DISPEPSIA

For patients without ALARM symptoms, lifestyle advice on healthy eating, weight
reduction and smoking cessation should be offered together with a review of
medication for potential causes of dyspepsia. If these fail to control symptoms,
treat ment options are 1 month of proton pump inhibitor (PPI) or to test and treat
for Helicobacter pylori (H. pylori).

Gastroprotection should be offered to all patients on chronic NSAID therapy to

reduce the risk of ulcer disease. The highest-risk groups are older people and
those with previous ulcer disease or gastro-intestinal bleeding, and NSAIDs should
be avoided where possible in these groups

Functional dyspepsia is difficult to treat; initial treatment options are to eradicate

H. pylori if present or to offer 1 month of low-dose PPI or an H2 antagonist.

Peptic ulcer disease

The two main causes of peptic ulcer disease are H. pylori infection and the use of
aspirin and NSAIDs.

Ibuprofen 2.0
Diclofenac 4.2
Naproxen 9.1
Indometacin 11.3
Piroxicam 13.7
Ketoprofen 23.7

Drug-related causes of gastro-oesophageal reflux disease

Some drug classes cause relaxation of the lower oesophageal sphincter,

increasing the risk of GORD. These include calcium channel blockers, nitrates and
theophylline
Smoking is also thought to reduce oesophageal sphincter pressure, although a
direct association has not been proven

ALARM DISPEPSIA

 Dysphagia
• Unintentional weight loss
• Melaena or haematemesis
• Anaemia
• Persistent vomiting
• Epigastric mass

These groups of patients are at a higher risk of underlying serious disease, such as
cancer, peptic ulcer disease or severe oesophagitis. Referral is also recommended
for patients over the age of 55 if symptoms are unexplained or persistent despite
initial management

The possibility of cardiac or biliary disease should be considered as part of the

differential diagnosis.

Peptic ulcer disease

Peptic ulcers classically present with epigastric pain, described as a gnawing or

burning sensation

Duodenal ulcers typically cause pain occurring 1–3 hours after meals, which is
relieved by food, whereas gastric ulcer pain is typically triggered by food.

Drugs causing dyspepsia

Antibiotics
• Bisphosphonates
• Calcium channel blockers
• Corticosteroids
• Drugs with antimuscarinic effects (e.g. tricyclic
antidepressants)
• Iron
• Nitrates
• Non-steroidal anti-inflammatory drugs, including aspirin
• Theophylline

TREATMENT

Patients should be advised to avoid known precipitants where possible, such as

smoking, alcohol, coffee, chocolate, fatty foods and being overweight

If these initial steps fail, options are either to test and treat for H. pylori or to offer
1 month of full-dose PPI

Treatment of non-steroidal anti-inflammatory drug-associated ulcers

PPIs are used irst line

Gastro-oesophageal reflux disease

A 4- to 8-week course of standard-dose PPI therapy is most effective for healing

of oesophagitis and in ENRD, being more effective than H2 antagonists If initial
courses fail, high-dose PPI, switching PPI, or adding an H2 antagonist at night are
options. Dosis tinggi seperti lanso dapat diberikan 2x30mg, dan omeprazole
1x40mg (bukan hanya untuk GERD, tapi juga utk gejala dyspepsia yang berat)
Prokinetics are no longer licensed for GORD because their evidence of eficacy is
poor, and following a safety review, licensed use of domperidone and
metoclopramide is now restricted to short-term use in nausea and vomiting only

Functional dyspepsia

Patients with dyspeptic symptoms but with a normal endoscopy are classiied as
having functional dyspepsia. Eradication of H. pylori,
if present, may improve symptoms and is recommended as first-line therapy by
NICE (2014a). Second-line therapy is low-dose PPI or an H2 antagonist for 4
weeks, for which there is little difference in eficacy for this indication

All PPIs are most effective if taken about 30 minutes before a meal because they
inhibit only actively secreting proton pumps, and meals are the main stimulus for
proton pump activity

Their eficacy and relative safety has led them to be irst-line agents for treating
dyspepsia, GORD and peptic ulcer disease

Efek samping PPI : diarrhoea, headaches, abdominal pain, nausea, fatigue and
dizziness

H2-receptor antagonists

All the available drugs (cimetidine, ranitidine, famotidine, nizatidine) have similar
properties . The evening dose of an H2-antagonist is particularly important
because during the daytime, gastric acid is buffered for long periods by food. The
role of H2-receptor antagonists in the management of dyspepsia has diminished
because PPIs are more effective and generally recommended as irst line. They do
provide an alternative or addition in those unresponsive to PPIs, and their
availability for purchase means they still have a role to play in self-management
of dyspepsia.

Sucralfate

Although it is a weak antacid, this is not its principal mode of action in peptic ulcer
disease. Sucralfate is now less commonly used in practice due to the practicalities
of managing other medicines.

Antacids

The choice of antacid lies between aluminium-based and magnesium-based

products, Calcium-based products are less suitable because calcium stimulates
acid secretion. Aluminium-based antacids cause constipation, and
magnesiumbased products cause diarrhoea. When combination products are
used, diarrhoea tends to predominate as a side effect
 Constipation and Diarrhoea
constipation may be secondary to hypothyroidism, hypokalaemia, diabetes,
multiple sclerosis or GI obstruction. Likewise, diarrhoea may be secondary to
ulcerative colitis, Crohn’s disease, malabsorption or bowel carcinoma.

Constipation

would be considered to be fewer than three bowel actions a week. As well as

frequency, other criteria can be added into the deinition of constipation, such as
stool hardness, straining and the feeling of incomplete evacuation.

constipation is more common in women than in men, and that the incidence
increases with age, particularly after 65 years. In the elderly, contributing factors
have been identified such as poor diet, insuficient intake of luids, lack of exercise.
Changes in hormones and mechanical factors during pregnancy lead to an
increase in prevalence of constipation.

A person older than 50 years who has started to complain about constipation
without a previous history may require referral. Recurrent abdominal pain or
discomfort with constipation is more associated with IBS

Examples of medicines known to cause constipation :

 Antacid
 Trihexyphenidyl, hyoscine
 Antidepressant
 Carbamazepine
 Antipsychotic
 NSAID
 All proton pump inhibitors, sucralfate
Drug treatment

Bulk-forming agents are seen as the first-line treatment. Osmotic and stimulant
laxatives are used as second-line treatments.

In pregnancy there is very little evidence to support the use of laxatives. It is

generally accepted that a bulk-forming laxative would be the irst choice if non-
drug advice is unsuccessful followed by lactulose

Bulk-forming agents

spaghula formulated as powder, granules and effervescent granules,

methylcellulose tablets and sterculia granules are all bulk-forming agents

Bulk-forming agents can be used safely long-term during pregnancy or when

breast-feeding, but many users will experience problems with latulence and
distension

Stimulant laxative

Medicines in the stimulant laxative group include bisacodyl, sodium picosulfate,

senna and dantron.

They directly stimulate colonic nerves that cause movement of the faecal mass,
reduce transit time and result in the passage of stool within 6–12 hours. As a
consequence of their time to onset, oral dosing at bedtime is generally
recommended. Suppositories that contain laxatives have a more immediate
effect, causing defaecation within 20–60 minutes. Abdominal cramps are a
common side effect of stimulant laxatives

Osmotic laxatives

Osmotic laxatives include magnesium salts, phosphate enemas, sodium citrate

enemas, lactulose and macrogols.
Diarrhoea

The usual cause of acute diarrhoea, in all age groups, is viral or bacterial infection.
Other causes of acute diarrhoea include food allergies, anxiety or alcohol misuse.
Chronic diarrhoea can be associated with conditions such as IBS, inlammatory
bowel disease, colorectal cancer and malabsorption syndromes.

Many medicines (Table 14.4), particularly broad-spectrum antibiotics such as

ampicillin, erythromycin and neomycin, induce diarrhoea secondary to therapy.

Warning signs that warrant further investigation include blood in the stools,
persistent vomiting, unintentional and unexplained weight loss, or nocturnal
symptoms which disturb sleep

In general, stool culture is required in patients who are unwell (fever or

dehydration), immunocompromised, with blood or pus in the stool, or where
there is no improvement within a week

In babies, breast-feeding and bottle-feeding should be continued, although there

is some evidence that moving bottle-fed babies to lactose-free milk may be
beneficial

Drug treatment

Antimotility agents

In uncomplicated acute diarrhoea, antimotility agents such as loperamide,

diphenoxylate and codeine are occasionally useful for symptomatic control in
adults. Antimotility agents are not recommended for use in children because trial
results appear contradictory and any beneits are small with unacceptable levels
of side effects observed. Antimotility agents should be avoided in severe
gastroenteritis or dysentery.
Absorbants. Kaolin, used as an absorbant, is not recommended for the treatment
of acute diarrhoea.

Antimicrobials

Antibiotics should be reserved for patients who produce a positive stool culture
for bacteria and where the symptoms are not receding or for traveller’s diarrhea

liver disease
Symptoms

In patients who have liver disease, weakness, increased fatigue and general
malaise are common. Weight loss and anorexia are more commonly seen in
chronic liver disease. Abdominal pain is common in hepatobiliary disease,
frequently localised to the right upper quadrant. Tenderness over the liver is a
symptom of acute hepatitis, hepatic abscess or hepatic malignancy.

Hypertension
Hypertension can be defined as a condition in which blood pressure (BP) is
elevated as a systolic blood pressure equal to or greater than 140 mmHg and/or
diastolic blood pressure equal to or greater than 90 mmHg.

The complications of hypertension include stroke, myocardial infarction, heart

failure, renal failure and dissecting aortic aneurysm. Non-pharmacological
interventions are important and include weight reduction, avoidance of excessive
salt and alcohol, increased intake of fruit and vegetables and regular physical
activity. Other cardiovascular risk factors, such as smoking, dyslipidaemia and
diabetes.
For patients younger than 55 years, an angiotensin-converting enzyme (ACE)
inhibitor is recommended as first-line treatment. For older patients, a calcium
channel blocker is an appropriate initial choice

Treatment
Non-pharmacological approaches
Lifestyle advice should include discussion of weight loss, diet and physical activity,
as well as salt and alcohol intake and smoking cessation. This diet emphasises
fruit, vegetables and low-fat dairy produce in addition to fish, low-fat poultry and
whole grains while minimising red meat, confectionaries and sweetened drinks.
Subjects should reduce their salt intake, for example, by not adding salt to food
when cooking, using spices to add lavour and not adding additional salt to food on
the plate.

Drug treatment
Patients with severe hypertension (>180/110 mmHg) should be treated
immediately, and some guidance suggests that dual therapy should be
commenced immediately in patients at high risk or with markedly high baseline
blood pressure because monotherapy is unlikely to be effective

Target blood pressures

 People younger than 80 years : <140/90 mmHg

 People older than 80 years : <150/90 mmHg
 People with type 2 diabetes mellitus : 140/80 mmHg

Renin–angiotensin system antagonists

ARBs are an appropriate choice for patients who are intolerant of ACE inhibitors
because of cough

Calcium channel blockers

In contrast, the effect of verapamil and diltiazem are primarily on the heart,
reducing heart rate and cardiac output. Although effective for lowering blood
pressure and preventing cardiovascular events, adverse effects are common, for
example, oedema and flushing.

Diuretics
These drugs are both inexpensive and well tolerated by most patients. Although
generally well tolerated, thiazide and thiazide-like diuretics may cause
hypokalaemia, small increases in low-density lipoprotein (LDL) cholesterol and
triglycerides, and gout associated with impaired urate excretion. Erectile
dysfunction is also common.
Loop diuretics are no more effective at lowering blood pressure than thiazides
unless renal function is signiicantly impaired
Spironolactone, an aldosterone antagonist, is not suitable for irst-line therapy but
is an increasingly important treatment option at low dose (25 mg daily) for
patients with resistant hypertension
Spironolactone is a potassium-sparing diuretic and should be used with caution,
especially if used in combination with ACE inhibitors or ARBs,

β-Adrenoreceptor antagonists
β-Blockers do remain suitable for younger hypertensives who have another
indication for β-blockade, such as coronary heart disease. β-Blockers are also
effective in suppressing atrial fibrillation,

Step 1
ACE Inhibitor or low-cost angiotensin II receptor blocker (untuk < 55 tahun)or
Calcium-channel blocker (> 55 tahun)

Step 2
ACE Inhibitor or angiotensin II receptor blocker + calcium-channel blocker
Step 3
ACE Inhibitor or angiotensin II receptor blocker + calcium-channel blocker +
thiazide-like diuretic

Step 4, deined as resistant hypertension, recommends the addition of

spironolactone or a higher dose of thiazide-like diuretic,

Drug selection
Combinations of low doses of antihypertensive drugs are often better tolerated
than single drugs taken in high dose.
However, captopril was associated with a 25% higher stroke risk, perhaps
because it did not reduce blood pressure as effectively as conventional therapy in
this particular study

Efek samping obat

Angiotensinconverting enzyme inhibitor :
 Cough
Rash
Taste disturbance
Renal dysfunction
Angioedema
Angiotensin receptor blockers :
 Headache
Rash
Renal failure
Calcium channel blocker :
 Flushing
Ankle swelling
Headache
Diuretics :
 Hypokalaemia
Gout
Glucose intolerance
Hyperlipidaemia
Impotence
Uraemia
Dehydration
Beta-blockers :
 Tiredness/fatigue
Reduced exercise
tolerance
Bradycardia
Cold peripheries
Claudication
Wheezing
Impotence

Rekomendasi pengobatan
Diuretic therapy, in the form of a thiazide-type diuretic, is
recommended as an alternative if a CCB is not suitable, for example,
because of oedema or intolerance, or if there is evidence of heart
failure or a high risk of heart failure.
Calcium channel blockers and low-dose thiazide diuretics are safe and
effective treatments for elderly hypertensive people.
Thiazides, β-blockers, calcium channel blockers and α-blockers are all
suitable as add-on treatments to ACE inhibitors, which should be irst-
line therapy.
Methyldopa is the most suitable drug choice for use in pregnancy
because of its long-term safety record. Calcium channel blockers,
hydralazine and labetalol are also used.

Ancillary drug treatment

Aspirin
it is no longer recommended for primary prevention of cardiovascular events

Renal dysfunction : ACE inhibitor, ARB

Previous stroke : Any agent effectively lowering blood pressure
Angina pectoris : β-Blocker, CCB
Heart failure : Diuretic, β-blocker, ACE inhibitor, ARB, aldosterone antagonist
Isolated systolic hypertension (elderly) : Diuretic, CCB
Metabolic syndrome : ACE inhibitor, ARB, CCB
Diabetes mellitus : ACE inhibitor, ARB

Diuretics : Elderly, Heart failure. Kontraindikasi : Gout

β-Blockers : Myocardial infarction, Angina. Contraindications : Asthma/chronic
obstructive pulmonary disease Heart block

Coronary Heart Disease

Coronary heart disease (CHD), sometimes described as coronary artery disease

(CAD) or ischaemic heart disease (IHD), is a condition in which the vascular supply
to the heart is impeded by atheroma, thrombosis or spasm of coronary arteries

High dietary fat, smoking and sedentary lifestyle are risk factors
for CHD and require modification if present.

• Hypertension, hypercholesterolaemia, diabetes mellitus, obe

sity and personal stress are also risk factors and require optimal
management.
• Stable angina should be managed with nitrates for pain relief
and β-blockers, unless contraindicated, for long-term prophy
laxis. Where β-blockers are inappropriate, the use of calcium
channel blockers and/or nitrates may be considered.
• Acute coronary syndromes arise from unstable atheroma
tous plaques and may be classified as to whether there is
ST-elevation myocardial infarction (STEMI) or non-ST-elevation
myocardial infarction (NSTEMI).
• ST elevation on the electrocardiogram (ECG) indicates an
occluded coronary artery and is used to determine treatment
with fibrinolysis or primary angioplasty.
• Patients with NSTEMI may have experienced myocardial dam
age, are at increased risk of death

Clinical syndromes
The primary clinical manifestation of CHD is chest pain.

Stable angina
Stable angina is characterised by chest pain and breathlessness on exertion;
symptoms are relieved promptly by rest.
Stable angina is a clinical syndrome characterised by discomfort in the chest, jaw,
shoulder, back, or arms, typically elicited by exertion or emotional stress and
relieved by rest or nitroglycerin.
Many patients mistake the discomfort for indigestion. Some patients, particularly
diabetics and the elderly, may not experience pain at all but present with
breathlessness or fatigue; this is termed silent ischaemia.
The resting electrocardiogram (ECG) is normal in more than half of patients with
angina.

Stable angina for medical management

1, Short-acting subligual or buccal nitrate, prn
2. Aspirin 75–150 mg od
3. Statin
4. ACE inhibitor in proven CVD
5.β-blocker post-MI, β-blocker no prior MI
Aspirin
The optimal maintenance dose seems to be 75–150 mg/ day, with lower doses
having limited cardiac risk protection and higher doses increasing the risk of
gastro-intestinal side effects. Dyspepsia is relatively common in patients taking
aspirin, and patients should be advised to take the medicine with or immediately
after food. Adverse reactions to aspirin include allergy, including bronchospasm.

Angiotensin-converting enzyme inhibitors

ACE inhibitors are established treatments for hypertension and heart failure and
have proven beneicial post–myocardial infarction.

β-Blockers
β-Blockers are now considered irst-line agents in the management of angina. β-
Blockers reduce mortality in both patients who have suffered a previous
myocardial infarction and in those with heart failure.
β-Blockers should be used with caution in patients with diabetes because the
production of insulin is under adrenergic system control, and thus their
concomitant use may worsen glucose control.
Cardioselective agents such as atenolol, bisoprolol and metoprolol are preferred
because of their reduced tendency to cause bronchoconstriction,
propranolol and metoprolol, which should not be used in patients with psychiatric
disorders because make the nightmares, hallucinations and depression.
fatigue or lethargy is found in some patients with all β-blockers.
 Asthma
Asthma can present with a number of different symptoms but classically presents
with cough, wheeze and breathlessness, often induced by exposure to a wide
variety of trigger factors.
Asthma tends to demonstrate diurnal variation, generally with increased
symptoms at night and early in the morning.

Chronic treatment

Inhaled corticosteroids
Inhaled corticosteroids (ICSs) are recommended as the second step as a regular
preventative therapy in the BTS guidelines for all people with asthma, except
those with very mild and occasional symptoms, where ‘as-required’
symptomatic treatment with short-acting β2-agonists alone may be sufficient.

For adults, it is recommended that patients commence treatment at a dose of

200–800 micrograms/day of beclometasone dipropionate (BDP) or equivalent.
This can be increased to up to 2000 micrograms/day of beclometasone
dipropionate (BDP) or equivalent as a fourth step if patients have no response to
the addition of a long-acting β-agonist (LABA) or a trial of alternative agents (BTS
and SIGN, 2016). It should be noted, however, that at doses of 800
micrograms/day of BDP or equivalent, this will achieve 90% clinical beneit for the
patient. At doses higher than this there is a signiicant increase in adverse effects
(Holt et al., 2001). Budesonide, ciclesonide, luticasone and mometasone are
other ICSs that are available and widely used.
ICSs can cause oral candidiasis and dysphonia; hence, encouraging patients to
rinse the mouth after use is important. Long-term, high-dose ICS use will result in
some of the steroid being absorbed systemically, potentially leading to adverse
effects, including increased blood glucose and susceptibility to diabetes. ICSs can
also lead to osteoporosis, increasing the risk of fractures, muscle wasting and
impaired wound healing. They can also cause psychiatric reactions and mood
disorders, as well as adrenal suppression.

Short-acting β-agonists
Short-acting β-agonists (SABAs), such as salbutamol and terbutaline, are the irst-
line step and should be prescribed for all asthma patients and should be used on a
when-required basis. Patients with very infrequent signs and symptoms of asthma
may require only a SABA.
Additionally, oral SABAs are not recommended due their
higher risk of systemic side effects compared with administration via inhalation

Long-acting β-agonists
LABAs, such as salmeterol, formoterol fumarate and vilanterol,
are designed to be used regularly but have different characteristics
in terms of onset and duration of action

Theophylline preparations
Oral theophylline and aminophylline can be used as an
alternative in the same way as the leukotriene antagonists when
patients are unresponsive to LABAs or as an addition to an ICS/
LABA combination inhaler.

Oral corticosteroids
Oral corticosteroids, such as prednisolone, can be used for the treatment of both
exacerbations and chronic asthma.
Patients should be fully informed of the risks of long-term oral steroids. Other
treatments, such as calcium and vitamin D, bisphosphonates for bone protection
and medicines for gastric protection, may also be required when the patient is
prescribed oral corticosteroids.
Acute treatment
Oxygen : saturation maintained at 94–98%
Bronchodilators : Inhaled β-agonists should also be administered in emergency
situations to treat bronchoconstriction. If their response to nebulised β-agonists is
poor, or in cases of severe exacerbations, then there is evidence for the addition
of nebulised ipratropium for increased bronchodilation. Intravenous salbutamol
and terbutaline have also been used; however, these are no longer recommended
because nebulised salbutamol is a safer option. The only scenario where they
could be considered would be where a patient was not responding to
β-agonists via an inhaled route.
Corticosteroids : Oral prednisolone should be administered at a dose of 40–50 mg
daily. If the oral route is unavailable, then intravenous hydrocortisone may be
administered at a dose of 100 mg four times daily until the oral route is available
again.

Chronic Obstructive Pulmonary Disease

Clinical manifestations
The earliest symptoms of COPD are cough and expectoration of sputum.
If emphysema is prominent, the chest becomes visibly hyperinlated, which can
also be appreciated by a hyper-resonant percussion note, as part of the clinical
examination.
Other symptoms that may be experienced are sleep disturbance, dry mouth,
lethargy and weight loss, If respiratory failure develops, ankle oedema appears.
Two COPD stereotypes have been recognised, the so-called ‘pink puffer’ and ‘blue
bloater’. Pink puffers tend to have a more emphysematous phenotype, with
marked hyperinlation. These patients are typically thin. The blue bloater, in
contrast, tends to have less obvious hyperinlation and slips into respiratory failure
and hypoxic cor pulmonale. These patients are less breathless and tend to be
obese.
Investigations
Plain chest radiography has both poor sensitivity and speciicity for COPD but is
recommended when the diagnosis is irst being considered to exclude other
pathologies. In COPD the chest X-ray can be normal but often shows hyperinlated
lungs, increased lung markings due to bronchial wall thickening and regions of
lucency corresponding to areas of emphysema/bullae.

Mucolytics
Carbocysteine, the most commonly prescribed mucolytic, provides some
symptomatic beneit in those patients with a productive cough.

Prophylactic antibiotics
Currently, prophylactic antibiotic therapy with azithromycin is not currently
recommended in the GOLD (2017) guidance unless the patient is a former smoker
with recurrent exacerbations despite optimal pharmacological therapy.

Pharmacological management of exacerbations

of chronic obstructive pulmonary disease

Bronchodilators
Salbutamol 2.5 mg four times daily is usually adequate with the addition
of ipratropium 500 micrograms four times daily as an adjunct.

Antibiotics
Acute infective exacerbations may be bacterial or viral in origin.
If the exacerbation is bacterial in origin, suggested by purulent sputum, then
antibiotics should be prescribed. First-line antibiotics include amoxicillin,
doxycycline and clarithromycin. Antibiotic therapy is not indicated if sputum
is non-purulent (or similar in colour to normal) unless there is other evidence or
infection, such as infective consolidation, high fever
Corticosteroids
recommends a course of prednisolone 30 mg for
5–7 days only.

Schizophrenia
Schizophrenia is a complex chronic illness which varies greatly
in presentation (positive and negative symptoms)
Positive symptoms such as hallucinations, delusions and
thought disorder, which commonly occur in the acute phase of
the illness, usually respond to treatment with antipsychotics.
• Negative symptoms such as apathy, social withdrawal and lack
of drive, which occur commonly in the chronic phase of the
illness, are more resistant to medication
The term ‘atypical’ or ‘second generation’ is used to describe
the newer antipsychotics that generally do not cause the extra
pyramidal side effects (EPSE) or hyperprolactinaemia.
• However, the second generation antipsychotics are associated
with a range of metabolic side effects including weight gain
and diabetes, which in turn may have long-term effects on
morbidity and mortality.
• The older ‘typical’ or ‘first generation’ antipsychotics are often
associated with anticholinergic, sedative and cardiovascular
side effects, in addition to EPSE.
• Long-term treatment with first generation antipsychotics is
associated with the development of the movement disorder
tardive dyskinesia
Most first generation and second generation antipsychotics
have similar efficacy in the treatment of schizophrenia. The
exception is clozapine, which has greater efficacy than all other
antipsychotics and is therefore indicated for treatment-resistant
schizophrenia.