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1.

Discuss the pathophysiology and drug therapy of Atherosclerosis


PATHOPHYSIOLOGY OF ATHEROSCLEROSIS:
Limitation of blood flow to the heart causes ischemia (cell starvation secondary to a
lack of oxygen) of the myocardial cells. Myocardial cells may die from lack of oxygen
and this is called a myocardial infarction (commonly called a heart attack). It leads
to heart muscle damage, heart muscle death and later myocardial scarring without
heart muscle regrowth. Chronic high-grade stenosis of the coronary arteries can
induce transient ischemia which leads to the induction of a ventricular arrhythmia,
which may terminate into ventricular fibrillation leading to death.
Typically, coronary artery disease occurs when part of the smooth, elastic lining
inside a coronary artery (the arteries that supply blood to the heart muscle)
develops atherosclerosis. With atherosclerosis, the artery's lining becomes
hardened, stiffened, and swollen with all sorts of "gunge" - including calcium
deposits, fatty deposits, and abnormal inflammatory cells - to form a plaque.
Deposits of calcium phosphates (hydroxyapatites) in the muscular layer of the blood
vessels appear to play not only a significant role in stiffening arteries but also for
the induction of an early phase of coronary arteriosclerosis. This can be seen in a
so-called metastatic mechanism of calcification as it occurs in chronic kidney
disease and haemodialysis (Rainer Liedtke 2008). Although these patients suffer
from a kidney dysfunction, almost fifty percent of them die due to coronary artery
disease. Plaques can be thought of as large "pimples" that protrude into the channel
of an artery, causing a partial obstruction to blood flow. Patients with coronary
artery disease might have just one or two plaques, or might have dozens distributed
throughout their coronary arteries. However, there is a term in medicine called
cardiac syndrome X, which describes chest pain (Angina pectoris) and chest
discomfort in people who do not show signs of blockages in the larger coronary
arteries of their hearts when an angiogram (coronary angiogram) is being
performed.
DRUG THERAPY OF ATHEROSCLEROSIS:
Statins to Lower Bad Cholesterol (Cholesterol medications) : Statins cause
LDL levels to fall by up to 60%. They also raise levels of HDL or "good" cholesterol.
And they can help lower the level of triglycerides.
Anti-platelet medications :Anti-platelet medications, such as aspirin, clopidogrel
to reduce the likelihood that platelets will clump in narrowed arteries, form a blood
clot and cause further blockage.
Beta blocker medications: These medications are commonly used for coronary
artery disease. They lower your heart rate and blood pressure, reducing the demand

on your heart and often relieve symptoms of chest pain. Beta blockers reduce the
risk of heart attacks and some heart rhythm problems.
Angiotensin-converting enzyme (ACE) inhibitors: These medications may help
slow the progression of atherosclerosis by lowering blood pressure and producing
other beneficial effects on the heart arteries. ACE inhibitors can also reduce the risk
of recurrent heart attacks.
Calcium channel blockers: These medications lower blood pressure and are
sometimes used to treat angina.
Water pills (diuretics): High blood pressure is a major risk factor for
atherosclerosis. Diuretics lower blood pressure.
Fibrates to Reduce Triglycerides: Fibrates are drugs that reduce triglyceride
levels. Triglycerides are not cholesterol, but they are fats that contribute to
atherosclerosis. There are two fibrates used:

Gemfibrozil

Fenofibrate

Fibrates also slightly increase "good" cholesterol also called HDL.


Niacin to Improve Overall Cholesterol : Nicotinic acid, commonly called niacin,
is a vitamin everyone needs in small doses. Taken in large doses, it improves
cholesterol by reducing triglycerides and LDL. It also increases HDL.
Niacin also can increase blood sugar levels. This is a problem especially for people
with diabetes. Because of its side effects, niacin is much less frequently prescribed
than statins or fibrates.
Other Drugs for Atherosclerosis :
Zetia (ezetimibe) works by reducing absorption of cholesterol in the intestines. It
can lower LDL levels. But it doesnt work as well as statins. This drug is usually used
in addition to a statin to further lower bad cholesterol. There is no evidence, though,
that it reduces the risk of heart attacks or strokes.
Bile acid sequestrants (cholestyramine, colestipol, colesevelam) bind to bile acids in
the intestines. This leads to a lower bile acid level. This lowers blood cholesterol
levels.
Plant sterols are taken as supplements in pill form or in foods like margarine.
Getting plant sterols every day can reduce cholesterol modestly by about 10%.
Lovaza and Vascepa (both containing omega-3s) are prescription drugs that can be
used with diet to lower high levels of triglycerides.
Drugs to Reduce High Blood Pressure: Lowering blood pressure lowers the risk
of atherosclerosis and its complications. Diet and exercise alone don't usually bring
high blood pressure down to the safe range. Blood pressure should always be less

than 140 over 90. For people with atherosclerosis, the goal may be below 130 over
80.
2. Classify drugs used in atherosclerosis with suitable examples. What is the nonpharmacological treatment of atherosclerosis
DRUGS USED IN ATHEROSCLEROSIS:
There are several medications available to treat many of the underlying causes of
atherosclerosis, such as a high cholesterol level and high blood pressure
(hypertension).
High blood pressure (hypertension)
The most widely used medications for treating high blood pressure are outlined
below.
Angiotensin-converting enzyme (ACE) inhibitors
Angiotensin-converting enzyme (ACE) inhibitors work by blocking the actions of
some of the hormones that help regulate blood pressure. By stopping these
hormones from working, ACE inhibitors reduce the amount of water in your blood as
well as widening your arteries, both of which will lower your blood pressure.
ACE inhibitors are not suitable for:

pregnant or breastfeeding women

people with conditions that affect the blood supply to their kidneys

those with a history of heart disease

The side effects of ACE inhibitors include dizziness, tiredness and headaches. If the
side effects of ACE inhibitors become troublesome, angiotensin-2 receptor
antagonists may be recommended. They work in a similar way to ACE inhibitors.

Calcium channel blockers


Calcium channel blockers work by relaxing the muscles of your artery walls, which
causes your arteries to widen and lowers your blood pressure.Calcium channel
blockers are not recommended for people with a history of heart disease, liver
disease or circulation problems. Side effects include a flushed face, headaches,
swollen ankles and dizziness. You should not drink grapefruit juice if you are taking
calcium channel blockers because this can cause your blood pressure to fall.
Thiazide diuretics
Thiazide diuretics work by reducing the amount of water in your blood and widening
the walls of your arteries. They are not recommended for pregnant women or
people with gout (a type of arthritis where crystals develop inside the
joints).Thiazide diuretics have been known to reduce the level of potassium in your
blood, which can interfere with your heart and kidney functions. They can also raise
the level of sugar in your blood, which could lead to diabetes..
High cholesterol levels
Statins
Statins are a type of medication used to lower blood cholesterol levels. Statins block
the effects of an enzyme in your liver called HMG-CoA reductase, which is used to
make cholesterol. Statins sometimes have mild side effects, including constipation,
diarrhoea and headaches. Occasionally, statins can also cause muscle pain,
weakness and tenderness.
Preventing blood clots
As many of the serious complications that arise from atherosclerosis are associated
with blood clots, such as heart attack and stroke, you may be given medication to
help reduce the risk of a blood clot developing.
Antiplatelets
Medications used to prevent blood clots developing are known as antiplatelets.
Platelets are tiny particles in the blood that help it to clot. Antiplatelets work by
reducing the "stickiness" of platelets. You may be advised to take low-dose aspirin,
which, as well as being a painkiller, has blood-thinning properties. Clopidogrel can
also be used if you are allergic to aspirin.
3. Write the aetiology and drug treatment of congestive heart failure
AETIOLOGY OF CONGESTIVE HEART FAILURE:
Heart failure may also occur in situations of "high output," (termed "high output
cardiac failure") where the ventricular systolic function is normal but the heart can't
deal with an important augmentation of blood volume. ]This can occur in overload

situation (blood or serum infusions), renal diseases, chronic severe anemia, beriberi
(vitamin B1/thiamine deficiency), thyrotoxicosis, Paget's disease, arteriovenous
fistulae, or arteriovenous malformations.
A study of healthy adults in the United States found the following risk factors:
1. Ischaemic heart disease 62%
2. Cigarette smoking 16%
3. Hypertension (high blood pressure) 10%
4. Obesity 8%
5. Diabetes 3%
6. Valvular heart disease 2% (much higher in older populations)
Italians had the following underlying causes:
1. Ischaemic heart disease 40%
2. Dilated cardiomyopathy 32%
3. Valvular heart disease 12%
4. Hypertension 11%
5. Other 5%
Rarer causes of heart failure include:

Viral myocarditis (an infection of the heart muscle)

Infiltrations of the muscle such as amyloidosis

HIV cardiomyopathy (caused by human immunodeficiency virus)

Connective tissue diseases such as systemic lupus erythematosus

Abuse of drugs such as alcohol and cocaine

Pharmaceutical drugs such as chemotherapeutic agents

Arrhythmias.

Obstructive sleep apnea (a condition of sleep wherein disordered breathing overlaps


with obesity, hypertension, and/or diabetes) is regarded as an independent cause of
heart failure.
DRUG TREATMENT OF CONGESTIVE HEART FAILURE:

Ace inhibitors
Ace inhibitors (ACEI) are drugs that relax the blood vessels. Some commonly
prescribed ACEI include: Capoten (captopril); Vasotec (enalapril); Prinivil/Zestril
(lisinopril); Accupril (quinapril); Altace (ramipril); and Monopril (fosinopril).
Beta-blockers
Beta-blockers help lower blood pressure and slow your heart rate. They also block
the harmful effects of some of the hormone-like substances that advance heart
damage. Over time, Beta-blockers may also improve the pumping action of the
heart . Commonly prescribed beta-blockers include Coreg (carvedilol) and
Lopressor/Toprol (metoprolol).
Taking an ACEI or beta-blocker will improve heart function over time (months and
years). Both drugs, either taken alone or together, have been very useful in
improving heart conditions.
Diuretics
Diuretics or "water pills" help rid the body of excess fluid that may collect in your
lungs, stomach, or feet and ankles. Less fluid in your body will decrease the
workload of your heart.
In addition to excess fluid, diuretics may also deplete your body of potassium.
Potassium is a mineral that, among other things, helps to balance the fluid in your
body's cells. It is important for your muscles to work properly. The richest sources of
potassium are fruits and vegetables, especially bananas, dried prunes, raisins,
baked potatoes (with skin), and tomato juice.
Side effects include dizziness, weakness, gout and muscle cramps (usually due to
low potassium). Common diuretics include: Lasix (furosemide); Bumex
(bumetanide); Demadex (torsemide); and HCTZ (hydrochlorothiazide).
Spironolactone is a weak "water pill" but helps prevent loss of potassium and
scarring of the heart muscle.
Digoxin
Digoxin (lanoxin) is a medication that can help the heart muscle pump blood more
effectively. It can also regulate a heartbeat that is too rapid or irregular. However, if

your body's Digoxin level gets too high, you may have loss of appetite, nausea,
bluish or yellowish vision or rapid, forceful heartbeats.
4. Describe the pathophysiology and symptoms of cardiac arrhythmia
Discuss the therapeutic approach employed in the management of major cardiac
arrhythmias
SYMPTOMS OF CARDIAC ARRHYTHMIA:
The most common symptom of arrhythmia is an abnormal awareness of heartbeat,
called palpitations. These may be infrequent, frequent, or continuous. Some of
these arrhythmias are harmless (though distracting for patients) but many of them
predispose to adverse outcomes.
Some arrhythmias do not cause symptoms, and are not associated with increased
mortality. However, some asymptomatic arrhythmias are associated with adverse
events. Examples include a higher risk of blood clotting within the heart and a
higher risk of insufficient blood being transported to the heart because of weak
heartbeat. Other increased risks are of embolisation and stroke, heart failure and
sudden cardiac death.
If an arrhythmia results in a heartbeat that is too fast, too slow or too weak to
supply the body's needs, this manifests as a lower blood pressure and may cause
lightheadedness or dizziness, or syncope (fainting).
Some types of arrhythmia result in cardiac arrest, or sudden death.

5. Describe the symptoms and drug treatment of Myocardial Infarction


SYMPTOMS OF MYOCARDIAL INFARCTION:
The onset of symptoms in myocardial infarction (MI) is usually gradual, over
several minutes, and rarely instantaneous.Chest pain is the most common
symptom of acute MI and is often described as a sensation of tightness,
pressure, or squeezing. Chest pain due to ischemia (a lack of blood and hence
oxygen supply) of the heart muscle is termed angina pectoris. Pain radiates most
often to the left arm, but may also radiate to the lower jaw, neck, right arm,
back, and upper abdomen, where it may mimic heartburn. Levine's sign, in which
patients localize the chest pain by clenching their fists over their sternums, has
classically been thought to be predictive of cardiac chest pain, although a
prospective observational study showed it had a poor positive predictive value.

Shortness of breath (dyspnea) occurs when the damage to the heart limits the
output of the left ventricle, causing left ventricular failure and consequent
pulmonary edema. Other symptoms include diaphoresis (an excessive form of
sweating), weakness, light-headedness, nausea, vomiting, and palpitations.
These symptoms are likely induced by a massive surge of catecholamines from
the sympathetic nervous system which occurs in response to pain and the
hemodynamic abnormalities that result from cardiac dysfunction. Loss of
consciousness (due to inadequate blood flow to the brain and cardiogenic shock)
and sudden death (frequently due to the development of ventricular fibrillation)
can occur in MIs.
The most common symptoms of MI in women include dyspnea, weakness, and
fatigue. Fatigue, sleep disturbances, and dyspnea have been reported as
frequently occurring symptoms that may manifest as long as one month before
the actual clinically manifested ischemic event. In women, chest pain may be
less predictive of coronary ischemia than in men. Women may also experience
back or jaw pain during an episode.
Any group of symptoms compatible with a sudden interruption of the blood flow
to the heart are called an acute coronary syndrome.

6. Write the pathophysiology of hyperlipidaemia


Discuss the management of cardiac arrythmias
Explain various diagnostic tests of Angina Pectoris
MANAGEMENT OF CARDIAC ARRYTHMIAS:
The method of cardiac rhythm management depends firstly on whether or not
the affected person is stable or unstable. Treatments may include physical
maneuvers, medications, electricity conversion, or electro- or cryo-cautery.
Physical maneuvers
A number of physical acts can increase parasympathetic nervous supply to the
heart, resulting in blocking of electrical conduction through the AV node. This can
slow down or stop a number of arrhythmias that originate above or at the AV
node. Parasympathetic nervous supply to the heart is via the vagus nerve, and
these maneuvers are collectively known as vagal maneuvers.
Antiarrhythmic drugs
There are many classes of antiarrhythmic medications, with different
mechanisms of action and many different individual drugs within these classes.
Although the goal of drug therapy is to prevent arrhythmia, nearly every
antiarrhythmic drug has the potential to act as a pro-arrhythmic, and so must be
carefully selected and used under medical supervision.
Other drugs
A number of other drugs can be useful in cardiac arrhythmias.

Several groups of drugs slow conduction through the heart, without actually
preventing an arrhythmia. These drugs can be used to "rate control" a fast
rhythm and make it physically tolerable for the patient.
Some arrhythmias promote blood clotting within the heart, and increase risk of
embolus and stroke. Anticoagulant medications such as warfarin and heparins,
and anti-platelet drugs such as aspirin can reduce the risk of clotting.
Electricity
Dysrhythmias may also be treated electrically, by applying a shock across the
heart either externally to the chest wall, or internally to the heart via
implanted electrodes.Cardioversion is either achieved pharmacologically or via
the application of a shock synchronised to the underlying heartbeat. It is used for
treatment of supraventricular tachycardias. In elective cardioversion, the
recipient is usually sedated or lightly anesthetized for the procedure.
Defibrillation differs in that the shock is not synchronised. It is needed for the
chaotic rhythm of ventricular fibrillation and is also used for pulseless ventricular
tachycardia. Often, more electricity is required for defibrillation than for
cardioversion. In most defibrillation, the recipient has lost consciousness so there
is no need for sedation.
Defibrillation or cardioversion may be accomplished by an implantable
cardioverter-defibrillator (ICD).
Electrical treatment of dysrhythmia also includes cardiac pacing. Temporary
pacing may be necessary for reversible causes of very slow heartbeats, or
bradycardia, (for example, from drug overdose or myocardial infarction). A
permanent pacemaker may be placed in situations where the bradycardia is not
expected to recover.
Electrical cautery
Some cardiologists further sub-specialise into electrophysiology. In specialised
catheter laboratories, they use fine probes inserted through the blood vessels to
map electrical activity from within the heart. This allows abnormal areas of
conduction to be located very accurately, and subsequently destroyed with heat,
cold, electrical, or laser probes.
This pulmonary vein isolation may be completely curative for AV nodal reentrant
tachycardia and sometimes for atrial fibrillation, but for other forms of
arrhythmia the success rate remains disappointing.
DIAGNOSTIC TESTS OF ANGINA PECTORIS:
Electrocardiogram
The ECG is normal in about one-half of patients with angina who are not
experiencing an acute attack. Typical ST-Twave changes include depression, T-wave
inversion, and ST-segment elevation. Forms of ischemia other than exertional
angina may have ECG manifestations that are different; variant angina is associated
with ST-segment elevation, whereas silent ischemia may produce elevation or
depression. Significant ischemia is associated with STsegment depression of greater
than 2 mm, exertional hypotension,and reduced exercise tolerance.
Exercise Tolerance Testing

Exercise tolerance (stress) testing (ETT) is recommended for patients with


intermediate pretest probability of coronary artery disease (CAD) based on age,
gender, and symptoms, including those
with complete right bundle-branch block or <1 mm of rest ST depression. Although
ETT is insensitive for predicting coronary artery anatomy, it does correlate well with
outcome, such as the likelihood of progressing to angina, the occurrence of acute
MI, and cardiovascular death. Ischemic ST depression that occurs during ETT is an
independent risk factor for cardiac events and cardiovascular mortality. Thallium
(201Tl) myocardial perfusion scintigraphy may be used in conjunction with ETT to
detect reversible and irreversible defects in blood flow to the myocardium because
it is more sensitive than ETT.
Cardiac Imaging
Radionuclide angiocardiography (performed with technetium- 99m, a radioisotope)
is used to measure ejection fraction, regional ventricular performance, cardiac
output, ventricular volumes, valvular regurgitation, asynchrony or wall motion
abnormalities, and intracardiac shunts.24 Technetium pyrophosphate scans are
used routinely for detection and quantification of acute myocardial
infarction. Positron emission tomography is useful for quantifying ischemia with
metabolically important substrates such as oxygen, carbon, and nitrogen. Other
metabolic probes use radiolabeled fatty acids and glucose to study metabolic
processes that may be deranged during ischemia in animals and for investigative
purposes in man. A new method using ultrarapid computerized tomography (spiral
CT, ultrafast CT, electron-beam CT) minimizes artifact caused by motion of the heart
during contraction and relaxation and provides a semiquantitative assessment of
calcium content in coronary arteries.25 Calcium scores >150 provide a sensitivity of
74% and specificity of 89%; consequently, this method may be costeffective
compared with ETT.
Echocardiography
Echocardiography is useful if patients have history or physical examination
suggestive of valvular, pericardial disease or ventricular dysfunction. For patients
unable to exercise, pharmacologic stress echocardiography (dobutamine,
dipyridamole, or adenosine) or pacing may be done to identify abnormalities during
stress.
Cardiac Catheterization and Coronary Arteriography
Cardiac catheterization and angiography in patients with suspected coronary artery
disease are used diagnostically to document the presence and severity of disease,
as well as for prognostic purposes.
High-risk features during ETT suggesting the need for coronary angiography include
early and significant (2 mm) changes on the ECG during ETT as well as multiple
lead involvement, prolonged recovery from ischemia, low workload performance,
abnormal blood pressure response (reduction in blood pressure), or ventricular
arrhythmias. Multiple defects with thallium scans as well as lung uptake during
exercise or postexercise ventricular cavity dilation are also high-risk indications for
catheterization. Interventional catheterization is used for thrombolytic therapy in
patients with acute myocardial infarction and for the management of patients with
significant coronary artery disease to relieve obstruction through PTCA,
atherectomy, laser treatment, or stent placement. Catheterization and angiography
may be done after coronary artery bypass grafting (CABG) to determine if the graft
has closed or if coronary artery disease has progressed. Coronary artery

intravascular ultrasound is useful for directly imaging anatomy, calcified and fatty
plaques, and thrombosis superimposed on plaque as well as determining patency
following
revascularization procedures. Intravascular ultrasound guidance of stent
implantation may result in more effective stent expansion compared with
angiographic guidance alone.
7. Write the diagnosis of myocardial infarction
A cardiac troponin rise accompanied by either typical symptoms, pathological Q
waves, ST elevation or depression, or coronary intervention is diagnostic of MI.
WHO criteria formulated in 1979 have classically been used to diagnose MI; a
patient is diagnosed with MI if two (probable) or three (definite) of the following
criteria are satisfied:
1. Clinical history of ischemic type chest pain lasting for more than 20 minutes
2. Changes in serial ECG tracings
3. Rise and fall of serum cardiac biomarkers
At autopsy, a pathologist can diagnose an MI based on anatomopathological
findings.
Classification
Myocardial infarctions are generally classified into ST elevation MI (STEMI) and nonST elevation MI (NSTEMI) A STEMI is the combination of symptoms related to poor
oxygenation of the heart with elevation of the ST segments on the
electrocardiogram followed by an increase in proteins in the blood related to heart
muscles death. They make up abut 25 to 40 percent of cases.
The phrase "heart attack" is often used non-specifically to refer to a myocardial
infarction and to sudden cardiac death. An MI is different from, but can cause
cardiac arrest, which is the stopping of the heartbeat. It is also distinct from heart
failure, in which the pumping action of the heart is impaired. However, an MI may
lead to heart failure.
A 2007 consensus document classifies MI into five main types:

Type 1 spontaneous MI related to ischemia due to a primary coronary event


such as plaque erosion and/or rupture, fissuring, or dissection

Type 2 MI secondary to ischemia due to either increased oxygen demand or


decreased supply, e.g. coronary artery spasm, coronary embolism, anemia,
arrhythmias, hypertension, or hypotension

Type 3 sudden unexpected cardiac death, including cardiac arrest, often


with symptoms suggestive of myocardial ischemia, accompanied by new ST

elevation, or new left bundle branch block (LBBB), or evidence of fresh


thrombus in a coronary artery by angiography and/or at autopsy, but death
occurring before blood samples could be obtained, or at a time before the
appearance of cardiac biomarkers in the blood

Type 4 associated with coronary angioplasty or stents:


o

Type 4a MI associated with Percutaneous coronary intervention (PCI)

Type 4b MI associated with stent thrombosis as documented by


angiography or at autopsy

Type 5 MI associated with CABG

Electrocardiogram
For a person to qualify as having a STEMI, in addition to reported angina, the ECG
must show new ST elevation in two or more adjacent ECG leads. This must be
greater than 2 mm (0.2 mV) for males and greater than 1.5 mm (0.15mV) in
females if in leads V2 and V3 or greater than 1 mm (0.1 mV) if it is in other ECG
leads. A left bundle branch block that is believed to be new used to be considered
the same as ST elevation; however, this is no longer the case. In early STEMIs there
may just be peaked T waves with ST elevation developing later.
Cardiac biomarkers
While there are a number of different biomarkers, troponins are considered to be
the best. Copeptin may be useful to rule out MI when used along with troponin.
Imaging
A chest radiograph and routine blood tests may indicate complications or
precipitating causes, and are often performed upon arrival to an emergency
department. New regional wall motion abnormalities on an echocardiogram are also
suggestive of an MI. Echo may be performed in equivocal cases by the on-call
cardiologist. In stable patients whose symptoms have resolved by the time of
evaluation, technetium (99mTc) sestamibi (i.e. a "MIBI scan") or thallium-201
chloride can be used in nuclear medicine to visualize areas of reduced blood flow in
conjunction with physiological or pharmacological stress. Thallium may also be used
to determine viability of tissue, distinguishing whether nonfunctional myocardium is
actually dead or merely in a state of hibernation or of being stunned.
Medical societies recommend that the physician confirm a person is at high risk for
myocardial infarction before conducting imaging tests to make a diagnosis. Patients
who have a normal ECG and who are able to exercise, for example, do not merit
routine imaging. Imaging tests such as stress radionuclide myocardial perfusion
imaging or stress echocardiography can confirm a diagnosis when a patient's
history, physical exam, ECG, and cardiac biomarkers suggest the likelihood of a
problem.

8. Explain pathophysiology and pharmacotherapy of angina pectoris


PATHOPHYSIOLOGY OF ANGINA PECTORIS:
Angina results when there is an imbalance between the heart's oxygen demand and
supply. This imbalance can result from an increase in demand (e.g., during exercise)
without a proportional increase in supply (e.g., due to obstruction or atherosclerosis
of the coronary arteries).
PHARMACOTHERAPY OF ANGINA PECTORIS:
Generic name
nitrates
Nitroglycerin

Indication

Route with dosage

Relieve acute angina


Prevent exerciseinduced angina
Long-term prophylaxis
to decrease the
frequency and severity
of acute anginal
episodes

PO Immediate-release tablets, 2.59


mg 2 or 3 times per day
PO Sustained-release tablets or
capsules, 2.5 mg 3 or 4 times per day
SL 0.150.6 mg PRN for chest pain
Translingual spray, one or two
metered doses (0.4 mg/dose) sprayed
onto oral mucosa at onset of anginal
pain, to a maximum of 3 doses in 15
min
Transmucosal tablet, 1 mg q35h
while awake, placed between upper lip
and gum or cheek and gum
Topical ointment,half2 inches q48h;
do not rub in
Topical transdermal disc, applied once
daily
IV 510 mcg/min initially, increased in
10- to 20-mcg/min
increments up to 100 mcg/min or
more if necessary to relieve pain

Isosorbide
dinitrate

Treatment and
prevention of angina

SL 2.510 mg PRN or q24h


PO Regular tablets, 1060 mg q46h
PO Chewable tablets, 510 mg q23h
PO Sustained-release capsules, 40 mg
q612h

Isosorbide
mononitrate

Treatment and
prevention of angina

PO 20 mg twice daily, with first dose


on arising and the second dose 7 h
later

PO Extended-release tablets (Imdur),


3060 mg once daily in the morning,
increased after several days to 120
mg once daily if necessary
Beta Blockers
Propranolol

Long-term management
of angina, to re-duce
frequency and severity
of anginal
episodes

PO 1080 mg 2 to 4 times per day


IV 0.53 mg q4h until desired
response is obtained

atenolol

Long-term management
of angina, to re-duce
frequency and severity
of anginal
episodes

PO 50 mg once daily, initially,


increased to 100 mg/d after 1 wk if
necessary

metoprolol

Long-term management
of angina, to re-duce
frequency and severity
of anginal
episodes

PO 50 mg twice daily initially,


increased up to 400 mg daily if
necessary

Nadolol

Long-term management
of angina, to re-duce
frequency and severity
of anginal
episodes

PO 40240 mg/d in a single dose

Calcium channel
blockers
Amlodipine
Bepridil

Diltiazem

PO 510 mg once daily


Angina ,Hypertension
Angina

Angina
Hypertension
Atrial fibrillation and
flutter PSVT

PO 200 mg/d initially, increased to 300


mg daily after 10 d if necessary;
maximum dose, 400 mg daily
Angina or hypertension, immediaterelease, PO 6090 mg 4 times daily
before meals and at bedtime
Hypertension, sustained-release only,
PO 120180 mg twice daily
Dysrhythmias (Cardizem IV only) IV
injection 0.25 mg/kg (average dose 20

mg) over 2 min with a second dose of


0.35 mg/kg (average dose 25 mg) in
15 min if necessary, followed by IV
infusion of 515 mg/h up to 24 h
Felodipine
Isradipine
Nicardipine

Hypertension
Hypertension
Angina
Hypertension

PO 510 mg once daily


PO 2.55 mg twice daily
Angina, immediate-release only, PO
2040 mg 3 times daily
Hypertension, immediate-release,
same as for angina, above; sustainedrelease, PO 3060 mg twice daily

Nifedipine

Angina Hypertension

Nimodipine

Subarachnoid
hemorrhage

Angina, immediate-release, PO 1030


mg 3 times daily; sustained- release,
PO 3060 mg once daily
Hypertension, sustained-release only,
3060 mg once daily
PO 60 mg q4h for 21 consecutive d. If
patient unable to swallow, aspirate
contents of capsule into a syringe with
an 18-gauge needle, administer by
nasogastric tube, and follow with 30
mL normal saline.

Nisoldipine

Hypertension

PO, initially 20 mg once daily,


increased by 10 mg/wk or longer
intervals to a maximum of 60 mg
daily. Average maintenance dose, 20
40 mg
daily. Adults with liver impairment or
>65 y, PO, initially 10 mg once daily

Verapamil

Angina
Atrial fibrillation or
flutter
PSVT
Hypertension

Angina, PO 80120 mg 3 times daily


Dysrhythmias, PO 80120 mg 3 to 4
times daily; IV injection, 510 mg over
2 min or longer, with continuous
monitoring of electrocardiogram
and blood pressure
Hypertension, PO 80 mg 3 times daily
or 240 mg (sustained release) once
daily

9. Describe the electrophysiology of heart

An electrophysiology (EP) study is a test performed to assess heart's electrical system or activity
and is used to diagnose abnormal heartbeats or arrhythmia.
The test is performed by inserting catheters and then wire electrodes, which measure electrical
activity, through blood vessels that enter the heart.
The Procedure

The EP study is performed in the electrophysiology laboratory of the hospital, where a person
will be placed on an X-ray table. A camera and television screens , heart monitors and various
instruments will be close by. Electrodes will be placed on chest and back to connect to
monitoring equipment. A blood pressure cuff will be placed on upper arm to monitor blood
pressure.
To prevent infection, shave and cleanse the groin and possibly neck area where the catheters will
be inserted. The area will be cleansed with an antiseptic. Sterile sheets will be draped over body.
Depending on the type of study medications may be given intraveniously, administered in yarm,
to sedate or make sleepy. These medications help reduce anxiety and relieve discomfort.
A local anesthetic will be administered with a tiny needle to numb the area where the catheters
are inserted.
One or more catheters, which are thin, long, flexible wires, will be inserted into a large vein in
groin or neck. The catheters will be guided to heart. The positioning of catheters inside heart
will be monitored on a screen. The incision site is less than a quarter of an inch.
There are two parts to the EP study:

Recording the heart's electrical signals to assess the electrical function

Pacing the heart to bring on certain abnormal rhythms for observation under
controlled conditions

10.Explain the pathophysiology and pharmacotherapy of congestive cardiac failure


PATHOPHYSIOLOGY OF CONGESTIVE CARDIAC FAILURE:
Heart failure is caused by any condition which reduces the efficiency of the
myocardium, or heart muscle, through damage or overloading. As such, it can be
caused by a wide number of conditions, including myocardial infarction (in which

the heart muscle is starved of oxygen and dies), hypertension (which increases the
force of contraction needed to pump blood) and amyloidosis (in which protein is
deposited in the heart muscle, causing it to stiffen). Over time these increases in
workload will produce changes to the heart itself:

Reduced force of contraction, due to overloading of the ventricle. In a healthy


heart, increased filling of the ventricle results in increased force of
contraction (by the FrankStarling law of the heart) and thus a rise in cardiac
output. In heart failure this mechanism fails, as the ventricle is loaded with
blood to the point where heart muscle contraction becomes less efficient.
This is due to reduced ability to cross-link actin and myosin filaments in overstretched heart muscle.[26]

A reduced stroke volume, as a result of a failure of systole, diastole or both.


Increased end systolic volume is usually caused by reduced contractility.
Decreased end diastolic volume results from impaired ventricular filling as
occurs when the compliance of the ventricle falls (i.e. when the walls stiffen).

Reduced spare capacity. As the heart works harder to meet normal metabolic
demands, the amount cardiac output can increase in times of increased
oxygen demand (e.g. exercise) is reduced. This contributes to the exercise
intolerance commonly seen in heart failure. This translates to the loss of
one's cardiac reserve, or the ability of the heart to work harder during
strenuous physical activity. Since the heart has to work harder to meet the
normal metabolic demands, it is incapable of meeting the metabolic demands
of the body during exercise.

Increased heart rate, stimulated by increased sympathetic activity [27] in order


to maintain cardiac output. Initially, this helps compensate for heart failure by
maintaining blood pressure and perfusion, but places further strain on the
myocardium, increasing coronary perfusion requirements, which can lead to
worsening of ischemic heart disease. Sympathetic activity may also cause
potentially fatal arrhythmias.

Hypertrophy (an increase in physical size) of the myocardium, caused by the


terminally differentiated heart muscle fibres increasing in size in an attempt
to improve contractility. This may contribute to the increased stiffness and
decreased ability to relax during diastole.

Enlargement of the ventricles, contributing to the enlargement and spherical


shape of the failing heart. The increase in ventricular volume also causes a
reduction in stroke volume due to mechanical and contractile inefficiency. [28]

The general effect is one of reduced cardiac output and increased strain on the
heart. This increases the risk of cardiac arrest (specifically due to ventricular
dysrhythmias), and reduces blood supply to the rest of the body. In chronic disease
the reduced cardiac output causes a number of changes in the rest of the body,
some of which are physiological compensations, some of which are part of the
disease process:

Arterial blood pressure falls. This destimulates baroreceptors in the carotid


sinus and aortic arch which link to the nucleus tractus solitarii. This center in
the brain increases sympathetic activity, releasing catecholamines into the
blood stream. Binding to alpha-1 receptors results in systemic arterial
vasoconstriction. This helps restore blood pressure but also increases the
total peripheral resistance, increasing the workload of the heart. Binding to
beta-1 receptors in the myocardium increases the heart rate and make
contractions more forceful, in an attempt to increase cardiac output. This
also, however, increases the amount of work the heart has to perform.

Increased sympathetic stimulation also causes the posterior pituitary to


secrete vasopressin (also known as antidiuretic hormone or ADH), which
causes fluid retention at the kidneys. This increases the blood volume and
blood pressure.

Reduced perfusion (blood flow) to the kidneys stimulates the release of renin
an enzyme which catalyses the production of the potent vasopressor
angiotensin. Angiotensin and its metabolites cause further vasoconstriction,
and stimulate increased secretion of the steroid aldosterone from the adrenal
glands. This promotes salt and fluid retention at the kidneys.

The chronically high levels of circulating neuroendocrine hormones such as


catecholamines, renin, angiotensin, and aldosterone affects the myocardium
directly, causing structural remodelling of the heart over the long term. Many
of these remodelling effects seem to be mediated by transforming growth
factor beta (TGF-beta), which is a common downstream target of the signal
transduction cascade. initiated by catecholamines [29] and angiotensin II,[30]
and also by epidermal growth factor (EGF), which is a target of the signaling
pathway activated by aldosterone[31]

Reduced perfusion of skeletal muscle causes atrophy of the muscle fibres.


This can result in weakness, increased fatigueability and decreased peak
strength all contributing to exercise intolerance. [32]

The increased peripheral resistance and greater blood volume place further strain
on the heart and accelerates the process of damage to the myocardium.
Vasoconstriction and fluid retention produce an increased hydrostatic pressure in
the capillaries. This shifts the balance of forces in favour of interstitial fluid
formation as the increased pressure forces additional fluid out of the blood, into the
tissue. This results in edema (fluid build-up) in the tissues. In right-sided heart
failure this commonly starts in the ankles where venous pressure is high due to the
effects of gravity (although if the patient is bed-ridden, fluid accumulation may
begin in the sacral region.) It may also occur in the abdominal cavity, where the
fluid build-up is called ascites. In left-sided heart failure edema can occur in the
lungs this is called cardiogenic pulmonary edema. This reduces spare capacity for
ventilation, causes stiffening of the lungs and reduces the efficiency of gas
exchange by increasing the distance between the air and the blood. The
consequences of this are dyspnea (shortness of breath), orthopnea and paroxysmal
nocturnal dyspnea.

The symptoms of heart failure are largely determined by which side of the heart
fails. The left side pumps blood into the systemic circulation, whilst the right side
pumps blood into the pulmonary circulation. Whilst left-sided heart failure will
reduce cardiac output to the systemic circulation, the initial symptoms often
manifest due to effects on the pulmonary circulation. In systolic dysfunction, the
ejection fraction is decreased, leaving an abnormally elevated volume of blood in
the left ventricle. In diastolic dysfunction, end-diastolic ventricular pressure will be
high. This increase in volume or pressure backs up to the left atrium and then to the
pulmonary veins. Increased volume or pressure in the pulmonary veins impairs the
normal drainage of the alveoli and favors the flow of fluid from the capillaries to the
lung parenchyma, causing pulmonary edema. This impairs gas exchange. Thus, leftsided heart failure often presents with respiratory symptoms: shortness of breath,
orthopnea and paroxysmal nocturnal dyspnea.
In severe cardiomyopathy, the effects of decreased cardiac output and poor
perfusion become more apparent, and patients will manifest with cold and clammy
extremities, cyanosis, claudication, generalized weakness, dizziness, and syncope.
The resultant hypoxia caused by pulmonary edema causes vasoconstriction in the
pulmonary circulation, which results in pulmonary hypertension. Since the right
ventricle generates far lower pressures than the left ventricle (approximately 20
mmHg versus around 120 mmHg, respectively, in the healthy individual) but
nonetheless generates cardiac output exactly equal to the left ventricle, this means
that a small increase in pulmonary vascular resistance causes a large increase in
amount of work the right ventricle must perform. However, the main mechanism by
which left-sided heart failure causes right-sided heart failure is actually not well
understood. Some theories invoke mechanisms that are mediated by
neurohormonal activation.[33] Mechanical effects may also contribute. As the left
ventricle distends, the intraventricular septum bows into the right ventricle,
decreasing the capacity of the right ventricle.
PHARMACOTHERAPY OF CONGESTIVE HEART FAILURE:

Type

Angiotensinconverting
enzyme (ACE)
inhibitors

Drug

Benazepril

Captopril

Enalapril

Fosinopril

Lisinopril

Moexipril

Comments

ACE inhibitors cause blood vessels to


widen (dilate), thus decreasing the
amount of work the heart has to do;
they may also have direct beneficial
effects on the heart. These drugs are
the mainstay of heart failure treatment.
They reduce symptoms and the need
for hospitalization, and they prolong
life.

Angiotensin II
receptor
blockers

Other
vasodilators

Perindopril

Quinapril

Ramipril

Trandolapril

Candesartan

Eprosartan

Irbesartan

Losartan

Telmisartan

Valsartan

Hydralazine

Beta-blockers

Cardiac
glycosides

Angiotensin II receptor blockers have


effects similar to those of ACE inhibitors
and may be tolerated better. However,
their effects are still being evaluated in
people with heart failure.
They may be used with an ACE inhibitor
or used alone in people who cannot
take an ACE inhibitor.

Vasodilators cause blood vessels to


dilate. These vasodilators are usually
Isosorbide dinitrate given to people who cannot take an ACE
inhibitor or angiotensin II receptor
blocker. Nitroglycerin is particularly
Nitroglycerin
useful in people who have heart failure
and angina.

Bisoprolol

Carvedilol

Metoprolol

Digitoxin

Digoxin

Beta-blockers drugs slow the heart rate


and block excessive stimulation of the
heart. They are appropriate for some
people with heart failure. These drugs
are usually used with ACE inhibitors and
provide an added benefit. They may
temporarily worsen symptoms but
result in long-term improvement in
heart function.

Cardiac glycosides increase the force of


each heartbeat and slow a heart rate
that is too fast.

Loop diuretics

Potassiumsparing
diuretics

Thiazide and
thiazide-like
diuretics

Anticoagulants

Bumetanide

Ethacrynic acid

Furosemide

Amiloride

Spironolactone

Triamterene

Chlorthalidone

Because these diuretics prevent


potassium loss, they may be given in
addition to thiazide or loop diuretics,
which cause potassium to be lost.
Spironolactone
is particularly useful in the treatment of
severe heart failure.

The effects of these diuretics are similar


to but milder than those of loop
Hydrochlorothiazid diuretics. The two types of diuretics are
particularly effective when used
e
together.
Indapamide

Heparin

Warfarin

Opioids

Positive
inotropic drugs
(drugs that
make muscle
contract more
forcefully)

These diuretics help the kidneys


eliminate salt and water, thus
decreasing the volume of fluid in the
bloodstream.

Morphine

Inamrinone

Dobutamine

Dopamine

Milrinone

Anticoagulants may be given to prevent


clots from forming in the heart
chambers.

Morphine is given to relieve the anxiety


that usually accompanies acute
pulmonary edema, which is a medical
emergency.

For people who have severe symptoms,


these drugs may be given intravenously
to stimulate heart contractions and help
keep blood circulating.

11.Write a note on antihyperlipidemic agents

Hyperlipidemiais an increase (hyper) in the lipid(lipi), which are a group of fats or


fatlikesubstances inthe blood (demia). Cholesterol and the triglyceridesare the two
lipids in the blood. Elevation of one or bothof these lipids is seen in hyperlipidemia.
Serum choles-terol levels above 240 mg/dL and triglyceride levelsabove 150 mg/dL
are associated with atherosclerosis.Atherosclerosisis a disorder in which lipid
depositsaccumulate on the lining of the blood vessels, eventuallyproducing
degenerative changes and obstruction of blood flow. Atherosclerosis is considered to
be a majorcontributor in the development of heart disease.
The various types of drugs used to treathyperlipidemia are:
Bile acid sequestrants (cholestyramine, colestipol HCl, colesevelam HCl)
HMG-CoA reductase inhibitors
(atorvastatin,fluvastatin,lovastatin,pravastatin,simvastatin)
Fibric acid derivatives (clofibrate, fenofibrate, gemfibrozil)
Niacin
The target LDL level for treatment is less that 130 mg/dL. If the response to drug
treatment is adequate, lipid levels are monitored every 4 months. If the response is
inadequate, another drug or a combination of two drugs is used. Antihyperlipidemic
drugs decrease cholesterol and triglyceride levels in several ways. Although the end
result is a lower lipid blood level, each has a slightly different action
ACTIONS

Bile Acid Sequestrants

Cholestyramine (Questran) and colestipol (Colestid) are examples of bile acid


sequestrants. Bile, which is manufactured and secreted by the liver and stored in
the gall-bladder, emulsifies fat and lipids as these products pass through the
intestine. Once emulsified, fats and lipids are readily absorbed in the intestine.
These drugs bind to bile acids to form an insoluble substance that cannot be
absorbed by the intestine, so it is secreted in the feces. With increased loss of bile
acids, the liver uses cholesterol to manufacture more bile. This is followed by a
decrease in cholesterol levels

HMG-CoA Reductase Inhibitors

Another group of antihyperlipidemic drugs are called HMG-CoA reductase inhibitors.


HMG-CoA (3hydroxy-3-methyglutaryl coenzyme A) reductase is an enzyme that is a
catalyst (a substance that accelerates a chemical reaction without itself undergoing
a change) in the manufacture of cholesterol. These drugs appear tohave one of two
activities, namely, inhibiting the manufacture of cholesterol or promoting the
breakdown of cholesterol. This drug activity lowers the blood levels of cholesterol
and serum triglycerides and increases blood levels of HDLs. Examples of these
drugs are fluvastatin (Lescol), lovastatin (Mevacor), and simvastatin (Zocor).

Fibric Acid Derivatives

Fibric acid derivatives, the third group of antihyperlipidemic drugs, work in a variety
of ways. Clofibrate

(Atromid-S), acts to stimulate the liver to increase breakdown of verylow-density


lipoproteins (VLDL) to low-density lipoproteins (LDL), decreasing liver synthesis
ofVLDL and inhibiting cholesterol formation. Fenofibrate(Tricor) acts by reducing
VLDL and stimulating the catabolism of triglyceride-rich lipoproteins, resulting in a
decrease in plasma triglyceride and cholesterol. Gemfibrozil (Lopid) increases the
excretion of cholesterol in the feces and reduces the production of triglycerides by
the liver, thus lowering serum lipid levels.

Miscellaneous Antihyperlipidemic

Drug: Niacin
The mechanism by which niacin (nicotinic acid) lowers blood lipids is not fully
understood.
USES:
Bile Acid Sequestrants
The bile acid sequestrants are used as adjunctive therapy for the reduction of
elevated serum cholesterol in patients with hypercholesterolemia who do not have
an adequate response to a diet and exercise program. Cholestyramine may also be
used to relieve pruritus associated with partial biliary obstruction.
HMG-CoA Reductase Inhibitors
These drugs, along with a diet restricted in saturated fat and cholesterol, are used
to treat hyperlipidemia when diet and other nonpharmacologic treatments alone
have not resulted in lowered cholesterol levels.
Fibric Acid Derivatives
While the fibric acid derivatives have antihyperlipidemic effects, their use varies
depending on the drug.
For example, Clofibrate (Atromid-S) and gemfibrozil (Lopid) are used to treat
individuals with very high serum triglyceride levels who present a risk of abdominal
pain and pancreatitis and who do not experience a response to diet modifications.
Clofibrate is not used for the treatment of other types of hyperlipidemia and is not
thought to be effective for prevention of coronary heart disease. Fenofibrate (Tricor)
is used as adjunctive treatment for the reduction of LDL, total cholesterol, and
triglycerides in patients with hyperlipidemia.
Miscellaneous Antihyperlipidemic
Drug: Niacin
Niacin is used as adjunctive therapy for the treatment of very high serum
triglyceride levels in patients who present a risk of pancreatitis (inflammation of the
pancreas) and who do not experience an adequate response to dietary control.