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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5353_Библиотеки_им_академика_М_И_Перельмана.pdf
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- •Acknowledgements
- •Contents at a glance
- •Contents in full
- •Abbreviations
- •Clinical clerking abbreviations
- •2.1 Agonists and antagonists: drugs acting at receptors
- •1.2 So, what is pharmacology?
- •1.3 How to use this book
- •1.4 Comment for instructors
- •1.5 Online Resource Centre
- •2.2 How receptor activation changes cells
- •2.3 Ion channels as drug targets
- •2.4 Enzymes as drug targets
- •2.5 Transporter proteins as drug targets
- •3.1 The core principles of pharmacokinetics: ADME
- •3.2 Drug elimination: clearance
- •3.3 Volume of distribution
- •3.4 Half-life of a drug
- •3.5 Absorption and bioavailability
- •4.2 Drugs used in the treatment of thromboembolic disorders
- •WORKBOOK 1
- •5.1 The physiological control of arterial blood pressure
- •5.2 Antihypertensive drugs
- •5.3 Strategies for the drug treatment of hypertension
- •WORKBOOK 2
- •6.2 Atherosclerosis
- •6.3 Preventing atherosclerosis: lipid-lowering drugs
- •6.4 Ischaemic heart disease: angina
- •6.5 Ischaemic heart disease: myocardial infarction (MI)
- •WORKBOOK 3
- •7.1 Arrhythmias
- •7.2 Anti-arrhythmic drugs
- •7.4 Chronic heart failure
- •7.5 Drugs used in heart failure
- •WORKBOOK 4
- •8.1 Structure and physiology of the skin
- •8.2 Medication for topical application to the skin
- •8.3 Eczema/dermatitis
- •8.4 Treatment of dermatitis
- •8.5 Psoriasis
- •8.6 Treatment of psoriasis
- •8.7 Acne
- •8.8 Drug treatment of acne
- •8.9 Other dermatological conditions
- •WORKBOOK 5
- •9.1 What is rheumatoid arthritis?
- •9.2 Treatment of rheumatoid arthritis
- •9.4 Disease-modifying anti-rheumatic drugs (DMARDs)
- •9.5 Cytokine blockers: biological DMARDs
- •9.6 Choice of treatment for rheumatoid arthritis
- •WORKBOOK 6
- •10.1 Allergic rhinitis
- •10.2 Treatment of allergic rhinitis
- •10.3 Urticaria
- •10.4 Treatment and management of urticaria
- •WORKBOOK 7
- •11.1 Organization of the respiratory system
- •11.2 Common airway diseases: asthma and chronic obstructive pulmonary disease (COPD)
- •11.3 Asthma
- •11.4 Treating asthma
- •11.5 Chronic obstructive pulmonary disease (COPD)
- •WORKBOOK 8
- •12.1 Structure of the gastrointestinal wall
- •12.2 The stomach
- •12.3 Disorders of the upper gastrointestinal tract
- •12.5 Nausea and vomiting
- •12.6 Antiemetic therapy
- •WORKBOOK 9
- •13.1 The lower gastrointestinal tract
- •13.2 Diarrhoea
- •13.3 Constipation
- •13.4 Irritable bowel syndrome
- •WORKBOOK 10
- •14.1 Control of blood glucose levels
- •14.2 Diabetes mellitus
- •14.3 Complications of diabetes
- •14.4 Diagnosis of diabetes
- •14.5 Drug treatment of diabetes mellitus
- •14.6 Management of diabetes
- •14.7 Obesity
- •14.8 Management of obesity
- •WORKBOOK 11
- •15.1 The thyroid gland
- •15.2 Thyroid dysfunction
- •15.3 Contraception
- •15.4 Pharmacological methods of contraception
- •WORKBOOK 12
- •16.2 The biological basis of epilepsy: brakes and accelerators
- •16.3 Three mechanisms in the drug treatment of epilepsy
- •16.4 Drugs used in the treatment of epilepsy
- •16.5 Strategy and side effects in the drug treatment of epilepsy
- •WORKBOOK 13
- •17.1 Symptoms and diagnosis of Parkinson’s disease
- •17.2 Neurodegeneration: selective death of brain neurons
- •17.3 Drug treatment of Parkinson’s disease
- •17.4 Symptoms and diagnosis of Alzheimer’s disease: a brief comment
- •17.5 Drug treatment of Alzheimer’s disease
- •WORKBOOK 14
- •18.2 Drugs in clinical use for the treatment of schizophrenia
- •18.1 What is schizophrenia? Symptoms, diagnosis, and causes
- •WORKBOOK 15
- •19.1 Depression

WORKBOOK 4
Arrhythmias and chronic heart failure
Den, a serial heart disease patient: first, ischaemic heart
The patient: a simplified case history
Eoin, Sunita’s fiancé, is driving her and her parents to Heathrow for their flight to Singapore.
They are all very excited, for three good reasons: for all of them (except Eoin) it will be their first
transatlantic flight; in 10 days’ time Eoin will be competing in a Formula 1 championship race,
and 4 days after that, he and Sunita will be getting married. Being a racing driver, Eoin likes to
travel fast. Urged on by Sunita’s dad Den, Eoin steadily increases speed, ignoring the pleas of
Sunita and her mum to slow down.
But, unnoticed by Eoin, a police car has been following them for several miles. It flashes Eoin;
he pulls over and is berated by the female police officer. As she starts writing out a ticket, her
partner notices that Den, who tries to protest, appears to be struggling to breathe.
Sunita tells the police officers that her father has a heart condition, and insists that they call an
ambulance.
At the hospital, Den can just about manage to answer the doctor’s questions.
A table of clinical clerking abbreviations is given on page xviii.
CLINICAL CLERKING FOR DEN BURTS
Age: 65 years
Weight: 72 kg
PC: Shortness of breath and dizziness
HPC: Shortness of breath while trying to convince police officer not to issue speeding ticket to
daughter’s fiancé
PMH:
1) Hypertension for 20 years
2) Ischaemic heart disease for 10 years
3) Chronic heart failure for 5 years

WORKBOOK 4 Arrhythmias and chronic heart failure 163
Note: Chronic heart failure is also commonly referred to as congestive heart failure, due to the
congestion in the circulation.
Den suffers from chronic heart failure; his heart is unable to pump sufficiently well to maintain
adequate output. The ischaemic heart disease and hypertension that he also suffers from are both
major risk factors for chronic heart failure. (Hypertension itself increases the likelihood of
developing ischaemic heart disease.)
SH: Retired and lives with his wife and two daughters.
DH:
1) Furosemide (also called frusemide)
2) Bendroflumethiazide
3) Lisinopril.
Furosemide: Loop diuretic, to reduce preload and fluid retention (oedema) caused by chronic heart
failure (see below).
Bendroflumethiazide: Thiazide diuretic, to reduce preload, and antihypertensive.
Lisinopril: ACE inhibitor, to reduce cardiac workload in chronic heart failure. Also an
antihypertensive drug.
O/Q:
Den admits that for 2 weeks he has been experiencing the following.
1) Dyspnoea—shortness of breath; happens mostly on exertion
2) Orthopnoea—shortness of breath on lying down; he needs to elevate his head with several pillows
when sleeping
In chronic heart failure, pulmonary blood pressure increases as a result of the failure of the left
ventricle to pump enough blood. The excess blood ‘backs up’ in the pulmonary circulation, and the
increase in pressure forces fluid into the interstitial spaces of the lungs, or into the alveoli
themselves. During the day, the extra fluid accumulates in the ankles and feet, but on lying down it
redistributes to the lungs, leading to orthopnoea.
O/E:
1) Blood pressure = 140/85 mmHg (reference: <140/90 mmHg)
His blood pressure is not elevated.
2) Pulse = 130/minute and irregular (normal: 60/minute)
His pulse is extremely elevated, and the time between each beat varies irregularly (conventionally
described as irregularly irregular).
Biochemistry:
1) Sodium 140 mmol/l (normal: 135–145 mmol/l)
2) Potassium 3.5 mmol/l (normal: 3.5–5.5 mmol/l)
These are both within the recommended range.

164 Chapter 7 Arrhythmias and chronic heart failure
Investigations:
1) Electrocardiogram
• Irregularly irregular QRS complexes
• Absent P waves
An electrocardiogram (ECG) measures the electrical activity within the heart and detects
abnormalities in conduction as seen, for instance, after a myocardial infarction or with on-going
arrhythmias. The P wave on an ECG represents depolarization of the atria. An absence of P waves,
together with irregularly irregular intervals between QRS complexes, are the hallmarks of atrial
fibrillation (AF).
2) Chest X-ray
• Enlarged heart
A chest X-ray can be used to confirm chronic heart failure, and to determine if it has worsened. It
may also exclude other causes of shortness of breath, e.g. chest infection.
3) Echocardiogram
• Left ventricular ejection fraction (LVEF) = 35% (Reduced; normal LVEF is ~50%)
LVEF is the volume of blood ejected by the left ventricle in one beat, as a fraction of that held at the
end of the filling phase (end-diastolic volume). It is used to gauge the severity of heart failure. It can
be estimated from a two-dimensional echocardiographic image of the heart, which uses sound
waves to visualize and measure ventricular wall thickness, chamber size, valve function, and
pericardial thickness. The LVEF can be estimated from changes in the ventricle size between diastole
and systole.
Diagnosis: Atrial fibrillation (with continuing heart failure)
Plan: Admit and commence:
• digoxin (oral loading dose 500 micrograms, with further dose 12 hours later)
• furosemide infusion (also called frusemide).
Obtain chest X-ray and echocardiogram results from previous admission, and compare with current
results to determine the rate of deterioration of heart failure.
The doctor explains to Den that he is suffering from atrial fibrillation, a type of arrhythmia.
PART 1: EXPLORING DEN’S ARRHYTHMIA
1a) What is the meaning of the term arrhythmia?
1b) What is the meaning of the term dysrhythmia?
Den listens as the doctor and nurse discuss his ECG. He learns that the ECG is the recording
from the pads attached to his chest and his legs.
2a) Carefully draw a typical normal ECG recording, illustrating the P, QRS, and T waves (see Box 7.1).
2b) What do P waves correspond to?

WORKBOOK 4 Arrhythmias and chronic heart failure 165
The nurse and doctor also talk about the QRS complexes being irregularly irregular.
2c) What does the QRS complex correspond to?
They continue talking about different arrhythmias, and although Sunita, who is a pharmacist,
evidently understands what they are talking about, her parents and Eoin do not
understandaword.
3a) Define atrial fibrillation (AF).
3b) Name two other types of arrhythmia.
3c) What are the three main subtypes of AF, and what are their characteristic features?
Den has heard about arrhythmias causing sudden death and becomes extremely anxious.
4a) How might the doctor reassure him? Is AF normally life-threatening in the short term? Explain.
4b) Den’s ECG has no P waves. What does this tell us about the malfunctioning of his heart?
Den is told by the doctor that he might be prescribed warfarin, which he will have to take for
life. He is also advised that he will have to attend a coagulation clinic regularly to have the effect
of the drug monitored.
5a) Why might someone with AF take warfarin?
5b) What alternative might the doctor have considered? (See Box 7.2)
5c) Do you think that in Den’s case warfarin was the right choice? Justify your decision.
5d) Are there any (newer) anticoagulants which could replace warfarin? What would be the main
advantage in using one of these drugs? (See Section 4.2.1)
Den would like to know how long he will be in hospital, and what will happen to his daughter’s
wedding and their plans.
The doctor explains that Den will need to be monitored for a few days.
The ECG monitor starts bleeping. The doctor tells Den that he will have to call someone more
senior as it appears that the digoxin is not working.
The registrar comes in and tells Den that he will discuss with the consultant whether to add
another drug called amiodarone.

166 Chapter 7 Arrhythmias and chronic heart failure
6a) Anti-arrhythmic drugs are classified according to their mechanism of action. To which of the classes
does amiodarone belong?
6b) What is the mechanism of action of this class?
6c) List two other classes of anti-arrhythmics and their mechanism of action.
7) Drug treatment of AF may be aimed at rhythm control or rate control. Explain what these terms mean.
8) Which classes of anti-arrhythmic drugs (give examples) are used to achieve rhythm control and rate
control, and how do they work?
9) Which of these strategies has been used so far in the treatment of Den’s arrhythmia?
10a) Describe the two main mechanisms of action of digoxin on the heart.
10b) Which of these effects explains its benefit in AF?
Sunita knows that the effect of digoxin could be increased by amiodarone, and asks how safe it
is to use the two together.
The doctor is surprised that she knows this. He reassures her that the dose of digoxin has been
halved.
PART 2: DEN’S HEART FAILURE GETS WORSE. MANAGING
CHRONIC HEART FAILURE AND ATRIAL FIBRILLATION
Eoin and Sunita agree that their wedding will need to be postponed.
Although they are disappointed, they are happy that Den is receiving treatment. Next day the
doctors come to see Den bearing some bad news. They tell him that his chest X-ray and
echocardiogram results have been compared with the results from his last admission. The
comparison shows that his heart failure has worsened significantly.
11a) What is the underlying abnormality in chronic heart failure?
11b) What determines preload and afterload? How are these affected in chronic heart failure, and how
does this contribute to development of the condition?

WORKBOOK 4 Arrhythmias and chronic heart failure 167
ThedoctortellsDenthatthesizeofhishearthaschangedsignicantlysincehisprevious
admission.
12a) Why does the size of the heart change in chronic heart failure?
12b) Explain how this happens.
13) List two possible contributory factors in Den’s heart failure.
The doctors explain to Den that the ischaemic heart disease he has had for years has gradually
reduced cardiac output and led to fluid retention, a key sign of chronic heart failure.
14) What is cardiac output and what are its determinants? (See Chapter 5)
15) List the steps through which reduced renal blood flow, caused by reduced cardiac output, leads to
fluid retention.
Den complains that he feels even more tired and experiences greater shortness of breath.
The doctor explains that the shortness of breath is a result of the fluid retention in his lungs. He
also explains the origin of the other symptoms.
16) List two other symptoms of chronic heart failure.
The doctor tells Den that the dose of furosemide, treating his fluid retention, will be increased.
17a) To what class of drugs does furosemide belong?
17b) Explain the mechanism by which this class of drug reduces fluid retention.
Sunita tells Den that digoxin is a good drug to have for chronic heart failure, as well as for atrial
fibrillation.
18) Is Sunita right? Explain with reference to the mechanism(s) of action of digoxin.
Talking things over with the doctor, Sunita says it’s a good job Den hasn’t been taking
-blockers for his hypertension, since she know that they would reduce cardiac output, and so
make heart failure worse. The doctor says that this is not correct; some -blockers could be
prescribed specifically to help in the management of chronic heart failure.

168 Chapter 7 Arrhythmias and chronic heart failure
19a) Explain what is meant by chronic overstimulation of the heart by the sympathetic nervous system,
and how it comes about in chronic heart failure.
19b) What effect would a -adrenoceptor agonist have on the cardiac output of a patient with chronic
heart failure?
i) Immediately
ii) In the long term
19c) What effect would a -adrenoceptor antagonist (-blocker) have on the cardiac output of a patient
with chronic heart failure?
i) Immediately
ii) In the long term
Sunita asks why Den is not going to be put on -adrenoceptor antagonists. The doctor explains
that Den’s symptoms are not sufficiently under control, given that there is a risk of short-term
worsening of the symptoms with these drugs. They remain an option for longer-term
management.
The doctor tells Den that, instead, the dose of lisinopril, which he has been taking, will be
increased.
Den is not too happy because he has a persistent dry cough, which started soon after he began
taking the lisinopril. His GP advised him to persevere until the cough improved, but it hadn’t. He
had thought it pointless telling the GP, because he had the impression that no other drug could
replace it.
The doctor tells Den that actually there are other drugs he could try instead, if he cannot
tolerate the cough. He explains that the lisinopril can be changed for a drug belonging to the
class of angiotensin II receptor antagonists (or angiotensin receptor blockers; ARBs).
20a) Which class of drug does lisinopril belong to, and how does its mechanism of action help in the
treatment of chronic heart failure?
20b) Explain why ARBs are less likely to cause a dry cough.
Den improves significantly after 2 days and the furosemide infusion is changed to tablets. The
doctor approaches Sunita and tells her that he has decided, with respect to their earlier
discussion, that Den is now suitably controlled to justify the use of bisoprolol. He also stops the
amiodarone tablets because of the risk that the combination of amiodarone, digoxin, and
bisoprolol may cause bradycardia and possible heart block. He explains to Den that bisoprolol
has anti-arrhythmic effects.

WORKBOOK 4 Arrhythmias and chronic heart failure 169
21) What class of drug does bisoprolol belong to, and how is its action of benefit to Den?
After3weeksinhospitalDenisdischargedonthefollowingmedication:
• warfarin tablets
• candesartan tablets
• furosemide tablets
• digoxin tablets
• bisoprolol tablets.
Den improves significantly over the next 8 weeks. The wedding is rescheduled for April the
following year.


Part 3
Inflammation and
immune disease
Соседние файлы в папке Библиотека им академика М.И. Перельмана
