CONGESTIVE HEART 1

FAILURE
Clinical Pharmacy:
Pathophysiology and Pharmacotherapy
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Study flow chart Definition
4
Etiology

Pathophysiology Pathogenesis

Information on Diagnostic workout

Heart Failure

drugs used in
heart failure Clinical Presentation

Design of Pharmacotherapy plan

Pharmacotherapy
General Pharmacotherapy plan
for heart failure
Case
 HEART 5

Hollow muscular organ

Lies within pericardium in the mediastinum
Divided into 4 chambers
Right and Left Atria which receive blood
Right and Left Ventricles which supply blood
Composed of myocytes (functional unit of cardiac muscles)
 HEART 6

Normal cardiac output: 5L/min

Mean heart rate: 70 bpm
Ventricle normal volume: 130mL
Normal Ejection Fraction (EF): 50% of ventricular contents
 CONGESTIVE HEART FAILURE 7

“It is progressive systolic or diastolic dysfunctioning in which

heart is not able to generate sufficient output and force to

meet the metabolic requirements of body and to empty

chamber of the heart.”

 CONGESTIVE HEART FAILURE 8

The onset can be abrupt or gradual.

 ETIOLOGY 9

“Etiology is the study of origin of disease which

also include the underlying causes and modifying
factors.”
 ETIOLOGY 10

The factors causing heart failure are:

 ETIOLOGY 11

Inadequate
Ischemic heart myocardial
Hypertension
disease contractile
function

Massive
Myocardial Amyloid
ventricular
fibrosis deposition
hypertrophy
 ETIOLOGY 12

Increased
Constrictive Valve
tissue nutrition
pericarditis dysfunction
demand

Myocardial Atrial
infarction fibrillation
 PATHOGENESIS 13

“It is the study of development and progression of a disease

which help to describe how etiologic factors trigger cellular and
molecular changes that give rise to specific functional and
structural abnormalities that characterize the disease.”
 PATHOGENESIS 14

When myocardial output increase, compensatory mechanism are

triggered to compensate:
Activation of
Frank-
sympathetic
Tachycardia Starling Vasoconstriction
nervous
Mechanism
system

Ventricular
hypertrophy
 PATHOGENESIS 15

These mechanism in adjusting cardiac output

become responsible for symptoms of heart failure
and contribute to disease progression.
 PATHOGENESIS 16

Inadequate
Shortness Venous
blood Fatigue
of breath congestion
supply

Disturbed
Ankle water and
Edema
swelling electrolyte
balance
 PATHOGENESIS 17

Renal function impairment and associated water

retention may add burden on the heart causing
precipitation of heart failure
Cause of death:
Sudden cardiac necrosis
Recurrent myocardial infarction
 PATHOGENESIS 18

Heart failure is classified on basis of functional

status by New York Heart Association:
 PATHOGENESIS 19

Category Sign and Symptoms

I No symptoms with ordinary physical activity

II Slight limitation with dyspnea on moderate to

severe exertion
III Marked limitation of activity, Less than ordinary
activities causes dyspnea
IV Severe disability, dyspnea at rest
 PATHOGENESIS 20

In left ventricular dysfunction, EF is reduced to

45-35%
When fall to 10%, there is risk of thrombus
formation within left ventricle
It may occur in myocardial infarction/long standing
hypertension
 PATHOGENESIS 21

The signs and symptoms are:

 PATHOGENESIS 22

Pale Hands cold Renal

Confusion
appearance and sweaty failure

Abdominal
Hepatomegaly Anorexia Nausea
distention

Ankle and Sputum

Abdominal Pulmonary
abdomen frothy and
pain edema
swelling tinged red
 PATHOGENESIS 23

• Hepatomegaly due to GIT congestion

• Edema due to water and electrolyte imbalance
• Frothy and tinged red sputum due to fluid and blood leakage
from capillaries

• In case of acute failure, pulmonary edema is prominent and

may be life threatening
 DIAGNOSTIC WORKOUT 24

Perform following test in defined flow:

 DIAGNOSTIC WORKOUT 25

Physical Chest
ECG test
examination radiography

Urine test Blood test ECHO test

 DIAGNOSTIC WORKOUT 26

Physical examination include Blood pressure, heart rate,

exercise tolerance test and detection of heart sounds
Additional 3rd and 4th sound indicate dysfunctioning of valve
After suspection of heart failure, move to ECG test
 DIAGNOSTIC WORKOUT 27

If abnormal Electrocardiogram (ECG), move to chest

radiography
Heart failure may be suspected if chest radiography shows
enlarged cardiac shadow and consolidation in lungs due to
ventricular hypertrophy
Then move to Echocardiogram (ECHO) for confirmation of heart
failure, and quantify ejection fraction.
ECHO may also indicate abnormalities of pericardium,
myocardium, and heart valves
 DIAGNOSTIC WORKOUT 28

Then move to blood test to evaluate condition of patient.

Recommended parameters are:
Liver
Blood gas Serum
Urea Function
analysis creatinine
Tests (LFTs)

Complete
Thyroid Serum BNP or Fasting blood
Blood Count
Function Test NT pro-BNP glucose level
(CBC)
 CLINICAL PRESENTATION 29

“It is constellation of physical signs or symptoms associated with

a particular morbid process, the interpretation of which leads
to a specific diagnosis.”
 CLINICAL PRESENTATION 30

Patient presentation may range from asymptomatic to cardiogenic

shock

Primary symptoms: fatigue, dyspnea, exercise intolerance,

orthopnea, paroxysmal nocturnal dyspnea, tachypnea, cough

Fluid overload can result in pulmonary congestion and peripheral

edema

Fluid overload can result in pulmonary congestion and peripheral

edema
 CLINICAL PRESENTATION 31

Nonspecific symptoms: fatigue, nocturia, hemoptysis, abdominal

pain, anorexia, nausea, bloating, ascites, poor appetite, mental
status changes, weight gain

Physical examination: pulmonary crackes, S3 gallop, cool

extremeties, Cheyne-Stokes respiration, Tachycardia, narrow pulse
pressure, cardiomegaly, pulmonary edema, peripheral edema,
jugular venous distention, hepatojugular reflux, hepatomegaly
INFORMATION ON DRUGS USED IN
32
HEART FAILURE
Diuretics
ACEI
Drugs ARB
used in
Beta blockers
heart
failure Aldosterone antagonists
Inotropic agents
Direct acting Vaso- and Veno- Dilators
DIURETICS AND ALDOSTERONE
ANTAGONISTS 33

Drugs used are:

Bumetanide Furosemide Torsemide

Metolazone Eplerenone
 DIURETICS AND ALDOSTERONE
ANTAGONISTS 34

Metolazone and Eplerenone are potassium sparing diuretics and

aldosterone antagonists as well
Rest are loop diuretics

Increase urine flow and inhibit reabsorption of many ions (Na, K, Cl)

Loop diuretics more efficacious in poor renal function

Loop diuretics increase prostaglandin synthesis so prostaglandin
synthesis inhibitor reduce action
 DIURETICS AND ALDOSTERONE
ANTAGONISTS 35

Reduce acute pulmonary edema and cause hypokalemia

Rapid onset when given IV
ADR: ototoxicity, hyperuricemia, hypotension
Aldosterone antagonist inhibit sodium reabsorption and potassium
excretion
Contraindicated in renal dysfunction
Discontinue exogenous potassium supplementation
ADR: peptic ulcer, gynecomastia, lethargy and mental confusion
ADR occur more in old age
ANGIOTENSIN CONVERTING ENZYME
INHIBITOR (ACEI) 36

Drugs used in heart failure are:

Captopril Enalapril Fosinopril

Lisinopril Quinapril Ramipril

 ANGIOTENSIN CONVERTING ENZYME
INHIBITOR (ACEI) 37

Enalapril and Lisinopril are first line drugs

Block ACE which convert angiotensin I to Angiotensin II
(vasoconstrictor)
Breakdown bradykinin which increase production of NO and
prostacyclin (potent vasodilator)
Slow down progression of diabetic nephropathy and albuminuria

Fosinopril does not require dose adjustment in renal impairment

 ANGIOTENSIN CONVERTING ENZYME
INHIBITOR (ACEI) 38

Except captopril and lisinopril which require hepatic activation

by metabolism, all can be given in hepatic impairment
ADR: dry cough, skin rashes, hypotension
Monitor potassium level
Contraindicated in pregnancy
Take 1 hour before meal to achieve better absorption
Antacids decrease absorption
ANGIOTENSIN II RECEPTOR BLOCKER (ARB) 39

Drugs used are:

Candesartan Losartan Telmisartan

Valsartan
 ANGIOTENSIN II RECEPTOR BLOCKER (ARB) 40

Inhibit action of angiotensin II which stimulate aldosterone

Similar action and ADR to ACEI

First line treatment drugs

Contraindicated in pregnancy due to teratogenicity

Should not be given with ACEI otherwise ADR will be precipitated

BETA BLOCKER 41

Drugs used are:

Metoprolol
Bisoprolol Carvedilol
succinate

Metoprolol
tartarate
 BETA BLOCKER 42

Block Beta 1 and 2 receptor

Cause lowering of cardiac output and broncho-constriction
Cause disturbance of glucose metabolism
Bisoprolol and Metoprolol are selective beta 1 antagonist
Selectivity lost on high dose
Carvedilol is both alpha and beta blocker
All effective in chronic heart failure
 BETA BLOCKER 43

ADR: orthostatic hypotension, dizziness, fatigue

Extended release formulation of metoprolol is used

Carvedilol-decrease lipid peroxidation and vascular cell

thickening
When prescribed beta blocker, dose should be gradually titrated
and acute heart failure has passed 2 weeks past
INOTROPIC AGENTS 44

Drugs used are:

Digoxin (cardiac glycoside)

Milrinone (Phosphodiesterase III inhibitor)
Dobutamine (Alpha and Beta receptor agonist)
 INOTROPIC AGENTS 45

No evidence regarding appearance of withdrawal symptoms

when digoxin given with ACEI
No report states that digoxin can decrease mortality but can
decrease hospital admissions
Low dose digoxin-moderate to severe heart failure.
Digoxin-positive inotrope-increase contraction and thus increase
cardiac output
Can also be given in atrial fibrillation
 INOTROPIC AGENTS 46

Monitor serum level of digoxin to confirm toxicity but not advised

for daily
Low therapeutic index
ADR : fatigue, weakness, confusion, diarrhea, visual disturbances
Dobutamine-positive inotrope-dose should be tapered gradually
when to be discontinued
Milrinone-positive inotrope-cause thrombocytopenia-IV
administration cause increase in stroke volume-only in acute heart
failure
DIRECT ACTING VASO- AND VENO- DILATORS 47

Drugs used are:

Isosorbide FDC
Hydralazine
dinitrate hydralazine

Sodium
nitroprusside
 DIRECT ACTING VASO- AND VENO- DILATORS 48

Cause pulmonary vasodilation so reduce pulmonary congestion

Preferred when ACEI are contraindicated and combination of
nitrate with hydralazine is used
For acute heart failure, IV glyceryl trinitrate and loop diuretic is
used to relieve pulmonary congestion
Sodium nitroprusside rarely used for acute heart failure
Rapid onset and duration of action of 10 minutes
Ensure a nitrate free period to reduce risk of nitrate tolerance
 NOTE 49

Tolvaptan, Conivaptan (both vasopressin antagonist) and

Nesiritide (recombinant BNP)
May treat heart failure
BUT!!!!!!!!!!!!!
Due to some controversy,
It is not in use.
 DESIGN OF PHARMACOTHERAPY PLAN 50

Design of pharmacotherapy for ongoing process is based on

pharmaceutical care plan whose components are:
1. Diagnosis of disease
2. Prevention of symptoms
3. Preventing progression of disease
4. Avoiding medication related problems
5. Improve quality of life outcomes by education and counselling
6. Make data and patient profile
 DESIGN OF PHARMACOTHERAPY PLAN 51

Document pharmacotherapy plan

Implement drug therapy plan

Monitor pharmacotherapy plan

 DESIGN OF PHARMACOTHERAPY PLAN 52

Document pharmacotherapy plan by:

1. Data collection by SOAP
2. Develop CORE pharmacotherapy plan
3. Identify PRIME pharmacotherapy problems
4. Formulate FARM to assess progress
SOAP 53

SOAP

S O A P

Subjective Objective Assessment Plan

CORE 54

Condition
C
of patient
Outcome
O
desired
CORE
Regimen
R
selection
Efficacy
E
issues
PRIME 55

PRIME

P R I M E

Pharmaceu Risk to Efficacy

Interaction Mismatch
tical based patient issues
problems
FARM 56

FARM

F A R M

Finding Assessment Resolution Monitoring

 GENERAL PHARMACOTHERAPY PLAN FOR
HEART FAILURE 57

After having a brief knowledge of pathophysiology

of heart failure, drugs used in heart failure and
method of designing Pharmacotherapy plan,
We can design General Pharmacotherapy plan.
 SUBJECTIVE 58

Patient demographic
Diagnostic workout
Any history of disease or medication use
 OBJECTIVE 59

Stop progression of disease

Eliminate symptoms
Improve survival and quality of life
Make objective in accordance with wishes and expectation of
patient
Primary objective in acute heart failure is reduction of
symptoms of pulmonary congestion
ASSESSMENT 60

Determine etiologic factor of heart failure

Confirmation of disease
Category of heart failure
PLAN 61

Make therapy and counselling points

Dosage
Schedule
Frequency
Storage
Side effects
CONDITION 62

Evaluate condition of patient which include final

diagnosis
OUTCOME 63

Relieve of symptoms
Stop progression of disease
Treatment strategy is different for different type
of heart failure
 REGIMEN SELECTION 64

Ensure appropriate regimen selection

For acute heart failure, IV glyceryl trinitrate + IV loop diuretic
Chronic heart failure, ACEI + Beta blocker + loop diuretic
For ACEI intolerant patients, ARB is given
If ARB not suitable, hydralazine or nitrate can be used
For class I, prescribe ARB/ ACEI
For class II, prescribe ACEI + Beta blocker
For class III, prescribe ACEI (preferably aldosterone
antagonist)+ Beta antagonist+ diuretic + digoxin+ nitrate
EVALUATION 65

Evaluate vs. toxicity of regimen

Suppose, digoxin cannot be given if ACEI is more
efficacious
PHARMACEUTICAL BASED PROBLEMS 66

Compare different brands of same drug

Ensure cost-effectivess
 RISKS TO PATIENT 67

Determine risks posed by drugs

Risk in heart failure usually is water and electrolyte
imbalance which is life threatening
Make aware patient if there is any risk, extent of condition
and that how drug will affect their life
 INTERACTION 68

Some interaction are efficacious but some dangerous

Suppose, digoxin + sodium nitroprusside may cause
hyponatremia which is life threatening
There may be also drug-disease interaction
A heart failure patient with renal dysfunction cannot be given
potassium sparing diuretics
So check out for relative contraindication and absolute
contraindication
 INTERACTION 69

Avoid following drugs:

Calcium
Tricyclic Anti-
NSAIDs channel
antidepressants histamines
blockers

Macrolide
Minoxidil Antifungals
antibiotics

Glitazone Corticosteriods Tadalafil Lithium

MISMATCH 70

Review all otherwise mismatch may occur

Suppose, a heart failure patient with atrial
fibrillation is given diuretics and beta blocker
where digoxin can also be used for such a
condition
EFFICACY ISSUES 71

May occur if proper information is not taken

Suppose a patient was taking ACEI but physician
without knowing prescribe ARB which may cause
precipitation of heart failure
FINDINGS 72

Assign patient identifier code to access directly to

patient record which present findings
For heart failure report
Category of heart failure
Patient taking medicine
Complains
Signs and symptoms
Other problems
 ASSESSMENT 73

Pharmacist’s evaluation of current situation

Set outcome or end-point
Primary outcome-relieve of symptoms both in acute and
chronic heart failure
 RESOLUTION 74
Should reflect actions proposed to resolve MRP
Include dietary modification or assisting devices, dose reduction
If pharmacotherapy is advised; drug, dose, route, schedule,
frequency, and duration of therapy is specified
Patient educated about sign and symptoms to avoid toxicity events
and predict as well
Intraaortic balloon pump (IABP)-use in advanced heart failure who
do not respond to drug therapy
IV vasodilator and inotropic agent are used in conjunction
Ventricular assist devices-surgically implant for temporary
stabilization of patient to correct ventricular dysfunction
MONITORING 75

Advised to assess efficacy, following parameters are:

Renal Liver Water and

Chest
function function electrolyte
radiography
tests tests tests

ECG Blood test Body weight

 DRUG THERAY PLAN IMPLEMENTATION 76

Counsel patient after approving prescription

and care plan

Counsel Physician and paramedical staff

for follow-up and monitoring of patient
Advise patient to tell physician or pharmacist if
using drugs that have to be avoided in heart
failure
Advise patient :check weight on daily basis
to check edema, avoid sodium intake, stop
smoking and maintain BP to normal range
MONITORING OF PHARMACOTHERAPY PLAN 77

Weekly visit to cardiology specialist

Do diagnostic workout
FARM may be used to evaluate progress of
therapy
 CASE 78

Mr. Haris Salman, 72 years old, is suffering from severe

ventricular systolic dysfunction (EF<10%), confirmed by ECHO,
and angina.
What prescription you will make for Him???
ACEI (Lisinopril) 10mg daily
Furosemide (Loop diuretic)
Digoxin
Glyceryl trinitrate
Aspirin (75mg)
 CASE 79

Now Mr. Harris Salman is admitted to hospital with increasing

SOB at rest. Chest radiography show severe pulmonary edema.
BP is 110/70 and serum urea and electrolytes are within normal
range.
During admission, carvedilol is started.
 QUESTION 1 80

What therapeutic options would you choose to treat the acute

symptoms presented by patient at the beginning of admission?

For acute case, start IV loop diuretic (Furosemide) + IV glyceryl

trinitrate. Then shift back to loop diuretic orally if efficacious
otherwise metolazone will be prescribed.
 QUESTION 2 81

Is the addition of Bisoprolol appropriate for this patient?

No, It should be given in stable heart failure which has passed

two weeks ago. Dose should be gradually titrated to target dose.
 QUESTION 3 82

What other drug treatment options might be considered for this

patient in the longer term?

Dose of lisinopril may be increased.

 QUESTION 4 83

What if this patient has renal dysfunction?

The furosemide will be prescribed as it is contraindicated in

renal dysfunction. Fosinopril will be prescribed as it does not
require dose adjustment in this case
 QUESTION 5 84

What if patient was female 30 years and pregnant? Would you

prescribe ARB in place of ACEI?

No, ARB is contraindicated in pregnancy as it is teratogenic

 QUESTION 6 85

What if medical reports show that there is cell thickening and

lipid peroxidation? Which drug would you prescribe?

Carvedilol is correct drug as it decrease lipid peroxidation and

cell thickening.
 QUESTION 7 86

What would be the reason as patient complains that he feels

tired and weakness?

Digoxin is the reason

 REFERENCES 87
Kumar, Abbas, Aster Robbins Basic Pathology. ELSEVIER SAUNDERS.
9th edition.

Roger Walker, Cate Whittlesea Clinical Pharmacy and

Therapeutics. CHURCHILL LIVINGSTONE ELSEVIER. 5th edition.

Gerad A. McKay, Matthew R. Walters Clinical Pharmacology and

Therapeutics. WILEY-BLACK WELL. 9th edition

Russell J Greene, Norman D Harris Pathology and Therapeutics for

Pharmacists: A basis for clinical pharmacy practice.
PHARMACEUTICAL PRESS. 3rd edition
 REFERENCES 88
Philip Wiffen Oxford Handbook of Clinical Pharmacy. OXFORD UNIVERSITY
PRESS. 2nd edition.

Karen Whalen Lippincott Illustrated Reviews Pharmacology. WOLTERS

KLUWER. 6th edition.

Richard S. Snell Clinical Anatomy by regions. WOLTERS KLUWER. 9th

edition

Guyton and Hall Textbook of Medical Physiology. SAUNDERS ELSEVIER.

12th edition

Barbara, Joseph DiPiro Pharmacotherapy Handbook. MC GRAW HILL

EDUCATION. 9th edition
89