January 1997

1. Write the pharmacological basis for use of Morphine in acute LVF (25 marks)
a. LVF is a condition where left ventricle fails to contract and thus casing
inability to maintain adequate cardiac outputs resulting in inadequate
tissue perfusion
b. In LVF , symptoms are mainly related to pulmonary congestion which
includes breathlessness on exertion , orthopnea and paroxysmal
nocturnal dyspnea
c. Main therapeutic goals of management are
i. Reduce mortality
ii. Give sympathetic relief and improve quality of life ( decrease
cardiac workloard ,decrease heart rate (2X) and increase the
contractiity (2X)
iii. Reduce incidence of cardiac exacerbations and hospital
admissions
iv. Identify and control treatable etiologies
d. Morphine is an opioid analgesic drug used to analgesia in many
conditions . It is also beneficial in acute LVP as it has the following
cardiovascular effects
i. Impairs sympathetic vascular reflexes ( arterial and venous
dilatation )
ii. Stimulate vagal centre to reduce heart rate
iii. Release histamine which causes vasodilation
e. These peripheral vasodilation effects causes venous pooling causing
reduced venous return to heart and reduced peripheral vascular
resistance
f. So preload and afterload is reduced
g. Also bradycardia occurs and due to that oxygen demand is reduced
h. Morphine also has an action of acute pulmonary edema
i. Therefore morphine is effective in acute LVF and reduces its workload

August 2007 / July 2000

1. Describe the pharmacological basis for the use of Digoxin in heart failure
( 35marks)
a. Heart failure is a condition where ventricles fail to contract to maintain
adequate cardiac output resulting in hypo perfusion of organs and
reduction of blood pressure
b. By giving positive ionotropes and (-) chronotropes the contractility of
heart can be oncreased and heart rate is reduced. It helps to improve
the symptoms of heart failure
c. Digoxin is a cardiac glycoside which acts by dual mechanism in heart
failure . It has both (+) ionotropic and (-) chronotropic actions

d. Digoxin inhibits Na+/k+ Atpase and thus interfere with its function
(Also it acts on all excitable tissues , so intracellular (Na+) increases
and (K+) decreases .
e. It causes secondary increase in Ca2+ influx to cardiac mycocytes
i. Increased Ca2+ intracelullary ; causes phosphorylation of
myosin light chains which combine with actin to contract cardiac
myocytes
f. So digoxin increases force of cardiac contraction in N/ and failing
myocardium = (+ve) ionotropic action
g. Also its parasymphathetic action causes central vagal stimulation and
reduces AV nodal conduction velocity and increases refractory period
h. It results in bradycardia ; increases duration of diastole and good
ventricular filling which causes good myocardial contraction according
to starlings law
i. Decreased heart rate leads to decreased work load of heart
i. It is most effective for HF in combination with beta blocker an diuretic
j. Digoxin has not shown any mortality benefit but is known to reduce
incidence of hospital admission due to exacerbations
k. Use of digoxin is spared for patients who do not respond to first and
second line therapies of heart failure with concomitant AF or
tachycardia
l. Various degrees of bradyarrythmias ranging from 1 st degree heart block
to complete heart block can occur as adverse effects of digoxin
m. Close monitoring of S.K + levels who should be carried out as these
patients are often treated with loop diuretics as well
n. Therapy of digoxin is started with a digitalization dose ( 1mg divided in
to 2 doses ) and 1/3 to digitalized dose is continued as a
maintenance dose
2. What are the drugs to be avoided in heart failure
a. NSAIDS
i. Can inhibit the effects of diuretics and ACE inhibitors which
worsens CHF and renal functions.
b. COX 2 inhibitors
i. Can cause salt and water retention
c. Corticosteroids
d. CCB
i. Has direct negative ionotropic effects . example : Verapamil
e. TCA
i. Increases risk of arrhythmias
f. Metformin with cautions
3. Action of thiazide in patients with heart failure
a. HF is a complex syndrome which results from any structural or
functional cardiac disorder which impairs the ability of the heart to
function as a pump
b. It can be systolic or diastolic dysfunction of ventricles or a combination
of both

c. Thiazide is a moderately effective diuretic which can inhibit Na+/Clsymport in the distal convoluted tubules causing natriuresis of Clexcretion (1:1) in the urine .
d. It can case 5-10% loss of filtered Na+
e. Eventually it can cause water loss along with Na+ blood volume will
reduce .
f. Therefore it lowers the venous filling pressure and improves congestive
features of edema in the lungs and peripheries
g. Thiazide can act within 1-2 hours of oral administration with duration of
actions of 12-24 hours
h. Usually it should be administered early in the morning so the diuresis
does not interfere with sleep
4. Use of antihypertensive drugs during pregnancy ( 20 marks)
a. Hypertension is a common condition during the pregnancy and it can
develop as pregnancy induced hypertension or pre-existing
hypertension
b. Hypertensive disorders during pregnancy carry risjs for the woman and
also for the baby
c. So use of antihypertensive drugs is very important .
d. Some drugs carry increased risk of congenital abnormalities and IUGR
if used during pregnancy ( eg: ACE inhibitors . some beta blockers )
e. So alternative antihypertensive treatments shoulde be introduced to
pregnant women to keep their BP lower than 140/90 mmHg.
f. Therefore
PIH > 20 weeks
i. Labetolol
ii. Nifedipine
Risks = preeclampsia ,
iii. Methyldopa
eclampsia
iv. Hydralazine ( in emergency situations) are drugs which can be
used for hypertension with low risk for maternal and fetal
complications .
g. Beta blockers may cause IUGR , neonatal hypoglycemia and
bradycardia . Labetolol is safe ( alpha and beta blocker) .
h. Nifedipine is a calcium channel blocker which reduced blood pressure
via inihibiting L-type Ca2+ channels casing decreased contraction
i. Methyldopa acts in brainstem vasomotor centerwhich actsas as a
substrate for enzyme that synthesizes NA . but forms alpha methyl
noradrenaline which stimulates alpha 2 receptors
i. It causes decreased peripheral vascular resistance and
eventually hypotension
j. In emergencies ( eclampsia )- hydralazine can be given intravenously .
Labetolol

2005 DECEMBER
1. Describe the drug treatment in acute left ventricular failure ( 30 marks)

a. Acute left ventricular failure is a condition in which left ventricle is

nable to contract to maintain adequate cardiac output inorder to
achieve a satisfactory tissue perfusion
b. Acute heart failure may be denovo or it maybe a decopesation of
chronic heart failure
c. Acute MI, arrhythmias , aortic dissection , endocarditis can be a cause
of acute left ventricular failure . Paatients can be presented with
pulmonary congestion which incldes breathlessness , orthopnea and
PDD ( pulmoedema)
d. Therapeutic goals in the management of heart failure are
i. Reduce mortality
ii. Give symptomatic relief and imprive qulity of life
iii. Avoid converting into chronic heart failure and reduce incidence
of acute exacerbations and hospital admissions
iv. Identify and eliminate precipitating factors and treat aetiologies
e. Treatment plan
i. Initial management
1. adminitster high flow o2 = to improve saturation and to
decrease dyspnoea
2. cause should be identified and treated accordingly . eg: MI
, Endocarditis
st
ii. 1 line of therapy
1. ACE inhibitors = increases life expectancy and decreases
symtoms
2. Started with low doses of Captopril 6.25mg and titrate to
achieve an acceptable BP
iii. 2nd line of therapy
1. Beta blockers when patient is stable .
2. Decreases the mortality and minimize incidence of
arrhythmia and SCD
3. Cardio selective beta blockers are preferred . Eg:
Carvedilol 3.125 mgbd, Biscprolol, Metoprolol
iv. 3rd line of therapy
1. Spironolactone with minimum effective doses . helps to
imprive mortality
2. For symptomsatic relief loop diretics can be added to the
drug chart ( controls congestive symptoms and fluid
retention )
a. Eg : furosemide 20-40 mg bd
b. But no benefit on long term survival .
f. If patient remains severely symptomatic despite optimal therapy
Digoxin can be considered ( especially in the presence of tachy cardia
and AF )
g. It reduces exacerbations and no benefit on mortality . (improves
myocardial contractility and decreases the heart rate via increased
vagal tone )
h. High doses can case marked changes in plasma Na+ , glucose and
lipids. Serum electrolyte monitoring is important

i.
j.

It may be beneficial in patients with mild heart failure and good renal
function
They are ineffective in patients with poor renal functions ( c.creatinine
< 30ml/min)

2. Explain briefly the neuroendocrine compensatory systems activated in a

patient with chronic heart failure
a. Heart failure is a complex syndrome that results from any structural or
functional cardiac disorder which impairs the ability of the heart to
functions as a pump
b. Activation of neuro-hormonal compensatory system is initially helpful
to maintain cardiac output and arterial pressure , but when it becomes
chronic it is harmful
c. Early compensatory mechanisms are
i. Activation of sympathetic nervous system via baroreceptors to
provide ionotropic support and maintain cardiac output
ii. Angiotensin II is a potent vasoconstrictor of the renal efferent
arterioles and systemic circulation
1. It stimulates release of noradrenaline from sympathetic
nerve terminals , inihibits vagal tone and promotes
release of aldosterone
iii. Aldosterone leads to retention of Na+ and water and increased
K+ excretion
d. Chronic activation of the above vasoconstrictors contributes to cardiac
myocyte apoptosis , hypertrophy , focal myocardial necrosis and
eventually remodeling of the heart
e. Sustained sympathetic stimulation activates Renin- Angiotensin system
leading to increased venous and arterial tone (increased preload and
increased arterial tone )and also can cause down regulation of beta
receptors and endothelial dysfunction