Pharmacotherapeutics 1 &2-1

HYPERTENSION
Hypertension is blood pressure elevated enough to perfuse tissues and organs. It

occur when the body’s smaller blood vessels (known as arterioles) narrow, which cause
the blood to exert excessive pressure across the vessel walls. The heart must therefore
work harder to maintain this higher pressure. The body can tolerate increased blood
pressure for months and even years, and injury to blood vessels in the kidneys, the brain
and eyes can occur. It is not a disease but an important risk factor for cardiovascular
complications.
Blood pressure measurement includes systolic and diastolic components.

Systemic arterial BP is determined by cardiac output and total peripheral resistance.
Optimal BP is less than 120/80 mm Hg (Systolic / Diastolic). The systolic pressure is
measured as the heart contracts to pump out the blood. The diastolic pressure is measured
as the heart relaxes to allow the blood to flow into the heart.
CATEGORY SYSTOLIC DIASTOLIC

Normal <130 <85
High 130-139 85-89
Stage I [Mild] 140-159 90-99
Stage II [Moderate] 160-179 100-109
Stage III [Severe] 180-209 110-119
Stage IV [Very Severe] >209 >119
If there is disparity in these ranges, the higher category of either

measurement should be used to determine severity. E.g. If systolic pressure is 165
[moderate] and diastolic is 92 [mild] the patient would still be diagnosed with moderate
hypertension. Mild systolic hypertension, in fact, may be a warning sign for more severe
hypertension, even if diastolic pressure is normal. A child’s blood pressure is normally
much lower than an adult’s.
It is also classified as high BP & risk group denoted as A, B & C to help
determine treatment. E.g. group A has no risk factors for heart diseases or other medical
problems. People in this risk group who have mild hypertension would use diet and
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exercise to try to reduce their BP. Mild hypertension in group C, which covers major risk
factors for heart disease, however, would probably require medication.
EPIDEMIOLOGY
The 10 – 25 % of population is expected to benefit from drug treatment of
hypertension. The 90-95% has no underlying medical illness to cause high blood
pressure. This is essential hypertension. Aetiology is unknown. Genetic factors play a
major role. The 5-10% is secondary hypertension. Blood pressure increases with age in
westernized society. BP is common in elderly African Caribbean origin, are in risk of
stroke and renal failure. Other factors like salt, alcohol intake, obesity also leads to
hypertension.
AETIOLOGY
I. PRIMARY (ESSENTIAL) HYPERTENSION -
In 95% of cases no cause can be identified. The onset is usually between age 25
and 55. Elevations in pressure are often intermittent early in the course. The blood
pressure fluctuates widely in response to emotional stress and physical activity. Patient
with daytime average pressures less than 135/85 mmHg have a low rate of cardio
vascular complications and a low prevalence of left ventricular hypertrophy. The
pathogenesis of essential hypertension environmental factors also a significant.
The main factors are:

1. Sympathetic Nervous System Hyperactivity:
Mostly in younger hypertensives, who may exhibit tachycardia and an elevated
cardiac output. Correlations between plasma catecholamines and blood pressure are poor.
Insensitivity of the baro reflexes may play a role in the genesis of adrenergic
hyperactivity.
2. Renin-Angiotensin System:
Renin is a proteolytic enzyme secreted by the juxta glomerular cells surrounding
afferent arteriole, in response to a number of stimuli, including reduced renal perfusion
pressure, diminished intravascular volume, circulating catecholamines, increased
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sympathetic nervous system activity, increased arteriolar stretch and hypokalemia. Renin
acts on angiotensinogen to cleave off 10 aminoacid peptide angiotensin-I. This peptide is
then acted upon by angiotensin converting enzyme to create the 8 aminoacid peptide
angiotensin II, the potent vasoconstrictor and a major stimulant of aldosterone release
from the adrenal glands. This system regulated the blood pressure. Patients with low
plasma renin activity may have higher intravascular volumes.
3. Defects in Natriuresis:
Normal individuals increase their renal sodium. Excretion in response to
elevations in arterial pressure and to a sodium load. Hypertensive patients, particularly
when their BP is normal exhibit a diminished ability to excrete a sodium load. This defect
may result in increased plasma volume & hypertension. During chronic hypertension,
sodium load is usually handled normally.
4. Intracellular Sodium & Calcium:

Intracellular sodium is elevated in blood cells and other tissues in essential
hypertension. This may result from abnormalities in Na +-K+ exchange and other Na+
transport mechanisms. An increase in intracellular Na+ may lead to increased intracellular
calcium concentrations. As a result of facilitated exchange and explain the increase in
vascular smooth muscle tone that is characteristic of established hypertension.
5. Exacerbating Factors:
a. Obesity - It is associated with an increase in intravascular volume and an elevated
cardiac output. Weight reduction lowers BP moderately.
b. Sodium Intake - Hypertensive patients should consume not more than 100
mmol/d of salt. (2.4gm of sodium, 6gm of sodium chloride daily)
c. Excessive use of alcohol also raises BP, perhaps by increasing plasma
catecholamines. Hypertension can be difficult to control in patients who consume
more than 40 gm of ethanol daily.
d. Cigarette smoking raises BP, again by increasing plasma nor-epinephrine.
e. Exercise - Aerobic exercise lowers BP in previously sedentary individuals but
increase in the strenuous exercise in already active subject has less effect.
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f. Polycythemia - Whether primary or due to diminished plasma volume, increases
blood viscosity and may raise BP.
g. Non steroidal anti- inflammatory agents produce increase in BP averaging
5mmHg, and are best avoided in patients with border line or elevated blood
pressure.
h. Low Potassium Intake - Higher blood pressure in some patients, an intake of
90 mmol/ d is recommended.
II. SECONDARY HYPERTENSION -

Approximately 5% of patients suffer from secondary hypertension due to specific
causes. Patients who develop hypertension at an early stage without a positive family
history those who first exhibit hypertension when over age 50 or those previously well
controlled who become refractory to treatment are more likely to have secondary
hypertension. The main causes include -
1. Estrogen Use: An increase in blood pressure occurs in most women taking oral
contraceptives. This is caused by volume expansion due to increased activity of
the renin angiotensin aldosterone system. The primary abnormality is an increase
in the hepatic synthesis of renin substrate.
2. Renal Disease: Renal parenchymal disease is the most common cause of

secondary hypertension. Hypertension may result from glomerular diseases,
tubular interstitial disease, and polycystic kidneys. There is increase in
intravascular volume or increased activity of the renin angiotensin aldosterone
system. Diabetic nephropathy is another cause of chronic hypertension. Dilation
of the efferent arterioles by angiotensin converting enzyme inhibition reduces rate
of progression.
3. Renal Vascular Hypertension: Renal artery stenosis is present in 1-2% of

hypertensive patients. The mechanism of hypertension is excessive renin release
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due to reduction in renal blood flow and perfusion pressure. Renal vascular
hypertension should be suspected in -
1. If the documented onset is below age 20 or after age 50.
2. If there are epigastric or renal artery bruits.
3. If there is atherosclerotic disease of the aorta or peripheral arteries.
4. If there is abrupt deteriotion in renal function after administration Of Angiotensin
Converting Enzyme Inhibitors.
4. Primary Hyper Aldosteronism and Cushing’s syndrome: Patients with excess

aldosterone secretion make up less than 0.5% of all cases of hypertension. The
usual lesion is an adrenal adenoma, bilateral adrenal hyperplasia. Aldosterone
concentration in urine and blood are elevated. Potassium level decreases and
suppressed levels of plasma renin activity, serum sodium usually exceeds 140
mEq/L.
5. Pheochromocytoma: It may be episodic, most patients are sustained elevations,

and have orthostatic fall in BP and glucose intolerance.
6. Hypertension associated with Pregnancy: The causes are coarctation of the

aorta, pheochromocytoma, hyperaldosteronism and renovascular and renal
hypertension. Pregnant women with chronic hypertension require medication only
if the diastolic pressure is sustained at or above 100mmHg. For initiation of
treatment methyldopa is still the drug of choice in a dosage of 250 mg orally
twice daily. The goal is to keep the diastolic pressure between 80 and 100 mmHg.
Diuretics may be continued in pregnancy. ACE inhibitors should be replaced
because of reports of fetal and neonatal renal failure. Therapeutic abortion may be
indicated in cases of severe hypertension during pregnancy.
7. Other Causes: Hypertension has also been associated with hypocalcaemia due to
any cause, acromegaly, hyperthyroidism, hypothyroidism and a variety of
neurologic disorders causing increased intracranial pressure. Cyclosporins and
NSAIDS may cause or exacerbate hypertension.
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PATHOPHYSIOLOGY
Risk Factors: Family History, Age,

Obesity, Smoking, Stress, Excessive
Alcohol Consumption, High Salt Intake,
Low Potassium Intake
Changes in Arteriolar Bed, Increased
Systemic Vascular Resistance
Increased Afterload
Decreased Blood Flow to Organs Beta Receptor

Decreased
Renal Perfusion Activation
Decreased Blood Pressure
Hyponatremia Juxtagolmerular Cells Hypovolemia
Angiotensinogen Renin Angiotensin I
Angiotensin Converting Enzyme (ACE)
Arteriolar Constriction Angiotensin II
Adrenal Cortex Stimulation

Increased Peripheral
Resistance
Increased Aldosterone
Increased Na+ Reabsorption

Increased Blood
Pressure
Increased H2O Reabsorption
Increased Plasma Volume (ECF)
MANAGEMENT
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The basic goals of antihypertensive therapy are to reduce blood pressure and
atherogenesis, to prevent stroke and target organ disease, such as left ventricular
hypertrophy and retinopathy, and to modify risk factors. Management of the hypertensive
patient must be individualized. Effective management of hypertension requires lifestyle
modification, pharmacologic therapy, and for most patients, a combination of lifestyle
modification and pharmacotherapy. The therapy includes:
1. General Principles: Treatment primarily aims to lower blood pressure toward

“normal” with minimal side effects and to prevent or reverse organ damage.
Currently there is no cure for primary hypertension.
2. Pharmacologic Treatment: Diuretic and Beta adrenergic blocking agents
should be the initial choice of therapy, due to the fact that they have
demonstrated a reduction in morbidity and mortality when used as initial
monotherapy.
a. Beta-blockers and diuretics should be considered initial agents for treatment

unless there are specific indications for other medications. Agents such as ACE
inhibitors, α blockers, αβ blockers and calcium channel blockers have all been
recommended for patients that cannot receive a diuretic or a β blocker as initial
therapy or have a secondary indication for them. This may include a diabetic
nephropathy patient who might benefit from an ACE inhibitor in combination
with a diuretic, rather than a β blocker or diuretic alone as initial therapy.
DRUG DOSAGE SIDE EFFECTS

DIURETICS
THIAZIDE DIURETICS
12.5 – 25 mg daily PO Hyperglycemia, depression
Hydrochloro thiazide
and hypercalcemia.
Hyperglycemia,
LOOP DIURETICS 20 – 80 mg 2 or 3 times a
hypocalcemia and
Furosemide day IV/PO
Hypokalemia.
POTASSIUM SPARING
Hyperkalemia,
DIURETICS 25 mg 2 – 4 times daily po
diarrh$ea, gynecomastia
Spironolactone
CENTRALLY ACTING α – AGONISTS
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Postural hypotension, try
Clonidine 0.05 – 0.6 mg twice daily
mouth and drowsiness.
Sedation, postural
250 – 1000 mg twice daily
Methyl dopa hypotension, fatigue and
IV/PO
chronic hepatitis.
ADRENERGIC BLOCKERS
10 – 120 mg 2 – 4 times Bronchospasm, constipation
Propronolol (β1 & β2)
daily PO and hallucination.
Atenolol (β1) 25 – 100 mg daily PO

Raynaud’s syndrome,
psoriasis and
Esmolol (β1) 25 – 50 μg/kg/min IV
hypercholesterolemia.
Metoprolol (β1) 25 – 150 mg twice daily
Labetalol (α-β) 100 – 600 mg twice daily Postural hypotension,

bradycardia and
12.5 – 50 mg daily divided hypervolemia.
Cavidolol (α-β)
dose.
Head ache, sedation,
Prazosin (α1) 1 – 10 mg twice daily dizziness, tachycardia and
suddern syncope.
Postural hypotension,
10 – 50 mg once or twice
Phenoxy benzamine (α1α2) tachycardia, drymouth and
daily PO
nasal congestion.
VASODIALATORS
Weakness, nausea,
Nitroprusside 0.5 – 8 μg/kg/min IV vomiting, muscle twitching
and diaphoresis.
Hirsuitism, tachycardia,
aggravates angina, fluid
Minoxidil 2.5 – 40 mg twice daily PO
nretension and pericardial
effusions.
Head ache, angina pectoris,
10 – 75 mg 4 times daily PO
Hydralazine anorexia, fluid retension and
10 – 50 mg Q6H IV/IM
lupus like syndrome.
ANGIOTENSIN CONVERTING ENZYME INHIBITORES AND BLOCKERS
Hyperkalemia, leucopenia,
Captopril 12.5 – 75 mg twice daily cough, pancytopenia,
angioedema, acute renal
Ramipril 1.25 -20 mg daily failure, loss of taste and
hypotension.
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Enalapril 2.5 – 40 mg daily
25 – 50 mg once or twice Hypotension, acute renal

Losartan (AT1 blocker)
daily. PO failure and hyperkalemia.
CALCIUM CHENNAL BLOCKERS
Nifedipine 30 – 90 mg daily PO
Amlodipine 2.5 – 10 mg daily Tachy cardia, flushing,

gastro intestinal
disturbances, headache and
Diltiazem 30 – 240 mg 4 times daily edema.
Verapamil 40 – 80 mg 3 times daily
PATIENT COMPLIANCE
Because hypertension is usually a symptom less disease, “how the patient feels”
does not reflect the blood pressure level. In fact, the patient may actually report “feeling
normal” with an elevated blood pressure and “abnormal” during a hypotensive episode
because of the light headedness associated with a sudden drop in blood pressure. Because
essential requires a lifelong drug regimen, it is difficult to impress on patients the need
for compliance. Recognizing the seriousness of the consequences of non compliance is
key. Patients should be told that prolonged, untreated hypertension, known as the “silent
killer” can affect the heart, brain, kidneys and ocular fundi.
Before initiating anti hypertensive drug therapy patients are encouraged to

eliminate or minimize controllable risk factors. Lifestyle modification is important for all
hypertensives. Recommended lifestyle modifications are as follows:
(1) Weight Reduction, if patient is overweight, (2) Smoking Cessation, (3) Aerobic
Activity, and (4) Dietary Modifications to reduce and eliminate alcohol and caffeine
intake, sodium, and saturated fat. The amount of daily dietary intake of potassium,
calcium, and magnesium should be evaluated to determine if daily requirements are being
met since these elements contribute to the regulation of blood pressure. These
modifications are considered the initial management to reduce blood pressure and target
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organ disease. These modifications should continue to be implemented even if patients
require pharmacotherapy.
PATIENT COUNSELLING
Based on Disease Profile –
1. Educate the patient about the disease severity, the importance of adherence to
therapy, and the consequences of uncontrolled hypertension.
2. The patient needs to be informed about what they are, what actions to take to
relieve minor side effects, and what to do about intolerable or dangerous side
effects.
Based on Drug Profile –
1. Diuretics: Monitor for muscle weakness, confusion, dizziness.
2. Diuretics should be taking with food or milk to prevent GI upset and the dosage
should not interrupt sleep due to urination.
3. Beta Blockers: Monitor for hypotension, dizziness, headache, and bradycardia.
Explain the need for dose tapering before stopping the drug.
4. ACE Inhibitors: Advise to take them 1 hour before meals and monitor for
hypotension, dizziness, cough, taste disturbances and rash.
5. Calcium Channel Blockers: Monitor for swollen gums, chest pain, swollen
joints (with nifedipine), constipation, dizziness, and light-headedness.
6. Alpha Blockers: Monitor for hypotension.
Based on Lifestyle Modification –
1. Maintain a healthy body weight
2. Engage in Regular Aerobic Physical Activity such as Brisk Walking at least 30
minutes per day, 5-7 days a week.
3. Consume a diet rich in fruits, vegetables, and low-fat dairy products with a reduced
content of saturated fat.
4. Restrict Dietary Sodium Intake (2.4 gm sodium or 6 gm sodium chloride).
5. Smoking Cessation and Alcohol Abstinence.
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REFERENCES:
1. Joseph L.Saseen, Barry L.Carter, Hypertension. In:Joseph T. Dipiro,
Robert L. Talbert, Gary C. Yee, Gary R. Matzke, Barbara G. Wells,
L.Michael Posey, pharmacotherapy A PcGraw-Hill,p.185-218.
2. S.H.L.Thomas, Hypertension. In: Roger Walker, Clive Edwards, clinical
pharmacy and therapeutics, 3rd ed, Churchill Livingstone,2006,p.265-275
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CONGESTIVE HEART FAILURE
Congestive heart failure (CHF) is a complex clinical syndrome that results from
any cardiac disorder that impairs the ability of the ventricle to deliver adequate quantities
of blood to the metabolizing tissues during normal activity.
EPIDEMIOLOGY
Heart failure is a common condition with a prevalence ranging from
0.3% - 2% at a large 3 - 5 % in population. There is loss of cardiac reverse with age and
heart failure may often complicate the presence of other conditions in elderly. Ischemic
heart disease with CHF occurs in 47 % of female, 59 % in male followed by hypertension
in 37%, 30 % respectively.
AETIOLOGY
1. Pump Failure: Systolic failure, diastolic failure ischemic heart disease,
cardiomyopathy, arrhythmiasis, infection, inflammation, alcohol, systemic
disease, diffuse fibrosis, ischemia, cardiomyopathy and fibrosis.
2. Excessive Afterload: Hypertension, systemic-pulmonary (COPD), valve stenosis,
polycythemia
3. Excessive Preload: Fluid retention e.g. renal failure, aldosteronisim, excess IV
infusion and polycythaemia.
4. Excessive Demand & Obligatory: Hyperdynamic, regurgitation (valve
incompetence), vasodilatation (Beriberi, septicemia).
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PATHOPHYSIOLOGY
Increased Systemic
Vascular Resistance
Peripheral Artery
Constriction Increased Force of
LV Contraction
Coronary Artery
Contraction
Norepinephrine &
Epinephrine Release Increased LV
Oxygen Demand
Decreased Systemic B.P IV Hypoxia Decreased Oxygen Supply
Increased ADH Decreased Renal Decreased Force of

Blood Flow LV Contraction
Renin Increased LVEDP
Angiotensin Increased LV Preload
Aldosterone Increased LA Preload
Sodium & Water Pulmonary Edema

Retension
Increased Pulmonary
Vascular Resistance
Peripheral Edema
RV Failure
Increased RV Preload
Left- Sided Congestive Heart Failure from elevated Systemic Vascular Resistance which
then shifts to Right- Sided Failure. Systemic Vascular Resistance & Preload are exacerbated by
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renal & adrenal mechanisms. ADH – Antidiuretic Hormone, LA – Left Atria, LV – Left
Ventricle, LVEDP – Left Ventricular End Diastolic Pressure, RV – Right Ventricle
Pulmonary Edema
Backward Pulmonary Venous Dyspnoea, Paroxysmal Nocturnal
Congestion Dyspnoea, Orthopnoea, Cough,
Wheeze, Central Cyanosis.
Left Ventricular
( CO)
Peripheral Vasoconstriction,
Forward HYPOPERFUSION Cold Extremities, Polar Exercise
Intolerance, Fatigue, Tachycardia,
Tachypnoea, Rernal Fluid
Right Ventricular Failure
Jugular Venous Pressure Raised,
Systemic Venous Ankle Edema, Hepatic Edema,
Backward Congestion (Hepatomegaly, Abdominal Pain,
Nausea, Anorexia, and Ascites), Renal
Fluid Retention, Peripheral Cyanosis.
Left ventricular systolic dysfunction (LVSD) may be due to defects in systolic

contraction, diastolic relaxation or both. Systolic dysfunction arises from impaired
contractility, low ejection fraction and cardiac dilatation.
Diastolic dysfunction arises from impairment of the filling process due to

impaired relaxation. Diastolic filling is determined by rate of venous return.
MANAGEMENT
Vascular sites of action of vasodilators used in CHF
ARTERIOLES ARTERIOLES AND VEINS VEINS

Hydralazine ACEIs
Calcium Channel Blockers Alpha adrenergic blockers
Beta Blockers Thiazides /Loop diuretics Nitrates.
Dopaminergic Agonist Nitroprusside
DRUGS MECHANISM OF ACTION ADVERSE EFFECTS
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a) It inhibits the angiotensin-II
production by stimulating the
ACE inhibitor aldosterone, vasopressin release,
(Enalapril) stimulates the Na+/H2O retention, Hypotension,
increase venous pressure with increases angioedema, renal
in preload. dysfunction, cough
b) stimulate the arterial
constriction,increase after load
Angiotension II type I block the vasoconstrictor and
Hypotension, renal
Receptor Blocker aldosterone secretion by binding to
dysfunction.
(Losartan) angiotensin-II to the AT1 receptors
It decreases diastolic pressure by Hypotension, Head
Vasodilators
lowering peripheral vascular resistance. ache, tachycardia,
(Hydralazine)
It increases heart rate and cardiac systemic lupus
output. erythematosus.
Cardio Selective Beta Inhibits the direct stimulation of heart Hypotension,

Blockers muscle, inhibits arterial constriction bradycardia,
(Carvediol) and increase after load. CHF exacerbation.
Diuretics
Inhibits Na/water retention, stimulates Hypokalemia, hyponatremia,
( Thiazides )
increase venous pressure and increases Hypomagnesimia,
preload. hyperglycemia,
Hyperlipoprotenimia,
Direct effect on heart to increase the

Abdominal pain, fatigue,
force of myocardial contraction
confusion, blurred vision,
Digoxin positive inotropic action, negative
gynaecomastia, yellow vision,
chronotropic effect. After
photophobia, ventricular
administration, there is decreased
abnormal cardiac rhythms.
venous pressure blood volume.
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PATIENT COUNSELLING
1. Providing information regarding the severity of the disease.
2. Counsel the patient of what to do in the case of Emergency.
3. Educate the patient regarding possibility of nocturnal dreams, CNS problems,
hypotension, dizziness, headache, and bradycardia.
1. Advised to take ACE inhibitors 1 hour before meals.
2. Diuretics should be taking with food or milk to prevent GI upset and the dosage
should not interrupt sleep due to urination.
3. Digoxin should not be discontinued during therapy
4. Avoid over the counter drugs(Antacids, cold, allergy products & diet drugs)
5. Explain the need for dose tapering before stopping the drug.
1. Maintain a healthy body weight.
2. Regular physical activity (e.g. brisk walking) at least 30 minutes per day.
3. Restrict Dietary Sodium Intake and adopt a diet rich in fruits and vegetables.
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REFERENCES
1. Robert B.Parker, J.Herbert Patterson, Julie A.Johnson, Congestive Heart
Failure. In: Joseph T. Dipirio, Robert L. Talbert, Gary C. Yee, Gary R.
Matzke, Barbara G. Wells, L. Michael Posey,pharmacotherapy A
Pathophysiologic approach, 6th ed, McGraw-Hill,p.219-260
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ISCHEMIC HEART DISEASE
Ischemic heart disease (IHD) is a condition in which there is an insufficient

supply of oxygenated blood to the myocardium (cardiac tissue). So that oxygen demand
exceeds oxygen supply. The most common cause of myocardial ischemia is
atherosclerotic disease of epicardial coronary arteries.
TYPES OF IHD
1. Angina Pectoris (AP)
2. Myocardial Infarction (MI)
3. Chronic Ischemic Heart Disease (IHD)
4. Sudden Cardiac Death (SCD)
EPIDEMIOLOGY
 IHD still remains the most common cause of death in adults and accounts for
some 2 lakh deaths per year in UK including 70% of sudden natural deaths and 1
lakh 27 thousand infarction deaths.
 Females appear to be less susceptible to IHD than men although they seem to lose
this protection after the menopause, because of hormonal changes.
 Diabetes mellitus is a positive risk factor with high levels of IHD.
AETIOLOGY
1. Decreased Blood Flow:
a) Atherosclerosis is a where the coronary arteries are progressively
narrowed by smooth muscle proliferation and the accumulation of lipid
deposits (plaque) along the inner lining of the arteries.
b) Coronary artery spasm is a condition where a sustained contraction of one
or more coronary arteries can occur spontaneously or be induced by
irritation, exposure to cold. These spasms can cause prinzmetal’s angina
and even MI.
c) Traumatic injury can interfere with myocardial blood supply.
d) Embolic events can restrict the oxygen supply to the myocardium.
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2. Increased oxygen demand can occur with exertion and emotional stress
which increases sympathetic stimulation and thus the heart rate:
a) Diastole - Under normal circumstances, all of the oxygen is removed from
the arterial blood as it passes through the heart. Thus little remains to be
extracted if oxygen demand increases. To increase the coronary oxygen
supply blood flow has to increase. The normal response mechanism is for
the blood vessels to dilate there by increasing blood flow.
b) Systole - The contractile (inotropic) state of the heart influences the
amount of oxygen it requires to perform. Increases in systolic wall tension
increases oxygen demand. Lengthening of ejection time also increases
oxygen demand. Changes in heart rate influences oxygen consumption by
change the ejection time.
PATHOPHYSIOLOGY
Angina Pectoris
It is a symptom complex of IHD characterized by attacks, paroxysmal attack of
substernal or precordial chest discomfort caused by myocardial ischemia that falls
precariously short of inducing infarction.
Types of Angina
a) Stable Angina - It is characterized by exertion, emotional stress, or a heavy
meal precipitates chest discomfort. It is due to fixed obstruction in the
coronary artery.
b) Unstable Angina - The symptoms of unstable angina are caused by coronary
artery disease. It occurs in the recumbent position. Increased ventricular
volume increases oxygen demand.
c) Prinzmetals Angina (Vasospastic Angina or Variant Angina) - Coronary
artery spasm precipitates this angina. It occurs at rest rather than with exertion
or emotional stress.
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Myocardial Infarction
A portion of cardiac muscle suffers a severe and prolonged restriction of
oxygenated blood resulting in irreversible myocardial tissue necrosis. Platelet aggregation
and vasospasm may contribute and infrequently may they cause MI in the absence of
fixed critical stenosis.
Chronic Ischemic Heart Disease

Severe obstructive coronary artery disease may be present without acute or healed
infarction but with diffuse myocardial dysfunction.
Sudden Cardiac Death

It is defined as unexpected non traumatic death in clinically well or stable patients
who die with in one hour after onset of symptoms. The ultimate mechanism of sudden
death atmost always a lethal arrhythmias e.g., a systole, ventricular fibrillation.
MANAGEMENT
DRUGS COMMONLY USED FOR ANGINA PECTORIS
DRUG SIDE EFFECTS MECHANISM OF ACTION
Sublingual Nitroglycerin Nitrates cause venous dilation which
Flushing, headache
(NTG) reduces preload and myocardial wall
Isosorbide Dinitrate Flushing, headache, tension; decreasing oxygen demand
(SR, Oral, Sublingual) tolerance after 24 h nitrates also reduce arteriolar
Flushing, headache,
Transdermal NTG Patch resistance, which decreases myocardial
tolerance after 24 h
oxygen demand.
By reducing pressure In cardiac tissues
Isosorbide-5-Monitrate Flushing, headache,
Nitrites also facilitate collateral
(Oral, SR) tolerance after 24 h
circulation, which Increases blood
distribution Ischemic areas.
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Depression, constipation, β- Blockers reduce oxygen demand
impotence, both at rest and during exertion, by
Propranolol
bronchospasm, heart decreasing the heart rate and
failure, Bradycardia myocardial contractility which also
Metoprolol As above
Atenolol As above decreases arterial blood pressure.
These agents prevent and reverse
Nifedipine XL Hypotension, flushing
coronary spasm by inhibiting calcium
Constipation, AV influx into vascular smooth muscle and
Diltiazem SR conduction block, myocardial muscle. This results in
worsening heart failure increased blood flow which enhances
myocardial oxygen supply.
Constipation, AV
They also decrease total peripheral
Verapamil SR conduction block,
vascular resistance by dilating
worsening heart failure
peripheral arterioles.
Amlodipine Edema
DRUGS COMMONLY USED FOR MYOCARDIAL INFARCTION
DRUG SIDE EFFECTS MECHANISM OF ACTION

Nitroglycerine Flushing, headache Same as in angina treatment
It causes venous pooling and
Morphine Nausea, vomiting reduces preload, cardiac work load,
oxygen consumption.
Recombinant Tissue It causes thrombus clot to be lysed
Plasminogen Activator (t-PA) Internal bleeding In 60 to 90 % patents, restoring
Streptokinase blood flow.
Aspirin, Dipyridamole, Gastric ulceration, Prevents platelet aggregation and

Ticlopine, Clopidogrel Gastric bleeding reduce post - infarct mortality
Heparin Heamorrhage Enhancing the activity of anti

thrombin III,
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Warfarin Inhibit the vit K dependent clotting
factors anticoagulant protein C and
its cofactor protein S in liver.
Abciximab, Tirofiban, Nausea, vomiting,
Inhibiting glycoprotein receptor
Eptifibatide thrombocytopenia
Prevention of progressive left
Hypotension, cough,
Captopril, Enalapril ventricular dilation, Inhibit the
hyperkalemia.
angiotensin converting enzyme
Angioedema,
Lovastatin, Simvastatin rhabydomylosis, sleep Inhibit the HMG CoA reductase
disturbances
Each patient must be evaluated individually with respect to his or her expectations
and goals, control of symptoms, and prevention of adverse clinical outcomes such as
myocardial infarction and premature death. The degree of disability as well as the
physical and emotional stress that precipitate angina must be carefully recorded in order
to set treatment goals. Each management plan should consist of the following:
(1) Explanation and Reassurance, (2) Identification and Treatment of Aggravating
Conditions, (3) Adaptation of Activity, (4) Treatment of risk factors that will decrease the
occurrence of adverse coronary outcomes, (5) Drug Therapy for Angina, and
(6) Consideration of Mechanical Revascularization.
PATIENT COUNSELLING
1. Patients should be encouraged if they experience chest pain that is more than an
angina, to call for an Ambulance.
2. Patients also need up-to-date advice when faced with difficult choices regarding
medical treatment, angiographic procedures or surgery.
1. Statins: Educate the patient to take these drugs after food. It is advisable to take
these medications during night (except for atorvastatin). Ask the patient to report
22
to the doctor if any signs of muscle pain appear and not to worry in the case of
urine discoloration.
2. Nitrates: Sublingual administration, sublingual tablets should not be chewed or
crushed, use of transdermal patches, do not stand up immediately while using this
medication.Monitor for bluish colored lips, fingernails or palms.
3. Fibrates: Take with or immediately after food to lessen stomach upset. Monitor
for blood in urine, chest pain, and shortness of breath, stomach pain.
4. Anion Exchange Resins: This medicine should never be taken in dry form. Mix
the medicine with beverage or drinks.
5. Nicotinic Acid Derivatives: Do not crush, break or chew the extended release
medication. Monitor for darkening of urine, loss of appetite, severe stomach pain,
and yellow eyes.
1. Regular physical activity (e.g., brisk walking) at least 30 minutes per day, 5-7
days a week.
2. Eliminate Trans Fat Food like fried, oily food or baked food.
3. Restricted Dietary Sodium Intake.
23
REFERENCES
1. Robert L. Talbert, Ischemic Heart Disease. In: Joseph T. Dipiro,
Robert L. Talbert, Gary C. Yee, Gary R.Matzke, Barbara G. Wells, L.
Michael Posey, Pharmacotherapy A Pathophysiologic Approach,6th
ed, McGraw-Hill,p.261-290
2. Alan H. Mutnick, Barbara Szymusiak-Mutnick, Coronary Artery
Disease. In:Leon Shargel, Alan H. Mutnick,Paul F. Souney, Larry N.
Swanson, comprehensive Pharmacy Review,6th ed, Lippincott
Williams & Wilkins,2007,p.795-811
3. Brian R.Overholser, Kevin M.Sowinski, Ischemic Heart Disease. In:
Richard A. Helms, David J. Quan, Eric T. Herfindal, Dick R. Gourley,
textbook of Therapeutics Drug and Disease Management,8th ed,
Lippincott Williams & Wilkins, 2006, p.576-597
24
MYOCARDIAL INFARCTION
In myocardial infarction, a portion of the cardiac muscle suffers a severe and

prolonged restriction of oxygenated coronary blood or an occlusive or near occlusive
thrombus overlying or adjusted to a ruptured atherosclerotic plaque. Resulting in cellular
ischemia, tissue injury and tissue necrosis.
EPIDEMIOLOGY
The epidemiology of congestive heart failure (CHD) has been studied extensively
and lead to much debate concerning the associated risk factors. The increases in mortality
with age is probably not due to a particular age related factor but the cumulative effect of
risk factor that lead to a atherome and thrombosis and hence to CHD. Woman appears to
be less susceptible to CHD than men are although they seem to loss this protection after
the menopause, presumably because of hormonal changes.
AETIOLOGY
1. Decreased Blood Flow:
 Atherosclerosis
 Coronary Artery Spasm
 Traumatic Injury
 Embolic Events
2. Increased Oxygen Demand:
 Diastole
 Systole
3. Reduced Blood Oxygenation
4. Others: Hyperlipidemia, Hypertension, Smoking, Diabetes Mellitus, Obesity,
Gout, Oral Contraceptive Use.
25
PATHOPHYSIOLOGY
Injury to Endothelial Lining of
Hypercholesterolemia Coronary Arteries & other vessels
Suboendothelial Migration of
Monocytes or Lipid Accumulation
Migration and Proliferation of

Smooth Muscles
Fibroblast Synthesis & Secretion
Progression of Atherosclerosis
Narrowing of Blood Vessels
Reduction in Blood Flow
MANAGEMENT
Treatment Goals Include -
1. To relive chest pain and anxiety
2. To reduce cardiac work load and stabilize cardiac rhythm
3. To reduce MI by limiting the area affected and preventing function
4. To prevent or arrest complications such as lethal arrhythmias, CHF, Sudden
death.
5. To reopen closed coronary vessel with thrombolytic drugs.
FIRST LINE THERAPY:

1. Nitrates (Nitro glycerin):
Dose - Acute attacks 0.5 mg every 3 min through buccal mucosa 5 mcg/min through
infusion.
Mechanism of Action - The nitrates decrease oxygen demand and facilitate coronary
blood flow.
26
Contraindication - Cerebral trauma, cerebral hemorrhage hypertrophic cardiomyopathy.
2. Thrombolytic Therapy [Recombinant Tissue Plasminogen Activator (t-PA)]:

Front load regimen - Total dose of 100 mg or less that is dosed over 11/2 hours.
The initial dose of 15 mg is bloused IV.
 Infuse t-PA at the rate of 0.75 mg/kg over 30 min (not to exceed 50mg)
Followed by t-PA infused at 0.5 mg/kg over 60 min (not exceed 35mg)
 Contraindication t-PA includes active internal bleeding recent cerebrovascular
accident, intracranial neoplasm, pregnancy, arteriovenous malformation, spinal
surgery.
 Urokinase: It is enzyme produced by kidney and found in urine. The urokinase

converts endogenous plasminogen to enzyme plasmin. Plasmin degrades fibrin
clots.
The adverse effects of systemic bleeding, Allergic reaction and fever. t 1/2 is 20
minutes.
 Streptokinase: An IV dose of 1.5 million IU is infused over 60 minutes.

Contraindication - Streptokinase includes active internal bleeding, recent
cerebarovascular accident, intracranial or intraspinal surgery.
 Alteplase: It is genetically engineered drug. It is 10 times more expensive than

streptokinase. It is not antigenic & seldom causes hypotension. The standard
regimen is given over 90 minutes (bolous dose of 15 mg, followed by 0.75 mg/kg
of body weight, but not exceeding 50 mg, over 30 minutes and than 0.5 mg/kg
body weight but not exceeding 35 mg, over 60 minutes.
3. Post Thrombolytic Adjunctive Therapy
27

Aspirin: Administered 150 – 325 mg during acute thrombolytic therapy to affect
thrombolysis positively by preventing platelet aggregation and reduced post –
infarct mortality. Other agents include dipyridamol, Ticlopidine, and clopidogrel.

Heparin: Administered along with thrombolytic to prevent re-occlusion once a
coronary artery has been opened. Heparin has been given IV as a 4000 U bolus,
followed by a continuous infusion of 1000 U per hour. The goal of therapy is to
maintain the activated partial thromboplastin time (APTT) between 1.5-20 times
controls.

LMWH (Low Molecular Weight Heparins) [Enoxaparin, Dalteparin]:
Currently being evaluated as alternative to heparin.

Warfarin: The treatment of acute MI to reduce mortality and prevent recurrent MI
and other thromboembolic complication such as stroke. The target International
normalized ratio (INR) is 2.5- 3.5. The average half life of warfarin is 36-42 hours.
The peak antithrombotic effect of warfarin is delayed 96 hours, despite a
therapeutic INR. It takes approximately 10-14 days to achieve full anti coagulant
effect when warfarin initiated or dosage changes are made.
Mechanism of Action - Warfarin inhibits activation of the clotting factors that
depends on vitamin k for synthesis factors II, VII, IX, and X and the coagulation
inhibitor protein C and protein S.
SECOND LINE THERAPY:

1. Β- Adrenergic Blockers:
β- Blockers to reduce ischemia, reduce the potential zone of infarction, decrease
oxygen demand, preserve left ventricular function, and decrease cardiac work load.
β- Blockers to reduce significantly post MI mortality due to sudden death, risk of
reinfarction, cardiac rupture, and ventricular arrhythmias.
Early dosing regimens

IV doses
28
Propranolol - 0.1 mg/kg 2-3 divided doses every 10min.
Metaprolol - 15 mg in 3 divided dose every 5 min.
Atenolol - 5-10 mg in 2 divided doses every 5 – 10 min.
Late dosing regiments
Oral doses
Propranolol - 180-240 mg/d in 4 divided doses
Metaprolol - 200 mg/d in 2 divided doses
Atenolol - 100 mg/d as a single dose.
2. Calcium Channel Blockers:

This are not used in acute phase of MI and may be harmful to patient with
impaired left ventricular function they may decrease the incidence of reinfarction in
patients with non- Q- wave infarcts.
3. ACE Inhibitors:
It is used after MI has show improved exercise capacity and reduced mortality in-
patient with congestive heart failure. This agent is beneficial in patients with MI
presenting with left ventricular dysfunction.
4. Statins:
Use of lovastatin, simvastatin, and other agent to aggressively lower cholesterol
has shown reduced mortality in MI patients.
PATIENT COUNSELLING
1. Patients should be encouraged if they experience chest pain that is more than an
angina, to call for an Ambulance.
2. Patients also need up-to-date advice when faced with difficult choices regarding
medical treatment, angiographic procedures or surgery.
29
1. Nitrates: Sublingual administration, sublingual tablets should not be chewed or
crushed, use of transdermal patches, do not stand up immediately while using this
medication.Monitor for bluish colored lips, fingernails or palms.
2. Statins: Educate the patient to take these drugs after food. It is advisable to take
these medications during night (except for atorvastatin). Ask the patient to report
to the doctor if any signs of muscle pain appear and not to worry in the case of
urine discoloration.
3. Anticoagulant Therapy: Stop all sports and dangerous activities, soft –bristled
toothbrushes should be used, and electric razors can replace razors blades. Proper
monitoring of INR should be done, and if beyond 2.5- 3.5 inform to the physician.
4. Fibrates: Take with or immediately after food to lessen stomach upset. Monitor
for blood in urine, chest pain, and shortness of breath, stomach pain.
5. Beta Blockers: Monitor for hypotension, dizziness, headache, and bradycardia.
Explain the need for dose tapering before stopping the drug.
1. Regular physical activity (e.g., brisk walking) at least 30 minutes per day, 5-7
days a week.
2. Eliminate Trans Fat Food like fried, oily food or baked food.
3. Cocaine, Amphetamine use, and excessive caffeine intake should all be avoided.
4. Regularly monitor Blood Pressure, and Hematological Parameters.
5. Restricted Dietary Sodium Intake.
30
REFERENCES:
1. Sarah A. Spinler, simon de Denus, Acute Coronary Syndrome. In:Joseph
T.Dipirip, Robert L.Talbert, Gary C. Yee, Gary R. Matzke, Barbara G. Wells,
L. Michael Posey,Pharmacotherapy A Pathophysiologic Approach,6th ed,
McGraw-Hill,p.291-399
31
ASTHMA
The national institutes of health national asthma education and prevention

program (NAEPP) has defined asthma as a chronic inflammatory disorder of the airways
in which many cells and cellular elements play a role. In susceptible individuals,
inflammation causes recurrent episodes of wheezing, reathlessness, chest tightness and
coughing.
EPIDEMIOLOGY
The exact prevalence of asthma remains uncertain because of the differing ways
in which airway restriction is reported. It has been estimated that about 4% of the British
and American populations have asthma. The probability of children having asthma - like
symptoms is estimated to be between 5% and 12%, with a higher occurrence in boys than
girls and in children whose parents have an allergic disorder.
AETIOLOGY
Precipitating factors of an acute asthma exacerbation may include:
1. Allergens (e.g., pollen, house dust mite, animal dander, mold, cockroach, food)
2. Occupational exposures (e.g., chemical irritants, flour, wood, textile dusts)
3. Viral respiratory tract infections.
4. Exercise.
5. Emotions (e.g., anxiety, stress, hard laughter or crying)
6. Exposure to irritants (e.g., strong odors, chemicals, fumes)
7. Environmental exposures (e.g., weather changes, cold air, sulfur dioxide, cigarette
smoke)
8. Drugs - Reactions to drugs may occur due to hypersensitivity or as an extension
of the pharmacologic effect.
 Problematic drugs include:
a. Aspirin and other nonsteroidal anti-inflammatory drugs.
32
b. Antiadrenergic and cholinergic drugs (e.g.-adrenergic blockers,
bethanechol)
c. Medications that contain tartrazine, sulfites and other preservatives.
PATHOPHYSIOLOGY
Triggers: Infection,
Allergens, Exercise, Irritants
IgE – Mast cell mediated response
Release of meidators from Mast Cells,

Eosinphils, Macrophages, Lyphocytes
Early Phase Response Late Phase Response
Peaks in 5 – 6 hrs.
Peaks in 30 – 60 mins.  Infiltration with Eosinophils & Neutrophils

 Inflammation
 Bronchial Hyperactivity
Within 1 – 2 Days
 Hypertrophy & Hyperplasia of

Bronchial Smooth Muscle
Infiltration with Monocytes
 Acute Bronchoconstriction
& Lyphocytes
 Mucus Secretion
 Vascular Leakage
 Mucosal Edema
 Obstruction of Large & Small Airways

 Air Trapping
 Respiratory Acidosis
 Hypoxemia
33
MANAGEMENT
MECHANISM OF
CLASS OF DRUGS ADVERSE EFFECTS
ACTION
CORTICOSTEROIDS
1. Inhaled Corticosteroids
 Beclomethasone
 Budenoside Steroids reduce
Abnormalities in glucose
 Fluticasone inflammation reversing
metabolism, increased
mucosal edema,
 Flunisolide appetite, weight gain,
decreasing the
 Triamcinolone hypertension and
permeability of capillaries,
2. Oral Corticosteroids adrenal suppression.
inhibiting the release of
 Prednisone leukotrienes and cytokines.
 Prednisolone
 Methylprednisone
 Methylprednisolone
3. Long Acting Β2 Agonists
By increasing cAMP
 Salmeterol Tremor and tachycardia.
results in bronchodilation.
 Formoterol
4. Short Acting Β2 Agonists
Increased heart rate,
 Salbutamol Relax the smooth muscles
shakiness, nervous, jittery
 Terbutaline around the airways
feeling.
 Hexoprenaline
 Orciprenaline
Acts by inhibiting
physiological actions of
LTC4, LTD4 and LTE4 at
the cysLT1 receptor. It
Gastro-intestinal
reduces the sputum levels
5. Leukotriene Antagonists disturbance,
and causes
 Montelukast hypersensitivity
bronchodilation. It reduces
 Zafirlukast reactions.
the bronchial hyper
responsiveness, improves
the lung function, and
reduces bronchial
inflammation.
Parasympathetic
stimulation causes
6. Anti-Cholinergic bronchial constriction and
 Ipratropium Bromide mucus secretion.
Dry mouth and sedation.
 Oxitropium Bromide Anticholinergics are used
 Tiotropium to block these responses
and maintain bronchial
dilation of the airway.
34
They are effective Cromolyn-infrequent
prophylactic agents that laryngeal edema, cough,
7. Mast Cell Stabilizer
stabilize the membranes of and wheezing.
 Cromolyn Sodium
mast cells and prevent Nedocromil-unpleasant
 Nedocromil mediator release, probably taste.
by blocking calcium gates.
It increases levels of Tremor, insomnia,
cAMP by inhibiting the gastrointestinal distress,
8. Methyl Xanthines enzyme nausea, seizures and
 Theophylline phosphodiesterase, results arrhythmias.
in bronchodilation and has
anti-inflammatory effects.
In general, three types of medical treatments are available for asthma:
 Bronchodilator medications that relieve acute symptoms or prevent flare - ups.
 Corticosteroids and other medications that suppress airway inflammation over

days, weeks or months.
 Immunotherapy or allergy desensitization shots.
 Asthma treatment guidelines recommending inhaled corticosteroids as a safe,

effective and preferred first-line therapy for both children and adults who have
persistent asthma.
 The NAEPP also found that an inhaled corticosteroid plus a long-acting inhaled
bronchodilator may work better than inhaled corticosteroids alone for some
people with moderate, persistent asthma.
 Guidelines for the management of chronic asthma in adults and children.
Step 1 Occasional use of relief bronchodilators.
Step 2 Regular inhaled anti-inflammatory agents.
Step 3 High dose inhaled steroids or low dose inhaled steroids plus long acting inhaled β
agonists’ bronchodilator.
35
Step 4 High dose inhaled steroids and regular bronchodilators.
Step 5 Addition of regular steroid tablets.
A variety of medications are available for acute and longer - term treatment of
asthma.
Acute symptom relief

Bronchodilators are medications that open up constricted airways and provide
temporary relief of asthma symptoms. Bronchodilators may be short acting or long acting
and include,
Beta-2 Agonists - Short-acting beta-2 agonists begin working within minutes and
last 2 to 4 hours. Long - acting beta - 2 agonists last up to 12 hours. The most common
drugs, such as albuterol (Proventil, Ventolin) and pirbuterol (Maxair), act quickly to
relieve symptoms and can be used as a prevention measure before you exercise or breathe
cold air. Prescribed as needed, they may relieve your symptoms for up to 6 hours. Inhaled
beta-2 agonists won't correct underlying inflammation, however and can easily be
overused.
Salmeterol (Serevent) and Formoterol (Foradil) - These long-acting

bronchodilators relieve airway constriction for up to 12 hours. They're generally used to
prevent symptoms, especially at night.
Theophylline (Slo-Bid) - This type of bronchodilator is taken in pill form every

day. It's especially helpful for relieving night time symptoms of asthma.
A theophylline blood level between 5 - 15 mcg/ml usually gives relief of symptoms while
avoiding side effects.
Long-Term Anti-Inflammatory Treatment - Anti-inflammatory drugs are taken

continually to prevent attacks. Anti-inflammatory drugs reduce inflammation in your
airways and prevent blood vessels from leaking fluid into airway tissues. The most
widely used of these drugs include:
36
Corticosteroids: These drugs are the most effective medications for asthma. They help
decrease the frequency of attacks and lower the dosage of other medications needed to
calm symptoms. Long-term use of oral or intravenous corticosteroids can cause serious
side effects, however, including decreased resistance to infection, loss of bone mineral
(osteoporosis), muscle weakness, high blood pressure and thinning of the skin.
Leukotriene Modifiers: The drugs work by reducing the production, or blocking the
action, of leukotrienes - substances released by cells in your lungs during an asthma
attack. Leukotrienes cause the lining of your airways to become inflamed, which in turn
leads to wheezing, shortness of breath and mucous production.
Other Drugs: Although they're not effective for everyone, daily use of inhaled cromolyn
(Intal) or nedocromil (Tilade) may help prevent attacks of mild to moderate asthma. In
some cases they may also help prevent asthma triggered by exercise if taken an hour
before any vigorous activity.
Immunotherapy: If you have allergic asthma that can't be easily controlled by avoiding
triggers and using medication, allergy desensitization shots (immunotherapy) may help.
Immunotherapy carries the risk of an allergic reaction to the shot. Life-threatening
reactions are rare, but can occur.
PATIENT COUNSELLING
1. Providing information regarding the site and severity of the disease based on
Pulmonary Function Test results.
2. The patient should be able to monitor symptoms, peak flow measurements, drug
usuage and knowing how to deal with fluctuations in severity of asthma.
3. Counselling should lead to increase patient confidence in the ability to self

manage to asthma, decrease hospital admission rates.
37
1. Provide information regarding the action of each of the medicines they use.
2. The appropriate choice of inhalation devices should be made and the patient
should be educated to use them correctly.
3. An individualized self management plan should be developed for each patient.
4. Specific counselling on drugs used to relieve symptoms, drugs used to prevent the
asthma attacks and drugs which are given only as a reserve treatment for severe
attacks.
5. A self-management plan would also include details of when to increase the dose
of inhaled steroid, when to take oral corticosteroids and when to use a nebulizer.
Inhalation Technique Counselling for Dry Powder Inhalers (DPI):
1. Hold inhaler upright or level.
2. Take a rotacap capsule from its container. Insert the rotacap transparent end first,
into the raised square hole of the rotahaler.
3. Load inhaler with one dose. Press the rotacap firmly such that the top end of rota
cap is level within the top of the hole.
4. Holding the mouth piece firmly with one hand, rotate the base. Exhale gently as
much as comfortable.
5. Place mouthpiece in mouth and close lips around it. Inhale slowly, forcefully and
deeply through inhaler and releases a dose.
6. Removes inhaler and hold breathe for at least for 5sec then breathe out slowly, if
a second dose is prescribed, wait for 1min before repeating the above steps, rinse
mouth and replace dust cap.
38
Inhalation Technique Counselling for Metered Dose Inhalers (MDI):
1. Remove dust cap, shake inhaler well and hold inhaler upright or level.
2. Load inhaler with one dose, exhale gently as much as comfortable, place
mouthpiece in mouth and close lips around it.
3. Inhale slowly, forcefully and deeply through inhaler and release a dose.
4. Remove inhaler and hold breathe for at least for 5sec then breathe out slowly, if a
second dose is prescribed, wait for 1min before repeating the above steps.
5. Rinse, gargle the mouth and replace the cap.
1. Avoid environment that may be a reason for the Asthma attack and use
protectants according to the nature like Umbrella, Rain Coat, Sweater, Cap etc.
2. Take food at proper timings and must be rich in protein.
3. Perform exercises like walking and yoga.
4. Avoid any kind of Emotional Stress, Mental Tension, Anxiety or Excitement

which may trigger Asthma attacks.
5. Explain the importance of Smoking Cessation and technique for it.
6. Sleep only 2 hrs after any meal.
7. Monitor PFT bi- annually and visit the doctor on exact review dates.
39
REFERENCES
1. H. William Kelly, Cristine A. Sorkness, Asthma. In:Joseph

T.dipirio,Robert L.Talbert,Gary R. Matzke, Barbara G. Wells, L.Michael
Posey,Pharmacotherapy A Pathophysiologic Approach,6th ed, McGraw-
Hill,p.503-536
2. K.P.Gibbs,M.Small, Asthma. In: Roger Walker, Clive Edwards, Clinical

pharmacy and therapeutics,3rd ed, Churchill Livingstone,2006,p.375-396
3. Roy A.Pleasants, Asthma & COPD. In:Leon Shargel, Alan H. Mutnick,

Paul F.Souney, Larry N. Swanson,Comprehensive Pharmacy Review,6th
ed, Lippincott Williams & Wilkins,2007,p.1058-1081
40
41
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
 COPD stands for chronic obstructive pulmonary disease.

- Chronic means long term
- Obstructive refers to the fact that breathing is blocked
- Pulmonary indicates that the disease affects lungs.
 COPD is defined as a chronic, slowly progressive disorder characterized
 By airflow obstruction, causing reduced pulmonary inspiratory and expiratory
capacity.
EPIDEMIOLOGY
 14 million people in the United States have COPD.
 COPD is now the fourth leading cause of death in the United States, and it
 is the only common cause of death that is increasing in incidence.
 Respiratory diseases including chronic bronchitis are common in area of
 High atmospheric pollution and in people with dusty occupations such as foundry
workers and coal miners.
 6.5% of males and 4% of females are suffering from COPD.
AETIOLOGY
1. Cigarette smoking
2. Tobacco consumption
3. Alpha-1-antitrypsin deficiency develops emphysema with young adults.
4. Exposure to irritants such as sulfur dioxide, noxious gas, organic or inorganic
dust.
5. A history of respiratory infections or bronchial hyperactivity.
42
PATHOPHYSIOLOGY
 Tobacco Smoke
 Air Pollution
α1 – Antitrypsin
Deficiency
Continual Bronchial Breakdown of Elastin in

Irritation & Inflammation Connective Tissue of Lungs
Chronic Bronchitis Emphysema

 Bronchial Edema  Enlargement of Air Spaces
 Hypersecretion of Mucus  Destruction of Lung Parenchyma
 Chronic Cough  Destruction of Alveolar Septa
 Bronchospasm  Loss of Lung Elasticity
 Bronchiectasis  Airway Instability
 Closure of Small Airways
 Impaired Gas Exchange
 Release Neutrophil, Interleukin-8,

Leukotriene B4 & Macrophages
 Stimulate Mucus Hypersecretion
 Airway Obstruction
 Air Trapping
 Dyspnea
 Frequent Infections
 Abnormal Ventilation – Perfusion Ratio

 Hypoxemia
 Hypoventilation
 Cor pulmonale
43
MANAGEMENT
1. Smoking:
Smoking is the most important factor in the development of obstructive airway
disease. The nicotine absorbed reduces the effects associated with cigarette smoking such
as irritability, sleep disturbances, fatigue, headache and increased appetite.
2. Antibiotics and Vaccines:
Antibiotic therapy is vital if a patient develops purulent sputum. The normal
pathogens involved are Streptococcus pneumoniae, Haemophilus influenzae or Moraxella
catarrhalis. The usual antibiotics are co-amoxiclav, amoxicillin, erythromycin or
doxycycline.
3. Bronchodilators:
Bronchodilators in COPD are used to reverse air flow limitation. Patients may
report an improvement in exercise tolerance or relief of symptoms such as wheeze and
cough.
4. Inhaled β2 Adrenoceptor Agonists:
The higher doses (400-800 micrograms) may be required 6-hourly for COPD
patients. This dosing may result in an increased incidence of side effects. Short acting β 2
agonist should ideally be used when required for symptom relief.
5. Anti Cholinergic Drugs:

Inhaled anticholinergic drugs reverse the parasympathetic airway muscle
Tone and have a significant bronchodilator effect especially in the elderly. The drugs of
choice are ipratropium bromide and oxitropium.
6. Theophylline:
Theophylline is weak bronchodilators and are said to have additional
physiological effects in COPD. Persistent nocturnal symptoms such as cough or wheeze
may be helped by the night-time use of long acting theophylline.
7. Corticosteroids:
44
Steroid must be used in the smallest doses possible to minimize long - term
adverse effects and should be used in conjugation with inhaled steroids.
PATIENT COUNSELLING
1. Explain the patient about the site, severity and progressiveness of the disease.
2. Inform about the emergency management in the case of Exacerbation.
1. Use of Inhaled Therapy: The incorrect use of any inhaler will lead sub
therapeutic dosing.
2. Home Nebulizer Therapy: Patients are prescribed nebulizer therapy for use at
home should be counselled appropriately.
3. Domiciliary Oxygen Therapy: Portable oxygen cylinders can be used to increase
exercise tolerance during walking.
1. Pulmonary Rehabilitation: Advice and support on stopping smoking, nutritional
assessment aerobic exercise training to increase capacity and endurance for
exercise, breathing retraining.
2. Smoking Cessation: Members of the health care team can educate smokers about
the dangers and actively encourage and motivate those who want to give up.
3. Take food at proper timings and must be rich in protein.
4. Perform exercises like walking and yoga.
5. Avoid any kind of Emotional Stress, Mental Tension, Anxiety or Excitement

which may trigger Asthma attacks.
6. Sleep only 2 hrs after any meal.
7. Monitor PFT bi- annually and visit the doctor on exact review dates.
45
REFERENCES:
1. Sharya V. Bourder, Dennis M.Williams,COPD.In:Joseph T.Dipiro,

Robert L. Talbert, Gary C. Yee, Gary R. Matzke, Barbara G. Wells, L.
Micheal Posey, Pharmacotherapy A Pathophysiologic Approach,6th
ed,McGraw-Hill,p.537-556
2. K.P.Gibbs,M.Small, Asthma. In: Roger Walker, Clive Edwards,

Clinical pharmacy and therapeutics,3rd ed, Churchill
Livingstone,2007,p.1081-1089
46
DIABETES MELLITUS
The term diabetes mellitus (DM) describes a metabolic disorder of multiple

etiologies characterized by chronic hyperglycemia with disturbance of the carbohydrate,
fat and lipid metabolism resulting from defects in insulin secretion, insulin action or both.
CRITERIA OF DIAGNOSIS
The diagnosis criteria as per American Association Criteria for Diagnosis are as
follows:
DIABETES MELLITUS
In the absence of secondary causes, diabetes is diagnosed in presence of one or
more of the following results.
 Fasting plasma glucose ≥126 mg/dl on two occasions.
 Random plasma glucose ≥200mg/dl on two occasions with classical symptoms of
DM.
 Oral glucose tolerance test (OGTT) ≥200mg/dl 2-hour post 75 gm glucose load.
OGTT should not routinely be used for diagnosing DM.
GESTATIONAL DIABETES
Diagnosis is made with one or both of the following:
 Diagnosis is established using above criteria for DM.
 Two or more of the following are present: OGTT (100 gm glucose) fasting
>105 mg/dl; 1 hour post >190 mg/dl: 2 hour post >165 mg/dl; 3 hour post
>145 mg/dl.
EPIDEMIOLOGY
Global
47
According to the world health organization (WHO), approximately
150 million people worldwide have diabetes. By the year 2025, close to 300 millon
people globally will have diabetes.
India
In India, it is estimated that presently 19.4 million individuals are affected by this
deadly disease which is likely to go upto 57.2 million by the year 2025. The reason for
this escalation are changes in life style, people living longer than before and low birth
weight which could lead to diabetes during adulthood.
AETIOLOGIC CLASSIFICATION OF DIABETES MELLITUS:

I. TYPE 1 DIABETES (β -cell destruction, usually leading to absolute insulin
deficiency) A. Immune-mediated, B. Idiopathic.
II. TYPE 2 DIABETES (Secretary Defect with insulin resistance)
III. OTHER SPECIFIC TYPES OF DIABETES

A. Genetic defects of β -Cell Function characterized by Mutations in:
1. Hepatocyte nuclear transcription factor (HNF) 4 α (MODY 1)
2. Glucokinase (MODY 2)
3. HNF-1α (MODY 3)
4. Insulin promoter factor (IPF) 1 (MODY 4)
5. HNF-1 α (MODY 5)
6. Mitochondrial DNA
7. Proinsulin or insulin conversion
B. Genetic Defects in Insulin Action:
1. Type- A insulin resistance
2. Leprechaunism
3. Rabson-Mendenhall syndrome
4. Lipoatrophic diabetes
48
C. Diseases of the Exocrine Pancreas: Pancreatitis, pancreatectomy, neoplasia,
cystic fibrosis, hemochromatosis, fibrocalculous pancreatopathy.
D. Endocrinopathie: Acromegaly, Cushing's syndrome, glucagonoma,
pheochromocytoma, hyperthyroidism, somatostatinoma, aldosteronoma.
E. Drug or Chemical-Induced: Vacor, Pentamidine, Nicotinic Acid,
Glucocorticoids, Thyroid Hormone, Diazoxide, β-Adrenergic Agonists,
Thiazides, Phenytoin, α -Interferon, Protease Inhibitors, Clozapine, β-Blockers.
F. Infections: Congenital rubella, Cytomegalovirus, Coxsackie virus.
G. Uncommon forms of Immune-Mediated Diabetes: "Stiff-Man" Syndrome,
Anti-Insulin Receptor Antibodies.
H. Other genetic syndromes sometimes associated with Diabetes:
Down's syndrome, Klinefelter's syndrome, Turner's syndrome, Wolfram's
syndrome, Friedreich's ataxia, Huntington's chorea, Laurence-Moon-Biedl
syndrome, Myotonic Dystrophy, Porphyria, Prader-Willi syndrome.
IV. GESTATIONAL DIABETES MELLITUS (GDM)

NOTE: MODY : Maturity Onset of Diabetes of the Young.
HNF : Hepatocyte Nuclear transcription Factor.
IPF : Insulin Promoter Factor.
PATHOGENESIS OF TYPE 2 DIABETES MELLITUS

 Genetic Predisposition Environment
 Multiple Genetic Defects
Obesity
Primary Beta Cell Defect Peripheral Tissue Insulin Resistance
Deraged Insulin Secretion Inadequate Glucose Utilization
Hyperglycaemia
Beta Cell Exhaution
Hyperosmotic Plasma Blood Glucose > Renal Threshold
49
Dehydration of Cells Glucosuria: Urine has high Specific Gravity
Osmotic Diuresis:
 Polyuria
Hyperglycemic Coma
 Polydypsia
PATHOGENESIS OF TYPE 1 DIABETES MELLITUS  Hypokalemia
 Hyponatremia
95% patients express
HLA, DR3 or DR4
Genetic Predisposition
HLA DQ most specific
Coxsackie B4 Virus
Congenital Rubella
Environmental Insult
Cytomegalovirus
Cow’s milk (17-aa Fragment

of Bovine Albumin)
Insulitis characterized by invasion of Lymphocytes

Molecular Mimicry of
Bovine Milk Albumin
Homology btw GAD &

Coxsackie Virus Protein
Conversion of β-cell
from self to non self
Exposure of Cryptic Antigen
Release of Destructive
Cytokine by Virus
Houmoral, due to antibodies against Insulin,

Proinsulin, GAD, Carboxypeptidases & ICA
69 expressed on β-cells
Destruction of β-cells &
Development of DM
Cell Mediated, due to Natural Killer Cells,
Activated Cytotoxic Lymphocytes,
Macrophages that produce Cytokines IL – 1,
50
TNF-α which destroy β-cells by inducing NO
and superoxide
MANAGEMENT
Type 1 diabetes mellitus
All patients required treatment with insulin. There are types of insulin available
from different species, beef, pork and human. Human insulin is prepared by recombinant
DNA technology using E.Coli.
Insulin Preparations
Time to peak
Type Onset of action Duration of action
levels
Neutral Protamine 2 hrs 6-8 hrs 12-16 hrs
Lente 2 hrs 6-8 hrs 12-16 hrs
Ultra Lente 12 hrs 12-16 hrs 18-24 hrs
Regular 30 min 1-2 hrs 4-6 hrs
Lispro 15-30 min 1-2 hrs 2-4 hrs
Glargine 1 hr 24 hrs 24 hrs
Aspart 30-45 min 1-2 hrs 2-4 hrs
Subcutaneous route is used for the maintenance therapy. Insulin can be injected in to the
thigh, abdominal wall, buttocks or upper arm. Intravenous injection is used in the
management of ketoacidosis.
Insulin doses
Dose adjustment
Blood glucose mg/dl Meal timing
(Regular/ Lispro/ Aspart)
< 50 Decrease 2 U Inject and eat
51 – 70 Decrease 1 U Inject and eat
71 – 130 Routine dose Delay 30 minutes
131 – 150 Increase 1 U Delay 30 minutes
51
251 – 300 Increase 4 U Delay 1 hour
Treatment Protocol of Type 2 Diabetes

Newly diagnosed mild to moderate type 2 diabetes with suboptimal control despite diet
and exercise
Obese patients (insulin resistant) Lean patient (insulin deficient)
Normal hepatic function Abnormal Hepatic Function
Normal cardiac & Abnormal Renal Function, CHF

Renal function
Biguanide Thiazolidinedione Sulphonyl urea

Consider non consider α-Glucosidase consider secretagogue
Sulphonyl urea inhibitor Thiazolidinedione
SUBOPTIMAL CONTROL
Add Thiazolidinedione. Add sulphonyl urea Add biguanide

Add sulphonyl urea or other α-Glucosidase inhibitor Add α-Glucosidase inhibitor
Secretagogue.
INSULIN
52
DRUGS USED IN TYPE-2 DIABETES
DAILY DURATION
MECHANISM OF
GENERIC NAME DOSAGE OF ACTION, CLEARANCE
ACTION
RANGE, (mg) HRS
SULFONYLUREA
First generation
Chlorpropamide 100-500 48 Renal
Tolbutamide 500-3000 6-12 Hepatic
Second generation
Glimepiride 1-8 24 They promote Hepatic, renal
increased
Glipizide 2.5-40 12-18 pancreatic insulin Hepatic
Glipizide (E.R) 5-10 24 secretion, Hepatic
Glyburide 1.25-20 12-24 glycogensis, Hepatic, renal
Overcomes the
Glyburide peripheral insulin
0.75-12 12-24 Hepatic, renal
(micronized) resistance.
THIAZOLIDINEDIONES
Pioglitazone 15-30 OD 16-24 Increase insulin Hepatic
sensitivity in
Rosiglitazone 4-8 b.i.d 3-4 Hepatic
muscles
BIGUANIDES
Improvement in
1-2.5 gm with peripheral insulin
Metformin 7-12 Renal
meals t.i.d sensitivity, reduce
gluconeogenesis.
Α – GLUCOSIDASE INHIBITORS
75-300 with Competitive
Acarbose 4 -
food inhibitor of the
75-300 with enzymes of
Miglitol 4 -
food enterocytes.
PATIENT COUNSELLING
Based on Disease Profile -
1. The severity of the lifelong disease, its progression and complications like
Neuropathy, Nephropathy and Retinopathy.
2. The signs and symptoms of the disease.
3. Futher complications which includes Ketoacidosis and other Infections.
4. Hyperglycemia and Hypoglycemia - Signs and Symptoms and Treatment.
53
POSSIBLE
ADMINISTRATION DOSING
DRUGS SIDE COMMENTS
TIME SCHEDULE
EFFECTS
Interacts with
Taken with meals or Usually
Hypoglycemia, Oral
Glibenclamide 15- 30 mins before taken in 1 – 2
Obesity Anticoagulant
food doses
Action
Interacts with
Usually
Oral
Glimiperide Taken with meals taken in Hypoglycemia
Anticoagulant
single dose
Action
Interacts with
Usually
Oral
Glicazide Taken with meals taken in 1 – 2 Hypoglycemia
Anticoagulant
doses
Action
Interacts with
Usually
Oral
Glipizide Taken with meals taken in 1 – 2 Hypoglycemia
Anticoagulant
doses
Action
Should be
stopped before
Taken during or
Usually Surgery or any
immediately after a GI
Metformin taken in 1 – 3 Radiological
meal to minimize GI Disturbances
doses Procedures
effects
using Contrast
Media
Should be
stopped before
Swallow whole with
Usually Surgery or any
liquid before meal or GI
Acarbose taken in 1 – 3 Radiological
chew with first Disturbances
doses Procedures
mouthfuls of meal
using Contrast
Media
Usually
Repaglinide Taken with meals taken 3 times Hypoglycemia _
a day
Usually
Pioglitazone Taken with meals taken in Hypoglycemia _
single dose
54
INSULIN:
STEPS COUNSELLING TIPS
 Draw air into the Insulin syringe corresponding to the
amount to be taken and inject into vial.
Drawing of Insulin  Rotate the vial in the palm.
from the Vial  Invert the vial, draw up Insulin vertically from eye
level, inject excess Insulin back into the vial and pull
out the needle.
 Best sites for self injection are front and outer thighs
Site of self Injection
and abdomen.
 Clean injection site with spirit, insert the needle at 45
Technique of Injections degrees angle into subcutaneous tissue.
 Inject Insulin slowly.
 Insulin preparations should be taken 30 mins. Before
Time of Administration
food.
 Insulin should be stored at 2- 80C.
 If there is no refrigerator then place Insulin in a glass
Storage of Insulin of water.
 It is also adviced to carry Thermostat Bags which
retains the stability of the preparations.
 Patient should be monitored for Allergic Reactions
ADR (Bovine or Porcine preparation).
 Hypoglycemia.
 Insulin Pen has several advantages (easy to carry, less
Specialized Devices in pain, and accurate dose administration).
Administering Insulin  Suitable patients should be isolated and adviced by the
pharmacist.
Based on Lifestyle Modifications -

1. Exercise – benefits and effect on blood glucose control.
55
2. Dietary control is the mainstay of treatment in type 2 diabetes and an integral part
in type-1 diabetes.
3. Diabetes patient should limit their sugar intake.
4. Since there is an increased risk of death from coronary artery disease in diabetics,
it is wise to restrict saturated fats and to substitute them with unsaturated fats.
5. Dietary fibre has two useful properties. Firstly it is physically bulky and increases
satiety. Secondly, fiber delays the digestion and absorption of complex
carbohydrates, thereby minimizing hyperglycemia.
6. Home Blood Glucose Testing – Technique and Interpretation.
7. Foot Care.
8. Cardiovascular risk factors – Smoking, Hypertension, Obesity and

Hyperlipidaemia.
9. Regular Medical and Ophthalmologic Examinations.
56
REFERENCES
1. Stephen M. Setter , John R.Whites, R.Keith Caampbell, Diabetes
Mellitus.In:Richard A. helms, David J. Quan, Eric T. Herfindal, Dick R.
Gourley,Textbook of Therapeutics Drug and Disease Management,8th ed,
Lippincott, Williams & Wilkins,2006,p.1042-1075
2. J.A Cantril, J. Wood, Diabetes Mellitus. In:Roger Walker, Clive Edwards,
Clinical Pharmacy and Therapeutics,3rd ed, Churchill
57
THYROID DISORDERS
Thyroid disorders encompass a variety of disease status affecting thyroid hormone

production or secretion that result in alteration in metabolic stability. Hyperthyroidism
and hypothyroidism are defined as the clinical and biochemical syndrome resulting from
increased and decreased thyroid hormone production respectively.
TYPES OF THYROID DISORDER

1. Hyperthyroidism
2. Hypothyroidism
HYPERTHYROIDISM
EPIDEMIOLOGY
The most common cause of hyperthyroidism is Graves’s disease which accounts
for 90% of cases. Its affect any age group but it is uncommon in childhood. Women are
affected 10 times more than men.
AETIOLOGY
Hyperthyroidism is a disorder of various etiologies. The action of thyroid
stimulating antibodies which mimic the effect of TSH. These immunoglobulins are
antibodies to the TSH receptor on the thyroid gland.
Toxic nodular goiter is another form of hyperthyroidism. This diffuse or focal

autonomous nodal formation develops in the enlarged thyroid with associated
thyrotoxicosis. The well differentiated tumor that secretes excessive amounts of thyroid
hormones.
58
PATHOPHYSIOLOGY (Thyrotoxicosis)
Thyrotoxicosis results when tissues are exposed to excessive levels of T 4, T3 or
both. In Graves’ disease, it is results from the action of thyroid stimulating antibodies
(TSAb) directed against the thyrotropin receptor on the surface of the thyroid cell. These
immunoglobulin G (IgG) antibodies bind to the receptor and activate the enzyme
adenylate cyclase in the same manner as TSH.
Thyroid function test results in different thyroid condition,
T3 resin Free
Total T4 Free T4 Total T3 uptake thyroxin TSH
(μg/dl) (ng/dl) (ng/dl) (%) index (U) (μU/ml)
Normal 4.5-12.5 0.8-2.8 80-220 22-34 1- 4.3 0.25-6.7

Hyperthyroid ↑↑ ↑↑ ↑↑↑ ↑ ↑↑↑ ↓↓
Hypothyroid ↓↓ ↓↓ ↓ ↓↓ ↓↓↓ ↑↑
Increased TBG ↑ Normal ↑ ↓ Normal Normal
TSH: Thyroid stimulating hormone, TBG: Thyroid binding globulin.
MANAGEMENT
Maintenance dose Maximal dose
Modality
(mg/d) (mg/d)
Thiourea drug
- Propylthiouracil 200-600 1200
- Methimazole 10- 60 120
Β-Adrenergic antagonist
- Propranolol 80-160 480
- Nadolol 80-160 320
Iodine containing compounds
-Lugols solution 750 750
-Potassium iodide 10-300 400
Radio active iodine(RAI,131I) NA 2-10 mCi
NA: Not applicable.
HYPOTHYROIDISM
59
EPIDEMIOLOGY
The prevalence of previously undiagnosed spontaneous, overt hypothyroidism has
been estimated to be between 2 and 4 per thousand of the total population world wide.
All though the disease may occur at any age most patients present between 30 and 60
years of age.
AETIOLOGY
Hypothyroidism can be induced by variety of structural or functional
abnormalities. The principal classification is primary, secondary, and tertiary, peripheral.
Primary hypothyroidism due to failure of the thyroid gland and secondary disease due to
hypopituitarism and tertiary disease due to failure of the hypothalamus. Peripheral
hypothyroidism is due to tissue insensitivity to the action of thyroid hormone.
CLASSIFICATION OF HYPOTHYROIDISM
PRIMARY HYPOTHYROIDISM
 Congenital hypothyroidism
 Anti thyroid drugs.
 Hashimotos thyroiditis.
 Postpartum hypothyroidism
 Spontaneous hypothyroidism in Graves’s disease
 Postoperative hypothyroidism
 Hypothyroidism after radio active iodine
 External radiation
SECONDARY HYPOTHYROIDISM
 Hypopituitarism
 Selective thyroid stimulating hormone deficiency
TERITIARY HYPOTHYROIDISM
1. Hypothalamic disorder
PERIPHERAL HYPOTHYROIDISM
60
PATHOPHYSIOLOGY
The vast majority of hypothyroid patients have thyroid gland failure (primary
hypothyroidism). Causes include chronic autoimmune thyroiditis (Hashimoto’s disease),
iatrogenic hypothyroidism, iodine deficiency, enzyme defects, thyroid hypoplasia, and
goitrogens.
Pituitary failure (secondary hypothyroidism) is an uncommon cause resulting

from pituitary tumors, surgical therapy, external pituitary radiation, postpartum pituitary
necrosis, metastatic tumors, tuberculosis, histiocytosis, and autoimmune mechanisms.
MANAGEMENT
DRUG/ DOSAGE FORM COMMENTS/EQUIVALENCY
Unpredictable hormonal stability, inexpensive
Thyroid, USP
generic brands may not be bioequivalent
Standardized biologically to give T4, T3 ratio of
Thyroglobulin32, 65, 100, 130, 200mg
2.5:1 more expensive than thyroid extract
Stable, predictable potency, generic may be
L-Thyroxine, 25-300 μg
bioequivalent
Liothyronine 5-50 µg Tab Uniform absorption, rapid onset t1/2 = 1.5 /d
Lyotrix, 0.25-3 Tab Stable, predictable.
PATIENT COUNSELLING
1. Clinical Pharmacist should reassure patient that although Hypothyroidism is a
chronic condition, treatment is usually safe and effective.
2. Patient should be encouraged to report in the case of Unknown Pain.
Based on Drug Profile -
 Patient should not take Thyroid Hormone at the same time as Iron or Calcium
Supplements. This preparation required administration atleast 2 hours before or
after administration of Thyroid Hormone.
 Inform the patient not to stop medication when symptoms subsides, instead Drugs
should be tapered on Physician’s Advice to avoid any kind of Side- Effects.
Based on Lifestyle Modification -
61
1. Patient on Thyroid Hormone Replacement Therapy should limit the use of
Adrenergic Agents e.g. Non-Prescription Decongestants.
2. Reduce Body Weight by taking Low Carbohydrate Diet and stop Snacking.
3. Avoid Snacks and Fried Food.
4. Inform patient to use Moisturizers and Cold Creams to avoid Dry Skin in
Hypothyroidism.
5. Avoid Sedentary Lifestyle and perform regular Exercise.
6. Patient should take Iodized Salt in their Diet.
62
REFERENCES
1. Robert L. Talbart, Thyroid Disease.In:Joseph T. Dipirio, Robert L.
Talbart, Gary C.Yee, Gary R. Matzke, Barbara G. Wells, L. ,Michael
Posey,Pharmacotherapy A Pathophysiologic Approach,6th ed,McGraw-
Hill,p.1369-1390
2. J.A Cantril, J.Wood,Thyroid Disease. In:Roger Walker, Clive Edwards,
Clinical Pharmacy and Therapuetics,3rd ed, Churchill Livinstone,
2006,p.639-652.
63
OSTEOPOROSIS
Osteoporosis is a condition characterized by a decrease in the density of bone,

decreasing its strength and resulting in fragile bones. It leads to abnormally porous bone
that is compressible, like a sponge. This disorder of the skeleton weakens the bone and
results in frequent fractures in the bones.
EPIDEMOLOGY
Osteoporosis is a major public health threat which afflicts 55% of Americans aged
50 and above. Of these, approximately 80% are women. It is estimated that 1 in 3 women
and 1 in 12 men over the age of 50 worldwide have osteoporosis. It is responsible for
millions of fractures annually, mostly involving the lumbar vertebrae, hip, and wrist.
Fragility fractures of ribs are also common in men.
AETIOLOGY
1. Genetic –
 White or Asiatic Ethinicity
 Positive Family History
 Small Body Frame (Less than 58 kg)
2. Lifestyle –
 Smoking
 Inactivity
 Excessive Exercise
 Early Natural Menupause
 Late Menarche
3. Nutritional Factors –
 Milk Intolerance
 Lifelong Low Dietary Calcium Intake
 Excessive Alcohol Intake
 Consistently High Animal Protein Intake
64
4. Medical Disorders –
 Thyrotoxicosis
 Cushing’s Syndrome
 Type 1 Diabetes
 Rheumatoic Arthritis
 Long- Term Parenteral Nutrition
 Hemolytic Anaemia
 Ankylosing Spondylitis
5. Drugs –
 Thyroid Replacement Drugs
 Glucocorticoid Drugs
 Anticoagulants (Heparin)
 Chronic Lithium Therapy
 Chemotherapy
 Anticonvulsant Drugs
 Extended Tetracycline Use
 Cyclosporine
 Aluminium containing Antacids
PATHOPHYSIOLOGY
Estrogen Deficiency
Release of Interlukin- 1and

TNF- α from Blood Monocetes
Osteoclast Mediated Bone Loss
Dereased Parathroid
Hormone Secretion
Decreased 1, 25 Increased Renal

dihydroxyvitamin D Production Calcium Excretion
Decreased Intestinal Increased Bone Loss

Calium Absorption
65
MANAGEMENT
Antiresorptive Approaches –
1. CALCIUM
ELEMENTAL Ca2+ /
PREPARATION DOSE (mg)
TABLET (mg)
Calcium Carbonate 650 260
Calcium Gluconate 650 58.5
Calcium Lactate 650 84.5
Dibasic Calcium
500 115
Phosphate
2. DIURETICS
Thiazide Diuretics promote decrease in Renal Calcium Excretion. Along with
Estrogen, Diuretics results in Greater Bone Mineral Density than Estrogen alone.
3. VITAMIN D AND ITS METABOLITES
Vitamin D is metabolized in the Liver to 25- hydroxyvitamin D and then to the
Active Metabolite 1, 25- dihydrovitamin D in the Kidney. It increases Calcium
absorption and stimulates Osteoblasts and Osteoclasts.
4. HORMONE THERAPY
 Estrogen produces a decrease in Bone Resorption, an increase in Calcitriol
concentrations, and an increase in Intestinal Calcium absorption and
retention.
 A dose- response relationship exists between Bone Mass and conjugated
Estrogens in daily doses of 0.3- 2.5 mg, Estradiol 0.5- 2 mg, and
Transdermal estradiol 0.05- 0.1 mg.
 The suggested doses of ERT for osteoporosis prevention are conjugated
Estrogens 0.625 mg, Ethinyl Estradiol 0.02 mg, Estropipate 0.625 mg,
Esterified Estrogens 0.625 mg, Estradiol 0.5 mg, and Transdermal
Estradiol 0.05 mg /day.
5. TAMOXIFEN
It’s both an Estrogen Antagonist and an Estrogen Agonist. Tamoxifen 10 mg
twice daily for 5 years was associated with an increase in Lumbar Bone Density.
66
6. PROGESTERONES AND TESTOSTERONE
Progesterone is used in addition with Estrogen Therapy. In men who are deficient
in Testosterone, 10- 115 months of Replacement Therapy resulted in increased
Distal Bone Density or Spinal Bone Density.
7. CALCITONIN
Patient with high bone turnover responds best to Calcitonin and beneficial in
Steroid- Induced Osteoporosis. It is given IV or SC daily administration initially,
and then decreased to 50- 100 IU two to three times weekly.
8. BISPHOSPHONATES
 Etidronate Disodium 400 mg/ day 2 hrs before or after meals for 14 days,
given every 3- 3.5 months increases bone mass and is an alternative for
patients taking estrogens.
 Alendronate 10 mg/ day orally has increased bone mass and reduced
vertebral fractures and loss of height.
Bone Formation Approaches –
1. FLUORIDE
It increases bone formation in trabecular bone and may increase osteoblasts. Slow
release Fluoride appears to be useful in dose of 25 mg/ day for less than 5 years.
2. ANDROGENS AND ANABOLIC STEROIDS
It enhances osteoblast activity. Various androgens are Nandrolone Decanoate,
Stanozolol, and Methandrostenolone. Most of the women develop ADRs like LFT
alteration, Negative Lipid Effects, Hirsutism, Hoarseness, and Acne.
PATIENT COUNSELLING
1. Inform patient about the severity and complication of the disease.
2. Educate the patient that as age increases the Disease gets worsened.
1. Take the recommended amount of Calcium and Vitamin D everyday.
2. Sedatives should be discontinued or switched to short acting agents.
3. Diuretics should be given during day.
4. Orthostatic Blood Pressure problems should be resolved.
67
1. Perform Weight Bearing Exercises like Brisk Walking, Jogging, Dancing and
Aerobic Exercises on regular basis.
2. Smoking Cessation and Alcohol Abstinance.
3. Avoid Caffeinated Beverages which increases Calcium excretion.
4. Counsel the patient to monitor a Bone Mineral Density (BMD) if patient is above
65 years, on Long Term Steroid Treatment and who have gone through
menopause and have experienced a fracture.
5. Dietary Calcium Intake and Vitamin D must be increased.
68
REFERENCES:
1. Louise Parent-Stevens, Osteoporpsis. In: Richard A. Helms, David J.
Quan, Eric T. Herfindal, Dick R. Gourley, textbook of Therapeutics Drug
and Disease Management,8th ed,Lippincott Williams &
Wilkins,2006,p.1788-1802.
69
GLAUCOMA
Glaucomas are a group of ocular diseases characterized by changes in the optic

nerve head and loss of visual sensitivity and field.
EPIDEMIOLOGY
Glaucoma is classified according to the manner in which aqueous humour outflow
is impaired.
1. Primary open glaucoma

Primary open-glaucoma, also referred to as chronic simple glaucoma, is
associated with a relative obstruction to aqueous outflow through the trabecular
meshwork, and is a chronic progressive disease of insidious onset, usually affecting both
eyes.
2. Primary angle closure glaucoma

Primary angle glaucoma or closed angle glaucoma is a condition in which closure
of the angle by the peripheral iris results in a reduction in aqueous outflow. The disease
affects approximately 1 in 1000 adults over the age of 40 years, and occurs in four times
as many females as males.
AETIOLOGY
1. The factors that determine the levels of intraocular pressure are the rate of
aqueous humour production and resistance encounter in the out flow channels.
2. The production of aqueous humour is by two mechanisms: secretion due to active
metabolic process, and ultra filtration influenced by the level of blood pressure in
70
the ciliary capillaries and the level of intraocular pressure. Outflow of aqueous
humour occurs by two routes: 80% of total outflow is through the trabicular mesh
work into the canal of schlemm and into the venous circulation, the remaining
20% is the uveoscleral pathway.
PATHOPHYSIOLOGY
 The primary site of damage is optic nerve head so there is progressive loss of
visual field.
 In Primary Open Angle Glaucoma (POAG) increased resistance within the
drainage channel causes the rise in intraocular pressure (IOP). The main route of
resistance to aqueous outflow lies in the dense juxtacanalicular trabicular
meshwork or the endothelium lining the inner wall of schlemm’s canal.
 In Primary Angle Closure Glaucoma (PACG) the rise in IOP is caused by a
decreased outflow of aqueous humour due to closure of the chamber angle by the
peripheral iris.
MANAGEMENT
DRUG DOSE FORM STRENGTH%
β-adrenergic blockers
Betaxolol Solution, suspension 0.5, 0.25
Solution 1
Carteolol Solution 0.25, 0.5
Levobunolol Solution 0.3
Metapranolol Solution, 0.25, 0.5
Timolol gelling solution 0.25
Adrenergic agonists
α/β agonist
Epinephrine Hcl Solution 0.25, 0.5, 1, 2
Epinephrine bitartrate Solution 2
Epinephrine borate Solution 0.5, 1, 2
Dipivefrin Solution 0.1
α1 agonist Solution 1
Apraclonidine Solution 0.5
71
Parasympathomimetics
Direct acting
Pilocarpine Solution 0.25-10
Pilocarpine Gel 4
Carbachol Solution 0.75, 1.5, 2.25
Cholinesterase Inhibitors
Physostigmine
Demecarium Solution 0.25, 0.5
Echothiophate Solution 0.125
Isoflurophate Solution 0.23-0.25
Ointment 0.25
Carbonic Anhydrase Inhibitors
Dorzolamide
Solution 2
Prostaglandin analogues
Latanoprost Solution 0.005
Acetazolamide Inj, tablets, caps 500, 125, 500
Dichlorphenamide Tablets 50
Methazolamide Tablets 50
PATIENT COUNSELLING
1. Patients should be told that the disorder cannot be cured but only controlled by the
regular use of the prescribed treatment.
2. Risk Factors should be explained to the patients like above 45 years, family
history of Glaucoma, Long Term Steroid Use, and in Diabetes.
1. Patient’s technique for instillation of eye drops should be correct with emphasis
on the dose (one drop), the position of instillation, into the temporal side of the
lower conjunctival sac, and importance of punctual occlusion to minimize
systemic side effects.
2. The preferred time for administration of topical medication should be discussed.
3. The importance of allowing a reasonable interval between drops should be
mentioned.
4. Eye drops containing benzalkonium chloride and adrenaline should not instill
with soft contact lens in situ.
72
5. Only take your drops the prescribed number of times per day. If you forget your
drops one day don’t try to make it up on the next day. Try to be relatively
consistent with the time of day you use your drops.
1. Special information sould be provided regarding implant of Intraocular Lens.
2. Proper assistance about the instillation of Eye Drops must be provided. Only take
your drops the prescribed number of times per day. If you forget your drops one
day don’t try to make it up on the next day. Try to be relatively consistent with
the time of day you use your drops.
3. Patient should be informed about the Laser Surgery and Traditional Surgery to
treat Glaucoma.
73
REFERENCES
1.L.c. Titcomb, S.D.Andraw,Glaucoma.In:Roger Walker, Clive Edwards,
Clinical Pharmacy and Therapeutics,3rd ed,Churchill Livingstone,2006,p.825-
840
2.Timothy S.Lesar,Richard J.Fiscella,Deepak Edward,Glaucoma.In:Joseph
T.Dipirio, Robert L. Talbart,Gary C. Yee, Gary R. Matzke,Barbara
G.Wells,L.Michael Posey, Pharmacotherapy A Pathophysiologic Approach,6th
ed,McGraw-Hill,p.1713-1728
74
TUBERCULOSIS
Tuberculosis (TB) is a Chronic Granulomatous disease caused by

Mycobacterium tuberculosis by Droplet Infection.
EPIDEMIOLOGY
TB is one of the leading causes of infectious deaths in the world. Close contacts
of patients with pulmonary tuberculosis patients are at particularly high risk with an
estimated infection rate of 25 to 30%. The elderly, greater then 65 years of age comprise
the largest number of infected persons. In tuberculosis disease one or more body systems
show clinical evidence of disease
AETIOLOGY
Tuberculosis infection is caused by Tubercle bacilli, M. Tuberculosis, M. Bovis
and M. Africanum.
It is widely distributed in the environment often in soil, mud and water. Infection
occurs in most cases by the respiratory route. Sites of extrapulmonary tubeculosis can
include the pleura, lymph nodes, pericardium, kidneys, meningis, bones and joints,
larynx, skin, intestine, peritoneum and eyes. Transmission occurs through airborne
droplet nuclei by coughing or sneezing. There are four environments in which tubercle
bacilli live: (i) Open pulmonary cavities have a plentiful supply of oxygen and will have
large numbers of rapidly growing organisms. (ii) Bacilli in closed lesions will be oxygen
starved and therefore slow-growing or dormant. (iii) Intracellular tubercle bacilli will be
slow growing due to the low intracellular PH and lack of oxygen. (iv) Some bacilli grow
intermittently as their environment changes around them.
75
Incubation period: 2 to 10 weeks.
Other forms of Tuberculosis are: TB can usually be treated with a course of four
standard, or first-line, anti-TB drugs. If these drugs are misused or mismanaged, there
exists other forms of Tuberculosis like Multi-drug resistant tuberculosis (MDR-TB)
can develop. It is defined as TB that is resistant at least to isoniazid (INH) and rifampicin
(RMP), the two most powerful first-line anti-TB drugs. MDR-TB mostly develop in the
course of the treatment of fully sensitive TB and this is the result of patients missing
doses, doctors giving inappropriate treatment, or patients failing to complete a course of
treatment. It is unusual for MDR-TB to spread from person to person, except in the
context of HIV or some other cause of immune suppression.
MDR-TB takes longer to treat with second-line drugs, which are more expensive
and have more side-effects. Extensively drug-resistant tuberculosis (XDR-TB) can
develop when these second-line drugs are also misused or mismanaged or caused by
bacteria that are resistant to the most effective anti-TB drugs. It can spread from one
person to another.
RISK GROUPS
1. People infected with HIV.
2. Close contacts of patients with T.B, especially those with sputum - smear
positive pulmonary disease.
3. People from countries with the high prevalence of T.B.
4. Alcoholics and injecting drug users.
5. Diabetes mellitus.
6. Chronic renal failure.
7. Hematological disorders and other malignances.
8. Prolonged high dose corticosteroid therapy and immunosuppressive therapy.
76
PATHOPHYSIOLOGY
Primary Infection: Droplet with

Micro-organism (1- 5 mm size)
Escape Ciliary Epithelial Cells

Of Upper Respiratory Tract
Reaches Alveolar Surface: Micro-

organism implanted & multiplies
Ingested by Alveolar Macrophages- form Granuloma

with dead or multiplying Bacilli (Eggs/ Larvae)
Resist host immune response: Inhibit fusion of

Lysosmes to Phagosomes in Macrophages
Escape into Cytoplasm & multiply
Polysaccharides in Mycobacterial cell wall

Induce Immunosuppressive Cytokines
Block Macrophages activation & scavenges

Oxygen preventing Free Radical attack
Bacilli multiplication increases:

Macrophages Rupture to release Bacilli
Large numbers of Macrophages

Surround the TB Necrotic Area
Activates & multiplies T - Lymphocytes
77
MANAGEMENT
TREATMENT OF PULMONARY TUBERCULOSIS

The 6 months regimen consisting of rifampicin, isoniazid, pyrazinamide, and
ethambutol for initial 2 months followed by a further 4 months of rifampicin and
isoniazid. If pyrazinamide is resistant, treatment extended to 9 months and ethambutol
given for the initials 2 months. WHO recommended treatment strategy to use directly
observed treatment, short course (DOTS).
TREATMENT OF NON-PULMONARY TUBERCULOSIS

1. Tuberculous meningitis
It is a serious disease and treatment must be started promptly, treated effectively
with rifampicin and isoniazid for 12 months together with pyrazinamide and a fourth
drug for the first 2 months .This could be either streptomycin or ethambutol but both only
reach CSF through inflammed meninges. Corticosteroids are recommended in more
severe disease.
2. Tuberculosis of peripheral lymph nodes 6 months regimen is effective.
3. Bone and joint tuberculosis

Standard agents such as isoniazid and rifampicin for 6 months. The spine is the
most common site for bone tuberculosis and occasionally surgery may be needed to
relieve spinal cord compression or to correct spinal deformities.
4. Disseminated or miliary tuberculosis

Standard regimen containing both isoniazid and rifampicin are used. If the patient
is severely ill or hypoxaemic, corticosteroids may be used.
5. In children
Ethambutol should not used routinely because of visual toxicity,the child is
unable to report it.
78
6. Pregnancy
Streptomycin should not be used because it may be ototoxic to the fetus.
7. Renal disease
Patients with renal disease may be given isoniazid, rifampicin and pyrazinamide
in standard doses because they are eliminated by non renal routes. Ethambutol undergoes
renal elimination therefore dose reduction is needed. Rifampicin may be given in
standard doses to patients on dialysis.
8. Liver disease
Rifampicin, isoniazid and pyrazinamide are potentially hepatotoxic. Increase in
transaminases at the start of antitubercular treatment occurs frequently.
9. Immunocompromised patients
Immunocompromised including those with HIV infection should be treated with
normal first line agents unless multi drug resistant T.B is suspected.
STEROIDS
Corticosteroids have been used in the treatment of T.B. chiefly for their anti
inflammatory properties. A dose of around 60-80 mg of perdnisolone is used. Because of
enzyme induction the dose of corticosteroids should be adjusted if rifampicin is also used
in genitourinary T.B where they help to reduce the symptoms of cystitis and obstruction.
DRUG RESISTANCE
Isoniazid is the most usual agents to which resistance is seen. At least three agents
to which the organisms are sensitive should be given. If rifampicin is not included in the
regimen the duration of the treatment will have to be increased to 12-18 months. The
fluoroquinolones, especially ciprofloxacin and ofloxacin have been used in patients with
drug resistance.
79
DISEASE CONTROL AND PREVENTION
Chemoprophylaxis is routinely offered to the following groups.
 Children under 16 years old with Heaf Grade 2-4 and no history of BCG.
 Children under 5 years old in closed contact with smear positive adult.
 It may be considered in:
 Children under 16 years old with strongly positive (Grade 3-4) Heaf who have
had BCG.
 Adults who have recently converted to tuberculin positivity.
 Asian adults contacts under 35 years old either Heaf positive or Heaf negative.
Vaccination against tuberculosis is carried out routinely at about 13 years of age.

BCG intra dermal contains a live attenuated strain of M. bovis and should be
administered by strict intra dermal injection. After vaccination, there is usually a local
reaction with in 2-6 weeks.
DRUGS USED IN TUBERCULOSIS
MECHANISM OF
DRUGS SIDE EFFECTS
ACTION
FIRST LINE DRUGS
Peripheral neuritis,
Inhibit synthesis of mycolic
Isoniazid (H) hepatitis, rashes,
acids in the bacterial cell wall
arthralgia and acne.
Hepatits, respiratory
syndrome, shock and
Inhibits DNA dependent
Rifampicin (R) renal failure, flu
RNA synthesis
syndrome, abdominal
syndrome.
Hyperuricemia
Pyrazinamide (Z) Tuberclocidal hepatototoxicity,
arthralgia and flushing.
Lose of vision, nausea,
Ethambutol (E) Tuberclostatic rashes, hyperuricemia,
neurological changes.
Ototoxicity,
Streptomycin (S) Inhibit the protein synthesis
nephrotoxicity
SECOND LINE DRUGS
Hepatitis, exfoliative
Thiacetazone (T) Tuberculostatic dermatitis, S.J
Syndrome,
Para amino salicylic acid Folate reductase inhibitor Anorexia, nausea,
80
epigastric pain, rashes,
(PAS) fever, goiter, liver
dysfunction.
G.I upset, ache and
Ethionamide (Etm) Not known pains, rashes, hepatitis,
mental disturbances.
Inhibit bacterial cell wall Sleepiness, headache,
Cycloserine (Cys)
synthesis. tremor and psychosis.
Ototoxicity,
Kanamycin (Kmc) Inhibit protein synthesis
nephrotoxicity.
Ototoxicity,
Amikacin (Am) Inhibit protein synthesis
nephrotoxicity.
Capreomycin (Cpr)
NEWER DRUGS
G.I upset, headache, sleep
Ciprofloxacin, disorders, mental
Inhibit the DNA gyrase enzyme
ofloxacin disruptions, blood
disorders, tendon damage.
G.I upset, headache, ARF,
Clarithromycin and
Inhibit protein synthesis hepatitis, S.J. syndrome,
azithromycin
myalgia, arthralgia, vertigo.
Inhibits DNA dependent RNA G.I intolerance, rashes,
Rifabutin
synthesis. granulocytopenia, uveitis
Drug regimens currently used in India.

REGIMEN WITH DRUGS AND DURATION
REGIMEN CODE
DOSAGE (MONTHS)
STANDARD REGIMENS/CONVENTIONAL REGIMENS
2 STH/10 TH 12
R1 a). intensive Phase (2 Months)
81
S= 0.75 gm, H= 300 mg, T= 150 mg,
b). continuation phase (10 months)
H= 300 mg, T= 150 mg
12 TH
R2 12
H= 300 mg, T= 150 mg
SHORT COURSE CHEMOTHERAPY REGIMENS
2 EHRZ/6 TH
a). intensive phase (2 months)
E= 800 mg, H= 300 mg, R= 450 mg, Z=
RA 1.5 gm 8
H= 300 mg, T= 150 mg.
2 SHRZ/4 S2 H2 R2
a). intensive Phase (2 Months)
S= 0.75 gm, H=300 mg, R=450 mg,
RB 6
Z=1.5 gm.
S=0.75gm, H=600 mg, R=600 mg
PATIENT COUNSELLING
1. Providing information regarding the severity of the disease.
2. Cover the mouth with separate Handkerchief while coughing or sneezing.
3. Inform the patient about isolation mainly from children and elderly people to
avoid easy spread of the disease.
1. Teaching the patient about the importance of continuing the drugs even after
improving disease conditions.
2. Don’t miss any dose and strictly adhere to the drug regimen.
3. Teach the importance of Vitamin Supplementation to the patient.
4. Inform the patient about body fluids discolouration and Itching while taking these
drugs is nothing to worry about.

1. Diet should be rich in Raw Fruits and Vegetables
2. Avoid Caffeinated Beverages and Fried Food.
3. Alcohol Abstinance and Smoking Cessation.
82
4. Avoid Stress, Mental Tension and Anxiety.
5. Monitor Liver Function Tests while taking Anti- TB Drugs.
6. Perform Exercise and Yoga.
REFERENCES
83
1. Charles A.Peloquin,Tuberculosis.In: Joseph T.Dipirio,Robert L.Talbart,
Gary C.Yee, Gary R. Matzke, Barbara G.Wells,L.Michael
Posey,Pharmacotherapy A Pathophysiologic Approach,6th ed,McGraw-
Hill,p.2015-2034
2. L.K.Nehval,Tuberculosis.In:Roger Walker,Clive Edwards,clinical
Pharmacy and Therapeutics,3rd ed, Churchill Livingstone,2006,p.583-595
84
MENINGITIS
Meningitis is a clinical syndrome characterized by inflammation of the meninges,

the membranes that cover the brain and spinal cord. It is usually caused by bacteria or
viruses (Aseptic Meningitis), and it can also be caused by certain medications or
illnesses. Clinically, this medical condition manifests with meningeal symptoms
(Headache, Nuchal Rigidity, and Photophobia) and an increased number of WBC in the
cerebrospinal fluid (Pleocytosis). It often remains undiagnosed because its symptoms can
be similar to those of the common flu.
Depending on the duration of symptoms, meningitis may be classified as acute or

chronic. Acute meningitis denotes the evolution of symptoms within hours to several
days, while chronic meningitis has an onset and duration of weeks to months. The
duration of symptoms of chronic meningitis is characteristically at least 4 weeks.
EPIDEMOLOGY
 The incidence of meningitis is presumed to be higher in developing countries
because of less access to preventative services such as vaccination. An incidence
rate that is 10-fold higher than that in developed countries has been reported.
 The incidence of Acute Bacterial Meningitis in the United States is
Approximately 3 cases per 100,000 persons per year.
 The overall Mortality Rate for patients with Meningitis ranges from 3% to 33%.
 Generally, 10% of patients who survive Meningitis may develop Neurologic
Disabilities and those surviving Gram- Negative Bacillary Meningitis have a 60%
chance of developing complications from their infection.
AETIOLOGY
Meningitis is caused mainly by Microorgainsms:
1. Viral Meningitis (Aseptic Meningitis) –
 Enterovirus : Polio Virus, Coxsackie Virus
 Herpesvirus : Varicella- Zoster Virus
85
 Paramyxovirus : Mumps Virus, Measles Virus
 Togavirus : Rubella Virus
 Flavivirus : Japanese Encephalitis
 Bunyavirus : California Encephalitis
 Alphavirus : Venezeulan Encephalitis
 Reovirus : Colorado Tick Fever Virus
 Arenavirus : LCM Virus
 Rhabdovirus : Rabies Virus
 Retrovirus : HIV
2. Bacterial Meningitis -
RISKS & PREDISPOSING FACTORS BACTERIAL PATHOGEN
S. agalactiae (group B streptococci)
Age 0-4 weeks E. coli K1
L.monocytogenes
S. agalactiae
E. coli
Age 4-12 weeks H. influenzae
S. pneumoniae
N. meningitides
N. meningitidis
Age 3 months to 18 years S. pneumoniae
H. influenza
S. pneumoniae
Age 18-50 years N. meningitidis
H. influenza
S. pneumoniae
N. meningitidis
Age older than 50 years
L. monocytogenes
Aerobic gram-negative bacilli
S. pneumoniae
N. meningitidis
Immunocompromised state
L. monocytogenes
Staphylococcus aureus
Intracranial Manipulation, including
Aerobic gram-negative bacilli, including
Neurosurgery
Pseudomonas aeruginosa
S. pneumoniae
Basilar Skull Fracture H. influenzae
Group A streptococci
CSF Shunts S. aureus
86
Propionibacterium acnes
3. Parasitic Meningitis –
 N. fowleri
 Acanthamoeba species
 Balamuthia species
 Angiostrongylus cantonensis
 G. spinigerum
 Baylisascaris procyonis
 S. stercoralis
 Taenia solium (cysticercosis)
4. Fungal Meningitis –
 Cryptococcus neoformans
 C. immitis
 B. dermatitidis
 H. capsulatum
 Candida species
 Aspergillus species
87
PATHOPHYSIOLOGY
Infectious Agent colonizes Mainly in Skin, Nasopharynx,
or establishes localized Respiratory Tract, GI Tract, or
Infection in host Genitourinary Tract
Retrograde Neuronal Pathway

and Direct Contagious Spread
Invasion of the Bloodstream

(Bacteremia, Viremia,
Fungemia, Parasitemia)
Subsequent Hematogenous
Seeding of the CNS
(Brain and Parenchyma)
Escapes Immunosurveillence
and Organism becomes Rich
Rupture into Subarachnoid Space
Adhesions Vasculitis Encephalitis
Cerebral
Edema
Stroke especially Basal
Inter-
Basal Ganglia, Internal
Pedicular
Cisterns Carotid, Proximal Middle
Fossa Increased ICP,
Cerebral Artery Territories
TNF- α, IL-1,
IL-6, and IL-8
Cranial Nerve  Interstitial Edema

Palsy, Internal  Cytotoxic Edema
Carotid Stenosis  Vasogenic Edema
88
Hydrocephalus
MANAGEMENT
Antimicrobial Agent Infants and Children Adults
ANTIBACTERIALS -
Ampicillin 75 mg/ kg q6h 2 gm q4h
Aztreonam - 2gm q6-8h
Cefepime 50 mg/ kg q8h 2 gm q8h
Cefotaxime 75 mg/ kg q6-8h 2 gm q4-6h
Ceftazidime 50 mg/ kg q8h 2 gm q8h
Ceftriaxone 100 mg/ kg once daily 2 gm q12-24h
Chloramphenicol 25 mg/ kg q6h 1- 1.5 gm q6h
Ciprofloxacin 10 mg/ kg q8h 400 mg q8-12h
Colistin 5 mg/ kg once daily 5 mg/ kg once daily
Gentamicin 2.5 mg/ kg q8h 2 mg/ kg q8h
Linezolid 10 mg/ kg q8h 600 mg q12h
Meropenam 40 mg/ kg q8h 2 mg q8h
Moxifloxacin - 400 mg once daily
Oxacillin / Naficillin 50 mg/ kg q6h 2 mg q4h
Pencillin G 0.05 Million Units/kg q4-6h 2 Million Units q4h
Piperacillin 50 mg/ kg q4-6h 3 gm q4-6h
Tobramycin 2.5 mg/ kg q8h 2 mg/ kg q8h
Trimethoprim-
5 mg/ kg q6-12h 5 mg/ kg q6-12h
Sulphmethoxazole
Vancomycin 15 mg/ kg q6h 15 mg/ kg q8-12h
ANTIMYCOBACTERIALS -
Isoniazide 10- 15 mg/ kg once daily 5 mg/ kg once daily
Rifampin 10- 20 mg/ kg once daily 600 mg once daily
Pyrazinamide 15-30 mg/ kg once daily 15- 30 mg/ kg once daily
Ethambutol 15- 25 mg/ kg once daily 15-25 mg/ kg once daily
ANTIFUNGALS –
Amphotericin B - 0.7- 1 mg/ kg once daily
Lipid Amphotericin B - 4 mg/ kg once daily
Flucytosine - 25 mg/ kg q6h
Fluconazole - 400- 800 mg once daily
6 mg/ kg q12h X 2doses
Voriconazole -
then, 4 mg/ kg q12h
ANTIVIRALS -
Acyclovir 20 mg/ kg q8h 10 mg/ kg q8h
Foscarnet - 60 mg/ kg q8-12h
PATIENT COUNSELLING
89
1. Begin Education during first Admission.
2. Provide Information to patient regarding the Sverity and Complication of Disease.
3. Educate the patient about various symptoms of the Disease.
4. Teach Signs of Dehydration, Signs of inadequate PO Intake.
5. Notice any kind of Behavioural Changes and Siezure Activity.
6. Review who to contact for problems and reasons to call physician.
1. Preventive Antibiotics are prescribed in people who are in close contact with the
patient.
2. Oral Fluids are always the preferred source of Hydration.
3. Use medicine to treat fever and headache.
1. Educate Families about Personnel Hygiene and Good Hand Washing.
2. If patient has Nausea and Vomitting start with Clear Liquid Diet and advance as
Tolerated to Regular Diet for Age.
3. Discourage sharing of Drinking and Eating Utensils.
4. Offer Plenty of Fluids.
90
REFERENCES
1. elizabeth D.Hermsen, John C. Rotschafer, CNS Infections. In:Joseph T,
Dipirio, Robert L. Talbert, Gary C. Yee, Gary R. Matzke, Barbara G.
Wells, L. Micheal Posey,Pharmacotherapy A Pathophysiologic
Approachi,6th ed, McGraw-Hill,p.1923-1931
91
RESPIRATORY TRACT INFECTION
These infections are the most common of acute illness. Etiological agents
include viruses, bacteria, mycoplasma, and rarely other organisms. Approximately 95%
of upper respiratory tract infection is due to viruses. Lower respiratory tract infection
often indicates an impairment of post defenses.
TYPES OF RESPIRATORY TRACT INFECTIONS

Respiratory tract infections are the commonest group of infections in the world.
The respiratory tract is divided to two types.
1. Upper Respiratory Tract

a. Pharyngitis
b. Cold and flu
c. Acute epiglottitis
d. Otitis media
e. Acute sinusitis
2. Lower Respiratory Tract
a. Bronchitis
b. Pneumonia.
UPPER RESPIRATORY TRACT INFECTION
EPIDEMIOLOGY
Upper respiratory tract infection follows seasonal variation, with the incidence
being highest in winter and lowest in summer. This type of virus’s infection is
transmitted mainly through the coughing and sneezing of infectious aerosolized droplets,
92
but transmission occurs principally through contamination of hands and objects by nasal
secretions and saliva.
AETIOLOGY
More than 150 serotypes, representing 12 groups of viruses have been associated
with upper respiratory infections. Rhinoviruses cause 40 % of respiratory illness;
adenoviruses cause 2-10 % with the remainder being caused by respiratory syncytial
virus, coronovirus, or influenza viruses.
PATHOPHYSIOLOGY
Respiratory viruses cause mucosal sloughing and consequently decrease lung
defense mechanism. This predisposes to serious bacterial infection, although this supra
infection occurs in only a minority of patients.
Milder infections are usually termed ‘Colds’ while more severe infections maybe
known as ‘Flu’.
With Otitis Media, the patient has an antecedent event that results in congestion
of the respiratory mucosa, causing secretion to accumulate and proliferate. This can
impair the capillary action needed to prevent nasopharyngeal reflux.
Sinusitis conditions that affect patency of the sinus ostia, normal function of the
mucociliary sinus epithelium; normal immuno defenses cause sinus ostia obstructions,
and lead to retention of secretion. The infection of the maxillary molar teeth predisposes
to maxillary and chronic sinusitis.
Epiglottitis is a true airway emergency in which acute airway obstruction caused

primarily by H. influenza type B.
MANAGEMENT
93
DOSE
DISEASE DRUG CHILDREN
ADULT
mg/kg
Amoxicillin/ Clavulanate 14-15 250-500 mg Q8hr
Cefprozil 7.5-15 250-500 mg Q12hr
Sinusitis Cefdinir 7-14 300-600 mg Q12hr
Sulfamethoxazole/ Trimethoprim 40/8 800/160 mg Q12hr
Clarithromycin 7.5 250-500 mg Q12hr
Amoxicillin/ Clavulanate 13-15 500 mg Q8hr

Otitis Media
Cephalexin 19-25 250-500 mg Q6hr
Benzathine Penicillin G 3-6 lakhs U 1.2 million U
Pharyngitis Cefuroxime Axetil 25 250 mg Q12hr
Azithromycin 12 500 mg Q24hr
LOWER RESPIRATORY INFECTION
EPIDEMIOLOGY
This most commonly occurs during the winter month cold, damp climates, and
presents of high concentration of irritating substances such as air pollution or cigarette
smoke, may precipitate attacks.
AETIOLOGY
The infectious agent like common cold viruses, rhinovirus and corona virus, and
lower respiratory tract pathogens including influenza virus, adenovirus, and respiratory
syncytial virus for the majority case of lower respiratory tract infection.
PATHOPHYSIOLOGY
The bronchiolitides is the inflammatory process does not extent to include the
alveoli. The infection of the trachea and bronchi yields hyperemic and edematous
mucous membranes with an increase in bronchial secretion. The increased secretion,
which can become thick and tenacious, impairs mucociliary activity.
The pneumonia caused by the impaired alveolar macrophage function and

mucociliary clearance, thus setting the stage for secondary bacterial pneumonia.
94
MANAGEMENT
DISEASE DRUG DOSE
Trimethoprim- Sulfamethoxazole 1000 mg/bd/day
Amoxicillin/ Clavulanic Acid 500 mg /tid/day
Bronchitis
Gatifloxacin 400 mg/day
Levofloxacin 500-750 mg/day
Amoxicillin/ Clavulanic Acid 250-1000 mg/tid/day
Gatifloxacin 400 mg/day
Pneumonia
Cefepime 2- 4 g/ day
Erythromycin/ Tetracycline 1- 2 g/day
PATIENT COUNSELLING
1. Provide Information to the Patient Regarding the cause and Severity of the
Disease.
2. Patient should be informed to review the Physician if symptoms still persist.
3. Inform the patient about the various symptoms to report if the Infection Flares up.
1. The patient should take full course of antibiotic even if he or she feels better.
2. Patient should be educated to take Medication at the Exact Time Prescribed, not
to skip Doses, not to share Medication with others, and not to save it for Later.
1. Exercise Regularly and Eat Nutritious Diet.
2. Smoking Cessation.
3. Avoid Excessive Dry Heat, Environmental Irritants and Allergens, Second Hand
Smoking, Contact Infected People.
4. Get adequate Rest and Sleep.
5. Maintain Good Oral Hygiene.
95
REFERENCES
2. S.F.Pedler, A.W.Berrington, Respiratory Tract Infection.In:Roger Walker, Clive
Edwards,Clinical Pharmacy and Therapeutics,3rd ed, Churchill
Livingstone,2006,p.529-579.
96
GASTROENTERITIS
Gastroenteritis is inflammation of the gastrointestinal tract, involving both the

stomach and the small intestine and resulting in a sickness of fever, diarrhoea, crampy
abdominal pain, nausea, and vomiting caused by an infectious virus, bacterium or
parasite. It typically is of acute onset, usually lasting less than 10 days and self-limiting.
It can be transferred by contact with contaminated food and water. It’s also known as
gastric flu or stomach flu, although unrelated to influenza.
EPIDEMOLOGY
Worldwide diarrhea caused 4.6 million deaths in children in 1980 alone, and most
of these in the developing world. This figure has now come down considerably to
approximately 1.5 million deaths yearly, mainly due to global introduction of correct oral
rehydration therapy. The commonness in the developed countries is as high as 1-2.5 cases
per child per year and a major cause of hospitalization in this age group.
AETIOLOGY
Gastroenteritis has many causes. Viruses and bacteria are the most common.
Gastroenteritis caused by viruses may last one to two days and bacterial cases can last for
a longer period of time.
1. Viruses:
 Rotavirus is the most common cause of sporadic, severe, dehydrating

diarrhea in young children.
 Norovirus most commonly infects older children and adults.
 Astrovirus can infect people of all ages but usually infects infants and
young children.
97
 Adenoviruses are the 4th most common cause of childhood viral
gastroenteritis.
2. Bacteria:
 Shigella, Salmonella, Campylobacter, some E. coli subtypes invade the
mucosa of the small bowel or colon.
 Vibrio cholerae adhere to intestinal mucosa without invading and produce
enterotoxins.
 Staphylococcus aureus, Bacillus cereus, Clostridium perfringens produce
an exotoxin that is ingested in contaminated food.
3. Parasites:
 Giardia lamblia adhere to or invade the intestinal mucosa.
 Cryptosporidium parvu, Enterocytozoon bieneusi, Encephalitozoon
intestinali, Entamoeba histolytic, Cyclospora cayetanensis causes watery
or bloody diarrhoea.
PATHOPHYSIOLOGY
Ingestion of Micro-organism Particle
Infection of Stimulation of the Enteric Enterotoxins

Absorptive Intestinal Nervous System
Villus Cells
Decresed Absorption Decresed

of Salt and Water Dissacharride Activity
Net Fluid Secretion Carbohydrate Net Fluid Secretion

Malabsorption
Osmotic Diarrhoea
Dehydration Metabolic Acidosis
MANAGEMENT
Oral Rehydration Solutions –
98
Lytren Ricelyte
WHO- Pedialyte Rehydrate Resol
INGREDIENTS (Mead (Mead
ORS (Ross) (Ross) (Wyeth)
Johnson) Johnson)
Osmolarity (mOsm/
333 220 249 304 200 269
Litre)
Carbohydrate (gm/
20 20 25 25 30 20
Litre)
Calories (cal/ Litre) 77 85 100 100 126 80
Electrolytes (mEq/
Litre)
 Sodium
 Potassium 90 50 45 75 50 50
 Chloride 20 25 20 20 25 20
 Citrate 80 45 35 65 45 50
- 30 30 30 34 34
 Bicarbonate
30 - - - - -
 Calcium
- - - - - 4
 Magnesium - - - - - 4
 Sulfate - - - - - -
 Phosphate - - - - - 5
Selected Antidiarrhoeal Preparations –

DRUGS DOSAGE FORM ADULT DOSE
Antimotility
 Diphenoxylate 2.5 mg/ Tablet, 2.5 mg/5ml 5 mg qid
 Loperamide 2.5 mg/ Capsule 2- 4mg upto 16 mg/ Day
 Prochlorperazine Injection 5- 10 mg IV tid or qid
 Promethazine Injection 12.5-25 mg IM tid or qid
 Opium Tincture 2 mg/ 5ml Morphine 0.6 ml qid
 Atropine 0.3, 0.4, 0.6 mg/ Tablet 0.4- 0.6 mg every 4- 6hrs
Adsorbents
 Kaolin- Pectin 0.98 gm Kaolin + 21.7 mg 30- 120 ml after each loose
Mixture Pectin per 5 ml stools
 Polycarbophil 500 mg/ ml 2 Tablets qid
Antisecretory (Bismuth
300 mg/ Tablet 8 Doses / Day
Subsalicylate)
3- 4 Drops taken with Milk
Enzymes (Lactase) 525 mg/ 30 ml
or Dairy Products
Prebiotics & Probiotics 2 Tablets or 1 Granule
-
(Lactobacillus Species) Packet 3- 4 Times Daily
Antimicrobials Agents –
MICROORGANISM DRUGS ADULT DOSE CHILD DOSE
99
 Ciprofloxacin 1gm N/A
 Doxycycline 300 mg single 6 mg/kg x 1
dose dose
Vibrio cholerae
 Trimethoprim- 1 Double Stregth
Sulfamethoxazole (DS) tablet bid 4–6 mg/ kg bid
(TMP-SMX) for 3 days for 5 days
250 mg qid or 7.5 mg/kg qid
 Metronidazole 500 mg tid for for 10 days
Clostridium difficile 10 days
 Vancomycin 125–250 mg qid 10 mg/kg qid for
for 10 days 10 days
N/A
 Ciprofloxacin 500 mg po bid
Shigella for 5 days
4–6 mg/ kg bid
 TMP-SMX 1 DS tablet bid
for 5 days
250 mg tid for 5 5 mg/kg tid for
 Metronidazole days 5days
Giardia lamblia
500 mg bid for 3 100- 200 mg bid
 Nitazoxanide
days for 3 days
Entamoeba 750 mg tid for 12–16 mg/kg tid
 Metronidazole
histolytica 5–10 days for 10 days
500 mg bid for 5 N/A

 Ciprofloxacin days
Campylobacter jejuni
 Azithromycin 500 mg 10 mg/kg
once/day for 3 once/day for 3
days days
PATIENT COUNSELLING
Disease.
2. Inform the patient that it is caused by a Self- Limiting Condition and Infectious.
2. Inform patient to take drugs only for the prescribed time period.
100
1. Prevention includes throwing out the Expired or Perishable Food and also avoids
eating unknown or potentially poisonous plants and mushrooms.
2. Prevention also includes resting the stomach by not eating solid foods until
symptoms have passed for a period of time and ensuring adequate hydration.
3. Personnel Hygiene should be maintained by frequently washing hands after using
Bathroom and before eating food to avoid spread of the disease.
4. Bed Rest is always adviced for the Patient.
5. Diet should contain clear fluids and Bland Foods like Cereals, Rice, Soup, and
Tender Coconut Water.
6. Avoid Fried Foods, Spicy Foods, Fruits and Vegetables.
7. Gradual Addition of Solid Food and then return to Normal Diet.
101
REFERENCES
1. William J. Spruill, William E. Wade, Diarrhoea and
Constipation. In:Joseph T. Dipirio, Robert L. Talbert, Gary C.
Yee, Gary R. Matzke, Barbara G. Wells, L.Micheal
Posey,Pharmacotherapy A Pathophysiologic Approach, 6th ed,
McGraw-Hill,p.677-684
2. R.Walker, Diarrohea and Constipation. In:roger Walker, Clive

Livingstone, 2006,p.185-189
102
URINARY TRACT INFECTION
The term urinary tract infection (UTI) usually refers to the presence of organisms
in urinary tract together with symptoms and sometimes signs of inflammation.
EPIDEMIOLOGY
They constitute most commonly occurring nosocomial infection, 20% of females
will suffer with multiple recurrences. In males infections are associated with
complications, such as septicemia and pyelonephritis.The overall incidence of UTI
increases substantially in the elderly, with the majority of these infections being
asymptomatic.
AETIOLOGY
The 20% of UTIs are caused by gram negative enteric bacteria such as klebsiella,
proteus species gram positive enterococci, and Staphylococcus saprophyticus. E. coli is
the commonest bacterium, being responsible for about 80 % of infections. More resistant
organism such as Pseudomonas aeruginosa, Enterobacter and serratia species causes UTI
associated with structural abnormalities.
PATHOPHYSIOLOGY
 UTIs can be acquired via three possible routes: the ascending, hematogenous or
lymphatic pathways.
 In female, the short length of the urethra and proximity to the perirectal area make
colonization of the urethra. Bacteria are then believed to enter the bladder from
the urethra.
 Once in the bladder, the organisms multiply quickly and can ascend the ureters to
the kidney.
 Infection of the kidney by hematogenous spread of organisms occurs as the result
of dissemination of organisms from a distant primary infection in the body.
103
 Three factors determine the development of infection: The size of inoculum, the
virulence of microorganism and the competence of the natural host defence
mechanisms.
 Patients who are unable to void urine completely are at greater risk of developing
UTIs and frequently have recurrent infections.
 An important virulence factor of bacteria is their ability to adhere to urinary
epithelial cells. Other virulence factor including hemolysin, a cytotoxic protein
produced by bacteria that lysis a wide range of cells including erythrocytes,
polymorphonuclear leucocytes and monocytes, and aerobactin which facilitates
binding and uptake of iron by E.coli.
MANAGEMENT
ORAL ANTIBIOTICS USED FOR LOWER TRACT INFECTION
ANTIBIOTICS DOSE SIDE EFFECTS CONTRAINDICATION
Nausea, diarrhea,
Amoxycillin 250-500 mg tid Penicillin hypersensitivity
Allergy
Nausea, diarrhea,
Co-amoxiclav 375-625 mg tid Penicillin hypersensitivity
Allergy
Nausea, diarrhea, Cephalosporin hypersensitivity,

Cefalexin 250-500 mg qid
Allergy porphyria.
Nausea, pruritis, Porhyria, pregnancy, neonates,

Trimethoprim 200 mg bid
Allergy folate deficiency.
Nausea, allergy, Renal failure, neonates,

Nitrofurantoin 50 mg qid
Neuropathy. Porphyria, G6PD deficiency.
Ciprofloxacin Rash, pruritis,

250-500 mg bid Pregnancy, children.
Tendonitis
104
PARENTRAL ANTIBIOTICS USED FOR PYLEONEPHRITIS.
ANTIBIOTICS DOSE SIDE EFFECTS CONTRAINDICATION
Cephalosporin
Nausea, diarrhea,
Cefuroxime 750 mg tid hypersensitivity
Allergy
Porphyria.
Cephalosporin
Nausea, diarrhea,
Ceftazidimine 1 gms tid hypersensitivity
Allergy
Porphyria.
Nausea, diarrhea, Penicillin hypersensitivity.
Co-amoxiclav 1.2 gms tid
Allergy
80-120 mg tid or Nephrotoxicity, Pregnanacy, myasthenia
Gentamycin
5 mgs / kg od. Ottotoxicity. gravis.
Rash, pruritis,
Ciprofloxacin 200-400 mg bid Pregnancy, children.
Tendinitis
Meropenem 500 mg tid Rash, convulsion. -
PATIENT COUNSELLING
Disease.
3. Inform the patient about the various symptoms to report if the Infection Flares up.
2. Inform patient to take drugs only for the prescribed time period.
3. Inform patient to avoid any OTC Drugs.
1. Various behavioral factors, such as voiding after intercourse, direction of toilet
paper use after bowel movements, type of menstrual protection used, and method
of contraception, have all been investigated to asses their impact on the frequency
of UTI.
2. Maintain Personnel Hygiene; use Water to clean the infected area and not soap.
3. Women with a recurrent UTI should be encouraged to use a method of birth
control.
105
4. Urination every 2 hours, taking the time to empty the bladder completely, also
helps to prevent UTI.
5. Foods that irritate the bladder include tea coffee, alcohol, cola, chocolate, and
spicy foods should be avoided.
6. Encourage the patient to Drink Extra Fluids to help clear the infection.
7. Educate the patient how to collect Midstream Urine for Routine Urine Check Up.
106
REFERENCES
1. cinda L.Christensen, Urinary Tract Infection. In:Richard A.Helms, David

J.Quan, Eric T. Herfindal, Dick R.Gourley,Textbook of therapeutics Drug and
Disease Management,8th ed,Lippincott Williams&Wilkins,2006,p.1967-1983
107
RHEUMATOID ARTHRITIS
Rheumatoid arthritis (RA) is a chronic and usually progressive inflammatory

disorder of unknown aetiology characterized by polyarticular symmetrical joint
involvement and systemic manifestations.
EPIDEMIOLOGY
 Approximately 1% of the world wide population is affected by RA, with about
twice as many female sufferers as male.
 The prevalence of RA increases with age in both sexes with nearly 5% of women
and 2% of men over 55 years, of age affected. Some ethnic variation has also
been observed in the prevalence of RA.
 Comparative studies among urban and rural populations suggest that
environmental factors associated with modern urban life may also be important.
AETIOLOGY
The cause of this disease remains unknown; however the following factors may
play a role.
1. When patients with antigen HLA-DR4 are exposed to certain environmental
factors and inappropriate immune response occurs which result in chronic
inflammation.
2. Some infectious agents may be involved in precipitating RA in patients
genetically predisposed.
3. Although no specific agent has been identified the occurrence of polyarthritis in
association with microbial organism including bacteria has been noticed.
108
4. Tumor necrosis factor (TNF) levels have been found to be high in certain
inflammatory condition such as RA and crohn’s disease.
PATHOPHYSIOLOGY
Neuropeptides triggers Mast Cells,
Granulocytes, and Macrophages
which Phagocytizes Antigen
Antigen is presented to T- Cells
Activated T- Cells stimulates T-

and B- Lymphocytes production
Recruitment of Cells and Adhesion

of Cells to the Endothelium
Immunoglobulin Rheumatoid Factor

Migration of Cells into the Endothelium
Immune Complex Formation

Interaction between Cells like
Leucocytes, Marcophages in the
Synovium (Pannus Formation)
Compliment Activation
Cell Mediated Response
Release of Cytokines (TNF- α, IL- 1),

Chemokines, Peptide Mediators, Lipid
Cartilage and Bone Damage Synovial Inflammatory Systemic Manifestations

Proliferation
109
MANAGEMENT
CLASS OF DRUGS MECHANISM OF ACTION ADVERSE EFFECTS
GI effects including peptic
NSAIDS
ulceration, renal damage,
a. Aspirin
Inhibits the prostaglandin mild hepatic dysfunction,
b. Other NSAIDS
synthesis and release. CNS effects such as
(Ibuprofen, Naproxen, Sulindac,
drowsiness, anxiety, and
Piroxicam)
confusion.
It acts by inhibiting dihydrofolate GI, pulmonary,
Methotrexate reductase thus inhibiting DNA hematological and
synthesis hepatic.
It accumulates within
lymphocytes, macrophages, Nausea, epigastric pain,
Hydroxychloroquine
polymorphs and fibroblasts and retinopathy.
inhibits phagocyte function.
Gastrointestinal,
Decreases the production of dermatologic(rash),
Sulfasalazine inflammatory cytokines and the Hematologic and hepatic
production of IgMRF. effects.
Skin rash, metallic taste,

It inhibits T- cell mediated
glomerular nephritis,
immunity by obstructing the
Penicillamine stomatitis, anorexia,
conversion of monocytes to
nausea, vomiting and
macrophages.
dyspepsia.
Bone marrow suppression,
suppresses T- cell function
Azathioprine and stomatitis, GI intolerance,
leading inhibition of leukocyte
Cyclophophamide infections, hepatoxicity
proliferation
and oncogenic potential.
Hypertension,
It inhibits transcription of
hyperglycemia,
interleukin-2, a crucial activator
Cyclosporine nephrotoxicity, tremor, GI
of T- cell activity.
intolerance, hirsutism and
gingival hyperplasia.
NONSTEROIDAL ANTIINFLAMMATORY DRUGS

NSAIDS are effective for symptom relief only and do not slow disease
progression or prevent bony erosions or joint deformity. These drugs possess both
analgesic and anti inflammatory properties and are the first line therapy for treatment of
mild RA symptoms.
110
ANTIRHEUMATIC DRUGS (DMARDs)
1. METHOTREXATE
Methotrexate is selected especially for patients with more severe disease. Nausea and
stomatitis can be managed by the addition of folic acid to methotrexate therapy.
2. GOLD COMPOUNDS
IM or oral gold preparations are effective but the onset may be delayed for 3-6
months. Oral gold is more convenient than IM gold but it is less effective.
3. HYDROXYCHLOROQUINE
The antimalarial hydroxychloroquine is a good initial choice for patients with
mild disease because of its safety, convience and low cost. It lacks the myelosuppressive,
hepatic and renal toxicities is seen with others antirheumatic drugs.
4. SULFASALAZINE
Sulfasalazine has a high continuation rate, a low rate of serious adverse effects. It
is used in mild to moderate disease.
5. PENICILLAMINE
It is seldom used due to toxicity and poor long term efficacy.
6. AZATHIOPRINE AND CYCLOPHOPHAMIDE

Azathioprine has a steroid - sparing effect and cyclophosphamide is a potent
cytotoxic agent used in the management of rheumatoid vasulitis. Both have the potential
to cause infertility and development of malignancies.
7. CYCLOSPORINE
It is an immunosuppressive agent used in RA.
PATIENT COUNSELLING
111
1. Inform the Patient about the Severity and Complications of the Disease.
2. Advice the patient to inform about the medications they are taking and the
presence of any Renal Problem.

1. NSAID preparation should be taken with or after food and patients should be
warned of potential adverse effects and what to do if these occur.
2. Patients must be warned not to supplement their prescribed NSAIDS with
purchased ibuprofen or aspirin and should be careful of consuming additional
‘Hidden’ paracetamol.
3. Alopecia is likely to occur but it is reversible and encourage adequate fluid intake
to prevent hemorrhagic cystitis and to facilitate uric acid excretion with
cyclophosphamide.
4. Encourage compliance with therapy and follow up visits.
5. Explain to the Patient about the possible Side- Effects of drugs and to report if
they occur.
1. Avoid foods containing Furocoumarin such as Carrots, Celery, Figs and Mustard.
2. Avoid Milk, Meat and Processed Foods which may exacerbate the Disease.
3. Diet must be Low in Fat, Saturated Fats and Cholesterol.
4. Protect Skin for 8 hours after oral administration due to Photoreaction.
5. Monitor Blood and Liver Function Tests regularly due to certain Medication
Toxicity.
6. Swimming and other Motion Exercises are recommended.
112
REFERENCES
1. Arthur A. Schuna, Rheumatoid Arthritis. In:Joseph T.Dipiro,Robert
L.Talbart, Gary C.Yee, Gary R. Matzke, Barbara G.Wells,L.Michael
Posey.Pharmacotherapy A Pathophysiologic Approach,6th
ed,McGraw-Hill,,p.1671-1684
113
GOUT
Gout is a term that represents a heterogenous group of disease usually associated

with hyperuricaemia. The hyperuricaemia may be due to an increased rate of synthesis of
purine precursors of uric acid or to a decreased elimination of uric acid by kidney or both.
EPIDEMIOLOGY
Gout is a condition that most frequently affects middle-aged men, with only
approximately 5% of cases occurring in women. The risk of acute gout secondary to
hyperuricaemia is equal to both sexes. The incidence and prevalence of gout increases
with the level of serum uric acid.
AETIOLOGY
Gout is caused by overproduction of uric acid or under excretion of uric acid. It is
characterized by recurrent attacks of acute arthritis associated with:
1. Monosodium Urate Crystals in Leucocytes found in Synovial Fluid
2. Deposits of Monosodium Urate Crystals in Tissues [Tophi]
3. Intestinal Renal Disease
4. Uric Acid Nephrolithiasis
PATHOPHYSIOLOGY
 The normal person would convert dietary protein to urea but People with gout
convert greater proportion of dietary component to uric acid instead of being
excreted. The uric acid deposits as the urate in the joints, kidney and soft tissues.
 Normal individuals produce 600 – 800 mg of uric acid daily and excrete less than
600mg in urine.
 Individuals who excrete more than 600 mg considered as overproducers and who
excrete less than 600 mg in 24 hours may be defined as under excretors of uric
acid.
114
Degradation of Purines
Uric Acid (Urate Pool)
 Increased conc. of Phosphoribosyl Under Excretion of Uric Acid due to drugs like:
Pyrophosphate [PRPP] Diuretics, Salicylates, Pyrazinamide,
 Deficiency of Hypoxanthine-Guanine Ethambutol, Nicotinic Acid & Cytotoxic Drugs
Phosphoribosyl Transferase [HGPRT]
 Overproduction of Uric Acid

 Increased breakdown of
Tissue Nucleic Acids
 Myeloproliferative Disorders
 Hyperuricaemia
Deposition of Urate Crystals in

Synovial Fluid causing Inflammation
 Uric Acid Nephrolithiasis

 Acute Urate Nephropathy
 Chrnic Urate Nephropathy
 Tophi Late Complication of Hyperuricaemia
MANAGEMENT
Acute Attacks -
DRUGS DOSE SIDE EFFECTS
Oral 1 mg initially followed by

Aplastic anemia,
0.5 mg Every 2 hours, until pain relief
Colchicine thrombocytopenia,
occurs. IV single dose of 2 mg with 30ml
agranulocytosis,
NS over 5 minutes.
115
Seizures, heart failure,
NSAIDS 50 mg t.i.d daily until pain subsides GI bleeding, Stevens
Indomethacin Johnson syndrome.
Naproxen 750 mg followed by 250 mg every Thrombocytopenia,

Sulindac 8 hours. 200 mg b.i.d for 7 days agranulocytosis, neutropenia
gi bleeding, nephrotric
Syndrome, renal failure.
Corticosteroids Seizures, arrythmias,

Methylprednisolone Intra-articular dose of 5-10 mg for thromboembolism,
acetate small joints to 20-60 mg for large joints Fatal arrest, pancreatitis.
Methylprednisolone, IV 50-150 mg daily for 5 days Acute adrenal insufficiency.

Prednisone Oral 30-50 mg/day 7-10 days
Prophylactic Control of Hyperuricaemia -
Hypersensitivity reaction,
100-300 mg of single dose for maculopapular rash,
Allopurinol
7-10 days daily. urticaria, myalgia, hepatic
Damage.
Probenecid 250-500 mg b.i.d daily for 1-2weeks Skin rash, GI irritation.
Blood dyscrasia,
Sulfinpyrazone 50-200 mg b.i.d daily
Bronchoconstriction.
PATIENT COUNSELLING
1. Patient should be advised about factors that may contribute to hyperuricaemia,
such as fasting, obesity and alcohol excess.
2. Advice the patient to inform about the medications they are taking and the
presence of any Renal Problem.
116
1. Should avoid aspirin and instead use paracetamol for analgesia.
2. Patient receiving Allopurinol should continue single daily dose, warned of
potential side effects and told to report any adverse skin reactions.
3. Patients on Corticosteroids should be informed to report any Acidity Problems,
Delayed Healing, Bone or Muscle Problems, and Night Sweats.
1. Renal function test should be monitored frequently.
2. Patient taking Uricosuric Agents should be with Good Fluid Intake to reduce the
risk of Renal Calculus Formation.
3. A diet free of purine is advisable to keep uric acid levels within the normal range.
4. Reduce the foods like Caffeinated Beverages, Fats and Oils, Miscellaneous
(Cinnamon, Clove, Cardamom, Cumin seeds, Chilly, Pepper, All Spicy Foods,
Sugar, Vinegar, Custard, Popcorns, and Salt).
5. Diet includes foods like Cereals, Vegetables, Fruits, Low Fat Milk, and Egg.
6. Avoid Grapefruit and Grapefruit Juice as it decreases the activity of the
Uricosuric Agents.
117
REFERENCES:
1. A.Alldred,E.A. Kay, Gout and Hyperuricemia. In:Roger Walker, Clive Edwards, Clinical
Pharmacy and Therapeutics,3rd ed, Churchill Livingstone,2006,p.813-820
2. William W. McClosekey. Maria D. Kostka, Gout. In:Richard A.Helms, David J.Quan, Eric T.
Herfindal, Dick R. Gourley,Textbook of Therapeutics Drug and Disease Management,8th ed,
Lippincott Williams&Wilkins, 2006,p.1753-1766
118
ACUTE RENAL FAILURE
Acute renal failure (ARF) is defined as the abrupt deterioration in renal function
that results in the inability of the kidney to regulate water and the solute balance.
EPIDEMIOLOGY
Now a day, approximately 5% of hospitalized patients develop ARF.
The national kidney and urological diseases advisory board 1990. Long-range plan
concluded that ARF is the most costly kidney condition requiring hospitalization and that
the number of cases has increased recently. Clinical conditions associated with ARF
include the use of nephrotoxic drugs, hypotension, hypoxia and sepsis [infected with pus
producing organism].
ARF is classified according to the amount of urine produced per day.

a. Anuric [less than 100 mL/day] complete suppression of the urine from the kidney.
b. Oliguric [100-400 ml/day] diminished urine secretion in relation to fluid intake.
c. Monooliguric [greater than 400 ml/day]
Mild ARF has been defined as a rise in serum creatinine concentration to greater
than 2-3 mg/dl. Severe cases rises of serum creatinine above 5mg/dl. The rate of
creatinine rise will vary depending on the extent of renal injury, dietary intake and
muscle mass of the patient.
AETIOLOGY
The causes of ARF may be divided into 3 types.
1. Pre - Renal
2. Intra - Renal
3. Post - Renal.
119
1] Pre - Renal -
It occurs when a renal blood flow is reduced to a level adequate to maintain
normal glumarular filtration rate (GFR). In this condition cellular injury does not occur
and the decrease in GFR can be rapidly restored once the athophysiologic state is
corrected. Reduced RBF [renal blood flow] results in decreased renal perfusion or intense
renal vasoconstriction.
Causes of Pre-Renal Acute Renal Failure:

 Decreased cardiac output
 Congestive heart failure
 Pulmonary embolism
 Cardiomyopathy
 Myocardial infraction
Hypovolemia: [diminished total quantity of blood]

 Burns
 Hemorrhage
 Volume depletion [renal losses, skin, vomiting, diarrhea]
 Sequestration [hypoalbumineamia, pancreatitis]
Increase Renal Vascular Resistance:

 Renal vasoconstriction [norepinephrine, dopamine]
 Systemic vasodilation [sepsis, vasodilatory agents]
 Anesthesia
 Surgery
Systemic Vasodilation: Bacterial sepsis, antihypertensives
120
Renal hypoperfusion which may produce by drugs the 3 groups most commonly
implicated are:
a] Excessive diuretic therapy.
b] Non-steroidal anti-inflammatory drugs - This cause renal damage and ARF by
inhibiting prostaglandin synthesis in the kidney. These prostaglandins are all potent
vasodialators and produce an increase in blood flow to the glomerulus and the medulla.
Increased amounts of vasoconstrictor substances such as angiotensin II or (Antidiuretic
hormone) ADH in the blood occur in variety of clinical conditions such as volume
depletion, congestive cardiac failure. In this condition the patient render on the release of
vasodialatory prostaglandins for the maintenance of renal blood flow. Inhibition of
prostaglandin synthesis may cause renal hypoperfusion.
c] Angiotensin converting enzyme [ACE] inhibitors may also produce a reduction
in renal function.
2] Intra – Renal -
Acute intrinsic renal failure refers to decrease in renal function resulting from
more severe or prolonged ischemic, toxic, or immunologic mechanisms and is associated
with structural damage to glomeruli tubules, vascular supply.
Intrinsic causes of Acute Renal Failure:
 Nephrotoxic Agents [Drugs and Radiocontrast].
 Ischemic Events Pregnancy [Postpartum Renal Failure].
 Crush Injury.
 Septic Shock.
 Transfusion Reaction.
 Arterial Thrombosis.
Glomerular:
 Drug Induced Vasculitis.
 Malignant Hypertension.
Tubulo Interstitial:
121
 Acute Tubular Necrosis.
 Hyperurecemia.
 Hypercalcemia.
1. The commonest form of intra renal damage and indeed the classic form of ARF is
acute tubular necrosis, which results from direct nephrotoxic damage to the
tubule.
2. The high metabolic activity of the proximal tubule renders it particularly
vulnerable to ischemia and toxins.
3. The most frequent cause is renal hypoperfusion and acute tubular necrosis may
also cause by wide variety of potentially nephrotoxic drugs including
aminoglycoside antibiotics cyclosporin, and radiographic contrast media.
4. Interstitial damage also causes nephrotoxins with inflammation affecting those
cells lying between the nephrons.
5. Glomerulonephritis is a relatively rare cause of ARF.
3] Post - Renal -
It is simply an accumulation of nitrogenous wastes secondary to obstruction of
urine flow.
Causes of Post-Renal Acute Renal Failures

 Bilateral urethral obstruction
 Intraurethral [emboli, stones, crystals]
 Extra urethral [tumour, reteroperitoneal fibrosis]
 Papillary necrosis [acute pyelonephritis]
 Bladder obstruction
 Mechanical [malignancy, infection]
 Functional [anticholinergics, ganglionic blockers, neuropathy]
 Urethral obstruction
122
PATHOPHYSIOLOGY
Ischemia
Increased Sarcolemmal
Calcium Permiability
Increased Calcium Activation

of Myosin Light Chain Kinase
Hypersensitivity to Renal Increased Constriction of Glomerular

Nerve Stimulation Afferent Arterioles and Mesangial Cells
Decreased Glomerular Loss of Renal

Increased Renal
Cappilary Surface Area Autoregulation
Vascular Resistance
and Permeability
Decreased Glomerular
Filteration Rate
Intermitent Cell Injury
and Tubular Debris
Tubular Obstruction
MANAGEMENT Acute Renal Failure

a. Discontinue nephrotoxic drugs.
123
b. Treat underlying infection.
c. Remove any urinary tract obstructions.
d. Correct and maintain proper fluid and electrolyte balance.
e. Treat body chemistry alterations.
f. Improve urine output. Fluid intake should match fluid losses.
Patient should receive a high calorie, low protein diet to reduce renal workload by
decreasing production of end products of protein catabolism that the kidneys cannot
excrete, it also prevent.
KETOACIDOSIS
1] TREATMENT OF HYPERKALEMIA -
a. Dialysis
b. Calcium Chloride or Calcium Gluconate: It replaces and maintains body calcium.
Counteracting the cardiac effects of acute hyperkalemia. Calcium chloride is given
intravenously, as 5 to 10ml of a 10% solution administered over 2 minutes. Calcium
gluconate is administered as 10 ml of a 10% solution over 2-5 minutes. Adverse effects
include hypotension, tingling sensations, and renal calculus formation.
c. Sodium Bicarbonate: for severe hyperkalemia or metabolic acidosis. It restores
bicarbonate that the renal tubules cannot reabsorb from the glomerular filtrate and
increases arterial pH. This results in a shift of potassium into cells and reduces serum
potassium concentration.
d. Regular Insulin with Dextrose: The insulin causes and intracellular shift of
potassium combination of insulin with dextrose deposits potassium with glycogen in the
liver, reducing the serum potassium.
e. Sodium Polystyrene Sulfonate: It is a potassium removing resin that exchanges
sodium ions for potassium ions in the intestine.
2] TREATMENT OF HYPERPHOSPHATEMIA -
a. IV calcium is the first line therapy for severe cases.
124
b. Dialysis used for acute, life threatening hyperphosphatemia accompanied by acute
hypocalcemia and when volume overload is present.
c. Aluminium Hydroxide: Aluminium binds excess phosphate in the intestine, and
reduces Phosphate Concentration.
3] TREATMENT OF HYPOCALCEMIA -
a. Calcium Gluconate replaces and maintains body calcium, raising the serum
calcium level immediately. Intravenousely in a dosage of 1-2g over a period of 10
minutes, followed by a slow infusion of 1g.
b. Oral calcium salts for mild hypocalcemia.
4] TREATMENT OF HYPONATREMIA -
a. Moderate hyponatreamia require only fluid restriction.
b. Sodium chloride given for severe symptomatic hyponatremia. It replaces and
maintains sodium and chloride concentration.
MANAGEMENT OF SYSTEMIC MANIFESTATIONS

Treatment of Fluid Overload and Edema -
1. Loop (High – Ceiling) Diuretics [Furosemide, Bumetanide, and Ethacrynic
Acid]: It inhibits sodium and chloride reabsorption at the loop of henle,
promoting water excretion.
2. Mannitol (Osmotic Diuretic): It increases the osmotic pressure of the glomerular
filtrate. Fluid from interstitial spaces is drawn into blood vessels expanding
plasma volume and maintaining or increasing the urine flow.
3. Dopamine: It is a vasopressor, an immediate metabolic precursor of adrenaline
and noradrenaline. It dilates mesenteric and renal blood vessels, which leads to
enhanced renal blood flow increased GFR, sodium excretion, and urine output.
Intravenously at 1-3 μg/kg /min.
4. Dialysis Hemodialysis or Peritoneal Dialysis may be necessary in patients who
develop anuria, acute fluid overload, severe hyperkalemia, metabolic acidosis, or
blood urea nitrogen (BUN) level above 100 mg/dl.
125
PATIENT COUNSELLING
1. Patient should be informed about the Severity and Complication of the Disease.
2. Educate patient about the Risk Factors which could worsen the disease like
Diabetes Mellitus, Hypertension, Family History, and Age- related risk.
3. Inform patient about the symptoms of the disease getting Worsened like High
Blood Pressure, Blood in Urine, and Pain in Lower Back at about the Waistline,
Swelling especially in the Arms, and Frequent Urination at Night, Nausea and
Vomiting.
1. Thiazide diuretic should be taken in the morning to prevent nocturia.
2. Drug should be taken with food to minimize gastric irritation.
3. Take Vitamins and Mineral Supplements which are recommended.
1. Maintain the Ideal Body Weight, weigh each day in the morning and inform the
dietitian in case of losing or gaining of too much body weight.
2. Add potassium-rich food in the Diet like Banana, Spinach and other Green Leafy
Vegetables.
3. Sun screens should be used to protect from sunlight.
4. Do not need to limit the amount of fluids in the earlier stages of kidney disease.
5. Take the right amount of the protein as instructed.
6. Reduce Dietary Sodium Intake.
126
REFERENCES
1. J.Marriott, S.Smith Acute Renal Failure. In:Roger Walker, Clive
127
CHRONIC RENAL FAILURE
Chronic renal failure (CRF) is a condition characterized by anemia, acidosis,

osteodystrophy, neuropathy and general debility frequently accompanied by
hypertension, oedema and susceptibility to infection resulting from a significant
reduction in the excretory, homeostatic, metabolic and endocrine functions of the kidney.
EPIDEMIOLOGY
 The incidence of CRF
 In men is at least 1.5 times greater than in women.
 The increasing incidence of CRF with age is attributable to non-immunological
causes including vascular disease and undiagnosed prostatic disease in men.
 There are also racial differences in the incidence of CRF, with treatment required
3-5 times more often in Afro-Caribbean and Asian populations in comparison
with white populations.
AETIOLOGY
Causes of CRF in adults include
1. Diabetic Nephropathy.
2. Hypertension.
3. Glomerulonephritis.
4. Polycystic kidney disease.
5. Long-standing vascular disease. (e.g. Renal artery stenosis)
6. Long-standing obstructive uropathy. (e.g. Renal calculi)
7. Exposure to nephrotoxic agents.
128
PATHOPHYSIOLOGY
Initial Pathogenic Injury
Glomerular Cell Injury
Diabetes Mellitus Reduced Filtration Area Arteriosclerosis
Adaptive Hemodynamic Changes Systemic Hypertension
Increased Glomerular Blood Flow Increased Glomerular Cappilary Pressure
PROGRESSIVE RENAL
Glomerular Hypertrophy DISEASE
Endothelial Injury Hyperlipidemia
Epithelial Injury Mesangial Injury
Focal Detachment of
Epithelial Foot Process
Mesangial Expansion
Proteinuria
Microaneurysm
Formation
Glomerular Hyaline
Deposition
Microthrombi occluding
Glomerular Capillaries
GLOMERULAR
SCLEROSIS
129
1. CRF progresses slowly through mild impairment to end stage renal disease with a
total loss of kidney function. Renal reverse capacity may delay changes in
Bloodureanitrogen and creatinine level until glomerular filtrate rate has decreased
by 50%.
 Mild to Moderate CRF is characterized by decreased renal reserve (GFR of 30

- 60 ml/min)
 Severe CRF, where GFR is less than 15ml/min, is characterized by some
clinical evidence of renal failure. At this stage, slight azotemia occurs.
 End stage renal disease, when GFR is below 15 ml/min, is characterized by
frank uremia. Fluid and electrolyte imbalances develop, azotemia worsens,
and systemic manifestations appear.
2. As CRF progresses, nephron destruction worsen, leading to detoriation in the
kidneys filtration, reabsorption, and endocrine functions.
3. Renal function typically does not diminish until about 75% of kidney tissue is
damaged. Ultimately the kidneys become shrunken, fibrotic masses.2
MANAGEMENT
MECHANISM OF
CLASS OF DRUGS ADVERSE EFFECTS
ACTION
Diuretics
Osmotic and Loop Sodium and volume Headache and blurred vision.
Diuretics depletion promote Hypokalemia, hyperurecimia,
Thiazide diuretics diuresis. thrombocytopenia.
(Metolazone)
Inhibit the conversion
of angiotensin
Antihypertensive Agents converting
Postural hypotension, disturbance
enzymedecrease in
of taste, rashes, angioedema.
ACE inhibitors fluid volume along
with peripheral
vasodilation
Increases the serum Headache, dizziness, soft tissue
Vitamin D
calcium concentration calcification.
 Digitalis preparations and diuretics to manage edema and CHF and to increase
urine output.
130
 Antihypertensive agents may be need if blood pressure becomes dangerously high
as a result of edema and the high renin levels that occur in CRF.
 Phosphate binder in the treatment of hyperphosphatemia.
 Oral calcium salts and Vitamin D for the treatment of hypocalcaemia.
 Treatment of anemia includes administration of iron, folate supplements, and
erythropoietin. Erythropoietin stimulates the production of red cell progenitors
and the production of hemoglobin and also accelerates the release of reticulocytes
from the bone marrow.
 Antiemetics to control nausea and vomiting, docusate sodium to prevent
constipation, enemas to remove blood from the GI tract.
 An antipruritic agent, such as diphenhydramine, may be used to alleviate itching.
 Long term dialysis or renal transplantation is necessary to prolong life.
1. Hemodialysis is the preferred dialysis method for patients with a reduced

potential membrane, hyper catabolism or acute hyperkalemia. This technique
involves shunting of the patient’s blood through a dialysis membrane-containing
unit for diffusion, osmosis, and ultrafiltration. The blood is then returned to the
patient’s circulation. The patient receives heparin during hemodialysis to prevent
clotting.
2. Peritoneal dialysis is the preferred dialysis method for patients with
bleeding disorders and cardiovascular disease. The peritoneum is used as a semi
permeable membrane. A plastic catheter inserted into the peritoneum provides
access for the dialysate, which draws fluids, wastes, and electrolytes across the
membrane by osmosis and diffusion.
 Renal transplantation allows some patients with end-stage renal disease to live
normal and, in many cases longer lives.
 Histocompatibility must be tested to minimize the risk of transplant rejection
and failure.
PATIENT COUNSELLING
131
1. Patient should be informed about the Severity and Complication of the Disease.
2. Educate patient about the Risk Factors which could worsen the disease like
Diabetes Mellitus, Hypertension, Family History, and Age- related risk.
3. Inform patient about the symptoms of the disease getting Worsened and what to
do in the case of Emergency.
1. Thiazide diuretic should be taken in the morning to prevent nocturia.
2. Drug should be taken with food to minimize gastric irritation.
3. Take Vitamins and Mineral Supplements which are recommended.
1. Maintain the ideal body weight, weigh each day in the morning and inform the
dietitian in case of losing or gaining of too much body weight.
2. Add potassium-rich food in the Diet like Banana, Spinach and other Green Leafy
Vegetables.
3. Sun screens should be used to protect from sunlight.
4. Do not need to limit the amount of fluids in the earlier stages of kidney disease.
5. Take the right amount of the protein as instructed.
6. Reduce Dietary Sodium Intake.
132
REFERENCES:
1. Andrew L.Wilson, Renal Failure. In:Leon Shargel,alan H. Mutnick, Paul F. Souney, Larry N.
Swanson, Comprehensive nPharmacy Review,6th ed, Lippincott
Williams&Wilkins,2007,p.1229-1233
PSORIASIS
133
Psoriasis is a chronic, autoimmune disease that appears on the skin. It occurs when
the immune system sends out faulty signals that speed up the growth cycle of skin cells.
Psoriasis is not contagious and commonly causes red, scaly patches to appear on the skin,
although some patients have no dermatological symptoms. The scaly patches caused by
psoriasis, called psoriatic plaques, are areas of inflammation and excessive skin
production. Skin rapidly accumulates at these sites which gives it a silvery-white
appearance. Plaques frequently occur on the skin of the elbows and knees, but can affect
any area including the scalp, palms of hands and soles of feet, and genitals. In contrast to
eczema, psoriasis is more likely to be found on the outer side of the joint.
It can be classified as:
1. NON POSTULAR PSORIASIS -
 Psoriasis Vulgaris (Plaque Psoriasis)
 Psoriatic Erythroderma
2. POSTULAR PSORIASIS -
 Generalized Postular Psoriasis
 Palmoplantar Psoriasis
 Annular Postular Psoriasis
 Acrodermatitis continua
 Impetigo herpetiformis
3. OTHER PSORIASIS -
 Drug –Induced Psoriasis

 Seborrheic- like Psoriasis
 Nail Psoriasis
 Psoriatic Arthritis
134
EPIDEMOLOGY
Psoriasis affects both sexes equally and can occur at any age, although it most
commonly appears for the first time between the ages of 15 and 25 years. The prevalence
of psoriasis in Western populations is estimated to be around 2-3%. The prevalence of
psoriasis among 7.5 million patients who were registered with a general practitioner in
the United Kingdom was 1.5%. A survey conducted by the National Psoriasis Foundation
found a prevalence of 2.1% among adult Americans. The study found that 35% of people
with psoriasis could be classified as having moderate to severe psoriasis. Around one-
third of people with psoriasis report a family history of the disease.
AETIOLOGY
The cause of psoriasis is not fully understood. There are two main hypotheses
about the process that occurs in the development of the disease:
1. Psoriasis as primarily a disorder of excessive growth and reproduction of skin
cells and its simply seen as a fault of the epidermis and its keratinocytes.
2. Psoriasis an immune-mediated disorder in which the excessive reproduction of
skin cells is secondary to factors produced by the immune system. T cells become
active, migrate to the dermis and trigger the release of cytokines which cause
inflammation and the rapid production of skin cells.
Hence the possible etiologic factors of Psoriasis are:

1. Defects in Epidermal Cell Cycle
2. Disruption in Arachidonic Acid Metabolism
3. Genetic Factors
4. Immunological Mechanism
5. Exogenous Trigger Factors
 Climate
 Stress
 Infection
 Trauma
 Drugs
135
PATHOPHYSIOLOGY
Antigen Presenting Complex (APC)

presents Antigen to the T-Cell Receptor
T-Cells Activation by
Antigen in the Lymphnode
T-cell binding to the

Endothelium in the Vasculature
Migration into the

Dermis and Epidermis
Keratocytic Changes
Cytokines & TNF- α Released
T-Cell Reactivation by a
Second Exposure to Antigen
T-Cells Activation by
Antigen in the Lymphnode
Aborted Maturation and Excessive

Proliferation of Keratocytes forming
Plaques
136
MANAGEMENT
Topical Treatment Guidelines –
Active
Formulation Strength Regimen Side Effects
Ingredient
Lotions, Folliculitis,
3- 4 Times
Emollients Creams, N/A Contact
Daily
Ointments Dermatitis
Salicylic Acid 2- 3 Times Irritating
Gels, Lotions 2- 10%
(Keratolytic) Daily Sensation
Apply in
Creams, Gels,
Evening, allow Messy,
Lotions,
Coal Tar 1- 48.5% to remain Irritating,
Ointments,
through the Photoreactions
Solutions
Night
Apply in
Evening, allow Stains Skin and
Creams,
Anthralin 0.1- 1% to remain Clothes, can be
Ointments
through the Irritating
Night
Twice Daily,
No more than Burning &
Calcipotriene Ointments 50µg/ gm 100 gm/ week, Stinging in few
for upto to 8 Patients
Days
Local Tissue
Lotions, Atrophy, Striae,
2- 4 Times
Creams, Variable Epidermal
Corticosteroids Daily for
Ointments, Potency Thinning,
maintenance
Solutions Systemic
Effects
Apply to area Photoreaction,
Methxsalen Lotions 1% prior to UVA Exaggerated
Therapy Burning
137
Oral Treatment Guidelines -
Active
Formulation Strength Regimen Side Effects
Ingredient
Suspensions, 250 mg/ 5ml,
Sulfasalazine 3- 4 gm/ Day GI Upset
Tablets 500 mg
Burns,
Erythema, GI
2 hrs before
Methoxsalen Capsules 10 mg Upset, CNS
UVA Therapy
Effects, Ocular
& Skin Damage
2.5- 5 mg every
Tablets, 2.5 mg, 12 hrs for 3 Pancytopenia,
Methotrexate
Injections 20- 25 mg/ ml doses every GI Upset
week
Dry Mouth &
Lips, Eye
0.75- 1
Irritation, GI
Etretinate Capsules 10- 25 mg mg/kg/Day in
Upset,
Divided Doses
Hematologic &
Hepatic Effects
3- 4mg/kg/Day
in Divided Nephrotoxicity,
Doses, may GI Upset,
Capsules, 25 mg, 100 mg,
Cyclosporine increase to 5 Hypertension,
Solutions 100 mg/ ml
mg/kg/Day in 1 Tremor,
Month if no Monitor LFTs
response
Nephrotoxicity,
0.15 mg/kg
GI Upset,
twice daily,
Tarcolimus Capsules 1 mg, 5 mg Hypertension,
titrate based on
Tremor,
Side Effects
Monitor LFTs
PATIENT COUNSELLING
Based on Disease Profile
1. Provide complete information to the patient regarding the severity of the disease.
2. Provide the patient with information booklets
Based on Drug Profile
138
1. Explain the patient about the importance of adhering to the Medication for better
treatment.
2. Inform patient to apply Moisturizer, Creams, and Ointments regularly.
3. Monitor Blood and Liver Function Tests regularly due to certain Medication
Toxicity.
Based on Lifestyle Modification

1. Avoid any kind of Stress or Worries which triggers Psoriasis.
2. Wake up a little early in the morning drink 2 glasses of warm water then sit cross
legged on the floor and do deep breathing and meditate.
3. Closely monitor climatic changes and adjust accordingly especially in the
travelling and always try to limit Travelling.
4. Breathe Fresh Air and Sleep Well.
5. Educate patient about the possible Photo Therapies.
139
REFERENCES:
1. M.M Carr, Psoriasis and Ezcema. In:Roger Walker, Clive
Edwards,Clinical Pharmacy and therapeutics,3rd ed, Churchill
140

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HYPERTENSION

Hypertension is blood pressure elevated enough to perfuse tissues and organs. It

Blood pressure measurement includes systolic and diastolic components.

CATEGORY SYSTOLIC DIASTOLIC

If there is disparity in these ranges, the higher category of either

The main factors are:

4. Intracellular Sodium & Calcium:

II. SECONDARY HYPERTENSION -

2. Renal Disease: Renal parenchymal disease is the most common cause of

3. Renal Vascular Hypertension: Renal artery stenosis is present in 1-2% of

4. Primary Hyper Aldosteronism and Cushing’s syndrome: Patients with excess

5. Pheochromocytoma: It may be episodic, most patients are sustained elevations,

6. Hypertension associated with Pregnancy: The causes are coarctation of the

Risk Factors: Family History, Age,

Decreased Blood Flow to Organs Beta Receptor

Hyponatremia Juxtagolmerular Cells Hypovolemia

Angiotensinogen Renin Angiotensin I

Angiotensin Converting Enzyme (ACE)

Arteriolar Constriction Angiotensin II

Adrenal Cortex Stimulation

Increased Na+ Reabsorption

Increased Plasma Volume (ECF)

1. General Principles: Treatment primarily aims to lower blood pressure toward

a. Beta-blockers and diuretics should be considered initial agents for treatment

DRUG DOSAGE SIDE EFFECTS

Atenolol (β1) 25 – 100 mg daily PO

Metoprolol (β1) 25 – 150 mg twice daily

Labetalol (α-β) 100 – 600 mg twice daily Postural hypotension,

25 – 50 mg once or twice Hypotension, acute renal

Amlodipine 2.5 – 10 mg daily Tachy cardia, flushing,

Verapamil 40 – 80 mg 3 times daily

Before initiating anti hypertensive drug therapy patients are encouraged to

Decreased Systemic B.P IV Hypoxia Decreased Oxygen Supply

Increased ADH Decreased Renal Decreased Force of

Renin Increased LVEDP

Angiotensin Increased LV Preload

Aldosterone Increased LA Preload

Sodium & Water Pulmonary Edema

Left ventricular systolic dysfunction (LVSD) may be due to defects in systolic

Diastolic dysfunction arises from impairment of the filling process due to

ARTERIOLES ARTERIOLES AND VEINS VEINS

DRUGS MECHANISM OF ACTION ADVERSE EFFECTS

Cardio Selective Beta Inhibits the direct stimulation of heart Hypotension,

Direct effect on heart to increase the

Ischemic heart disease (IHD) is a condition in which there is an insufficient

Chronic Ischemic Heart Disease

Sudden Cardiac Death

DRUGS COMMONLY USED FOR MYOCARDIAL INFARCTION

DRUG SIDE EFFECTS MECHANISM OF ACTION

Aspirin, Dipyridamole, Gastric ulceration, Prevents platelet aggregation and

Heparin Heamorrhage Enhancing the activity of anti

In myocardial infarction, a portion of the cardiac muscle suffers a severe and

Migration and Proliferation of

Fibroblast Synthesis & Secretion

Narrowing of Blood Vessels

Reduction in Blood Flow

FIRST LINE THERAPY:

2. Thrombolytic Therapy [Recombinant Tissue Plasminogen Activator (t-PA)]:

 Urokinase: It is enzyme produced by kidney and found in urine. The urokinase

 Streptokinase: An IV dose of 1.5 million IU is infused over 60 minutes.

 Alteplase: It is genetically engineered drug. It is 10 times more expensive than

3. Post Thrombolytic Adjunctive Therapy