient.
❖It is important for a nurse to complete a full
cardiac assessment to fully understand the health
status of the patient, the safe implementation of
the medication, and the expected effectiveness of
the medication.
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6. Nursing Process Related to Cardiovascular Medications…..
❖Many cardiovascular medications alter a
patient’s BP or HR.
•assess a patient’s BP and HR prior to
administration.
❖Medications that alter electrolytes, such as
loop diuretics, require a review of
laboratory values before administration.
✓assess for signs of dehydration
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7. Nursing Process Related to Cardiovascular Medications…..
❖In addition, a nurse must appropriately
assess and report abnormal laboratory
values such as worsening serum creatinine
and glomerular filtration rates (GFR).
❖important to assess for signs of
dehydration, as well as intake and output in
patients taking diuretics.
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8. Nursing Process Related to Cardiovascular Medications…..
❖Before administration of any CVS, it is vital for
the nurse to determine if this particular cardiac
medication is safe for this patient at this time.
❖It is also important to consider the effect of the
medication before administering it at the
ordered time.
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9. Nursing Process Related to Cardiovascular Medications…..
❖It is always important to evaluate the
patient’s response to a medication
compared to what is expected.
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10. ❖The most commonly encountered cardiovascular
disorders include:
•Hypertension
•congestive heart failure
•angina pectoris and
•cardiac arrhythmias.
❖Most drugs available currently are able to reduce
the morbidity and mortality due to these disorders.
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11. Heart Failure
❖HFisacommonclinicalsyndromerepresentingtheend‐stage
ofanumberofdifferentcardiacdiseases
–Canresultfromanystructuralor functionalcardiac
disorderthatimpairstheabilityof theventricletofill
with or ejectblood
❖currentlythereisnocure
–ThereisnosinglediagnostictestforHF(largely aclinical)
–based onacarefulhistoryandphysicalexamination
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12. Heart failure…
❖Heart failure is usually caused by one of the following:
✓Ischemic heart disease
✓Hypertension
✓Heart muscle disorders
✓Valvular heart disease
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13. The NYHA functional classification of HF
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14. TheACC/AHAstageclassificationofHFanditsrelationship
toNYHAfunctionalclassification
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15. Classification and treatment of chronic heart
failure.
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ACC/AHA
Stage
NYHA
Class
Description Management
A PrefailureNo symptoms but risk
factors present
Treat obesity,
hypertension, diabetes,
hyperlipidemia, etc
B I Symptoms with severe
exercise
ACEI/ARB, β blocker,
diuretic
C II/IIISymptoms with marked
(class II) or mild
(class III) exercise
Add aldosterone
antagonist, digoxin; CRT,
ARNI, hydralazine/nitrate
D IV Severe symptoms at restTransplant, LVAD

16. ❖Drugs used to treat heart failure can be broadly divided
into:
A.Drugs with positive inotropic effect.
✓Drugs with positive inotropic effect increase the force
of contraction of the heart muscle
✓Cardiac glycosides,
✓Bipyridine derivatives and
✓Sympathomimetics
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Drug used in heart failure
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An inotrope or inotropic is an agent that alters the force or energy of muscular contractions.
Negatively inotropic: weaken the force of contractions.
Positively inotropic: increase the strength of muscular contraction.

17. Drugs used to treat heart failure…
B. Drugs without positive inotropic effect
✓Diuretics, e.g. hydrochlorothiazide, furosemide
✓Vasodilators, e.g. hydralazine, sodium nitroprusside
✓Angiotensin converting enzyme inhibitors
e.g. captopril, enalapril
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✓drugs which increase renal excretion of
salt and water
✓are principally used to remove excessive
extracellular fluid from the body
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18. Drugs with positive inotropic effect
Cardiac glycosides
✓Cardiac glycosides comprise a group of steroid compounds that can
increase cardiac out put and alter the electrical functions.
✓Commonly used cardiac glycosides are digoxinand digitoxin.
✓All cardiac glycosides exhibit similar pharmacodynamic properties but
do differin their pharmacokineticproperties.
▪Digitoxin is more lipid soluble and has long half-life than digoxin.
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19. The mechanism of inotropic action
❖Inhibitionof the membrane-bound Na+/K+ ATPase called
the “Sodium Pump”.
✓Results in an increasedintracellular movement of sodiumand
accumulationof sodium in the cells.
✓As a consequence of the higher intracellular sodium, decreased
transmembrane exchangeof sodium and calcium will take place
✓Leading to an increasein the intracellular calciumthat acts on
contractile proteins.
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20. Figure #: Mechanism of action of digoxin.
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21. Cardiac glycosides…
❖Therapeutic uses of cardiac glycosides include:
–Congestive heart failure
–Atrial fibrillation
–Atrial flutter, and
–Paroxysmal atrial tachycardia.
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22. Toxicity of cardiac glycosides include:
•GI effects such as anorexia, nausea, vomiting, diarrhoea
•Cardiac effects such as bradycardia, heart block, arrhythmias
•CNS effects such as headache, malaise, hallucinations, delirium,
visual disturbances (yellow vision)
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23. Toxicity of cardiac glycosides…
Toxicity managment
✓For Mild toxicities-reducing the dose of the drug.
✓For the management of arrhythmias or serious toxicity:
•Potassium supplementation,
•Administration of anti-arrhythmic drugs (e.g. lidocaine)
•Use of digoxin antibodies
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24. Drug Interactions
✓Diuretics:
✓ACE Inhibitors and ARBs: AKI
✓Quinidine
•displacing digoxin from tissue binding sites
•reducing the renal excretion of digoxin
✓Verapamil
•a calcium channel blocker, can significantly increase plasma levels of
digoxin
oa reduction in clearance and/or in volume of distribution
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✓because of their potential for decreasing plasma
potassium levels (i.e., producing hypokalemia).
✓Hypokalemia results in increased digoxin binding to
the Na
+
/K
+
-ATPase and thereby enhances digoxin's
therapeutic and toxic effects.

25. Bipyridine derivatives
❖These drugs possess both positive inotropic effect and
vasodilatoreffects.
•E.g. amrinone, milrinone
❖Bipyridine derivatives are used in cases of Heart failure resistant
to treatment with cardiac glycosides and vasodilators.
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26. Bipyridinederivatives…
❖Since amrinone is rarely used, this section focuses on milrinone
❖Following IV administration, milrinone is approximately 70% bound to
plasma proteins, and the elimination half‐life is about 2 h
✓The drug is primarily eliminated unchanged in the urine
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27. Mechanism of action
❖At therapeutic doses, milrinone is a selective inhibitor of
PDE3in both myocardium and vascular smooth muscle
✓Inhibition of PDE3 in cardiomyocytes causes increased
levels of 3′‐5′‐cyclic adenosine monophosphate (cAMP)
✓which in turn cause increases in intracellular Ca2+
✓thereby leading to smooth muscle relaxation and
vasodilation
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28. Clinical Uses
✓Milrinone is indicated for the short‐term IV treatment of patients
with acute decompensated HF
Adverse Effects and Drug Interactions
✓common adverse effects of milrinone -ventriculararrhythmias
✓other CV adverse effects include hypotensionand angina
✓may also cause headaches, usually mild to moderate
✓Milrinone is contraindicated in patients who are hypersensitiveto it.
✓The drug is in pregnancy category: C
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29. Beta-adrenergic stimulants
❖Also known as sympathomimeticdrugs
❖Dobutamineand dopamineare β‐adrenergic receptor
agoniststhat stimulate cardiac contractility
•Dopamine is a natural catecholamine
•Dobutamine is a synthetic catecholamine
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30. Table #: Major pharmacokinetic properties of
dobutamine and dopamine
Drug Onset of
Action
Elimination Half
Life
Metabolism and Elimination
Dobutamine1-2min 2min
✓Catechol-O-methyl
transferase (COMT)
✓eliminated in the urine
Dopamine <5min 2min
✓Monoamine oxidase, COMT
✓eliminated in the urine
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31. Dopamine
❖Dopamine produces positivechronotropic and inotropic
effects on the myocardium
•resulting in increased heart rate and cardiac contractility
❖This effect is accomplished
✓directlyby exerting an agonistaction on β‐adrenergic receptors
✓indirectlyby causing releaseofnorepinephrinefrom storage
sites in sympathetic nerve endings
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Chronotropicdrugsmay
change the HR and rhythm
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32. Dopamine…
❖Thecardiovasculareffectsofdopaminearedoserelated:
✓Atlowratesofinfusion(0.5–2µg/kg/min)
•itcausesvasodilationpossiblyduetospecificactivationof
dopaminereceptorsintherenal,coronary,andintracerebral
vascularbeds
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33. Dopamine…
✓At intermediate rates of infusion (2–10 µg/kg/ min)
•dopamine acts to stimulate the β1‐adrenergic receptors, resulting in
oaugmented myocardial contractility
oincreased sinus rate, and
oenhanced impulse conduction in the heart
✓At higher rates of infusion (10–20 µg/kg/min)
•dopamine causes activation of α‐adrenergic receptors
oleading to vasoconstrictionand increased blood pressure
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34. Dobutamine
✓isasyntheticcatecholamine thatcausesselective activation of
beta1-adrenergicreceptors
•thedrugcanincreasemyocardialcontractility,and canthereby
improvecardiacperformance
•In contrasttodopamine,dobutaminedoesnot activate
alpha1receptors(doesnotincreasevascularresistance)
•Asa result,the drugisgenerallypreferredto dopaminefor
short-termtreatmentofacuteHF
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35. Clinical uses
Dobutamine
✓Dobutamine injection is indicated when parenteral therapy is
necessary for inotropic support.
✓is indicated for the correction of hemodynamic imbalances
present in the shock syndrome
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36. Adverse Effects and Drug Interactions
Adverse Effects
•The major adverse effects of dobutamineand dopamine are related
to the cardiovascular responses
•including increased heart rate and blood pressure, and
ventricular arrhythmias
•Other uncommon effects may include nausea, headache, anginal
pain, nonspecific chest pain, palpitations, and SOB
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37. Drug Interactions
✓Dobutaminemay be ineffective if the patient has recently received a
β‐blocker
✓MAOIs(e.g. Phenelzine, Selegiline)
•inhibition of MAO prolongs and potentiates the effect of dopamine
✓With cyclopropane or halogenated hydrocarbon anestheticsto cause
arrhythmia
✓With Phenytoin has been reported to lead to hypotensionand bradycardia
•Pregnancy category: B(dobutamine) and C(dopamine)
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38. Drugs without positive inotropic effect
Diuretics
•Diuretics inhibit the reabsorption of sodium or chloride at
specific sites in the renal tubules
•Diuretics are first –line drugs for treatment of patients with HF.
•In mildfailure-a thiazidemay be sufficient
•Moderate or severe failure -requires a loop diuretic.
•In acute failure-diuretics play important role by reducing
ventricular preload.
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39. Diuretics…
Loop diuretics
•The most potent diuretic drugs among the other diuretic classes and have
emerged as the preferreddiuretic agents for use in most patients with HF
Thiazide and thiazide‐type diuretics
•considered in hypertensive patients with HF and mild fluid retention because
they confer more persistent antihypertensive effects
Potassium‐sparing diuretics
•These agents have been shown to retard the disease progressionand reduce
mortality of systolic HF independent of their diuretic activity
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40. β‐Blockers for HF
Patients with HF have excessive activation of the SNS
which damages the heart and leads to progression of the disease
Beta-adrenergic antagonists block the cardiac actions of the SNS.
thus slowing the heart rate and reducing blood pressure.
Workload on the heart is decreased; after several months of therapy,
heart size, shape, and function return to normal in some patients
Three β‐blockers have been shown to be effective in reducing the
risk of death in patients with chronic systolic HF.
bisoprolol, carvedilol, and sustained‐release metoprolol succinate.
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41. Vasodilators
•Effective in acute heart failure because they provide:
•Reduction in preload (through venous dilation), or
•Reduction in after-load (through arteriolar dilation), or both.
•Hydralazine-has a direct vasodilator effect confined to arterial bed.
•Reduction in SVR leads to a considerable rise in cardiac out put.
•Sodium nitroprusside-is a mixed venous and arteriolar dilator
used also for acute reduction of blood pressure.
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Vasodilator agents are
generally reserved for
patients who are intolerant
of or who have
contraindications to ACE
inhibitors.

42. InhibitorsoftheRAAS
•Include ACEIs,ARBs, aldosteronereceptorantagonists
and directrenininhibitors
ACEIs (Captopril, Enalapril,, Lisinopril, Ramipril…)
•Remain the first choice for inhibition of the RAAS in systolic HF
•A number of large clinical trials have demonstrated that ACEIs can
decrease the risk of death and reduce hospitalization.
•Unless there is a contraindication, ACEIs are used together with a
β‐blocker to achieve additive benefits
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43. Mechanism of Action
ACEIs block the angiotensin-converting enzyme, thus preventing
the formationof angiotensin II.
Also preventthe breakdownof the vasodilating substance,
bradykininb/c ACE catalyzes breakdown of bradykinin to inactive
peptides
Result: decreasedsystemic vascular resistance (afterload),
vasodilation
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44. Figure #:RAAS pathway and other processes inhibited by ACE inhibitors (ACEI)
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45. Angiotensin Receptor Blockers (ARBs)
•E.gCandesartan, Losartan, Telmisartan, Valsartan….
•Reduced hospitalization and mortality of patients with
systolic HF
•ARBs can now be considered a reasonable alternative for
ACEIs so are used in patients with systolic HF who are ACEI
intolerant (i.e. dry cough)
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46. Mechanism of Action
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Potent vasoconstrictor
Aldostrenoproduction
Salt and water retention
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47. Aldosterone receptor antagonists
•Aldosterone plays an important role in the pathophysiology of HF.
•This substance
•promotes retention of sodium and loss of potassium
•activates the SNS and myocardial and vascular fibrosis, and
•causes baroreceptor dysfunction.
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48. Aldosterone receptor antagonists….
spironolactoneand eplerenoneexert beneficial effects in
SHF
reduced the risk of both morbidity and death among patients
with severe diastolic HF
The substantial benefits of aldosterone receptor antagonist
therapy, clinicians should strongly consider the addition of
spironolactone or eplerenonefor all patients with HF with
reducedejectionfraction
who are already on ACEIs (or ARBs) and β‐blockers
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49. Long-term management of chronic heart failure
•Modify cardiovascular risk factor profile (e.g. cigarette smoking, obesity, salt
intake
•Underlying causes should be treated (e.g. anemia, hypertension, valvular
disease)
•If this proves inadequate:
•Diuretic should be given.
•Give ACEIs and digitalis (ACE inhibitors may be used before digitalis).
•In patients with persisting symptoms give vasodilators besides increasing
the dose of diuretic and ACE inhibitors.
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