Anh văn chuyên ngành quản lý và cung ứng thuốc

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, a certain intestinal disease colitis.. Before using this medication, tel

PREFACE

The Drug Supply and Management textbook is especially compiled to meet the

demand of equipping students of the Pharmacy Department at Lac Hong University

with vocabulary and reading comprehension ability

This textbook is designed to help pharmacy – majored students build vocabulary and

access pharmaceutical materials It introduces terms relating to pharmaceutical

contexts which are widely used in pharmaceutical prescriptions, reports, journals, and

studies In addition, it also enhances students‟ reading and translation skills through

authentic reading texts with carefully planned activities

In spite of the efforts to make it an efficient aid in the study of this ESP course, the

compilers are aware of the deficiencies that remain in the textbook Needless to say,

the compilers will greatly appreciate all positive contributions sent to

the General English Department via generalenglishdept@lhu.edu.vn

TABLE OF CONTENTS

Page

PREFACE i

TABLE OF CONTENTS ii

UNIT 1 Drug Information 1

Cefixime 1

Glipizide 7

UNIT 2 The pharmacological basis of Therapeutics 13

Certirizine 13

Betamethasone 19

UNIT 3 The pharmacological basis of disease treatment 29

Omeprazole 29

Chlorpromazine 38

UNIT 4 Leaflet 46

Augmentin 46

Amlodipin Stada 59

UNIT 5 Pharmacovigilance 65

UNIT 6 Good stockage practices 76

UNIT 7 Pharmaceutical care 91

UNIT 8 Improving global health by closing gaps in the development,

distribution, and responsible use of medicines 99

UNIT 9 Medical status reports 107

UNIT 10 Purchase Orders 142

UNIT 11 Pharmaceutical and Clinical Journals 149

GLOSSARY 182

REFERENCES 190

UNIT 1 DRUG INFORMATION

GUIDED STUDY

CEFIXIME SCRUB UP

1 Work in pairs Write the correct words or phrases given in the table under the corresponding pictures

1 antibiotic

2 vomit

3 breast-feeding

4 diarrhea

5 rash

6 sore throat

7 dizziness

8 patch

9 diet

a - b - c -

d - e - f -

g - h - i -

2 Work in pairs Match each phonetic spelling to one of the words or phrases above Try to say them to your partner a /ˌæntibaɪˈɒːtɪk/ _ c /sɔː θrəʊt/ _ e /ˈdɪzɪnəs/ _

b /ˌdaɪəˈriːə/ _ d /ˈvɒmɪt/ _

READING COMPREHENSION

1 Read the passage below and decide if these sentences are true (T) or false (F)

a Cefixim is always safe _

b An over dose of this medication sometimes causes death _

c This medication may have effects on stomach _

d Pregnant women must be careful with this drug _

e The dosage of children is based on age _

f This medication requires a medical prescription to be dispensed _

g If a patient missed a dose, he or she would take a double dose to catch up the missed dose _

2 Fill in each blank with a suitable word

a Antibiotics do not fight infections caused by cold and _ viruses

b Do not stop taking the antibiotics early even if _ disappear after a few days

c You should check with your doctor immediately if any of these side effects, such as stomach upset/pain, diarrhea, nausea, gas, headache, or _ occurs when taking cefixime

d Because no information is available on the effect of cefixime on breast milk, you should consult your doctor before _

e Do not save any of the antibiotics for another _ unless told to do so by your doctor

f Keep cefixime out of the reach of _ and away from pets

3 Translate the following sentences into Vietnamese

a If you are taking the chewable tablets, chew thoroughly and then swallow

b Stopping the medication too early may allow bacteria to continue to grow, which may result in a relapse of the infection

c Use of this medication for prolonged or repeated periods may result in oral thrush or a new vaginal yeast infection (oral or vaginal fungal infection)

d This medication should be used only when clearly needed during pregnancy Discuss the risks and benefits with your doctor

e Although most antibiotics probably do not affect hormonal birth control such as pills, patch, or ring, some antibiotics may decrease their effectiveness

2 How to use cefixime

Take this medication by mouth with or without food as directed by your doctor, usually once a day For children, this medication may also be taken twice a day (every

12 hours) If you are taking the chewable tablets, chew thoroughly and then swallow The dosage is based on your medical condition and response to treatment For children, the dosage is also based on weight

Antibiotics work best when the amount of medicine in your body is kept at a constant level Therefore, take this drug at evenly spaced intervals

Continue to use this medication until the full prescribed amount is finished, even if symptoms disappear after a few days Stopping the medication too early may allow bacteria to continue to grow, which may result in a relapse of the infection

Tell your doctor if your condition persists or worsens

Tell your doctor immediately if any of these rare but very serious side effects occur: severe stomach/abdominal pain, persistent nausea/vomiting, yellowing eyes/skin, dark urine, unusual tiredness, new signs of infection (e.g., persistent sore throat, fever),

easy bruising/bleeding, change in the amount of urine, mental/mood changes (such as confusion)

This medication may rarely cause a severe intestinal condition (Clostridium associated diarrhea) due to a resistant bacteria This condition may occur weeks to months after treatment has stopped Do not use anti-diarrhea products or narcotic pain medications if you have the following symptoms because these products may make them worse Tell your doctor immediately if you develop: persistent diarrhea, abdominal or stomach pain/cramping, or blood/mucus in your stool

difficile-Use of this medication for prolonged or repeated periods may result in oral thrush or a new vaginal yeast infection (oral or vaginal fungal infection) Contact your doctor if you notice white patches in your mouth, a change in vaginal discharge, or other new symptoms

A very serious allergic reaction to this drug is rare However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing

This is not a complete list of possible side effects If you notice other effects not listed above, contact your doctor or pharmacist

4 Precautions

Before taking cefixime, tell your doctor or pharmacist if you are allergic to it; or to penicillins or other cephalosporin antibiotics (e.g., cephalexin); or if you have any other allergies This product may contain inactive ingredients, which can cause allergic reactions or other problems Talk to your pharmacist for more details

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, a certain intestinal disease (colitis)

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products)

The chewable form of this medication may contain aspartame If you have phenylketonuria (PKU) or any other condition that requires you to limit/avoid

aspartame (or phenylalanine) in your diet, ask your doctor or pharmacist about using this medication safely

This medication should be used only when clearly needed during pregnancy Discuss the risks and benefits with your doctor

It is unknown if this medication passes into breast milk Consult your doctor before breast-feeding

5 Interactions

Drug interactions may change how your medications work or increase your risk for serious side effects This document does not contain all possible drug interactions Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist Do not start, stop,

or change the dosage of any medicines without your doctor's approval

Some products that may interact with this drug include: "blood thinners" (e.g., warfarin), live bacterial vaccines

Although most antibiotics probably do not affect hormonal birth control such as pills, patch, or ring, some antibiotics may decrease their effectiveness This could cause pregnancy Examples include rifamycins such as rifampin or rifabutin Be sure to ask your doctor or pharmacist if you should use additional reliable birth control methods while using this antibiotic

This medication may cause false positive results with certain diabetic urine testing products (cupric sulfate-type) This drug may also affect the results of certain lab tests Make sure laboratory personnel and all your doctors know you use this drug

6 Overdose

If overdose is suspected, contact a poison control center or emergency room immediately Symptoms of overdose may include: severe vomiting, seizures

Notes

Do not share this medication with others

This medication has been prescribed for your current condition only Do not use it later for another infection unless told to do so by your doctor A different medication may be necessary in those cases

7 Missed dose

If you miss a dose, take it as soon as you remember If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule Do not double the dose to catch up

8 Storage

Store at room temperature away from light and moisture Do not store in the bathroom Keep all medications away from children and pets

Do not flush medications down the toilet or pour them into a drain unless instructed to

do so Properly discard this product when it is expired or no longer needed Consult your pharmacist or local waste disposal company

SELF-STUDY

GLIPIZIDE READING COMPREHENSION

1 Answer the questions about the text

a How should glipizide be used?

b Can glipizide cause upset stomach?

c Will taking glipizide for diabetes make people gain weight?

d Are people with type 1 diabetes allowed to use glipizide?

e What should people do if they forget a dose?

f What side effects can this medication cause?

g What should people know about storage and disposal of this medication?

2 Translate the following paragraphs into Vietnamese

a Glipizide is used with a proper diet and exercise program to control high blood sugar in people with type 2 diabetes It may also be used with other diabetes medications Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems Proper control of diabetes may also lessen your risk of a heart attack or stroke Glipizide belongs to the class of drugs known as sulfonylureas It lowers blood sugar by causing the release of your body's natural insulin

b Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, kidney disease, thyroid disease, certain hormonal conditions (adrenal/pituitary insufficiency, syndrome of inappropriate secretion of antidiuretic hormone-SIADH), electrolyte imbalance (hyponatremia)

c Store at room temperature away from light and moisture Do not store in the

bathroom Keep all medications away from children and pets

d Do not flush medications down the toilet or pour them into a drain unless instructed to do so Properly discard this product when it is expired or no longer needed Consult your pharmacist or local company waste disposal

2 How to use glipizide

Take this medication by mouth 30 minutes before breakfast or the first meal of the day

as directed by your doctor, usually once daily Some patients, especially those taking higher doses, may be directed to take this drug twice a day The dosage is based on your medical condition and response to treatment

To reduce your risk of side effects, your doctor may direct you to start this medication

at a low dose and gradually increase your dose Follow your doctor's instructions carefully

If you are already taking another anti-diabetic drug (such as chlorpropamide), follow your doctor's directions carefully for stopping the old drug and starting glipizide Colesevelam can decrease the absorption of glipizide If you are taking colesevelam, take glipizide at least 4 hours before taking colesevelam

Use this medication regularly to get the most benefit from it To help you remember, take it at the same time(s) each day

Tell your doctor if your condition does not improve or if it worsens (your blood sugar levels are too high or too low)

3 Side effects

Nausea, vomiting, loss of appetite, diarrhea, constipation, upset stomach, headache, and weight gain may occur If any of these effects persist or worsen, tell your doctor or

pharmacist promptly

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects Many people using this medication do not have serious side effects

Tell your doctor right away if you have any serious side effects, including: signs of infection (such as persistent sore throat, fever), easy bleeding/bruising, stomach pain, yellowing eyes/skin, dark urine, unusual tiredness/weakness, unusual/sudden weight gain, mental/mood changes, swelling hands/feet, seizures

This medication can cause low blood sugar (hypoglycemia) This may occur if you do not consume enough calories from food or if you do unusually heavy exercise Symptoms of low blood sugar include sudden sweating, shaking, fast heartbeat, hunger, blurred vision, dizziness, or tingling hands/feet It is a good habit to carry glucose tablets or gel to treat low blood sugar If you don't have these reliable forms of glucose, rapidly raise your blood sugar by eating a quick source of sugar such as table sugar, honey, or candy, or drink fruit juice or non-diet soda Tell your doctor immediately about the reaction and the use of this product To help prevent low blood sugar, eat meals on a regular schedule, and do not skip meals Check with your doctor

or pharmacist to find out what you should do if you miss a meal

Symptoms of high blood sugar (hyperglycemia) include thirst, increased urination, confusion, drowsiness, flushing, rapid breathing, and fruity breath odor If these symptoms occur, tell your doctor immediately Your dosage may need to be increased

A very serious allergic reaction to this drug is rare However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing

This is not a complete list of possible side effects If you notice other effects not listed above, contact your doctor or pharmacist

4 Precautions

Before taking glipizide, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies This product may contain inactive ingredients, which can cause allergic reactions or other problems Talk to your pharmacist for more details

Before using this medication, tell your doctor or pharmacist your medical history, especially

of: liver disease, kidney disease, thyroid disease, certain hormonal conditions (adrenal/pituitary insufficiency, syndrome of inappropriate secretion of antidiuretic hormone-SIADH), electrolyte imbalance (hyponatremia)

You may experience blurred vision, dizziness, or drowsiness due to extremely low or high blood sugar levels Do not drive, use machinery, or do any activity that requires alertness or clear vision until you are sure you can perform such activities safely Limit alcohol while taking this medication because it can increase your risk of developing low blood sugar Alcohol can rarely interact with glipizide and cause a serious reaction disulfiram-like reaction) with symptoms such as facial flushing, nausea, vomiting, dizziness, or stomach pain Consult your doctor or pharmacist about the safe use of alcohol

It may be harder to control your blood sugar when your body is stressed (such as due

to fever, infection, injury, or surgery) Consult your doctor because this may require a change in your treatment plan, medications, or blood sugar testing

This medication may make you more sensitive to the sun Avoid prolonged sun exposure, tanning booths, and sunlamps Use a sunscreen and wear protective clothing when outdoors

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products)

Older adults may be more sensitive to the side effects of this drug, especially low blood sugar

During pregnancy, this medication should be used only when clearly needed Discuss the risks and benefits with your doctor

Pregnancy may cause or worsen diabetes Discuss a plan with your doctor for managing your blood sugar while pregnant Your doctor may change your diabetes treatment during your pregnancy (such as diet and medications including insulin)

It is unknown if this medication passes into breast milk However, similar drugs pass into breast milk Consult your doctor before breast-feeding

5 Interactions

Drug interactions may change how your medications work or increase your risk for serious side effects This document does not contain all possible drug interactions Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist Do not start, stop,

or change the dosage of any medicines without your doctor's approval

Many drugs can affect your blood sugar levels, making it more difficult to control your blood sugar Before you start, stop, or change any medication, talk with your doctor or pharmacist about how the medication may affect your blood sugar Check your blood sugar levels regularly as directed by your doctor Tell your doctor about the results and

of any symptoms of high or low blood sugar (See also Side Effects section.) Your doctor may need to adjust your anti-diabetic medication, exercise program, or diet Beta-blocker medications (including metoprolol, propranolol, glaucoma eye drops such as timolol) may prevent the fast/pounding heartbeat you would usually feel when your blood sugar level falls too low (hypoglycemia) Other symptoms of low blood sugar such as dizziness, hunger, or sweating are unaffected by these drugs

Check the labels on all your medicines (such as cough-and-cold products) because they may contain ingredients that could affect your blood sugar Ask your pharmacist about using those products safely

6 Overdose

If overdose is suspected, contact a poison control center or emergency room immediately Symptoms of overdose may include: shakiness, fast heartbeat, sweating, loss of consciousness

Notes

Do not share this medication with others

Attend a diabetes education program to learn more about diabetes and the important aspects of its treatment, including medications, diet, exercise, and getting regular eye/foot/medical exams

Learn the symptoms of high and low blood sugar and how to treat low blood sugar Check your blood sugar levels regularly as directed

Keep all regular medical and laboratory appointments Laboratory and/or medical tests (such as liver and kidney function tests, fasting blood glucose, hemoglobin A1c, complete blood counts) should be performed periodically to monitor your progress or check for side effects

7 Missed dose

If you miss a dose, take it as soon as you remember If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule Do not double the dose to catch up

8 Storage

Store at room temperature away from light and moisture Do not store in the bathroom Keep all medications away from children and pets

Do not flush medications down the toilet or pour them into a drain unless instructed to

do so Properly discard this product when it is expired or no longer needed Consult your pharmacist or local waste disposal company

UNIT 2 THE PHARMACOLOGICAL BASIS OF THERAPEUTICS GUIDED STUDY

CERTIZINE SCRUB UP

1 Work with a partner Match each phonetic spelling in column A to one of the words in column B How do you pronounce those eight words?

READING COMPREHENSION

1 Choose the word or phrase marked a, b, c, or d that best complete each sentence.

1 Certirizine is used to treat _

2 Certirizine is available in the forms of _

3 Serious side effects of certirizine contain _

a difficulty urinating b drowsiness

4 Chewable tablets may be taken with _

5 The common side effect of certirizine is _

6 Do not use any other antihistamines applied to the skin, such as _

2 Answer the questions about the text

a Should antihistamines be used by women who are breast feeding?

b Does certirizine interact with other medications?

c What is cetirizine indicated for?

d Are patients allowed to crush or chew enteric-coated preparations of certirizine?

e What should we know about storage and disposal of this medication?

3 Read the passage below and decide if these sentences are true (T) or false (F)

a Certirizine is available without a prescription _

b Certirizine causes anxiety _

c People using this medication may become drowsy _

d It is okay to take certirizine during pregnancy _

e It is possible to take certirizine tablet twice a day _

f People who have missed a dose of certirizine can doube it to catch up _

2 How to use cetirizine

If you are taking the over-the-counter product to self-treat, read all directions on the product package before taking this medication If you have any questions, consult your pharmacist If your doctor has prescribed this medication, take it as directed, usually once daily

If you are using the chewable tablets, chew each tablet well and swallow If you are using the rapidly-dissolving tablet, allow the tablet to dissolve on the tongue and then swallow, with or without water If you are using the liquid form of this medication, measure the dose carefully using a special measuring device/spoon Do not use a household spoon because you may not get the correct dose

The dosage is based on your age, medical condition, and response to treatment Do not increase your dose or take this medication more often than directed

Tell your doctor if your allergy symptoms do not improve, if your hives do not improve after 3 days of treatment, or if your hives last more than 6 weeks Get medical help right away if your condition worsens or if you think you have a serious medical problem (such as a very serious allergic reaction/anaphylaxis)

3 Side effects

Drowsiness, tiredness, and dry mouth may occur Stomach pain may also occur, especially in children If any of these effects persist or worsen, tell your doctor or pharmacist promptly

If your doctor has prescribed this medication, remember that he or she has judged that the benefit to you is greater than the risk of side effects Many people using this medication do not have serious side effects

Tell your doctor right away if you have any serious side effects, including: difficulty urinating, weakness

A very serious allergic reaction to this drug is rare However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing

This is not a complete list of possible side effects If you notice other effects not listed above, contact your doctor or pharmacist

List cetirizine side effects by likelihood and severity

4 Precautions

Before taking cetirizine, tell your doctor or pharmacist if you are allergic to it; or to hydroxyzine; or to levocetirizine; or if you have any other allergies This product may contain inactive ingredients, which can cause allergic reactions or other problems Talk to your pharmacist for more details

Before using this medication, tell your doctor or pharmacist your medical history, especially of: difficulty urinating (such as due to an enlarged prostate), kidney disease, liver disease

If you are using this medication to treat hives, tell your doctor right away if you have any of these other symptoms because they may be signs of a more serious condition: hives that are an unusual color, hives that look bruised or blistered, hives that do not itch

This drug may make you drowsy Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely Avoid alcoholic beverages

Liquid products may contain sugar Caution is advised if you have diabetes Ask your doctor or pharmacist about using this product safely

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products)

During pregnancy, this medication should be used only when clearly needed Discuss the risks and benefits with your doctor

This medication passes into breast milk Consult your doctor before breast-feeding

5 Interactions

Drug interactions may change how your medications work or increase your risk for serious side effects This document does not contain all possible drug interactions Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist Do not start, stop,

or change the dosage of any medicines without your doctor's approval

Tell your doctor or pharmacist if you are taking other products that cause drowsiness including alcohol, other antihistamines (such as diphenhydramine), drugs for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants, and narcotic pain relievers (such as codeine)

Check the labels on all your medicines (such as cough-and-cold products) because they may contain ingredients that cause drowsiness Ask your pharmacist about using those products safely

Do not use with any other antihistamines applied to the skin (such as diphenhydramine cream, ointment, spray) because increased side effects may occur

Cetirizine is very similar to hydroxyzine and levocetirizine Do not use these medications while using cetirizine

This medication may interfere with certain laboratory tests (including allergy skin testing), possibly causing false test results Make sure laboratory personnel and all your doctors know you use this drug

6 Overdose

If overdose is suspected, contact a poison control center or emergency room right away Symptoms of overdose may include: severe drowsiness In children, mental/mood changes (such as restlessness, irritability) may occur before drowsiness

8 Storage

Store at room temperature away from light and moisture Do not store in the bathroom Different brands of this medication may have different storage needs Check the product package for instructions on how to store your brand, or ask your pharmacist Keep all medications away from children and pets

Do not flush medications down the toilet or pour them into a drain unless instructed to

do so Properly discard this product when it is expired or no longer needed Consult your pharmacist or local waste disposal company

SELF-STUDY

BETAMETHASONE READING COMPREHENSION

1 Complete these sentences using the bold words in the text There are more words than sentences

a Immunologic side effects have included delayed wound healing and increased susceptibility to bacterial, viral and _ parasitic infections

b _ suppression can persist for up to twelve months after long-term corticosteroid therapy

c Women during pregnancy should use corticosteroids in caution because they may show harmful effects on _ or neonatal adrenal suppression

d Corticosteroids should never be withdrawn suddenly, but rather must be _ slowly

e Tell your doctor or pharmacist if you have a history of heart problems (eg, congestive _ failure [CHF]) and heart attack)

f _ changes or other eye problems can be found upon prolonged use of ophthalmic preparations containing corticosteroids

g Corticosteroids use may get women to experience _ abnormalities

h The _ of betamethasone are usually applied one to four times a day following the directions on your prescription

2 Find the synonym from the text of each word below

Reading 2

BETAMETHASONE

1 Pharmacopoeias

Ph Eur 6.2 (Betamethasone) A white or almost white, crystalline powder

Practically insoluble in water; sparingly soluble in dehydrated alcohol; very slightly soluble in dichloromethane Protect from light

USP 31 (Betamethasone) A white to practically white, odourless, crystalline powder

Soluble 1 in 5300 of water, 1 in 65 of alcohol, 1 in 15 of warm alcohol, 1 in 325 of chloroform, and 1 in 3 of methyl alcohol; sparingly soluble in acetone and in dioxan; very slightly soluble in ether Store in airtight containers at a temperature between 2° and 30°

2 Treatment, adverse effects, withdrawal, and precautions

2.1 Treatment

Betamethasone is used for:

Treating certain conditions associated with decreased adrenal gland function It

is used to treat severe inflammation caused by certain conditions, including severe asthma, severe allergies, rheumatoid arthritis, ulcerative colitis, certain blood disorders, lupus, multiple sclerosis, and certain eye and skin conditions It may be used for certain types of cancer (e.g., leukemia) It may also be used for other conditions as determined by your doctor

Betamethasone is a corticosteroid It works by modifying the body's immune response to various conditions and decreasing inflammation

2.2 Adverse effects of corticosteroids

The adverse effects of corticosteroids may result from unwanted mineralocorticoid or glucocorticoid actions, or from inhibition of the hypothalamic-pituitary-adrenal axis

Mineralocorticoid adverse effects are manifest in the retention of sodium and water,

with oedema and hypertension, and in the increased excretion of potassium with the possibility of hypokalaemic alkalosis In susceptible patients, cardiac failure may be induced Disturbances of electrolyte balance are common with the naturally occurring corticosteroids, such as cortisone and hydrocortisone, but are less frequent with many synthetic glucocorticoids, which have little or no mineralocorticoid activity

Adverse glucocorticoid effects lead to mobilisation of calcium and phosphorus, with

osteoporosis and spontaneous fractures; muscle wasting and nitrogen depletion; and hyperglycaemia with accentuation or precipitation of the diabetic state The insulin requirements of diabetic patients are increased Increased appetite is often reported

Impaired tissue repair and immune function can lead to delayed wound healing, and

increased susceptibility to infection Increased susceptibility to all kinds of infection,

including septicaemia, tuberculosis, fungal infections, and viral infections, has been

reported in patients on corticosteroid therapy Infections may also be masked by the anti-inflammatory, analgesic, and antipyretic effects of glucocorticoids The increased severity of varicella and measles may lead to a fatal outcome in non-immune patients receiving systemic corticosteroid therapy

Other adverse effects include menstrual irregularities, amenorrhoea, hyperhidrosis,

skin thinning, ocular changes including development of glaucoma and cataract, mental and neurological disturbances, benign intracranial hypertension, acute pancreatitis, and avascular necrosis of bone An increase in the coagulability of the blood may lead to thromboembolic complications Peptic ulceration has been reported but reviews of the literature do not always agree that corticosteroids are responsible for an increased incidence

The negative feedback effects of glucocorticoids on the hypothalamic-pituitary-adrenal (HPA) axis may lead to adrenal atrophy, in some cases after therapy for as little as 7 days This produces secondary adrenocortical insufficiency which may become manifest after overly rapid withdrawal of treatment or be precipitated by some stress such as infection or trauma Patients vary considerably in the degree and duration of

adrenal suppression after a given course of corticosteroid, but adrenal atrophy may

persist for months or years, and withdrawal should be gradual in those who have been treated for any length of time (see also Withdrawal, below) High doses of

corticosteroids given during pregnancy may cause fetal or neonatal adrenal

suppression Although the precise mechanism is uncertain, growth retardation may follow the use of even relatively small doses of corticosteroids in children

Large doses of corticosteroids, or of corticotropin, may produce Cushingoid symptoms typical of hyperactivity of the adrenal cortex, with moon-face, sometimes with hirsutism, buffalo hump, flushing, increased bruising, ecchymoses, striae, and acne

Giving large intravenous doses of corticosteroids too rapidly may cause

or its equivalent (see Uses and Administration, below, for equivalent doses of other corticosteroids) Short courses at high dosage for emergencies appear to cause fewer adverse effects than prolonged courses with lower doses

Most topically applied (including inhaled) corticosteroids may, under certain circumstances, be absorbed in sufficient amounts to produce systemic effects The topical application of corticosteroid preparations to the eyes has produced corneal ulcers, raised intra-ocular pressure, and reduced visual function Application of corticosteroids to the skin has led to loss of skin collagen and subcutaneous atrophy; local hypopigmentation of deeply pigmented skins has been reported after both the intradermal injection and topical application of potent corticosteroids Dryness, irritation, epistaxis, and rarely ulceration or perforation of the nasal septum have followed intranasal use; smell and taste disturbances may also occur Hoarseness and candidiasis of the mouth or throat may occur in patients receiving inhaled corticosteroids

Intrathecal dosage (including inadvertent intrathecal dosage after attempted epidural injection) has been associated with arachnoiditis

Adverse effects should be treated symptomatically, with the corticosteroid dosage reduced or slowly withdrawn where possible

2.3 Withdrawal of corticosteroids

The use of pharmacological doses of corticosteroids suppresses the endogenous secretion of corticotropin by Hie anterior pituitary, with the result that the adrenal cortex becomes atrophied Sudden withdrawal or reduction in dosage, or an increase in corticosteroid requirements associated with the stress of infection or accidental or surgical trauma, may then precipitate acute adrenocortical insufficiency; deaths have

followed the abrupt withdrawal of corticosteroids Adrenocortical insufficiency has also occurred after the effective reduction in systemic corticosteroid concentrations produced by overly rapid transfer from oral to inhaled corticosteroid therapy For the emergency treatment of acute adrenocortical insufficiency caused by abrupt withdrawal of corticosteroids

In some instances, withdrawal symptoms may involve or resemble a clinical relapse

of the disease for which the patient has been undergoing treatment Other ef fects that may occur during withdrawal or change of corticosteroid therapy include fever, myalgia, arthralgia, weight loss, benign intracranial hypertension with headache and vomiting, and papilledema caused by cerebral oedema Latent rhinitis or eczema may be unmasked

Duration of treatment and dosage are important factors in determining suppression

of the pituitary-adrenal response to stress on cessation of corticosteroid treatment, and individual liability to suppression is also important

After short courses at moderate doses it may be appropriate to withdraw

corticosteroids without tapering the dose (see below) However, after high-dose or

prolonged therapy, withdrawal should be gradual, the rate depending upon the individual patient's response, the dose, the disease being treated, and the duration of therapy Recommendations for initial reduction, stated in terms of prednisolone, have varied from as little as steps of 1 mg monthly to 2.5 to 5 mg every 2 to 7 days Provided the disease is unlikely to relapse the dose of systemic corticosteroid may

be reduced rapidly to physiological values; dose reduction should then be slower to allow recovery of pituitary-adrenal function Symptoms attributable to over-rapid withdrawal should be countered by resuming a higher dose and continuing the reduction at a slower rate Giving corticotropin does not help to re-establish adrenal responsiveness

This gradual withdrawal of corticosteroid therapy permits a return of adrenal function adequate for daily needs, but years may sometimes be required for the re -turn of function necessary to meet the stress of infection, surgery, or trauma On such occasions patients with a history of recent corticosteroid withdrawal should be protected by means of supplementary corticosteroid therapy as described under Precautions below

2.4 Precautions for corticosteroids

Systemic corticosteroids should be used with great caution in the presence of heart failure, recent myocardial infarction, or hypertension, in patients with diabetes

mellitus, epilepsy (but see below for use in infantile seizures), glaucoma, hypothyroidism, hepatic failure, osteoporosis, peptic ulceration, psychoses or severe affective disorders, and renal impairment Children may be at increased risk of some adverse effects; in addition, corticosteroids may cause growth retardation, and prolonged use is rarely justified The elderly too may be at greater risk from adverse effects

Corticosteroids are usually contra-indicated in the presence of acute infections uncontrolled by appropriate antimicrobial therapy Similarly, patients already receiving corticosteroids are more susceptible to infection, the symptoms of which, moreover, may be masked until an advanced stage has been reached Patients with active or doubtfully quiescent tuberculosis should not be given corticosteroids except, very rarely, as adjuncts to treatment with antitubercular drugs Patients with quiescent tuberculosis should be observed closely and should receive chemoprophylaxis if corti-costeroid therapy is prolonged

The risks of chickenpox and probably of severe herpes zoster are increased in

non-immune patients receiving therapeutic doses of systemic corticosteroids, and patients should avoid close personal contact with either infection Passive immunisation is recommended for non-immune patients who do come into contact with chickenpox Similar precautions apply to measles Live vaccines should not be given to patients receiving high-dose systemic corticosteroid therapy nor for at least 3 months afterwards; killed vaccines or toxoids may be given although the response may be attenuated During prolonged courses of corticosteroid therapy, patients should be examined regularly Sodium intake may need to be reduced and calcium and potassium supplements may be necessary Monitoring of the fluid intake and output, and daily weight records may give early warning of fluid retention Back pain may signify osteoporosis Children are at special risk from raised intracranial pressure Patients should carry cards (and preferably also wear bracelets) giving full details of their corticosteroid therapy; they and their relatives should be fully conversant with the implications of their therapy and the precautions to be taken

Measures to compensate for the adrenals" inability to respond to stress (see Withdrawal, above) include increasing the dose to cover minor intercurrent illnesses or trauma such as surgery (with intramuscular doses to cover vomiting)

Rapid intravenous injection of massive doses of corticosteroids may sometimes cause cardiovascular collapse and injections should therefore be given slowly or by infusion Many drugs have been reported to interfere with certain assay procedures for corticosteroids in body fluids and corticosteroids themselves may interfere with or alter the results of assays for some endogenous substances or drugs

The risk of systemic absorption should always be considered when applying corticosteroids topically They should not be applied with an occlusive dressing to large areas of the body Long-term topical use is best avoided, especially in children Also they should not be used for the treatment of ulcerative conditions, nor of rosacea, and should not be used indiscriminately for pruritus Occasionally they may be used with the addition of a suitable antimicrobial substance in the treatment of infected skin but there is a risk of sensitivity reactions occurring

Height should be monitored in children receiving prolonged therapy with inhaled or

nasal corticosteroids High doses of inhaled corticosteroids should preferably be

inhaled using large-volume spacer devices to reduce oropharyngeal deposition and hence the incidence of candidiasis; rinsing the mouth with water after inhalation may also be helpful In addition the use of spacer devices may reduce systemic absorption Paradoxical bronchospasm has occurred with inhaled corticosteroids and may require therapy to be stopped, although if mild it may be prevented by inhalation of a beta adrenoceptor agonist, or by transfer from an aerosol to a dry powder formulation

Caution is required when corticosteroids are used locally to treat eye disorders

Betamethasone has little or no effect on sodium and water retention

When applied topically, particularly to large areas, when the skin is broken, or under occlusive dressings, or when given intranasally, corticosteroids may be absorbed in sufficient amounts to cause systemic effects Prolonged use of ophthalmic preparations

containing corticosteroids has caused raised intra-ocular pressure and reduced visual

function

Anosmia Complete anosmia was reported in 2 patients after the use of nasal drops

containing betamethasone and neomycin sulfate1 and, in one patient, showed no sign

of resolving 1 year later The reaction was thought to be due to the preservative thi- omersal present in the drops, although it was noted that neomycin could exert a toxic effect on the olfactory mucosa and that there have been several reports of anosmia associated with the use of betamethasone alone

1 Whittet HB, et al Anosmia due to nasal administration of corticosteroid BMJ

1991; 303: 651

3 Interactions

Concurrent use of barbiturates, carbamazepine, phenytoin, primidone, or rifampicin may enhance the metabolism and reduce the effects of systemic corticosteroids Conversely oral contraceptives or ritonavir may increase plasma concentrations of corticosteroids Use of corticosteroids with potassium-depleting diuretics, such as thiazides or furosemide, may cause excessive potassium loss There is also an increased risk of hypokalaemia with concurrent amphotericin B or bronchodilator therapy with xanthines or beta agonists There may be an increased incidence of gastrointestinal bleeding and ulceration when corticosteroids are given with NSAIDs Response to anticoagulants may be altered by corticosteroids and requirements of antidiabetic drugs and antihypertensives may be increased Corticosteroids may decrease serum concentrations of salicylates and may decrease the effect of anticholinesterases in myasthenia gravis

4 Pharmacokinetics of corticosteroids

Corticosteroids are, in general, readily absorbed from the gastrointestinal tract They are also absorbed when given locally after topical use, particularly under an occlusive dressing or when the skin is broken, or use rectally as an enema, sufficient corticosteroid may be absorbed to give systemic effects; this is also a possibility with other local routes such as inhalation Water- soluble forms of corticosteroids are given

by intravenous injection for a rapid response; more prolonged effects are achieved

using lipid-soluble forms of corticosteroids by intramuscular injection

Corticosteroids are rapidly distributed to all body tissues They cross the placenta to varying degrees and may be distributed in small amounts into breast milk

Most corticosteroids in the circulation are extensively bound to plasma proteins, mainly to globulin and less so to albumin The corticosteroid-binding globulin (transcortin) has high affinity but low binding capacity, while albumin has low affinity but large binding capacity The synthetic corticosteroids are less extensively protein bound than hydrocortisone (Cortisol) They also tend to have longer half-lives Corticosteroids are metabolised mainly in the liver but also in other tissues, and are excreted in the urine The slower metabolism of the synthetic corticosteroids with their lower protein-binding affinity may account for their increased potency compared with the natural corticosteroids

4 Derendorf H, etal Pharmacokinetics and pharmacodynamics of inhaled

corticosteroids J Allergy Clin Immunol 1998; 101 (suppl 2): S440-6

5 Czock D, et al Pharmacokinetics and pharmacodynamics of systemic ally

administered glucocorticoids Clin Pharmacokinet 2005; 44:61-98

5 Uses and administration

Betamethasone is a corticosteroid with mainly glucocorticoid activity; the inflammatory activity of 750 micrograms of betamethasone is equivalent to about 5

anti-mg of prednisolone It has been used, either in the form of the free alcohol or in one of the esterified forms, in the treatment of conditions for which corticosteroid therapy is indicated, except adrenal-deficiency states for which hydrocortisone with

supplementary fludrocortisone is preferred Its virtual lack of mineralocorticoid

properties makes betamethasone particularly suitable for treating conditions in which water retention would be a disadvantage

The dose is usually expressed in terms of the base, and the following are each equivalent to about 1 mg of betamethasone:

 betamethasone acetate 1.1 mg

 betamethasone benzoate 1.3 mg

 betamethasone dipropionate 1.3 mg

 betamethasone sodium phosphate 1.3 mg

 betamethasone valerate 1.2 mg

When given orally betamethasone or betamethasone sodium phosphate are used; the usual dose, expressed in terms of betamethasone, ranges from 0.5 to 5 mg daily

For parenteral use the sodium phosphate ester may be given intravenously by injection or

infusion or intramuscularly by injection in doses equivalent to 4 to 20 mg of

betamethasone It may also be given by local injection into soft tissues in doses equivalent

to 4 to 8mg of betamethasone Doses in children, as a slow intravenous injection, are:

 infants aged up to 1 year: the equivalent of 1 mg of betamethasone

 1 to 5 years: 2 mg

 6 to 12 years: 4 mg

Doses may be repeated 3 or 4 times in 24 hours if necessary, depending on the condition

being treated and the clinical response The sodium phosphate ester is also sometimes used with the acetate or dipropionate esters, which have a slower and more prolonged action Betamethasone sodium phosphate is also used in the topical treatment of allergic and inflammatory conditions of the eyes, ears, or nose, usually as drops or ointment containing 0.1%

For topical application in the treatment of various skin disorders the dipropionate and valerate esters of betamethasone are extensively used; the usual concentrations available are the equivalent of 0.05% of betamethasone as the dipropionate, and 0.025 or 0.1% as the valerate For recommendations concerning the correct use of corticosteroids on the skin, and a rough guide to the clinical potencies of topical corticosteroids

Betamethasone valerate has also been used by inhalation for the prophylaxis of asthma Other esters of betamethasone which have occasionally been used include the benzoate, butyrate propionate, phosphate, salicylate (cortobenzolone), and valeroacetate

Betamethasone adamantoate has been used in veterinary practice

UNIT 3 THE PHARMACOLOGICAL BASIS OF DISEASE

TREATMENT

GUIDED STUDY

OMEPRAZOLE SCRUB UP

1 Work with a partner Match each of the words below to a stress pattern

1 urticaria _ a red spots on the skin that itch (= make you want to

scratch), caused by an allergic reaction, for example to certain foods

2 nausea _ b the feeling that you have when you want to vomit, for

example because you are ill/sick or are disgusted by something

3 tumour _ c a mass of cells growing in or on a part of the body where

they should not, usually causing medical problems

4 intravenous _ d (of drugs or food) going into a vein

5 antibacterial _ e that kills bacteria

6 insomnia _ f the condition of being unable to sleep

7 malaise _ g a general feeling of being ill/sick, unhappy or not

satisfied, without signs of any particular problem

8 flatulence _ h an uncomfortable feeling caused by having too much

gas in the stomach

READING COMPREHENSION

1 Fill in each blank with a suitable word

a Omeprazole is used to treat symptoms of _ disease and other conditions caused by excess stomach acid

b This medication may cause the following symptoms of headache, abdominal pain (diarrhea), and skin _

c _ infections may be found when using proton pump inhibitors due to their acid suppressive effects

d Before using this medicine, consult your doctor or pharmacist if you have the medical problem of _ impairment

e Patients should avoid the combination of omeprazole with _ because omeprazole may reduce exposure to atazanavir

f The half-life of omeprazole is almost entirely cleared from _ within

0.5-3 hours

g The recommended adult oral dose for the treatment of patients with

symptomatic Gastroesophageal _ Disease (GERD) is 20 mg daily for up

3 Translate the following sentences into Vietnamese

a It works by decreasing the amount of acid your stomach makes

b The adverse effects reported most often with omeprazole and other proton pump inhibitors have been headache, diarrhoea, and skin rashes

c Proton pump inhibitors may increase the risk of gastrointestinal infections because of their acid suppressive effects

d The usual dose for the treatment of gastro-oesopha- geal reflux disease is 20 mg orally once daily for 4 weeks, followed by a further 4 to 8 weeks if not fully healed

e For the eradication of Helicobacter pylori in peptic ulceration omeprazole may

be combined with antibacterials in dual or triple therapy

f The initial recommended dosage for patients with the Zollinger-Ellison

syndrome is 60 mg orally once daily, adjusted as required

of drugs known as proton pump inhibitors (PPIs)

If you are self-treating with this medication, over-the-counter omeprazole products are used to treat frequent heartburn (occurring 2 or more days a week) Since it may take 1

to 4 days to have full effect, these products do not relieve heartburn right away

For over-the-counter products, carefully read the package instructions to make sure the product is right for you Check the ingredients on the label even if you have used the product before The manufacturer may have changed the ingredients Also, products with similar brand names may contain different ingredients meant for different purposes Taking the wrong product could harm you

2 Pharmacopoeias In Chin., Eur., and US

Ph Eur 6.2 (Omeprazole) A white or almost white powder It exhibits

polymorphism Very slightly soluble in water; sparingly soluble in alcohol and in methyl alcohol; soluble in dichloromethane It dissolves in dilute solutions of alkali hydroxides Store in airtight containers at a temperature between 2° and 8° Protect from light

USP 31 (Omeprazole) A white to off-white powder Very slightly soluble in water;

sparingly soluble in alcohol and in methyl alcohol; soluble in dichloromethane Store

in airtight containers at a temperature not exceeding 8° Protect from moisture

3 Adverse effects

Proton pump inhibitors are generally well tolerated, and adverse effects are relatively infrequent The adverse effects reported most often with omeprazole and other proton pump inhibitors have been headache, diarrhoea, and skin rashes; they have sometimes been severe enough to require stopping treatment Other effects include pruritus, dizziness, fatigue, constipation, nausea and vomiting, flatulence, abdominal pain, ar-thralgia and myalgia, urticaria, and dry mouth Isolated cases of photosensitivity, bullous eruption, erythema multiforme, Stevens-Johnson syndrome, and toxic ep-idermal necrolysis have occurred Hypersensitivity reactions, including fever, bronchospasm, angioedema, and anaphylaxis have been reported Effects on the CNS include occasional insomnia, somnolence, and vertigo; reversible confusional states, agitation, depression, and hallucinations have occurred in severely ill patients Raised liver enzymes, and isolated cases of hepatitis, jaundice, hepatic failure, and hepatic encephalopathy, have been reported Other adverse effects reported rarely include paraesthesia, blurred vision, alopecia, stomatitis, increased sweating, taste disturbances, peripheral oedema, malaise, hyponatremia, blood disorders (including agranulocytosis, leucopenia, and thrombocytopenia), gynaecomastia, impotence, and interstitial nephritis Proton pump inhibitors may increase the risk of gastrointestinal infections because of their acid suppressive effects

Early toxicological studies identified carcinoid-like tumours of the gastric mucosa in rats given very high doses of omeprazole over long periods

4 Incidence of adverse effects Prescription-event monitoring for 16 205

patients prescribed omeprazole, 17 329 prescribed lansoprazole, and 11 541 prescribed pantoprazole indicated that adverse events were reported infrequently, with the most common being gastrointestinal disturbances and headache The incidences of diarrhoea, the most commonly reported event, per 1000 days of exposure, were 0.18 for omeprazole, 0.39 for lansoprazole, and 0.23 for pantoprazole Despite the inherent biases of such a cohort study, there did seem to be some evidence that lansoprazole might be associated with a somewhat greater risk of diarrhoea, particularly in the elderly

1 Martin RM, et al The rates of common adverse events reported during treatment with proton pump inhibitors used in general practice in England:

cohort studies Br J Clin Pharmacol 2000; 50: 366-72

5 Precautions

Before giving omeprazole or other proton pump inhibitors to patients with gastric ulcers the possibility of malignancy should be excluded since these drugs may mask symptoms and delay diagnosis Omeprazole and other proton pump inhibitors should

be used with caution in hepatic impairment and dose adjustment may be required Gastric carcinoma Proton pump inhibitors relieve dyspeptic symptoms associated with gastric carcinoma and can therefore delay its diagnosis In addition, there is some evidence that they may also endoscopically 'heal' early gastric carcinoma so that the diagnosis is missed.1 Consequently, some commentators recommend that proton pump inhibitors should not be prescribed for symptom control before endoscopy in patients

at risk for gastric carcinoma.2

1 Wayman J, et al The response of early gastric cancer to proton- pump

inhibitors N Engl J Med 1998; 338: 1924-5

2 Griffin SM, Raimes SA Proton pump inhibitors may mask early gastric cancer: dyspeptic patients over 45 should undergo endoscopy before these drugs are

started BMJ 1998; 317: 1606-7

5.1 Helicobacter infection Treatment with proton pump inhibitors may cause

false-negative results in the urea breath test for Helicobacter pylori infection In one study in patients with H pylori infection, 4 weeks of treatment with lansoprazole 30

mg daily caused 33% of patients to have negative urea breath tests.1 The breath test became positive again in all patients within 2 weeks of stopping lansoprazole therapy

In a similar study, 52% of patients had negative urea breath tests for H pylori while ceiving omeprazole 20 mg daily, and the breath test became positive again in all patients within 2 to 6 days of stopping treatment.2 The manufacturers of the urea breath test for H pylori recommend that it should not be performed for at least 2 weeks after stopping treatment with an antisecretory drug

re-For a discussion of the link between proton pump inhibitors, H pylori, and gastritis, see under Gastrointestinal Tumours above

1 Laine L, et al Effect of proton-pump inhibitor therapy on diagnostic testing for

Helicobacter pylori Ann Intern Med 1998; 129: 547-50

2 Connor SJ, et al The effect of dosing with omeprazole on the accuracy of the

C-urea breath test in Helicobacter pylori-in- fected subjects Aliment Pharmacol

Ther 1999; 13: 1287-93

5.2 Hepatic impairment In patients with cirrhosis an increase in omeprazole

bioavailability, and elimination half-life has been reported.1 For dosage adjustment in hepatic impairment see Administration in Hepatic Impairment, below

1 Andersson T, et al Pharmacokinetics of [C]omeprazole in patients with liver

cirrhosis Clin Pharmacokinet 1993; 24: 71-8

5.3 Pregnancy Proton pump inhibitors are not generally licensed for use

during pregnancy (although the UK has licensed omeprazole for such use), but a analysis1 of 5 studies of exposure to proton pump inhibitors during the first trimester, involving 593 exposed infants, found the relative risk of major abnormalities associated with such exposure to be only 1.18, with a 95% confidence interval ranging from 0.72 to 1.94 Meta-analysis of exposures to omeprazole (from 4 studies only) gave a relative risk of 1.05 (95% confidence interval 0.59 to 1.85) It was concluded that exposure to proton pump inhibitors, and omeprazole in particular, did not pose an important teratogenic risk A retrospective epidemiological study of data from the Swedish Medical Birth Registry, which identified 955 exposed infants, also found no evidence of significant risk after exposure to omeprazole during pregnancy.2

meta-1 Nikfar S, et al Use of proton pump inhibitors during pregnancy and rates of

major malformations: a meta-analysis Dig Dis Sci 2002; 47: 1526-9

2 Kallen BAJ Use of omeprazole during pregnancy-no hazard demonstrated in

955 infants exposed during pregnancy Eur J Obstet Gynecol ReprodBiol 2001;

96: 63-8

6 Interactions

Omeprazole and other proton pump inhibitors are metabolised by the cytochrome P450 system, primarily by isoenzyme CYP2C19, and to a smaller extent by CYP3A4 Inhibitors or inducers of these isoenzymes may affect exposure to omeprazole and other proton pump inhibitors In turn, proton pump inhibitors may alter the metabolism

of some drugs metabolised by Ihese enzymes Omeprazole may prolong the tion of diazepam, phenytoin, and warfarin (but see below) Omeprazole and other proton pump inhibitors can reduce the absorption of drugs such as dasatinib, ketoconazole, and itraconazole, whose absorption is dependent on an acid gastric pH With voriconazole, the plasma concentration of both drugs may be increased Other proton pump inhibitors may be similarly affected by voriconazole Omeprazole and other proton pump inhibitors should not be used with atazanavir, as it substantially reduces exposure to atazanavir

elimina-7 Pharmacokinetics

Omeprazole is rapidly but variably absorbed after oral doses Absorption is not significantly affected by food Omeprazole is acid-labile and the pharmacokinetics of the various formulations developed to improve oral bioavailability may vary The absorption of omeprazole also appears to be dose-dependent; increasing the dosage above 40 mg has been reported to increase the plasma concentrations in a non-linear fashion because of saturable first-pass hepatic metabolism In addition, bioavailability

is higher after long-term use

Bioavailability of omeprazole may be increased in elderly patients, in some ethnic groups such as Chinese, and in patients with hepatic impairment, but is not markedly affected in patients with renal impairment

On absorption, omeprazole is almost completely metabolised in the liver, primarily by the cytochrome P450 isoenzyme CYP2C19 to form hydroxy-omepra- zole, and to a small extent by CYP3 A4 to form omeprazole sulfone The metabolites are inactive, and are excreted mostly in the urine and to a lesser extent in bile The elimination half-life from plasma is reported to be about 0.5 to 3 hours Omeprazole is about 95% bound to plasma proteins

References

1 Andersson T, et al Pharmacokinetics of various single intravenous and oral

doses of omeprazole Eur J Clin Pharmacol 1990; 39: 195-7

2 Andersson T, Regardh C-G Pharmacokinetics of omeprazole and metabolites

following single intravenous and oral doses of 40 and 80 mg Drug Invest 1990;

2: 255-63

8 Metabolism The major enzyme involved in omeprazole metabolism is

cytochrome P450 isoenzyme CYP2C19 This enzyme is polymorphic ally expressed, and individuals who are deficient in the enzyme are poor metabolisers of omeprazole This occurs in about 3% of Caucasians and 15% of Chinese, Japanese, and Koreans These individuals have markedly higher plasma concentrations of omeprazole, and they may require dosage adjustment Some omeprazole is metabolised by CYP3A4, and some by C YP2D6 to form desmethylomeprazole

9 Uses and administration

Omeprazole is a proton pump inhibitor It suppresses secretion of gastric acid by inhibiting the enzyme system of hydrogen/potassium adenosine triphosphatase (H+/K+ATPase), the 'proton pump' of the gastric parietal cell It is used in conditions where inhibition of gastric acid secretion may be beneficial, including aspiration syndromes, dyspepsia , gas-tro-oesophageal reflux disease, peptic ulcer disease, and the Zollinger-Ellison syndrome

Esomeprazole, an isomer of omeprazole, is also used

Omeprazole may be given orally as the base or magnesium salt, or intravenously as the sodium salt Doses are expressed in terms of the base Omeprazole magnesium 10.32

mg and omeprazole sodium 10.64 mg are each equivalent to about 10 mg of omeprazole

For the relief of acid-related dyspepsia omeprazole is given in usual doses of 10 or 20

mg daily orally for 2 to 4 weeks

The usual dose for the treatment of gastro-oesopha- geal reflux disease is 20 mg orally once daily for 4 weeks, followed by a further 4 to 8 weeks if not fully healed In refractory oesophagitis, a dose of 40 mg daily may be used Maintenance therapy after healing of oesophagitis is 20 mg once daily, and for acid reflux is 10 mg daily For dosage in children see below

In the management of peptic ulcer disease a single daily dose of 20 mg orally, or 40

mg in severe cases, is given Treatment is continued for 4 weeks for duodenal ulcer and 8 weeks for gastric ulcer Where appropriate, a dose of 10 to 20 mg once daily may be given for maintenance

For the eradication of Helicobacter pylori in peptic ulceration omeprazole may be combined with antibacterials in dual or triple therapy Effective triple therapy regimens include omeprazole 20 mg twice daily or 40 mg once daily combined with: amoxicillin 500 mg and metronidazole 400 mg, both three times daily; clarithromycin

250 mg and metronidazole 400 mg (or tinidazole 500 mg) both twice daily; or with amoxicillin 1 g and clarithromycin 500 mg, both twice daily These regimens are given for 1 week Dual therapy regimens such as omeprazole 20 mg twice daily or 40 mg daily with either amoxicillin 750 mg to 1 g twice daily or clarithromycin 500 mg three times daily, are less effective and must be given for 2 weeks Omeprazole alone may

be continued for a further 4 to 8 weeks

Doses of 20 mg daily orally are used in the treatment of NSAID-associated ulceration;

a dose of 20 mg daily may also be used for prophylaxis in patients with a history of gastroduodenal lesions who require continued NSAID treatment

The initial recommended dosage for patients with the Zollinger-Ellison syndrome is 60

mg orally once daily, adjusted as required The majority of patients are effectively controlled by doses in the range 20 to 120 mg daily, but doses up to 120 mg three times daily have been used Daily doses above 80 mg should be given as divided doses (usually 2)

Omeprazole is also used for the prophylaxis of acid aspiration during general anaesthesia, in a dose of 40 mg the evening before surgery and a further 40 mg two to six hours before the procedure

The dose of omeprazole may need to be reduced in patients with hepatic impairment

10 Parenteral dosage

In patients who are unsuited to receive oral therapy omeprazole sodium maybe given

on a short-term basis by intravenous infusion, in a usual dose equivalent to 40 mg of the base over a period of 20 to 30 minutes in 100 mL of sodium chloride 0.9% or glucose 5% It may also be given by slow intravenous injection Higher intravenous doses have been given to patients with Zollinger-Ellison syndrome

SELF- STUDY

CHLORPROMAZINE READING COMPREHENSION

1 Read the passage above and decide if these sentences are true (T) or false (F)

a Chlorpromazine cannot be used to treat hiccups that last a month or longer

b This medication may cause changes in behavior

c Before taking chlorpromazine, there is no need to tell your doctor if you have or have ever had asthma

d The medicine can also make your skin more sensitive to sunlight You should avoid unnecessary or prolonged sun exposure while taking chlorpromazine

e Chlorpromazine may make it harder for your body to cool down after it gets very hot, so use caution in extreme heat or during vigorous exercise and drink plenty of fluids when the weather is hot

f This medicine does not harm a breastfeeding baby because it is not excreted in the breast milk

g Double up on doses to make up for a missed one

2 Answer the questions about the text

a What is Chlorpromazine used for?

b How do I take Chlorpromazine?

c What are the side effects?

d What do I do if I take too much?

e How do I store Chlorpromazine?

3 Translate the entire Reading 2 into Vietnamese