Clinical pharmacy complete notes 4th proff Pharm D.

1. Reference
Dr. Hamid Lectures
Dr. Furqan Lectures
Roger Walker Clinical Pharmacy and Therapeutics
Dipiro - Pharmacotherapy Handbook
Pharmacotherapy- A Pathophysiologic Approach
GHULAM MURTAZA HAMAD
4th PROFF. EVENING
PUNJAB UNIVERSITY COLLEGE OF PHARMACY, LAHORE
CLINICAL PHARMACY
4th
PROFESSIONAL

2. GM Hamad
TABLE OF CONTENTS
Contents
1. General Introduction to Clinical Pharmacy
2. Disease Management
3. Patient Profile and Patient Counseling
4. Clinical Trials of Drug Substances
5. Emergency Treatment
6. Drug Interactions
7. ADRs and Pharmacovigilance
8. Pharmacotherapy Plan
9. Drug Induced Diseases
10. Utilization of Clinical Drug Literature
11. Online Pharmaceutical Care Services and Globalizations
12. Pharmaceutical Care in Multiple Environment

3. GM Hamad
GENERAL INTRODUCTION TO CLINICAL
PHARMACY
HISTORICAL BACKGROUND
• In 1944 Clinical Pharmacy was initiated as an educational experiment by
Professor L. Wait Rising, University of Washington & later by Professor H.
W. Youngken Jr.
• The program suffered a setback after a vote by American Council on
Education.
• Dean Joseph Kowalewski, University of Cincinnati, Ohio & Dr Harry C.
Shirkey (pharmacist & physician)—1948.
• Pharmacy students were shown an anaesthetized patient before surgery.
They could then witness the stages of anesthesia and apply the techniques
as they had been taught.
• Clinical pharmacy has brought a wind of change, a new base of hope into
pharmacy profession.
• A new era of dynamism where pharmacists are reshaping their profession.
• Pharmacists in various specialties are working like pediatrics, geriatrics,
oncology, diabetic & asthma clinics.
THE ORIGIN OF CLINICAL PHARMACY
• Whitney (Michigan) 1930s & Clark (New York Hospital) 1940s are believed
to be pioneers in this field.
• In late 40s Flack (Jefferson Hospital Philadelphia), Purdum (John Hopkins's)
& Francke (Michigan) developed programs which combined internship &
advanced degrees in clinical pharmacy.
• The experiment (clinical pharmacy) worked & the U.S Government, by Act
of Congress, gave capitation grants to schools of pharmacy offering
undergraduate clinical orientation in their curricula.
• The changes were not confined to the U.S, they spread to Canada, then to
Europe such as Britain, France & African countries as Zimbabwe & Nigeria.
1

4. GM Hamad
• Even Pakistan is not behind this. Few years back the Pharmacy council of
Pakistan introduced a new scheme of study spanning over a period of 5-
year Doctor of Pharmacy (Pharm-D) degree program (more patient-
oriented).
INTRODUCTION
• The term “clinical “means “reclining in bed”
• Clinical implies observation or examination of living patient in order to
make a proper judgment or decision.
• With respect to pharmacy, clinical means that the pharmacy should be
practiced on hospital patients.
• Today the term has been used to describe a concept, a role, a philosophy, a
mode of practice, an emphasis, an orientation and a type of pharmacist, but
the centerpiece of all activities still is a patient.
DEFINITION
• Clinical pharmacy can be defined as:
“The area within the pharmacy practice dealing with patient care with
particular emphasis on drug therapy”
• It is patient-oriented and includes not only dispensing of the required
medication but also advising patients on proper use of all medications
(both prescribed & patient selected)
• It also utilizes pharmacist as the source of information for other health-care
professionals & all matters pertaining to drugs & their dosage forms.
“Clinical Pharmacy means the philosophy of safe & appropriate drug
usage in patients”
• Pharmacy practice is moving toward a model that integrates Patient-
focused Care & Drug Distribution Services.
• Clinical pharmacy is a health specialty → describes the activities & services
of Pharmacist to develop & promote the Rational and Appropriate use of
medicinal products & devices.
• Clinical pharmacy encourages pharmacist & support staff to shift their focus
from a solely product-oriented role towards more direct engagement with
patients & and the problems they encounter with medicines.
• Clinical Pharmacy—for its importance to patient care is now engaged in
more patient- oriented concept → “PHARMACEUTICAL CARE”
2

5. GM Hamad
OBJECTIVE
• The objective of clinical pharmacy practice is to optimize patient outcomes
by working to achieve quality use of medicine (QUM).
QUALITY USE OF MEDICINE (QUM)
• Judiciously, using medicines only after considering all other options.
• Appropriately, choosing a medicine after appraisal of factors including risk-
benefit analysis, treatment length and cost.
• Safely, minimizing misuse and abuse.
• Efficaciously, having a quantifiable benefit to the patient’s health and/or
quality of life.
• Clinical pharmacy practice is the practice of pharmacy as part of a
multidisciplinary healthcare team directed at achieving QUM. This may
include:
- Participation in the management of individual patients.
- Application of the best available evidence in daily clinical practice.
- Contribution of clinical knowledge and skills to the healthcare team.
- Identification and reduction in risks associated with medicines use.
- Involvement in the education of patients, carers, and other health
professionals.
- Involvement in research.
KEY POINTS—CLINICAL PHARMACY
• Comprises a set of functions that promote the safe, effective & economic
use medicines for individuals.
• Allowed pharmacists to shift from a product-oriented role towards direct
engagement with patients & the problems they encounter with medicines.
• The practice is generally an essential component of Pharmaceutical care.
• Pharmaceutical care is a co-operative patient centered system for achieving
specific & positive patient outcomes from responsible provision of
medicines.
• Three elements:
I. Patient assessment.
II. Determination of care plan.
III. Evaluating the outcome.
3

6. GM Hamad
• Ability to consult with patients is a key process in the delivery of
pharmaceutical care & requires regular reviews & development regardless
of experience.
DEVELOPMENT OF CLINICAL PRACTICE IN PHARMACY
• USA → Approach was to develop unit dose dispensing & pursue
decentralization of pharmacy services.
• UK → Unification of the prescription and the administration record &
pharmacist required to visit the ward to order medicines.
• Clinical pharmacy emerged from the presence of pharmacist in patient
areas and their interest in promoting safe use of medicines.
• In 1980s the clinical pharmacy practice grew because of its ability to
promote safe use of medicines in hospitals.
• This role of pharmacist was recognized in UK in 1988—endorsed the
implementation of clinical pharmacy services to secure value for money
from medicines.
DEFINITIONS (TO IDENTIFY PRACTICE AREAS)
CLINICAL PHARMACY
“It comprises a set of functions that promote the safe, effective & economic
use of medicines for individual patients. Clinical pharmacy process requires
the application of knowledge of pharmacology, ph-kinetics, pharmaceutics &
therapeutics to patient care”
PHARMACEUTICAL CARE
“It is a co-operative, patient centered system for achieving specific & positive
patient outcomes from the responsible provision of medicines”
MEDICINES MANAGEMENT
“It encompasses the way in which medicines are selected, procured, delivered,
prescribed, administered & reviewed to optimize the contribution that
medicines make to producing informed and desired outcomes of patient care”
PHARMACEUTICAL CARE
• Pharmaceutical care—a landmark in the landscape of pharmacy practice.
• It is defined as:
4

7. GM Hamad
“Responsible provision of drug therapy for the purpose of achieving
definite outcomes that improve the patient’s quality of life”
• The delivery of pharmaceutical care is dependent on the practice of clinical
pharmacy, but the key feature of care is that practitioner takes
responsibility for patients’ drug-related needs and is held accountable for
that commitment.
• Pharmaceutical care is predicted on a patient-centered approach to
identifying, preventing or resolving MRPs.
• Center to this is to establish a therapeutic relationship—a partnership in
which the pharmacist takes responsibility for resolving MRPs in line with
patient’s wishes, expectations and priorities.
BENEFITS OF PHARMACEUTICAL CARE
• The ability to demonstrate that clinical pharmacy improves pt. outcomes is
of great importance to pharmaceutical care model.
• Example:
- “In USA pharmacist participating in ward rounds has been shown to
reduce adverse drug events by 66% to 78% in general medical and
intensive care settings”
- In Pakistan if this system is in place it will definitely contribute to
reduce the mortalities as result of drug misadventures.
KEY ELEMENTS OF CARE PROCESS
Elements Purpose
Assessment To establish a full medication history &
highlight actual & potential drug
related problems.
Care plan To optimize care & the responsibilities
of both the pharmacist & patient in
attaining the stated goal.
Evaluation Reviews the progress against the
stated patient outcomes.
MEDICATION RELATED PROBLEMS (MRP)
• When the outcome is not optimal.
• Some MRPs are associated with significant morbidity & mortality.
5

8. GM Hamad
• Non-compliance & inappropriate prescribing and monitoring may be the
causes.
• Identification of underlying medication related problems is very important.
CATEGORIES OF MRP
• Untreated indication.
• Treatment without indication.
• Improper drug selection.
• Too little drug.
• Too much drug.
• Non-compliance.
• Adverse drug reactions.
• Drug interactions.
Pharmacists working in community pharmacy can contribute to great extent to
reduce MRPs.
PHARMACEUTICAL CONSULTATION
• Pharmaceutical care requires more than scientific expertise.
• A system that clearly describes the role & responsibilities of pharmacist &
provides the necessary infrastructure to support them.
• A clear process by which the pharmacist can deliver their contribution to
patient care.
CONSULTATION PROCESS
• The ability of pharmacist to consult effectively is fundamental to
pharmaceutical care.
• To establish a therapeutic relationship.
• Description of pharmaceutical care has been confined to the use of
mnemonics as WWHAM, ENCORE & AS METTHOD.
WWHAM
• Who is it for?
• What are the symptoms?
• How long has it been going on?
• Action taken?
• Medicines taken?
6

9. GM Hamad
ENCORE
• Evaluate the symptoms (onset, recurrence & duration)
• No medication is always an option.
• Care—when dealing with specific patient group (elderly, children, young,
pregnant women, nursing mothers etc.)
• Observe the patient for signs of systemic disturbance, ask about fever, loss
of weight.
• Refer when in doubt.
• Explain any course of action recommended.
AS METTHOD
• Age of the patient?
• Self or for someone else?
• Medication being taken.
• Exactly want do you mean (by the symptoms)
• Time & duration of the symptoms?
• Taken any action (medicine or seen a doctor)
• History of any disease?
• Other symptoms?
• Doing anything to alleviate the symptoms?
PHARMACEUTICAL CONSULTATION PROCESS
Element Goal Examples
Introduction Building a therapeutic
relationship.
Invites pt. to discuss
medication or health-
related issue, discuss
structure & purpose of
consultation.
Data collection &
problem identification
Identify the patient’s
medication related
needs.
Take full medication
history, establish pt.’s
understanding of illness
& prescribed treatment.
Actions & solutions Establishing an
acceptable management
plan with patient.
Involve pt. in designing
management plan.
Tailor info to address
pt.’s perception of illness
7

10. GM Hamad
& treatment, Check pt.’s
understanding, refer
appropriately.
Closure Negotiating safety
netting strategies with
patient.
Provide info to guide
patient when it
experiences problem.
CONSULTATION BEHAVIORS
• Active listening.
• Appropriate use of open & closed questions.
• Respect patient.
• Avoid jargon (slang, inappropriate language)
• Demonstrate empathy.
• Deals sensitively with potentially embarrassing or sensitive issues.
DRUG USE PROCESS (DUP)
• A system necessary to aggregate large amount of data in a reliable manner
DUP STAGES
• Need for a drug.
• Drug selection.
• Regimen selection.
• Drug provision.
• Drug administration.
• Monitoring drug therapy.
• Patient counseling.
• Evaluation of effectiveness.
DRUG USE PROCESS (DUP) INDICATORS
DUP Stage Action
Need for a drug Appropriate indication for each drug and all medication
conditions are addressed therapeutically.
Drug selection Selection and recommendation of most appropriate drug
based upon the ability to reach therapeutic goals with
consideration of patient variables, formulary and cost of
therapy.
8

11. GM Hamad
Regimen
selection
Select the most appropriate drug regimen for achieving the
desired therapeutic goals at the least cost without diminishing
effectiveness or causing toxicity.
Drug provision Facilitate the dispensing and supply process for accurate
preparation of drugs, ready to administer form and delivered
to patient on a timely basis.
Drug
administration
Ensure that appropriate devices and techniques are used for
drug administration.
Monitoring
drug therapy
Monitor drug therapy for effectiveness or adverse effects in
order to determine whether to maintain, modify or
discontinue.
Patient
counseling
Counsel and educate patients or caregivers about the
patient’s therapy to ensure proper use of medicines.
Evaluation of
effectiveness
By reviewing all the previous steps of DUP and taking
appropriate steps to ensure that the therapeutic goals are
achieved.
ROLE OF CLINICAL PHARMACIST
• Cares for patients in all healthcare settings.
• In-depth knowledge of medications, integrated with foundational
understanding of the biomedical, pharmaceutical, sociobehavioral and
clinical sciences.
• Applies evidence-based therapeutic guidelines, evolving sciences, emerging
technologies and relevant legal, ethical, social, cultural, economic and
professional principles.
• Assumes responsibility and accountability for managing medication therapy
in direct patient care settings, practicing independently or in consultation
or collaboration with other healthcare professionals.
• As researchers generate, disseminate and apply new knowledge that
contributes to improved health and quality of life.
• Expert in the therapeutic use of medication, evaluate and recommend to
patient and other healthcare professionals.
• Primary source of scientifically valid information and advice regarding safe,
appropriate and cost-effective use of drugs.
CLINICAL PHARMACY FUNCTIONS
1) Establishing the need for drug therapy.
9

12. GM Hamad
2) Selecting the medicine.
3) Administering the medicine.
4) Providing the medicine.
5) Monitoring therapy.
6) Patient advice & education.
7) Evaluating effectiveness.
1. ESTABLISHING THE NEED FOR DRUG THERAPY
• Establishment of diagnosis & then balancing the risks and benefits of
treatment against the risks posed by the disease.
• Pharmacist’s role:
- Providing information to the prescriber on the expected risks of
drug therapy.
RELEVANT PATIENT DETAILS
• Background information on patient’s health & social circumstances → help
in prevention of existing and potential MRPs.
• Once diagnosis & previous medical history (PMH) are established → it is
possible to identify the medicines that are expected to be prescribed for
each indication.
MEDICATION HISTORY
• Identifies & documents allergies or serious adverse drug reactions.
2. SELECTING THE MEDICINE
• Clinical & cost-effective selection of a medicine in the context of
individual patient care.
• Scrutinize for appropriateness.
IDENTIFY DRUG-PATIENT INTERACTIONS
• Contraindications & cautions (related to age group)
• Allergy or previous evidence of ADRs.
• Hepatic and renal functions or CHF.
IDENTIFY DRUG-DISEASE INTERACTIONS
• When a medicine has potential to make pre-existing condition worse.
10

13. GM Hamad
DRUG-DRUG INTERACTIONS
• The change in the effect of one drug by prior or concurrent use of another
drug.
DRUG-FOOD INTERACTIONS
• Different nutritional ingredients (vitamins, amino acids, minerals etc.) in the
diet may affect drugs in many ways.
3. ADMINISTERING THE MEDICINE
• Several factors influencing the bioavailability should be considered i.e.
rate & extent of absorption, degree of plasma protein binding & volume
of distribution, hepatic metabolism.
• Calculating the appropriate dose.
• Selecting an appropriate regimen.
SPECIALIZED AREAS IN PHARMACY PRACTICE
• Pharmaceutical care / patient care.
• Medication use evaluation / medication utilization reviews.
• Home medication review (HMR).
• Medication therapy management (MTM).
• Drug use process (DUP).
• Chronic disease management (CDM) [Asthma, Warfarin, Diabetes, CVD,
Arthritis]
• Quality use of medicine (QUM), rational use of drugs (RUD).
• Community pharmacy.
• Public health pharmacy (disease prevention / communicable diseases /
vaccination).
• Minor illness treatment (flu, cough etc.)
11

14. GM Hamad
DISEASE MANAGEMENT
UNIT I: CARDIOVASCULAR UNIT (HYPERTENSION, ISCHEMIC HEART
DISEASES E.G. ANGINA PECTORIS, MI, HEART FAILURE)
HYPERTENSION
DEFINITION
“Hypertension is defined as persistently elevated arterial blood pressure (BP)”
• Blood pressure measurement includes systolic and diastolic components,
and both are important in determining an individual's cardiovascular risk.
Classification of Blood Pressure in Adults
Classification Systolic (mm Hg) Diastolic (mm Hg)
Normal <120 And <80
Prehypertension 120–139 Or 80–89
Stage 1 hypertension 140–159 Or 90–99
Stage 2 hypertension ≥160 Or ≥100
• Isolated systolic hypertension is diastolic blood pressure (DBP) values less
than 90 mm Hg and systolic blood pressure (SBP) values of 140 mm Hg or
more.
• Hypertensive crisis (BP >180/120 mm Hg) may be categorized as
hypertensive emergency (extreme BP elevation with acute or progressing
end-organ damage) or hypertensive urgency (high BP elevation without
acute or progressing end-organ injury).
12

15. GM Hamad
PATHOPHYSIOLOGY
PRIMARY HYPERTENSION
• Hypertension may result from an unknown etiology (primary or essential
hypertension).
Factors contributing to development of primary hypertension include:
• Humoral abnormalities involving the renin–angiotensin–aldosterone
system (RAAS) or natriuretic hormone.
• Disturbance in the CNS, autonomic nerve fibers, adrenergic receptors, or
baroreceptors.
• Abnormalities in renal or tissue autoregulatory processes for sodium
excretion, plasma volume, and arteriolar constriction.
• Deficiency in synthesis of vasodilating substances in vascular endothelium
(prostacyclin, bradykinin, and nitric oxide) or excess vasoconstricting
substances (angiotensin II, endothelin I)
• High sodium intake or lack of dietary calcium.
SECONDARY HYPERTENSION
• Secondary hypertension (<10% of cases) is usually caused by chronic kidney
disease (CKD) or renovascular disease. Other conditions are Cushing
syndrome, coarctation of the aorta, obstructive sleep apnea,
hyperparathyroidism, pheochromocytoma, primary aldosteronism, and
hyperthyroidism.
• Some drugs that may increase BP include corticosteroids, estrogens,
nonsteroidal anti-inflammatory drugs (NSAIDs), amphetamines,
sibutramine, cyclosporine, tacrolimus, erythropoietin, and venlafaxine.
HYPERTENSION
PRIMARY
HYPERTENSION
SECONDARY
HYPERTENSION
13

16. GM Hamad
TARGET ORGAN DAMAGE DUE TO HYPERTENSION
CARDIOVASCULAR
• Constriction of arterioles and insufficient blood flow to coronary
vasculature leads to angina, myocardial infarction; left ventricular
hypertrophy may occur due to increased cardiac output leading to heart
failure.
RENAL
• Arteriolar nephrosclerosis leads to polyuria, nocturia, protein and red blood
cells in urine, elevated serum creatinine, renal insufficiency.
CEREBRAL
• Decreased blood flow and decreased oxygen supply lead to transient
ischemic attacks, cerebral thrombosis, hemorrhage.
RETINAL
• Damage to arterioles of retina leads to hemorrhage, visual disturbances.
CLINICAL PRESENTATION
• Patients with uncomplicated primary hypertension are usually
asymptomatic initially.
• Patients with secondary hypertension may have symptoms of the
underlying disorder.
• Patients with pheochromocytoma may have headaches, sweating,
tachycardia, palpitations, and orthostatic hypotension. In primary
aldosteronism, hypokalemic symptoms of muscle cramps and weakness
may be present. Patients with Cushing syndrome may have weight gain,
polyuria, edema, menstrual irregularities, recurrent acne, or muscular
weakness in addition to classic features (moon face, buffalo hump, and
hirsutism).
DIAGNOSIS
• Elevated BP may be the only sign of primary hypertension on physical
examination.
• Signs of end-organ damage occur primarily in the eye, brain, heart,
kidneys, and peripheral blood vessels.
14

17. GM Hamad
• Funduscopic examination may reveal arteriolar narrowing, focal arteriolar
constrictions, arteriovenous nicking, retinal hemorrhages and exudates,
and disk edema. Presence of papilledema usually indicates a hypertensive
emergency requiring rapid treatment.
• Cardiopulmonary examination may reveal abnormal heart rate or rhythm,
left ventricular (LV) hypertrophy, coronary heart disease, or heart failure
(HF).
• Peripheral vascular examination may reveal aortic or abdominal bruits,
distended veins, diminished or absent peripheral pulses, or lower extremity
edema.
• Patients with renal artery stenosis may have an abdominal systolic-diastolic
bruit.
• Baseline hypokalemia may suggest mineralocorticoid-induced
hypertension. Protein, blood cells, and casts in the urine may indicate
renovascular disease.
• Laboratory tests: Blood urea nitrogen (BUN)/serum creatinine, fasting lipid
panel, fasting blood glucose, serum electrolytes (sodium and potassium),
hemoglobin and hematocrit, spot urine albumin-to-creatinine ratio, and
estimated glomerular filtration rate. A 12-lead electrocardiogram (ECG)
should also be obtained.
• Laboratory tests to diagnose secondary hypertension: Plasma
norepinephrine and urinary metanephrine levels for pheochromocytoma,
plasma and urinary aldosterone concentrations for primary aldosteronism,
plasma renin activity, captopril stimulation test, renal vein renin, and renal
artery angiography for renovascular disease.
TREATMENT
TREATMENT GOALS
• The overall goal is to reduce morbidity and mortality by the least intrusive
means possible. The goal BP for most patients, including those with
diabetes or CKD (no dialysis), is less than 140/90 mm Hg. Lower goals may
be an option in certain populations. The goal for patients 80 years of age or
older without diabetes or CKD is less than 150/90 mm Hg.
15

18. GM Hamad
NONPHARMACOLOGIC THERAPY
• LIFESTYLE MODIFICATIONS
1. Weight loss if overweight or obese.
2. Exercise.
3. Diet (low salt intake)
4. Smoking cessation
5. Alcohol restriction
• Lifestyle modification alone is sufficient for most patients with
prehypertension but inadequate for patients with hypertension and
additional CV risk factors or target-organ damage.
PHARMACOLOGIC THERAPY
• Initial drug selection depends on the degree of BP elevation and presence
of compelling indications for selected drugs.
• Angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor
blockers (ARBs), calcium channel blockers (CCBs), and thiazide diuretics are
acceptable first-line options.
• β-Blockers are used to either treat a specific compelling indication or as
combination therapy with a first-line antihypertensive agent for patients
without a compelling indication.
• Most patients with stage 1 hypertension should be treated initially with a
first-line antihypertensive drug or a two-drug combination. Combination
therapy is recommended for patients with stage 2 hypertension, preferably
with two first-line agents.
DRUG THERAPY
• Diuretics: reduce blood volume.
• Sympatholytics: reduce ability of sympathetic system to raise blood
pressure.
• Calcium channel blockers: reduce peripheral resistance.
• ACE inhibitors, angiotensin II antagonists: reduce peripheral resistance.
1. ANGIOTENSIN-CONVERTING ENZYME INHIBITORS
• ACE inhibitors are a first-line option, and if they are not the first agent
used, they should be the second agent tried in most patients.
16

19. GM Hamad
• ACE inhibitors block conversion of angiotensin I to angiotensin II, a
potent vasoconstrictor and stimulator of aldosterone secretion. ACE
inhibitors also block degradation of bradykinin and stimulate synthesis
of other vasodilating substances, including prostaglandin E2 and
prostacyclin.
• Starting doses should be low with slow dose titration. Acute
hypotension may occur at the onset of therapy, especially in patients
who are sodium or volume depleted, in HF exacerbation, very elderly, or
on concurrent vasodilators or diuretics. Start administering doses in
such patients, using half the normal dose followed by slow dose
titration.
• E.g. Captopril, Enalapril, Ramipril, Fosinopril.
SIDE EFFECTS
• Hypotension (especially first dose)
• Hyperkalemia
• Cough
• Renal impairment
2. ANGIOTENSIN II RECEPTOR BLOCKERS
• ARBs are a first-line therapy option in most patients with hypertension
and reduce CV events similar to ACE inhibitors. The combination of an
ACE inhibitor and ARB has no additional CV event lowering but is
associated with a higher risk of side effects (renal dysfunction,
hypotension).
• Angiotensin II is generated by the renin–angiotensin pathway (which
involves ACE) and an alternative pathway that uses other enzymes such
as chymases. ACE inhibitors block only the renin–angiotensin pathway,
whereas ARBs antagonize angiotensin II generated by either pathway.
The ARBs directly block the angiotensin II type 1 receptor that mediates
the effects of angiotensin II.
• Unlike ACE inhibitors, ARBs do not block bradykinin breakdown.
Although this accounts for the lack of cough as a side effect, there may
be negative consequences because some of the antihypertensive effect
of ACE inhibitors may be due to increased levels of bradykinin.
17

20. GM Hamad
• All ARBs have similar antihypertensive efficacy and fairly flat dose-
response curves.
• Addition of a CCB or thiazide diuretic significantly increases
antihypertensive efficacy.
• E.g. Candesartan, Losartan, Valsartan, Telmisartan, Amlodipine.
SIDE EFFECTS
• Renal insufficiency
• Hyperkalemia
• Orthostatic hypotension.
3. CALCIUM CHANNEL BLOCKERS
• Calcium channel blockers (CCBs), including both dihydropyridine and
non-dihydropyridine types, are first-line therapy options. They are also
used in addition to or instead of other first-line antihypertensives for the
compelling indications of coronary artery disease and diabetes.
• CCBs cause relaxation of cardiac and smooth muscle by blocking voltage-
sensitive calcium channels, thereby reducing entry of extracellular
calcium into cells. This leads to vasodilation and a corresponding
reduction in BP.
• Verapamil decreases heart rate, slows atrioventricular (AV) nodal
conduction, and produces a negative inotropic effect that may
precipitate HF in patients with borderline cardiac reserve. Diltiazem
decreases AV conduction and heart rate to a lesser extent than
verapamil.
SIDE EFFECTS
• Cardiac conduction abnormalities such as bradycardia, AV block, and HF.
• Constipation.
• Dizziness, Flushing, Headache, Gingival hyperplasia, and Peripheral edema.
4. DIURETICS
• Diuretics lower BP by causing diuresis. The reduction in plasma volume
and stroke volume associated with diuresis decreases cardiac output
and BP. The initial drop in cardiac output causes a compensatory
increase in peripheral vascular resistance.
18

21. GM Hamad
• With chronic therapy, extracellular fluid volume and plasma volume
return to near pretreatment levels, and peripheral vascular resistance
falls below baseline. Reduced peripheral vascular resistance is
responsible for the long-term hypotensive effects.
• Thiazides (e.g. Bendroflumethiazide, indapamide)
• Loop diuretics (e.g. furosemide) are used mainly in pulmonary oedema
due to ventricular failure, chronic heart failure.
• Potassium-sparing diuretics (e.g. amiloride (+ hydrochlorothiazide),
spironolactone)
• Caution: Hypokalemia.
THIAZIDE DIURETICS
• Thiazides are the preferred type of diuretic and are considered a first-line
option for most patients with hypertension.
• Reduce sodium and water retention in the distal convoluted tubule in the
kidney resulting in a reduction of the peripheral resistance.
• Cause loss of potassium and magnesium salts.
• Potassium supplementation should be considered.
• Maximal hypotensive effect is reached at relatively low doses.
POTASSIUM-SPARING DIURETICS
• Retain potassium and therefore no need to consider potassium
supplementation.
• Act in the distal convoluted tubule.
• Are weak diuretics and in fact may be found in combination products with
thiazides.
SIDE EFFECTS
• Side effects of thiazides include hypokalemia, hypomagnesemia,
hypercalcemia, hyperuricemia, hyperglycemia, dyslipidemia, and sexual
dysfunction.
• Loop diuretics have less effect on serum lipids and glucose, but
hypokalemia is more pronounced, and hypocalcemia may occur.
19

22. GM Hamad
• Potassium-sparing diuretics may cause hyperkalemia, especially in patients
with CKD or diabetes and in patients receiving concurrent treatment with
an ACE inhibitor, ARB, direct renin inhibitor, or potassium supplement.
5. B-BLOCKERS
• β-Blockers are only considered appropriate first-line agents to treat
specific compelling indications (e.g., post-MI and coronary artery
disease). Their hypotensive mechanism may involve decreased cardiac
output through negative chronotropic and inotropic effects on the heart
and inhibition of renin release from the kidney.
• Atenolol, betaxolol, bisoprolol, metoprolol, and nebivolol are cardio
selective at low doses and bind more avidly to β1-receptors than to β2-
receptors.
• Acebutolol, carteolol, and pindolol possess intrinsic sympathomimetic
activity (ISA) or partial β-receptor agonist activity.
• Atenolol and nadolol have relatively long half-lives and are excreted
renally; the dosage may need to be reduced in patients with renal
insufficiency.
SIDE EFFECTS
• Bradycardia, Heart failure, Hypotension, Bronchospasm, Peripheral
vasoconstriction, Fatigue, Depression, Vivid dreams.
6. α1-RECEPTOR BLOCKERS
• Prazosin, terazosin, and doxazosin are selective α1-receptor blockers
that inhibit catecholamine uptake in smooth muscle cells of peripheral
vasculature, resulting in vasodilation and BP lowering.
• A first-dose phenomenon characterized by orthostatic hypotension
accompanied by transient dizziness or faintness, palpitations, and even
syncope may occur within 1 to 3 hours of the first dose or after later
dosage increases. The patient should take the first dose (and
subsequent first increased doses) at bedtime. Occasionally, orthostatic
hypotension and dizziness persist with chronic administration.
20

23. GM Hamad
LAST LINE DRUGS
CENTRAL α2-AGONISTS
• Clonidine, guanabenz, moxonidine, and methyldopa lower BP primarily by
stimulating α2-adrenergic receptors in the brain.
SIDE EFFECTS
• Depression
• Vasodilation
DIRECT ARTERIAL VASODILATORS
• Hydralazine and minoxidil cause direct arteriolar smooth muscle
relaxation. Compensatory activation of baroreceptor reflexes results in
increased sympathetic outflow from the vasomotor center, increasing heart
rate, cardiac output, and renin release.
SIDE EFFECTS
• Potent vasodilation
• Marked fluid retention
• Hirsutism
• Reflex tachycardia
RESERPINE
• Reserpine depletes norepinephrine from sympathetic nerve endings and
blocks transport of norepinephrine into storage granules. When the nerve
is stimulated, less than the usual amount of norepinephrine is released into
the synapse. This reduces sympathetic tone, decreasing peripheral vascular
resistance and BP.
SIDE EFFECTS
• Nasal stuffiness
• Increased gastric acid secretion
• Diarrhea
• Bradycardia
DIRECT RENIN INHIBITOR
• Aliskiren blocks the RAAS at its point of activation, resulting in reduced
plasma renin activity and BP.
21

24. GM Hamad
SIDE EFFECTS
• Many of the cautions and adverse effects seen with ACE inhibitors and
ARBs apply to aliskiren.
COMPELLING INDICATIONS
• Compelling indications for specific therapy involve high-risk conditions that
can be direct sequelae of hypertension (HF, IHD, chronic kidney disease,
recurrent stroke) or commonly associated with hypertension (diabetes,
high coronary disease risk).
1. HEART FAILURE WITH REDUCED EJECTION FRACTION (HFREF)
• Standard pharmacotherapy consists of three to four drugs: ACE inhibitor
or ARB plus diuretic therapy, followed by addition of an evidence-based
β-blocker (i.e., bisoprolol, carvedilol, and metoprolol succinate) and
possibly an aldosterone receptor antagonist.
• After implementation of a standard three-drug regimen, an aldosterone
antagonist (spironolactone and eplerenone) may be considered.
2. POSTMYOCARDIAL INFARCTION
• β-Blockers (without ISA) and ACE inhibitors (or ARBs) are recommended.
β-Blockers decrease cardiac adrenergic stimulation and reduce risk of
subsequent MI or sudden cardiac death. ACE inhibitors improve cardiac
function and reduce CV events after MI. These two drug classes, with β-
blockers first, are the drugs of first choice for post-MI patients.
3. CORONARY ARTERY DISEASE
• β-Blockers (without ISA) are first-line therapy in chronic stable angina;
they reduce BP and decrease myocardial oxygen consumption and
demand. Long-acting CCBs (the nondihydropyridine CCBs diltiazem and
verapamil) may be either alternatives or add-on therapy
(dihydropyridines) to β-blockers in chronic stable angina. Once ischemic
symptoms are controlled with β-blocker and/or CCB therapy, other
antihypertensives (e.g., ACE inhibitor or ARB) can be added to provide
additional CV risk reduction. Thiazide diuretics may be added thereafter
to provide additional BP lowering and further reduce CV risk.
22

25. GM Hamad
• For acute coronary syndromes, first-line therapy includes a β-blocker
and ACE inhibitor (or ARB); the combination lowers BP, controls acute
ischemia, and reduces CV risk.
4. DIABETES MELLITUS
• Treat all patients with diabetes and hypertension with an ACE inhibitor
or ARB. Both classes provide nephroprotection and reduced CV risk.
• CCBs are the most appropriate add-on agents for BP control in patients
with diabetes. The combination of an ACE inhibitor with a CCB is more
effective in reducing CV events than an ACE inhibitor plus a thiazide
diuretic.
• A thiazide diuretic is recommended add-on therapy to lower BP and
provide additional CV risk reduction.
• β-Blockers, similar to CCBs, are useful add-on agents for BP control in
patients with diabetes.
5. CHRONIC KIDNEY DISEASE
• In addition to lowering BP, ACE inhibitors and ARBs reduce
intraglomerular pressure, which may further slow CKD progression.
• Start with low doses and evaluate the serum creatinine soon after
starting therapy to minimize the risk of rapid and profound BP drops
that could precipitate acute kidney failure.
6. RECURRENT STROKE PREVENTION
• A thiazide diuretic, either as monotherapy or combined with an ACE
inhibitor, is recommended for patients with history of stroke or
transient ischemic attack.
• Implement antihypertensive drug therapy only after patients have
stabilized after an acute cerebrovascular event.
SPECIAL POPULATIONS
DRUG THERAPY IN ELDERLY
• Calcium channel blockers indicated as first-line agents.
• Diuretics less effective when there is compromised renal function.
• Beta-blockers less potent in the elderly.
• Effect of ACE inhibitors may be decreased due to lower renin levels.
23

26. GM Hamad
CHILDREN AND ADOLESCENTS
• Secondary hypertension is more common in children and adolescents than
in adults.
• Medical or surgical management of the underlying disorder usually
normalizes BP.
• Nonpharmacologic treatment (particularly weight loss in obese children) is
the cornerstone of therapy of primary hypertension.
• ACE inhibitors, ARBs, β-blockers, CCBs, and thiazide diuretics are all
acceptable drug therapy choices.
HYPERTENSION IN PREGNANCY
• Two conditions associated with hypertension in pregnancy are:
- Pre-eclampsia – pregnancy-induced hypertension, 140/90 mmHg
developing during pregnancy in a woman whose blood pressure was
previously normal.
- Eclampsia – occurrence of convulsions caused by hypertension.
• Methyldopa is the drug of choice.
• Calcium channel blockers (amlodipine and nifedipine): manufacturer
advises avoidance, but risk of uncontrolled maternal hypertension should
be balanced against risk of use of drug.
• Beta-blockers tend to cause birth of smaller babies.
• ACE-Is and ARBs cannot be used – they may damage the fetus and cause
problems in the neonate.
• Diuretics avoided because of decreased intravascular volume.
HYPERTENSIVE URGENCIES AND EMERGENCIES
HYPERTENSIVE URGENCIES
• Hypertensive urgencies are ideally managed by adjusting maintenance
therapy, adding a new antihypertensive, and/or increasing the dose of a
present medication.
• Acute administration of a short-acting oral drug (captopril, clonidine, or
labetalol) followed by careful observation for several hours to ensure a
gradual BP reduction is an option.
- Oral captopril doses of 25 to 50 mg may be given at 1- to 2-hour
intervals. The onset of action is 15 to 30 minutes.
24

27. GM Hamad
- Labetalol can be given in a dose of 200 to 400 mg, followed by
additional doses every 2 to 3 hours.
HYPERTENSIVE EMERGENCIES
• Hypertensive emergencies require immediate BP reduction to limit new or
progressing end-organ damage.
• This may be a medical emergency and requires prompt reduction of blood
pressure within minutes to 1 hour.
• Conditions that predispose to hypertensive emergency include
pheochromocytoma, renal vascular disease, head injury, severe burns,
eclampsia.
• Goal of treatment: diastolic pressure 100–119 mmHg.
• Nitroprusside is the agent of choice for minute-to-minute control in most
cases. It is usually given as a continuous IV infusion at a rate of 0.25 to 10
mcg/kg/min.
• Major complications that occur in a hypertensive emergency include:
- Angina
- Myocardial infarction
- Congestive heart failure
- Cerebral infarction
- Intracranial hemorrhage
EVIDENCE BASED RECOMMENDATIONS IN TREATMENT OF
HYPERTENSION
QUALITY OF EVIDENCE
- 1 = Evidence from more than one properly randomized, controlled trial.
- 2 = Evidence from at least one well-designed clinical trial with
randomization; from cohort or case-controlled analytic studies; or dramatic
results from uncontrolled experiments or subgroup analyses.
- 3 = Evidence from opinions of respected authorities, based on clinical
experience, descriptive studies, or reports of expert communities.
STRENGTH OF RECOMMENDATIONS
- A = good
- B = moderate
- C = poor evidence to support recommendation.
25

28. GM Hamad
ALGORITHM FOR TREATMENT OF HYPERTENSION
26

29. GM Hamad
ISCHEMIC HEART DISEASE (IHD)
INTRODUCTION
• Ischemic heart disease (IHD), sometimes described as Coronary artery
disease (CAD) or Coronary heart disease (CHD).
“Ischemic heart disease (IHD) is defined as a lack of oxygen and decreased or no
blood flow to the myocardium resulting from coronary artery narrowing or
obstruction”
• IHD may present as an Acute Coronary Syndrome (ACS) which includes:
- Unstable angina
- Non–ST-segment elevation
- ST-segment elevation myocardial infarction (MI)
- Chronic stable exertional angina
- Ischemia without symptoms
- Ischemia due to coronary artery vasospasm (variant or Prinzmetal
angina).
PATHOPHYSIOLOGY
• Angina pectoris usually results from increased myocardial oxygen demand
(MVo2) in the setting of a fixed decrease in myocardial oxygen supply
because of atherosclerotic plaque.
• Major determinants of MVo2 are heart rate (HR), contractility, and
intramyocardial wall tension during systole. A doubling in any of these
individual parameters requires a 50% increase in coronary flow to maintain
myocardial supply.
• A clinically useful indirect estimate of MVO2 is the double product (DP),
which is HR multiplied by systolic blood pressure (SBP) (DP = HR × SBP).
• The caliber of the resistance vessels delivering blood to the myocardium
and MVO2 are the prime determinants in the occurrence of ischemia.
• The normal coronary system consists of large epicardial or surface vessels
(R1) that offer little resistance to myocardial flow and intramyocardial
27

30. GM Hamad
arteries and arterioles (R2), which branch into a dense capillary network to
supply basal blood flow.
• Under normal circumstances, the resistance in R2 is much greater than that
in R1. Myocardial blood flow is inversely related to arteriolar resistance and
directly related to the coronary driving pressure.
• Atherosclerotic lesions occluding R1 increase arteriolar resistance, and R2
can vasodilate to maintain coronary blood flow.
• With greater degrees of obstruction, this response is inadequate, and the
coronary flow reserve afforded by R2 vasodilation is insufficient to meet
oxygen demand.
• Relatively severe stenosis (greater than 70%) may provoke ischemia and
symptoms at rest, whereas less severe stenosis may allow a reserve of
coronary blood flow for exertion.
• The diameter and length of obstructing lesions and the influence of
pressure drop across an area of stenosis also affect coronary blood flow
and function of the collateral circulation.
• Dynamic coronary obstruction can occur in normal vessels and vessels with
stenosis in which vasomotion or spasm may be superimposed on a fixed
stenosis.
• Persisting ischemia may promote growth of developed collateral blood
flow.
• Critical stenosis occurs when the obstructing lesion encroaches on the
luminal diameter and exceeds 70%.
• Lesions → 50% to 70% obstruction may reduce blood flow → to clinical
events such as MI.
• If the lesion 80% to 90% enlarged, resistance in vessels is tripled.
• Abnormalities of ventricular contraction → regional loss of contractility →
burden on the remaining myocardial tissue, resulting in heart failure,
increased MVO2, and rapid depletion of blood flow.
• Zones of tissue with marginal blood flow may develop that are at risk for
more severe damage if the ischemic episode persists or becomes more
severe.
• Nonischemic areas of myocardium may compensate → developing more
tension than usual in an attempt to maintain cardiac output.
28

31. GM Hamad
• The left or right ventricular dysfunction → associated with clinical findings
of an S3 gallop, dyspnea, orthopnea, tachycardia, fluctuating blood
pressure, transient murmurs, and mitral or tricuspid regurgitation.
CLINICAL PRESENTATION
• Many episodes of ischemia do not cause symptoms of angina (silent
ischemia).
• Patients often have a reproducible pattern of pain or other symptoms that
appear after a specific amount of exertion.
• Increased symptom frequency, severity, or duration, and symptoms at rest
suggest an unstable pattern that requires immediate medical evaluation.
• Symptoms → a sensation of pressure or burning over the sternum or near
it, which often radiates to the left jaw, shoulder, and arm.
• Chest tightness and shortness of breath may also occur → sensation usually
lasts from 30 seconds to 30 minutes.
• Precipitating factors → exercise, cold environment, walking after a meal,
emotional upset, fright, anger, and coitus.
• Relief occurs with rest and within 45 seconds to 5 minutes of taking
nitroglycerin.
• Variant or Prinzmetal angina → secondary to coronary spasm are more
likely to experience pain at rest and in the early morning hours
• Pain is not usually brought on by exertion or emotional stress nor is it
relieved by rest; the electrocardiogram (ECG) pattern is that of current
injury with ST-segment elevation rather than depression.
• Unstable angina is stratified into categories of low, intermediate, or high
risk for short-term death or nonfatal MI.
• Features of high-risk unstable angina include (but are not limited to):
- Accelerating tempo of ischemic symptoms in the preceding 48 hours.
- Pain at rest lasting more than 20 minutes.
- Age greater than 75 years.
- ST-segment changes.
- Clinical findings of pulmonary edema, mitral regurgitation, S3, rales,
hypotension, bradycardia, or tachycardia.
29

32. GM Hamad
• Episodes of ischemia may also be painless, or “silent,” in at least 60% of
patients, perhaps due to a higher threshold and tolerance for pain than in
patients who have pain more frequently.
DIAGNOSIS
• Pain: gripping or tight in nature occurring in the retrosternal region of the
chest; pain may radiate to neck, back, left shoulder with possible
involvement of jaw, teeth or epigastrum.
• Sweating, pallor.
• Fever after myocardial infarction may occur within 12 hours.
• Differential diagnosis when symptoms are presented:
- Symptoms of ischemic heart disease may be very similar to chest
pain that is related to other conditions such as:
▪ Gastrointestinal problems: dyspepsia, gastroesophageal reflux
disease, ulceration, carcinoma.
▪ Musculoskeletal pains.
▪ Panic attack.
▪ Pulmonary embolism.
• Diagnostic tests
- ECG: ST-segment depression, T-wave inversion indicating angina and
ST-segment elevation indicating myocardial infarction.
- Exercise tolerance test (ETT).
- Blood tests: elevation of cardiac-specific troponin I and T, creatine
kinase.
TREATMENT
TREATMENT GOALS
• To prevent myocardial infarction and associated mortality.
• To increase length of pain-free survival with a good quality of life.
NON-PHARMACOLOGICAL THERAPY
RISK FACTOR MODIFICATION
• Primary prevention through the modification of risk factors should
significantly reduce the prevalence of IHD.
30

33. GM Hamad
• Secondary intervention is effective in reducing subsequent morbidity and
mortality.
• Risk factors for IHD are additive and can be classified as:
- Unalterable risk factors include gender, age, family history or genetic
composition, environmental influences, and, to some extent,
diabetes mellitus.
- Alterable risk factors include smoking, hypertension, hyperlipidemia,
obesity, sedentary lifestyle, hyperuricemia, psychosocial factors such
as stress and type A behavior patterns, and the use of drugs that may
be detrimental (e.g. progestins, corticosteroids and cyclosporine).
LIFESTYLE MODIFICATIONS
• Daily physical activity
• Weight management
• Dietary therapy
• Smoking cessation
• Psychological interventions
• Limitation of alcohol intake.
SURGICAL REVASCULARIZATION
• Surgical revascularization options for select patients include coronary artery
bypass grafting (CABG) or percutaneous coronary intervention (PCI) with or
without stent placement.
RATIONALE OF DRUG TREATMENT IN ANGINA
• Decrease workload of the heart.
• Improve coronary blood supply.
RATIONALE OF DRUG TREATMENT IN MYOCARDIAL INFARCTION
• Immediate care: remove pain, prevent deterioration, limit infarct size.
• Management of complications: heart failure, arrhythmias.
• Prevention of second infarction.
TREATMENT OF ANGINA
ANTIPLATELET THERAPY
31

34. GM Hamad
• Aspirin almost completely blocks cyclooxygenase-1 (COX-1) activity and
subsequent thromboxane A2 production, leading to reduced platelet
activation and aggregation for the life of the platelet. Aspirin 75 to 162 mg
daily should be continued indefinitely in the absence of contraindications.
• Clopidogrel 75 mg daily is an alternative for patients unable to take aspirin
due to allergy or intolerance.
NITRATES
• Acts on vascular smooth muscles.
• Reduce myocardial oxygen demand.
• Increase myocardial oxygen supply.
• Taken before exercise.
• E.g. Glyceryl trinitrate (GTN), Isosorbide mono/dinitrate.
BETA BLOCKERS
• Lower myocardial oxygen demand by reducing heart rate and blood
pressure.
• Can provoke bronchospasms in patients with asthma.
• E.g. Atenolol, Labetalol, Propranolol, Timolol, Bisoprolol.
CALCIUM CHANNEL BLOCKERS
• Inhibits the slow inward current caused by entry of extracellular calcium
through cell membrane of excitable cells results in decreasing myocardial
oxygen demand and lowering blood pressure.
• E.g. Verapamil, Diltiazem, Amlodipine, Nifedipine, Nicardipine.
OTHER DRUGS
• Nicorandil (Potassium channel activator)
• Ivabradine (Selective inhibitor of the sinus node) If, resulting in a decrease
in heart rate, maintains myocardial contractility, atrioventricular
conduction and ventricular repolarization, Particularly, indicated in patients
who have a contraindication or intolerance to beta-blockers.
• Trimetazidine (3-ketoacyl-CoA thiolase (KAT) inhibitor) which results in
decreased fatty acid oxidation in the myocardium, thus decreasing
32

35. GM Hamad
metabolic damage due to ischemia. It can be used in combination therapy
with other anti-anginal drugs).
TREATMENT OF MYOCARDIAL INFARCTION
• Oxygen to counteract the occurrence of hypoxia, pulmonary edema or
continuing myocardial ischemia.
• Intravenous diamorphine, sublingual glyceryl trinitrate or intravenous
glyceryl trinitrate or isosorbide dinitrate against pain and distress.
• Intravenous metoclopramide or prochlorperazine as antiemetics.
• Drugs used to limit infarct size: thrombolytics aspirin, heparin, beta-
blockers, ACE (angiotensin-converting enzyme) inhibitors or angiotensin II
receptor antagonists.
CONTINUOUS PREVENTIVE TREATMENT IN ANGINA
• Beta-blockers and oral long-acting nitrates.
• Verapamil: highly negative inotropic calcium channel blocker which reduces
cardiac output and slows heart rate. May precipitate heart failure, not to be
used in conjunction with beta-blockers.
• Beta-blocker + amlodipine/nifedipine, nicorandil.
PATIENT MONITORING
• Monitor blood pressure.
• Target total cholesterol level 5 mmol/L, low-density lipoprotein (LDL) 3
mmol/L.
• Monitor occurrence of diabetes.
HEART FAILURE
INTRODUCTION
HEART FAILURE
“Heart failure (HF) is a progressive clinical syndrome caused by inability of the
heart to pump sufficient blood to meet the body’s metabolic needs”
• Acute (following a heart attack or volume loading) or Chronic.
33

36. GM Hamad
UNDERLYING CAUSE
• Failure of the heart muscle.
• Sustained arrhythmias (atrial fibrillation).
• Failure of the heart valves.
LEADING CAUSE OF CHF
• Ischemic heart disease (IHD)
• Hypertension
- Hypertension → Increased after-load → hypertrophy of the heart.
DEFINITIONS
CONGESTIVE HEART FAILURE
• Congestive heart failure (CHF) is a specific subset of HF characterized by left
ventricular systolic dysfunction & volume excess presenting as an enlarged,
blood congested heart.
AFTERLOAD
• Tension developed in the ventricular wall as contraction (systole) occurs.
Regulated by systemic vascular resistance (SVR) or impedance in ventricle
which is chiefly determined by arterial blood pressure (BP).
PRELOAD
• Forces acting on venous circulation to affect myocardial wall tension.
Elevated preload aggravates congestive failure.
CONTRACTILITY
• The inherent ability of myocardium to develop force (contract)
independent of preload or afterload. Contractility is synonymous with
inotropism.
EJECTION FRACTION
• Percent of LV volume expelled during systole. Normal 60% to 70%; <40%
indicates left ventricular systolic dysfunction.
34

37. GM Hamad
CLASSIFICATION
LEFT-SIDED FAILURE
• Most common type & is often secondary to hypertension.
• Left ventricular (systolic) dysfunction with poor output leading to increased
left atrial & pulmonary venous pressure → pulmonary congestion & edema.
RIGHT-SIDED FAILURE
• Often due to chronic lung disease (cor pulmonale).
• Right ventricular output falls, leading to increased venous pressure, with
peripheral edema.
BIVENTRICULAR FAILURE
• Both main chambers are affected as left & right ventricular failure often
coincide (IHD may have affected both ventricles).
• Often left ventricular failure leads to pulmonary congestion, which in turn
impairs right ventricular function, causing failure on the right side.
NEW YORK HEART ASSOCIATION (NYHA) CLASSIFICATION OF HEART
FAILURE
Class Characteristics
Class I No symptoms with ordinary physical activity (such as walking or
climbing stairs)
Class II Slight limitation with dyspnea on moderate to severe exertion
(climbing stairs or walking uphill)
Class III Marked limitation of activity, less than ordinary activity causes
dyspnea (restricting walking distance and limiting climbing to one
flight of stairs)
Class IV Severe disability, dyspnea at rest (unable to carry on physical
activity without discomfort)
CLASSIFICATION & ETIOLOGY OF LV DYSFUNCTION
Type of failure Characteristics
Contributing
factor
Etiology
Low-output,
systolic,
dysfunction
Hypo functioning left
ventricle, enlarged
heart, increased left
ventricular end
Decreased
contractility,
Increased
afterload.
Coronary ischemia, MI,
alcoholism, nutritional
deficiency,
Hypertension.
35

38. GM Hamad
diastolic volume, EF <
40%, decreased
stroke volume.
Low-output,
diastolic
dysfunction
Normal LV
contractility, normal
size heart, stiff left
ventricle, impaired
left ventricular
relaxation & filling,
decreased left
ventricular end-
diastolic volume,
normal EF, decreased
stroke volume.
Thickened
left ventricle,
Stiff left
ventricle,
Increased
preload.
Coronary ischemia, MI,
hypertension,
Amyloidosis,
sarcoidosis, Na & H2O
retention.
PATHOPHYSIOLOGY
• For compensating of circulatory failure → activation of renin-angiotensin-
aldosterone system (RAAS) with increased release of anti-diuretic hormone
(ADH). Also, there is release of atrial natriuretic peptide (ANP) from the
dilated heart.
• Increased sympathetic & RAAS activities increase arterial vascular
resistance (afterload) & venous return (preload) thus increasing the
workload of the heart.
• The increased sympathetic activity will also attempt to increase the force of
cardiac contraction → cardiac arrhythmias.
• As a result of increased peripheral resistance → impaired renal function,
with additional salt & water retention → further RAAS activation.
• A consequence of these changes is edema (congestion) at different sites in
the body → hence the term is used Congestive Heart Failure.
• Neurohormonal activation also leads to monocyte dysfunction → increased
aldosterone activity leading to fibrosis & stiffening of cardiac muscle,
further impairing pump activity.
CLINICAL PRESENTATION
CARDIOVASCULAR-RELATED FEATURES
• Reduced EF (<45%) as identified on an echocardiogram.
36

39. GM Hamad
• Hypotension leading to tiredness & possibly dizziness.
• Reduced urine flow.
• Cold peripheries.
• Breathlessness.
• Edema.
NON-SPECIFIC SYMPTOMS
• Fatigue, listlessness.
• Poor exercise tolerance.
• Weight loss or even weight gain due to edema.
DIAGNOSIS
Investigation Comment
Blood test Following assessments are usually performed:
• Blood gas analysis to assess respiratory gas
exchange.
• Serum creatinine and urea to assess renal function.
• Serum alanine and aspartate-aminotransferase plus
other LFTs.
• Full blood count to investigate possibility of anemia.
• Thyroid function tests to investigate possibility of
thyrotoxicosis.
• Serum BNP or NT pro-BNP to indicate likelihood of a
diagnosis of HF (screening test).
• Fasting blood glucose to investigate possibility of
DM.
12-lead ECG A normal ECG usually excludes the presence of LV systolic
dysfunction. Abnormal requires further investigation.
Chest radiograph A chest radiograph (X-ray) is performed to look for
enlarged cardiac shadow and consolidation in the lungs.
Echocardiography An echocardiogram is used to confirm the diagnosis of HF
and any underlying causes e.g. Valvular heart disease.
TREATMENT OF CHRONIC HEART FAILURE
TREATMENT GOALS
• Increase the quality of life.
• Avoid hospitalization.
37

40. GM Hamad
• Minimize adverse drug events.
• Increase survival time.
PHARMACOLOGICAL THERAPY
DIURETICS
• Indicated in both diastolic & systolic HF for patients with circulatory
congestion and/or cardiac distention.
• Thiazide diuretics (e.g. hydrochlorothiazide) are relatively weak and are
infrequently used alone in HF. However, thiazides or the thiazide-like
diuretic metolazone can be used in combination with a loop diuretic to
promote very effective diuresis.
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS
• Mixed preload & afterload properties + mild diuretic effects (aldosterone
inhibition). They are preferred over drugs like Digoxin.
• Choice of drug & dosing → efficient in systolic HF → initiate with short-
acting (captopril) switch to long acting.
• Monitor patient for hypotension, non-productive cough & hyperkalemia.
• Effect on renal function → improve renal function if Cardiac output is
increased.
• Monitor BP, BUN creatinine regularly.
• E.g. Captopril, Enalapril, Lisinopril.
ANGIOTENSIN-RECEPTOR BLOCKERS
• Improve exercise tolerance & EF.
• Dry cough is less but the effects of hypokalemia, BUN & creatinine are
equal to that of ACE-inhibitors.
• E.g. Candesartan, Valsartan, Losartan.
BETA-BLOCKERS
• Start with low initial dose followed by gradual increase after 1—2 weeks.
• Should be prescribed to patients with stable systolic HF.
• Transient bradycardia, fluid retention, hypotension & fatigue are common
during first 24—48hrs.
38

41. GM Hamad
• Carvedilol → a recently approved agent for HF. It has mixed alpha-blocker &
nonselective beta-blocker activity. Also has antioxidant effects. Start with
minimum dose & increase after 2 weeks.
• Metabolism → 2D6.
• Metoprolol.
• Propranolol → avoid in systolic HF. May be used in patients with diastolic HF
not responding to diuretics + ACE-inhibitors.
ALDOSTERONE ANTAGONISTS
• Spironolactone 25—50mg/day combined with loop-diuretics.
• Hyperkalemia → more prevalent with spironolactone when combined with
ACE-Is & aspirin.
• Hypokalemia treatment → K supplementation or K-sparing diuretics (until K
<3.5mEq/L) especially in patients taking Digoxin (average K intake 20—
60mEq/L /day). Chloride salt of K should be used.
DIGITALIS GLYCOSIDES
• Reduces symptoms of HF → combination of +ve ionotropic & other
neurohumoral actions.
CALCIUM CHANNEL BLOCKERS
• Systolic HF → Diltiazem & verapamil can increase serum digoxin levels and
have additive AV blocking effects.
• Amlodipine is safest in HF patients with concurrent angina.
• Diastolic HF → vVerapamil alternative to beta-blockers.
TREATMENT OF ACUTE DECOMPENSATED HEART FAILURE
• Acute decompensated heart failure (ADHF) involves patients with new or
worsening signs or symptoms (often resulting from volume overload and/or
low cardiac output) requiring medical intervention, such as emergency
department visit or hospitalization.
TREATMENT GOALS
• The overall goal is to relieve symptoms while optimizing volume status and
cardiac output so the patient can be discharged in a stable compensated
state on oral drug therapy.
39

42. GM Hamad
PHARMACOLOGICAL THERAPY
DIURETICS
• IV loop diuretics, including furosemide, bumetanide, and torsemide, are
used for ADHF, with furosemide being the most widely studied and used
agent.
VASODILATORS
• Venodilators reduce preload by increasing venous capacitance, improving
symptoms of pulmonary congestion in patients with high ventricular filling
pressures.
• Arterial vasodilators reduce afterload and cause a reflex increase in cardiac
output, which may promote diuresis via improved renal perfusion.
• Mixed vasodilators act on both arterial resistance and venous capacitance
vessels, reducing congestive symptoms while increasing cardiac output.
NITROGLYCERIN
• IV nitroglycerin is often preferred for preload reduction in ADHF, especially
in patients with pulmonary congestion.
• In higher doses, nitroglycerin displays potent coronary vasodilating
properties and beneficial effects on myocardial oxygen demand and supply,
making it the vasodilator of choice for patients with severe HF and ischemic
heart disease.
VASOPRESSIN ANTAGONISTS
• The vasopressin receptor antagonists currently available affect one or two
arginine vasopressin (AVP; antidiuretic hormone) receptors, V1A or V2.
• Stimulation of V1A receptors (located in vascular smooth muscle cells and
myocardium) results in vasoconstriction, myocyte hypertrophy, coronary
vasoconstriction, and positive inotropic effects. V2 receptors are located in
renal tubules, where they regulate water reabsorption.
• E.g. Tolvaptan, Conivaptan.
INOTROPES
• Low cardiac output in ADHF may worsen renal perfusion, resulting in
resistance to diuretic therapy. IV inotropes may improve peripheral
40

43. GM Hamad
hypoperfusion and diuresis by improving central hemodynamics. However,
because of their adverse effect profile they should generally be reserved for
patients not responding to other modalities or those with clear evidence of
low cardiac output.
MILRINONE
• Milrinone inhibits phosphodiesterase III and produces positive inotropic
and arterial and venous vasodilating effects (an inodilator).
• During IV administration, milrinone increases stroke volume and cardiac
output with minimal change in heart rate.
Unit II: Pulmonary unit (Asthma e.g. acute, chronic, status asthamaticus,
childhood asthma, Pneumonia, COPD includes emphysema & chronic
bronchitis)
ASTHMA
DEFINITION
“Asthma, as defined by the Global Initiative for Asthma (GINA), is a
heterogeneous disease, usually characterized by chronic airway
inflammation”
• It is defined by a history of respiratory symptoms such as wheezing,
shortness of breath, chest tightness, and cough that vary over time and in
intensity, together with variable expiratory airflow limitation.
PATHOPHYSIOLOGY
• Variable degree of airflow obstruction (related to bronchospasm, edema,
and hypersecretion), bronchial hyperresponsiveness (BHR) and airway
inflammation.
• Inhaled allergens cause an early-phase allergic reaction characterized by
activation of cells bearing allergen-specific immunoglobulin E (IgE)
antibodies.
41

44. GM Hamad
• There is rapid activation of airway mast cells and macrophages, which
release pro-inflammatory mediators such as histamine and eicosanoids that
induce contraction of airway smooth muscle, mucus secretion, vasodilation,
and exudation of plasma in the airways.
• Plasma protein leakage induces a thickened, engorged, edematous airway
wall and a narrowing of the airway lumen with reduced mucus clearance.
• Histamine and other mediators of inflammation are released from mast
cells, for example:
- leukotrienes, prostaglandins, bradykinin, adenosine and
prostaglandin generating factor of anaphylaxis, as well as various
chemotactic agents that attract eosinophils and neutrophils.
• Macrophages release prostaglandins, thromboxane and platelet-activating
factor (PAF). PAF appears to sustain bronchial hyperreactivity and cause
respiratory capillaries to leak plasma, which increases mucosal edema.
• PAF also facilitates the accumulation of eosinophils within the airways,
a characteristic pathological feature of asthma.
• Epithelial damage results and thick viscous mucus is produced that causes
further deterioration in lung function. Mucus transport is dependent on its
viscosity. If it is very thick, it plugs the airways, which also become blocked
with epithelial and inflammatory cell debris.
AUTONOMIC & NON-AUTONOMIC MECHANISM
• The airway is innervated by parasympathetic, sympathetic, and non-
adrenergic inhibitory nerves.
• Parasympathetic nerves result in release of Ach acting on bronchial M3-
muscarinic receptors → bronchoconstriction & increased mucus secretion.
• β2-receptors linked via cAMP → bronchodilatation.
• β2-receptors → no direct innervations but respond to circulating adrenaline
which stimulates bronchodilatation.
• In addition, the mucus glands contain β2-receptors → inhibit mucus
secretion.
• There is also limited number of sympathetic fibers which release nor-AD
acting on β2-receptors at parasympathetic ganglia to inhibit transmission.
42

45. GM Hamad
• Non-adrenergic Non-cholinergic (NANC) fibers → nitric oxide (NO) &
vasoactive intestinal polypeptide are inhibitory transmitters & substance-
P* is an excitatory transmitter.
• These sensory nerve fibers are thought to play a role in local reflex
responses to irritant stimuli.
CLINICAL PRESENTATION
• Persistent cough.
• Recurrent episodes of difficulty in breathing (dyspnea)
• Wheezing.
• Acute asthmatic attack requires hospitalization (peak flow rate <100L/min)
[pulse rate 110 beats/min]
• Low oxygen saturation (SpO2 < 92%) → patient become fatigued, cyanosed,
confused and lethargic.
• CO2 tension (PaCO2) is low in acute asthma.
• High PaCO2 level (hypercapnia) that does not diminish is a more severe
problem and indicates progression towards respiratory failure.
DIAGNOSIS
SPIROMETRY
• Assess lungs volume, air flow dynamics.
• Gives index about degree of obstruction & degree of reversibility.
FORCED VITAL CAPACITY (FVC)
• Total vol. of air expired.
• Normal adult value in males = 4—5L (age, gender & body weight
dependent).
FORCED EXPIRATORY VOLUME IN ONE SECOND (FEV1)
• The amount of air expired during the 1st
second.
• FEV1 value in adult male = 3.2—4L (80% of FVC)
• The FEV1 is usually expressed as a percentage of the total volume of air
exhaled, reported as the FEV1/FVC ratio.
• Asthma → FEV1 is usually decreased, the FVC normal or slightly reduced and
the FEV1/FVC ratio decreased, usually < 0.7 measured by spirometer.
43

46. GM Hamad
PEAK EXPIRATORY FLOW RATE (PEFR)
• Maximum flow rate that can be produced during forced expiration
following a deep breath to full inspiration.
• Normal PEFR = 550—700L/min (adults) 150—220L/min (children)
• The diagnosis of asthma can be confirmed by measuring the response to a
bronchodilator or by examining a patient‘s day-to-day variation in PEF
readings. A diurnal variability of 60L/min (or more than 20%) is highly
suggestive of asthma.
CATEGORIES OF ASTHMA
• On the basis of severity
- Mild intermittent
- Mild persistent
- Moderate persistent
- Severe persistent
1. MILD INTERMITTENT ASTHMA
• With mild intermittent asthma, the symptoms are mild. This
classification means you will have symptoms up to two days per week or
two nights per month. This asthma type will usually not hinder any of
your activities and can include exercise-induced asthma.
SYMPTOMS
• Wheezing or whistling when breathing
• Coughing
• Swollen airways
• Development of mucus in the airways
2. MILD PERSISTENT ASTHMA
• If you have mild persistent asthma, your symptoms are still mild but
occur more than twice per week. For this type classification, you do not
have symptoms more than once per day.
SYMPTOMS
• Wheezing or whistling when breathing
• Coughing
44

47. GM Hamad
• Swollen airways
• Development of mucus in the airways
• Chest tightness or pain
TREATMENT
• At this asthma level your doctor may prescribe a low-dose inhaled
corticosteroid medication. An inhaled corticosteroid is taken by quickly
inhaling it. It is usually taken daily.
3. MODERATE PERSISTENT ASTHMA
• With moderate persistent asthma you will have symptoms once each
day, or most days. You will also have symptoms at least one night each
week.
SYMPTOMS
• Wheezing or whistling when breathing
• Coughing
• Swollen airways
• Development of mucus in the airways
• Chest tightness or pain
TREATMENT
• Slightly high doses of inhaled corticosteroids. Allergy medication if triggered
by allergies. Oral corticosteroids may also be added for people aged 50 and
older. A rescue inhaler.
4. SEVERE PERSISTENT ASTHMA
• If you have severe persistent asthma, you will have symptoms several
times during the day. These symptoms will occur almost every day. You
will also have symptoms many nights each week.
• Severe persistent asthma does not respond well to medications even
when taken regularly.
SYMPTOMS
• Wheezing or whistling sound when breathing
• Coughing
45

48. GM Hamad
• Swollen airways
• Development of mucus in the airways
• Chest tightness or pain
TREATMENT
• The medications used will include:
- Inhaled corticosteroids — at a higher dose than with other asthma
types.
- Oral corticosteroids — at a higher dose than with other asthma
types.
- Rescue inhaler.
- Medications that will help combat the cause or trigger.
TREATMENT
TREATMENT GOALS
• The GINA long-term goals for asthma management include:
- Achieve good control of symptoms and maintain normal activity
levels.
- Minimize future risk of exacerbations, fixed airflow limitation, and
side effects. For acute severe asthma, the primary goal is prevention
of life-threatening asthma by early recognition of signs of
deterioration and early intervention.
NON-PHARMACOLOGIC THERAPY
• Patient education is mandatory to improve medication adherence, self-
management skills, and use of healthcare services.
• Avoidance of known allergenic triggers can improve symptoms, reduce
medication use, and decrease BHR. Environmental triggers (e.g. animals)
should be avoided in sensitive patients, and smokers should be encouraged
to quit.
• Dehydration should be corrected.
PHARMACOTHERAPY
BETA-ADRENOCEPTOR AGONISTS
Short-acting Beta-adrenoceptor agonists
46

49. GM Hamad
• First choice.
• Act on bronchial smooth muscle to increase cAMP → rapid bronchodilation
& reversal of bronchospasm in early phase.
• Prolong usage → receptor down-regulation → less effective.
• Concomitant use of corticosteroids may reduce receptor down-regulation.
• E.g. Salbutamol, terbutaline.
Long-acting Beta-adrenoceptor agonists
• Rate of onset is slow b/c of lipophilic nature the molecules retained near
receptor for prolonged period → action persists.
• They are not used to reverse an attack but cause prolonged
bronchodilation.
• More effective than xanthines or cromones.
• E.g. Formoterol, Salmeterol.
CORTICOSTEROIDS
• Anti-inflammatory action via activation of intracellular receptors → altered
gene transcription.
• Decreased cytokine production & synthesis of lipocortin → inhibits
production of PGs & leukotrienes.
• Oral fungal infections → local immunosuppression.
• Laryngeal myopathy → hoarseness & bone resorption with increased doses.
• E.g. Beclomethasone, Budeunoside, Fluticasone, Prednisolone (oral).
XANTHINES
• Bronchodilators but not as effective as beta-agonists.
• Given orally (I.V aminophylline occasionally)
• They are Phosphodiesterase III & IV inhibitors & potentiate cAMP by
preventing its breakdown → bronchodilation.
• Blockade of adenosine receptors → bronchial smooth muscle relaxation.
• Anti-inflammatory action → reduction in mediator release.
• Narrow therapeutic index, CNS side-effects & nausea limit the use of
xanthines.
• E.g. Aminophylline, Theophylline.
MUSCARINIC M-RECEPTOR ANTAGONISTS
47

50. GM Hamad
• Given by inhalation.
• Blocks parasympathetic-mediated bronchoconstriction.
• They are of little or no value in the treatment of asthma (recent reports)
• E.g. Ipratropium.
LEUKOTRIENE RECEPTOR ANTAGONISTS
• New class of orally active drugs which block Leukotriene receptors and also
will oppose the bronchoconstriction & inflammatory action of Leukotrienes.
• E.g. Montelukast, Zafirlukast.
MONOCLONAL ANTIBODIES
• It is a monoclonal antibody.
• Novel agent has a role in the treatment- resistant asthma.
• It has been raised against IgE.
• E.g. Omalizumab
CROMONES
• Prevent both early & late phases.
• Uncertain actions but may include a reduction in sensory nerve reflexes,
stabilization of mast cells & decrease in release of PAF & cytokines.
• Only beneficial in children from 5—12years.
• Effective in exercise induced asthma.
• E.g. Nedocromil sodium, Sodium Cromoglicate.
STEP WISE MANAGEMNET OF ASTHAMA
STEP 1: MILD INTERMITTENT ASTHMA
• Inhaled short-acting β-2 agonist as required
STEP 2: REGULAR PREVENTER THERAPY
• Add inhaled steroid 200–800 μcg/day*
• 400 μcg is an appropriate starting dose for many patients
• Start a dose of inhaled steroid appropriate to severity of disease
STEP 3: ADD-ON THERAPY
1. Add inhaled long acting β2 agonist (LABA)
48

51. GM Hamad
2. Assess control of asthma:
- Good response to LABA – continue LABA
- Benefit from LABA but control still inadequate – continue LABA and
increase inhaled steroid dose to 800 μcg/day* (if not already on this
dose)
- No response to LABA – stop LABA and increase inhaled steroid to 800
μcg/day*. If control still inadequate, institute trial of other therapies,
e.g. leukotriene receptor antagonist or SR theophylline.
STEP 4: PERSISTENT POOR CONTROL
• Consider trials of:
- Increasing inhaled steroid up to 2000 μcg/day*
- Addition of a fourth drug e.g. leukotriene receptor antagonist, SR
theophylline, β2 agonist tablet.
STEP 5: CONTINUOUS OR FREQUENT USE OF ORAL STEROIDS
• Use daily steroid tablet in lowest dose providing adequate control.
• Maintain high dose inhaled steroid at 2000 μcg/day*
• Consider other treatments to minimize the use of steroid tablets
• Refer patient for specialist care.
PNEUMONIA
INTRODUCTION
• Pneumonia is an infection in one or both lungs.
• Pneumonia causes inflammation in the alveoli.
• The alveoli are filled with fluid or pus, making it difficult to breathe.
DEFINITION
“Inflammation and consolidation of lung tissue due to an infectious agent”
• COSOLIDATION = ‘Inflammatory induration of a normally aerated lung due
to the presence of cellular exudative in alveoli.
49

52. GM Hamad
TYPES OF PNEUMONIA
COMMUNITY ACQUIRED (CAP)
• Pneumonia developing in patients with no contact to a medical facility.
HOSPITAL ACQUIRED (HAP)
• Pneumonia developing within 48 hours after hospital admission.
VENTILATOR ASSOCIATED (VAP)
• Pneumonia developing within 48 – 72 hours after intubation and
mechanical ventilation.
PATHOPHYSIOLOGY
• Microorganisms gain access to the lower respiratory tract by three routes:
they may be inhaled as aerosolized particles, they may enter the lung via
the bloodstream from an extrapulmonary site of infection, or aspiration of
oropharyngeal contents may occur.
• Lung infections with viruses suppress the bacterial clearing activity of the
lung by impairing alveolar macrophage function and mucociliary clearance,
thus setting the stage for secondary bacterial pneumonia.
• The most prominent pathogen causing community-acquired pneumonia in
otherwise healthy adults is S. pneumoniae. Other common bacterial causes
are H. influenza, the “atypical” pathogens including M. pneumoniae,
Legionella species, Chlamydophila pneumoniae, and a variety of viruses.
• Anaerobic bacteria are the most common etiologic agents in pneumonia
that follows the gross aspiration of gastric or oropharyngeal contents.
DIAGNOSIS
SPUTUM
• Gram Staining
• AFB
• Giemsa or methenamine silver stain
• KOH mount
• Culture
X RAY
• Homogenous opacity with air bronchogram.
50

53. GM Hamad
CT THORAX
• Seldom used.
INVESTIGATIONS
• Complete white blood count
• Blood Sugar
• Electrolytes
• Creatinine
• Blood culture
• Screening for retro (ICTC)
• Oxygen saturation by pulse
oximetry
• ABG
• USG Chest
• Mantoux
CLINICAL PRESENTATION
SIGNS AND SYMPTOMS
• Abrupt onset of fever, chills, dyspnea, and productive cough.
• Rust-colored sputum or hemoptysis.
• Pleuritic chest pain.
PHYSICAL EXAMINATION
• Tachypnea and tachycardia.
• Dullness to percussion.
• Increased tactile fremitus, whisper pectoriloquy, and egophony.
• Chest wall retractions and grunting respirations.
• Diminished breath sounds over affected area.
• Inspiratory crackles during lung expansion.
CHEST RADIOGRAPH
• Dense lobar or segmental infiltrate.
LABORATORY TESTS
• Leukocytosis with predominance of polymorphonuclear cells.
• Low oxygen saturation on arterial blood gas or pulse oximetry.
TREATMENT
OUTPATIENTS TREATMENT (EMPIRICAL)
• Previously healthy and no antibiotics in past 3 months:
- A macrolide (clarithromycin or azithromycin) or Doxycycline.
• Comorbidities or antibiotics in past 3 months:
51

54. GM Hamad
- Respiratory fluoroquinolone (moxifloxacin, levofloxacin) or β-lactam
(high-dose amoxicillin or amoxicillin/clavulanate).
INPATIENTS
NON-ICU
• A respiratory fluoroquinolone (moxifloxacin, levofloxacin)
• β -lactam (cefotaxime, ceftriaxone, ampicillin) plus a macrolide (oral
clarithromycin or azithromycin)
ICU
• β-lactam plus Azithromycin or a fluoroquinolone.
PSEUDOMONAS
• An antipneumococcal, antipseudomonal β-lactam (piperacillin/tazobactam,
cefepime, imipenem, meropenem) plus fluoroquinolones.
• Above β-lactams plus an aminoglycoside and azithromycin.
• Above β-lactams plus an aminoglycoside plus an antipneumococcal
fluoroquinolone.
METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS
• If MRSA, add linezolid or vancomycin.
COMPLICATIONS
• Lung abscess
• Para-pneumonic effusions
• Empyema
• Sepsis
• ARDS, Respiratory failure
• Circulatory failure
• Renal failure
• Multi-organ failure
• Metastatic infections (meningitis, endocarditis, arthritis)
COURSE
• Most healthy people recover from pneumonia in one to three weeks, but
pneumonia can be life-threatening.
52

55. GM Hamad
• The mortality rate associated with community-acquired pneumonia (CAP) is
very low in most ambulatory patients and higher in patients requiring
hospitalization, being as high as 37 percent in patients admitted to the
intensive care unit (ICU).
CHRONIC OBSTRUCTIVE PULMONARY
DISEASE
DEFINITION
“Chronic obstructive pulmonary disease (COPD) is characterized by progressive
airflow limitation that is not fully reversible”
• Two principal conditions include:
CHRONIC BRONCHITIS
• Chronic or recurrent excess mucus secretion with cough that occurs on
most days for at least 3 months of the year for at least 2 consecutive years.
EMPHYSEMA
• Abnormal, permanent enlargement of the airspaces distal to the terminal
bronchioles, accompanied by destruction of their walls, without fibrosis.
PATHOPHYSIOLOGY
AIRWAYS
• Chronic inflammation.
• Increased numbers of goblet cells.
• Mucus gland hyperplasia.
• Fibrosis.
• Narrowing and reduction in the number of small airways.
• Airway collapse due to the loss of tethering caused by alveolar
wall destruction in emphysema.
53

56. GM Hamad
LUNG PARENCHYMA
• Emphysema affects the structures distal to the
terminal bronchiole, consisting of the respiratory
bronchiole, alveolar ducts, alveolar sacs, and
alveoli, known collectively as the acinus.
SUBTYPES OF EMPHYSEMA
Centrilobular emphysema (Proximal acinar)
• Abnormal dilation or destruction of the respiratory
bronchiole, the central portion of the acinus.
• It is commonly associated with cigarette smoking.
Panacinar emphysema
• Refers to enlargement or destruction of all parts of the
acinus.
• Seen in alpha-1 antitrypsin deficiency and in smokers.
Paraseptal emphysema
• Distal acinar - the alveolar ducts are predominantly
affected.
PULMONARY VASCULATURE
• Intimal hyperplasia and smooth muscle hypertrophy or hyperplasia thought
to be due to chronic hypoxic vasoconstriction of the small pulmonary
arteries.
• Destruction of alveoli due to emphysema can lead to loss of the associated
areas of the pulmonary capillary bed and pruning of the distal vasculature.
CLINICAL PRESENTATION
SYMPTOMS OF COPD
• The characteristic symptoms of COPD are chronic and progressive dyspnea,
cough, and sputum production that can be variable from day-to-day.
• Dyspnea: Progressive, persistent and characteristically worse with exercise.
• Chronic cough: May be intermittent and may be unproductive.
• Chronic sputum production: COPD patients commonly cough up sputum.
Normal Acinus
54

57. GM Hamad
OTHER CLINICAL FEATURES
• Wheezing.
• Chest tightness.
• Weight loss.
• Respiratory infections.
PHYSICAL EXAMINATION
• Physical examination is normal in most patients
in milder stages. When airflow limitation
becomes severe, patients may have cyanosis of
mucosal membranes, development of a “barrel
chest” due to hyperinflation of the lungs,
increased resting respiratory rate, shallow
breathing, pursing of lips during expiration, and
use of accessory respiratory muscles.
DIAGNOSIS
• Diagnosis is based in part on patient symptoms and history of exposure to
risk factors such as tobacco smoke and occupational substances.
• Classification of disease severity is based on assessment of airflow
limitation by spirometry, measurement of symptom severity, and
assessment of exacerbation frequency.
SPIROMETRY
• The presence of airflow limitation should be confirmed with spirometry.
The forced expiratory volume after 1 second (FEV1) is reduced except in
very mild disease. The forced vital capacity (FVC) may also be decreased.
The hallmark of COPD is reduced FEV1: FVC ratio to less than 70%.
CHEST X-RAY-CHRONIC BRONCHITIS
• No apparent abnormality or thickened and increased lung markings are
noted.
CHEST X-RAY EMPHYSEMA
• Marked over inflation is noted with flattened and low diaphragm.
• Intercostal space becomes widen.
• A horizontal pattern of ribs.
55

58. GM Hamad
• A long thin heart shadow.
• Decreased markings of lung peripheral vessels.
CT (COMPUTED TOMOGRAPHY)
• Greater sensitivity and specificity for emphysema.
• For evaluation of bullous disease.
LABORTORY EXAMINATION
BLOOD EXAMINATION
• In exacerbation or acute infection in airway, leukocytosis may be detected.
SPUTUM EXAMINATION
• Streptococcus pneumonia.
• Hemophilus influenzae.
• Moraxella catarrhalis.
• Klebsiella pneumonia.
ARTERIAL BLOOD GAS MEASUREMENT
• Significant changes in arterial blood gases (ABG) are not usually present
until FEV1 is less than 1 L. At this stage, hypoxemia and hypercapnia may
become chronic. Hypoxemia usually occurs initially with exertion but
develops at rest as the disease progresses.
• PaO2 < 8.0 kPa with or without PaCO2 > 6.7 kPa when breathing room air
indicates respiratory failure.
TREATMENT
TREATMENT GOALS
• Prevention of further progress of disease.
• Preservation and enhancement of pulmonary functional capacity.
• Avoidance of exacerbations in order to improve the quality of life.
PHARMACOTHERAPY
BRONCHODILATORS
• Bronchodilators are central to the symptomatic management of COPD.
• Improve emptying of the lungs, reduce dynamic hyperinflation and improve
exercise performance.
56

59. GM Hamad
• Three major classes of bronchodilators:
B2 - agonists
• Short acting: Salbutamol & terbutaline.
• Long acting: Salmeterol & formoterol.
Anticholinergic agents
• Ipratropium, tiotropium.
Theophylline
• A weak bronchodilator, which may have some anti-inflammatory
properties.
GLUCOCORTICOIDS
• Regular treatment with inhaled glucocorticoids is appropriate for
symptomatic patients with an FEV1 < 50% predicted and repeated
exacerbations.
• Chronic treatment with systemic glucocorticoids should be avoided because
of an unfavorable benefit-to-risk ratio.
COMBINATION THERAPY
• Combination therapy of long acting ß2-agonists and inhaled corticosteroids
show a significant additional effect on pulmonary function and a reduction
in symptoms.
• Mainly in patients with an FEV1 < 50% predicted.
PHOSPHODIESTERASE INHIBITORS
• Roflumilast (Daliresp) is a phosphodiesterase 4 (PDE4) indicated to reduce
risk of exacerbations in patients with severe COPD associated with chronic
bronchitis and a history of exacerbations.
OTHER PHARMACOLOGIC TREATMENTS
• Influenza vaccines can reduce serious illness. Pneumococcal
polysaccharide vaccine is recommended for COPD patients 65 years and
older and for COPD patients younger than age 65 with an FEV1 < 40%
predicted.
57

60. GM Hamad
• The use of antibiotics, other than for treating infectious exacerbations of
COPD and other bacterial infections, is currently not indicated.
OXYGEN THERAPY
• Oxygen → 15 h/d.
• Long-term oxygen therapy (LTOT) improves survival, exercise, sleep and
cognitive performance in patients with respiratory failure.
• The therapeutic goal is to maintain SaO2 ≥ 90% and PaO2 ≥ 60mmHg at sea
level and rest.
OTHER TREATMENTS
• Pulmonary rehabilitation.
• Nutrition.
• Surgery:
- Bullectomy.
- Lung volume reduction surgery.
- Lung transplantation.
COMPLICATIONS
• Pneumothorax.
• Cor pulmonale.
• Exacerbations of COPD.
• Respiratory failure.
COPD COMORBIDITIES
• COPD patients are at increased risk for:
- Cardiovascular diseases.
- Osteoporosis.
- Respiratory infections.
- Anxiety and Depression.
- Diabetes.
- Lung cancer.
- Bronchiectasis.
• These comorbid conditions may influence mortality and hospitalizations
and should be looked for routinely and treated appropriately.
58

61. GM Hamad
Unit III: Gastroenterology unit (Ulcer, Liver cirrhosis, Portal
hypertension, Hepatitis, Diarrhea, Inflammatory bowel disease (IBD)
ULCER
DEFINITION
“An ulcer is localized erosion in stomach or duodenum”
OR
“A break in superficial epithelial cells penetrating down to muscularis mucosa”
DUODENAL VS GASTRIC ULCERS
Duodenal Gastric
Incidence More common Less common
Anatomy
First part of duodenum –
anterior wall
Lesser curvature of stomach
Duration Acute or chronic Chronic
Malignancy Rare Benign or malignant
CAUSES OF PEPTIC ULCER
• H. Pylori
• NSAIDs
• Smoking
• Alcohol
• Radiation therapy
• Stomach cancers
PATHOPHYSIOLOGY
There are two common forms of peptic ulcer disease: those associated with the
organism H. pylori and those associated with the use of aspirin and NSAIDs. Less
common is ulcer disease associated with massive hypersecretion of acid which
occurs in the rare gastrinoma (Zollinger–Ellison) syndrome.
59

62. GM Hamad
HELICOBACTER PYLORI
• Urease producing, gram negative bacillus, colonize in stomach.
• Weakens the protective mucous coating of stomach and duodenum thus
allowing the acid to pass through sensitive lining.
• H. Pylori is able to survive in stomach acid because it secretes enzymes that
neutralize acid.
INFECTS MUCOSA OF STOMACH
• H. Pylori converts urea into carbon dioxide and ammonia.
• Ammonia is alkaline so it neutralizes the acidity. Therefore, H. Pylori is able
to move down to the cells of stomach with the help of flagella.
• Once in contact with epithelial cells, H. Pylori adheres using
lipopolysaccharide.
• Then it secretes Cag A (cytotoxin-associated gene A) proteins and
vacuolating cytotoxins, such as Vac A.
• Cag A disrupts cell integrity and also stimulates production of interleukin 8
which attracts neutrophils towards stomach area, which produces
inflammation. (Inflammation causes more secretion of Hcl)
• Vac A causes apoptosis of stomach cells.
• Combination of Cag A and Vac A produces ulcer.
NSAIDs
• NSAIDs inhibit the enzymes Cyclooxygenase (which is involved in the
synthesis of inflammatory prostaglandins)
• This reduces the prostaglandins over long period of time.
• Normally, Prostaglandins gets secreted into stomach and duodenum where
they stimulate mucus and bicarbonate secretion, which promotes growth
of new epithelial cells of gastric lining.
• Reduced prostaglandins lead to gastric mucosa susceptible to damage and
ulcer.
PROTECTIVES FOR ULCER
• Prostaglandins
• Mucus
• Bicarbonate
• Mucosal blood flow
• Epidermal growth factor &
transforming growth factor.
AGGRESSIVE FOR ULCER
• Acid
• Pepsin
60

63. GM Hamad
• NSAIDs • Helicobacter Pylori
CLINICAL PRESENTATION
• Abdominal pain is the most frequent PUD symptom. Pain is often epigastric
and described as burning but can present as vague discomfort, abdominal
fullness, or cramping. Nocturnal pain may awaken patients from sleep,
especially between 12 am – 3 am.
• Pain from duodenal ulcers often occurs 1 to 3 hours after meals and is
usually relieved by food, whereas food may precipitate or accentuate ulcer
pain in gastric ulcers. Antacids provide rapid pain relief in most ulcer
patients.
• Heartburn, belching, and bloating often accompany pain. Nausea, vomiting,
and anorexia are more common in gastric than duodenal ulcers and may be
signs of an ulcer-related complication.
• Severity of symptoms varies among patients and may be seasonal,
occurring more frequently in spring or fall.
• Presence or absence of epigastric pain does not define an ulcer. Ulcer
healing does not necessarily render the patient asymptomatic. Conversely,
absence of pain does not preclude an ulcer diagnosis, especially in the
elderly who may present with a “silent” ulcer complication.
• Ulcer complications include upper GI bleeding, perforation into the
peritoneal cavity, penetration into an adjacent structure (e.g. pancreas,
biliary tract, or liver), and gastric outlet obstruction. Bleeding may be occult
or present as melena or hematemesis.
• Perforation is associated with sudden, sharp, severe pain, beginning first in
the epigastrium but quickly spreading over the entire abdomen. Symptoms
of gastric outlet obstruction typically occur over several months and include
early satiety, bloating, anorexia, nausea, vomiting, and weight loss.
DIAGNOSIS
• Physical examination may reveal epigastric tenderness between the
umbilicus and the xiphoid process that less commonly radiates to the back.
• Routine blood tests are not helpful in establishing a diagnosis of PUD.
Hematocrit, hemoglobin, and stool guaiac tests are used to detect bleeding.
61

64. GM Hamad
• Diagnosis of PUD depends on visualizing the ulcer crater either by upper GI
radiography or endoscopy. Endoscopy is preferred because it provides a
more accurate diagnosis and permits direct visualization of the ulcer.
• Diagnosis of H. pylori infection can be made using endoscopic or non-
endoscopic (urea breath test [UBT], serologic antibody detection, and fecal
antigen) tests.
• Testing for HP is only recommended if eradication therapy is planned. If
endoscopy is not planned, serologic antibody testing is reasonable to
determine HP status. The UBT and fecal antigen tests are the preferred non
endoscopic methods to verify HP eradication but must be delayed at least 4
weeks after completion of treatment to avoid confusing bacterial
suppression with eradication.
DIFFERENTIAL DIAGNOSES FOR EPIGASTRIC PAIN
SURGICAL
• Biliary colic, acute cholecystitis.
• Pancreatitis.
• Perforation of viscus.
• Acute appendicitis.
• Malignancy.
MEDICAL
• GORD
• MI
• PE
• Pneumonia
SYMPTOMS OF PUD
• Asymptomatic.
• Epigastric pain.
• Nausea.
• Oral flatulence, bloating, distension and intolerance of fatty food.
• Heartburn.
• Pain radiating to the back.
ALARMING SIGNS FOR EPIGASTRIC PAIN
• Chronic GI bleeding.
• Iron-deficiency anemia.
• Progressive unintentional weight loss.
• Progressive dysphagia.
• Persistent vomiting.
• Epigastric mass.
62

65. GM Hamad
• Patients aged 55 years and older with unexplained and persistent recent-
onset dyspepsia alone.
INVESTIGATIONS
H. PYLORI TESTING
• C-urea breath tests.
• Stool antigen tests.
• Serology.
• Endoscopy with biopsy.
C-Urea Breath Test
• Swallow urea labelled with uncommon isotope either carbon14
or carbon13
• In 10 – 30 mins, detection of isotope labelled carbon dioxide in exhaled
breath indicates that urea was split, thus, indicating urease is present in
stomach, hence H. Pylori bacteria present.
NSAIDs TESTING
• Stool antigen tests.
• Serology.
• C-urea breath tests.
- Only +ve for H. Pylori.
• Endoscopy with biopsy.
- If -ve for H. Pylori, then it is further investigated for NSAIDs.
TREATMENT
TREATMENT GOALS
• Overall goals are to relieve ulcer pain, heal the ulcer, prevent ulcer
recurrence, and reduce ulcer-related complications.
• In H. pylori-positive patients with an active ulcer, previously documented
ulcer, or history of an ulcer related complication, goals are to eradicate H.
pylori, heal the ulcer, and cure the disease with a cost-effective drug
regimen.
• The primary goal for a patient with an NSAID-induced ulcer is to heal the
ulcer as rapidly as possible.
63

66. GM Hamad
NONPHARMACOLOGIC TREATMENT
• Patients with PUD should eliminate or reduce psychological stress, cigarette
smoking, and use of NSAIDs (including aspirin). If possible, alternative
agents such as acetaminophen or a nonacetylated salicylate (e.g. salsalate)
should be used for pain relief.
• Although there is no need for a special diet, patients should avoid foods
and beverages that cause dyspepsia or exacerbate ulcer symptoms (e.g.
spicy foods, caffeine, and alcohol).
• Elective surgery is rarely performed because of highly effective medical
management.
• Emergency surgery may be required for bleeding, perforation, or
obstruction.
PHARMACOLOGIC TREATMENT
FOR H. PYLORI
Currently 8 H. Pylori Treatment Regimens have been approved by FDA
1. Omeprazole 40 mg QD + clarithromycin 500 mg TID x 2 weeks, then
omeprazole 20 mg QD x 2 weeks.
2. Ranitidine bismuth citrate (RBC) 400 mg BID + clarithromycin 500 mg TID x 2
weeks, then RBC 400 mg BID x 2 weeks.
3. Bismuth subsalicylate (Pepto Bismol®) 525 mg QID + metronidazole 250 mg
QID + tetracycline 500 mg QID* x 2 weeks + H2 receptor antagonist therapy
as directed x 4 weeks.
4. Lansoprazole 30 mg BID + amoxicillin 1 g BID + clarithromycin 500 mg TID x
10 days.
5. Lansoprazole 30 mg TID + amoxicillin 1 g TID x 2 weeks**
6. Ranitidine bismuth citrate 400 mg BID + clarithromycin 500 mg BID x 2
weeks, then RBC 400 mg BID x 2 weeks.
7. Omeprazole 20 mg BID + clarithromycin 500 mg BID + amoxicillin 1 g BID x
10 days (Triple Therapy)
8. Lansoprazole 30 mg BID + clarithromycin 500 mg BID + amoxicillin 1 g BID x
10 days.
FOR NSAIDs
64

67. GM Hamad
• NSAID-associated ulcers may be H. pylori positive. Although the presence of
H. pylori may enhance the efficacy of acid suppression, eradication is
generally recommended in infected patients with NSAID-associated ulcers
as it is difficult to differentiate between H. Pylori or NSAID as the cause of
the ulcer.
• If NSAIDs are discontinued, most uncomplicated ulcers heal using standard
doses of a PPI, H2-receptor antagonist, misoprostol or sucralfate.
PATIENT CARE
PATIENT EDUCATION AND COUNSELING
• It does not help to eat more often or increase the amount of milk and dairy
products you consume. These changes may even cause more stomach acid.
• Avoid foods and drinks that cause discomfort for you. For many people
these include alcohol, coffee, caffeinated soda, fatty foods, chocolate, and
spicy foods. Avoid eating late night snacks.
• Other things you can do to ease your symptoms and help healing include:
- If you smoke or chew tobacco, try to quit. Tobacco will slow the
healing of your ulcer and increase the chance that the ulcer will come
back.
- Try to reduce your stress level and learn ways to better manage
stress.
- Avoid drugs such as aspirin, ibuprofen, or naproxen. Take
acetaminophen to relieve pain. Take all medicines with plenty of
water.
SUMMARY
• A peptic ulcer is a break in superficial epithelial cells penetrating down to
muscularis mucosa.
• Duodenal > gastric ulcers.
• Can be asymptomatic.
• H. Pylori is a predominant risk factor.
• H. Pylori diagnosed by c-urea breath test, stool antigen or if validated
serology, treated with PAC500 or PMC250 regime.
• Complications of PUD can lead to acute emergency of upper GI bleed.
65

68. GM Hamad
LIVER CIRRHOSIS
INTRODUCTION
• Consequence of chronic liver disease characterized by replacement of liver
tissue by fibrosis, scar tissue and regenerative nodules leading to
progressive loss of liver function.
“Pathological condition with the development of fibrosis to the point that there
is architectural distortion with formation of regenerative nodules”
• Due to chronic scarring and damage liver becomes fibrotic which is not
reversible that is why it is referred as cirrhosis “End stage”
• Cirrhosis is characterized histologically by regenerative nodules surrounded
by fibrous tissue.
TYPES
• Clinically two types:
1. COMPENSATED
- Early symptoms, some fibrosis, liver functions.
2. DECOMPENSATED
- Late symptoms, liver stops functioning.
PATHOPHYSIOLOGY
• Irreversible chronic injury of the hepatic parenchyma.
• Extensive fibrosis - distortion of the hepatic architecture.
• Formation of regenerative nodules.
CLINICAL PRESENTATION
• Testicular atrophy
• Jaundice
• Hepatomegaly
• Splenomegaly
• Xanthoma
• Parotid gland enlargement (salivary glands)
66

69. GM Hamad
• Spider angiomas
- Spider angiomas is a type of telangiectasis (swollen blood vessels)
found slightly beneath the skin surface, often containing a central red
spot and reddish extensions which radiate outwards like a spider's
web.
• Palmar erythema
- Palms become red and swollen.
• Gynecomastia
- Increase in breast.
• Nail changes
- Muehrcke's nails.
- Terry’s nails.
• Fetor hepaticus
- A condition seen in portal hypertension where portosystemic
shunting allows thiols to pass directly into the lungs.
• Asterixis
- A tremor of the hand when the wrist is extended.
• Pigment gallstones
- Pigment gallstones of bilirubin and calcium salts.
• Cruveilhier-Baumgarten murmur
- There are prominent umbilical and paraumbilical
veins; auscultation over these vessels may reveal
a humming sound.
• Caput medusa
- Also known as palm tree sign, is the appearance
of distended and engorged superficial epigastric
veins, which are seen radiating from the
umbilicus across the abdomen.
DIAGNOSIS
• LIVER FUNCTION TESTS (LFTS)
- The enzyme tests.
- Tests of synthetic function.
67

70. GM Hamad
• RADIOLOGIC MODALITIES
- Can occasionally suggest the presence of cirrhosis, they are not
adequately sensitive or specific for use as a primary diagnostic
modality.
- Major utility of radiography in the evaluation of the cirrhotic patient
is in its ability to detect complications of cirrhosis.
• LIVER BIOPSY
- Obtained by either a percutaneous, trans-jugular, laparoscopic, or
radiographically guided fine-needle approach.
- Sensitivity of a liver biopsy for cirrhosis is in the range of 80 to 100
percent depending upon the method used, and the size and number
of specimens obtained.
- Liver biopsy is not necessary if the clinical, laboratory, and radiologic
data strongly suggest the presence of cirrhosis.
- Liver biopsy can reveal the underlying cause of cirrhosis.
• MORPHOLOGIC CLASSIFICATION
MICRONODULAR CIRRHOSIS
• Uniform, small nodules up to 3 mm in diameter.
• Often caused by alcohol damage, hemochromatosis, cholestatic causes of
cirrhosis.
MACRONODULAR CIRRHOSIS
• Nodules larger than 3 mm.
• Believed to be secondary to chronic viral hepatitis.
CAUSES AND TREATMENTS
1. ALCOHOLIC CIRRHOSIS
DIAGNOSIS
• Clinical features + physical examination findings + laboratory studies.
• Liver biopsy, ultrasonography, CT.
CLINICAL FEATURES
68