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Assignment On

Steriomerism of Omeprazole

& Ibuprofen & it’s effect on

pharmacological activity

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Created By: Md. Kamruzzaman Siam

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INDEX

Sr. Topic Page no.

1 About Stereochemistry. 3

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About Omeprazole and Ibuprofen:

a) History.

b) Definition

c) Structure.

d) Medical uses.

e) What should we avoid while taking

omeprazole & ibuprofen.

f) Chemistry of Omeprazole & ibuprofen.

g) Side effects.

h) Important information,.

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4 References

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What is Stereochemistry?

Stereochemistry is a Greek word in which ‘stereo’ means solid.

Stereochemistry deals with the spatial arrangements of atoms

and groups in a molecule.

Stereochemistry refers to the 3-dimensional properties and

reactions of molecules. It has its own language and terms that

need to be learned in order to fully communicate and

understand the concepts.

Isomers

Compounds that possess the same molecular formula but

differ from each other in physical and or chemical properties.

Stereoisomers

Stereoisomers are compounds made up of same atoms bonded

by the same bonds, but having different three-dimensional

structures that are not interchangeable.

Two stereoisomers of sugar glucose

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History of Omeprazole?

Omeprazole was first marketed in the United States in 1989 by

Astra AB, now AstraZeneca, under the brand name Losec. In

1990, at the request of the U.S. Food and Drug Administration,

the brand name Losec was changed to Prilosec to avoid

confusion with the diuretic Lasix (furosemide). The new name

led to confusion between omeprazole (Prilosec) and fluoxetine

(Prozac), an antidepressant.

When Prilosec's U.S. patent expired in April 2001, AstraZeneca

introduced esomeprazole (Nexium) as a patented replacement

drug. Many companies introduced generics as AstraZeneca's

patents expired worldwide, which are available under many

brand names.

What is Omeprazole?

• Omeprazole (Prilosec, Zegerid) belongs to group of drugs

called proton pump inhibitors. It decreases the amount of

acid produced in the stomach.

• Omeprazole is used to treat symptoms of gastroesophageal

reflux disease (GERD) and other conditions caused by

excess stomach acid. It is also used to promote healing of

erosive esophagitis (damage to your esophagus caused by

stomach acid).

• Omeprazole is not for immediate relief of heartburn

symptoms.

OMEPRAZOLE

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• Omeprazole may also be given together with antibiotics to

treat gastric ulcer caused by infection with helicobacter

pylori (H. pylori).

Structure of Omeprazole:

3D-structure of Omeprazole

Structure of Omeprazole

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Medical uses

Omeprazole can be used in the treatment of gastroesophageal

reflux disease (GERD), peptic ulcers, erosive esophagitis, and

Zollinger-Ellison syndrome.

What should we avoid while taking omeprazole?

This medicine can cause diarrhea, which may be a sign of a new

infection. If you have diarrhea that is watery or bloody, call your

doctor. Do not use anti-diarrhea medicine unless your doctor

tells you to.

Chemistry of Omeprazole:

Is Esomeprazole (Nexium) more effective than Omeprazole

(Prilosec) in reducing Heartburn and in increasing the Rate of

esophageal healing in adults with endoscopically diagnosed

Erosive Esophagitis (EE)??

(S)-(−) and (R)-(+)-enantiomers of omeprazole, a racemate (1:1

mixture of both enantiomers)

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Omeprazole contains a tricoordinated sulfinyl sulfur in a

pyramidal structure and therefore can exist as either the (S)- or

(R)-enantiomers. Omeprazole is a racemate, an equal mixture of

the two. In the acidic conditions of the canaliculi of parietal

cells, both enantiomers are converted to chiral products (sulfenic

acid and sulfenamide configurations) which react with a cysteine

group in H+/K+ ATPase, thereby inhibiting the ability of the

parietal cells to produce gastric acid.

AstraZeneca has also developed esomeprazole (Nexium) which

is a eutomer, purely the (S)-enantiomer, rather than a racemate

like omeprazole.

Omeprazole undergoes a chiral shift in vivo which converts the

inactive (R)-enantiomer to the active (S)-enantiomer, doubling

the concentration of the active form. This chiral shift is

accomplished by the CYP2C19 isozyme of cytochrome P450,

which is not found equally in all human populations. Those who

do not metabolize the drug effectively are called "poor

metabolizers". The proportion of the poor metabolizer

phenotype varies widely between populations, from 2.0–2.5% in

African Americans and white Americans to >20% in Asians;

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several pharmacogenomics studies have suggested that PPI

treatment should be tailored according to CYP2C19 metabolism

status.

Omeprazole side effects

Get emergency medical help if you have signs of an allergic

reaction to omeprazole: hives; difficulty breathing; swelling of

your face, lips, tongue, or throat.

Call your doctor at once if you have:

severe stomach pain, diarrhea that is watery or bloody;

seizure (convulsions);

kidney problems--urinating more or less than usual, blood

in your urine, swelling, rapid weight gain; or

symptoms of low magnesium--dizziness, confusion; fast or

uneven heart rate; tremors (shaking) or jerking muscle

movements; feeling jittery; muscle cramps, muscle spasms

in your hands and feet; cough or choking feeling.

Common omeprazole side effects may include:

stomach pain, gas;

nausea, vomiting, diarrhea; or

headache.

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Important information of Omeprazole

Omeprazole is not for immediate relief of heartburn

symptoms.

Heartburn is often confused with the first symptoms of a

heart attack. Seek emergency medical attention if you have

chest pain or heavy feeling, pain spreading to the arm or

shoulder, nausea, sweating, and a general ill feeling.

You should not take this medication if you are allergic to

omeprazole or to any other benzimidazole medication such

as albendazole or mebendazole.

Ask a doctor or pharmacist if it is safe for you to take

omeprazole if you have liver disease or heart disease, or

low levels of magnesium in your blood.

Some conditions are treated with a combination of

omeprazole and antibiotics. Use all medications as directed

by your doctor. Read the medication guide or patient

instructions provided with each medication. Do not change

your doses or medication schedule without your doctor's

advice.

Take omeprazole for the full prescribed length of time.

Your symptoms may improve before the infection is

completely cleared.

Prilosec OTC (over-the-counter) should be taken for no

longer than 14 days in a row. Allow at least 4 months to

pass before you start another 14-day treatment.

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History

Ibuprofen was derived from propionic acid by the research arm

of Boots Group during the 1960s. Its discovery was the result of

research during the 1950s and 1960s to find a safer alternative to

aspirin. It was discovered by a team led by Stewart Adams and

the patent application was filed in 1961.Adams initially tested

the drug as treatment for his hangover. The drug was launched

as a treatment for rheumatoid arthritis in the United Kingdom in

1969, and in the United States in 1974. Later, in 1983 and 1984,

it became the first NSAID (other than aspirin) to be available

over the counter (OTC) in these two countries.Dr. Adams was

subsequently awarded an OBE in 1987. Boots was awarded the

Queen's Award for Technical Achievement for the development

of the drug in 1987.

What is ibuprofen?

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID). It

works by reducing hormones that cause inflammation and pain

in the body.

Ibuprofen is used to reduce fever and treat pain or inflammation

caused by many conditions such as headache, toothache, back

pain, arthritis, menstrual cramps, or minor injury.

Ibuprofen is used in adults and children who are at least 6

months old.

IBUPROFEN

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Structure of Ibuprofen:

3D-structure of Ibuprofen

structure of Ibuprofen

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Medical uses

200-mg ibuprofen tablets

Ibuprofen is used primarily to treat fever (including

postimmunisation fever), mild to moderate pain (including pain

relief after surgery), painful menstruation, osteoarthritis, dental

pain, headaches, and pain from kidney stones. About 60% of

people respond to any NSAID; those who do not respond well to

a particular one may respond to another.

It is used for inflammatory diseases such as juvenile idiopathic

arthritis and rheumatoid arthritis. It is also used for pericarditis

and patent ductus arteriosus.

What should we avoid while taking ibuprofen?

Avoid drinking alcohol. It may increase your risk of

stomach bleeding.

Avoid taking aspirin while you are taking ibuprofen.

Avoid taking ibuprofen if you are taking aspirin to prevent

stroke or heart attack. Ibuprofen can make aspirin less

effective in protecting your heart and blood vessels. If you

must use both medications, take the ibuprofen at least 8

hours before or 30 minutes after you take the aspirin (non-

enteric coated form).

Ask a doctor or pharmacist before using any cold, allergy,

or pain medicine. Many medicines available over the

counter contain aspirin or other medicines similar to

ibuprofen. Taking certain products together can cause you

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to get too much of this type of medication. Check the label

to see if a medicine contains aspirin, ibuprofen, ketoprofen,

or naproxen.

Chemistry of Ibuprofen:

Ibuprofen is practically insoluble in water, but very soluble in

most organic solvents like ethanol (66.18 g/100mL at 40°C for

90% EtOH), methanol, acetone and dichloromethane.

The original synthesis of ibuprofen by the Boots Group started

with the compound 2-methylpropylbenzene. The synthesis took

six steps. A modern, greener technique for the synthesis

involves only three steps.

Stereochemistry

(R)-ibuprofen (S)-ibuprofen

It is an optically active compound with both S and R-isomers, of

which the S (dextrorotatory) isomer is the more biologically

active; this isomer has also been isolated and used medically

(see dexibuprofen for details). Ibuprofen is produced

industrially as a racemate. The compound, like other 2-

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arylpropionate derivatives (including ketoprofen, flurbiprofen,

naproxen, etc.), does contain a stereocenter in the α-position of

the propionate moiety. So two enantiomers of ibuprofen occur,

with the potential for different biological effects and metabolism

for each enantiomer. Indeed, the (S)-(+)-ibuprofen (

dexibuprofen ) was found to be the active form both in vitro and

in vivo.

An isomerase (alpha-methylacyl-CoA racemase) converts (R)-

ibuprofen to the active (S)-enantiomer.

Ibuprofen side effects:

Get emergency medical help if you have signs of an allergic

reaction to ibuprofen: sneezing, runny or stuffy nose;

wheezing or trouble breathing; hives; swelling of your face, lips,

tongue, or throat.

Get emergency medical help if you have signs of a heart attack

or stroke: chest pain spreading to your jaw or shoulder, sudden

numbness or weakness on one side of the body, slurred speech,

leg swelling, feeling short of breath.

Stop using ibuprofen and call your doctor at once if you have:

changes in your vision;

shortness of breath (even with mild exertion).

swelling or rapid weight gain;

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the first sign of any skin rash, no matter how mild.

signs of stomach bleeding - bloody or tarry stools,

coughing up blood or vomit that looks like coffee grounds,

liver problems - nausea, upper stomach pain, itching, tired

feeling, flu-like symptoms, loss of appetite, dark urine,clay-

colored stools, jaundice (yellowing of the skin or eyes).

kidney problems - little or no urinating, painful or difficult

urination, swelling in your feet or ankles, feeling tired or

short of breath.

low red blood cells (anemia) - pale skin, feeling light-

headed or short of breath, rapid heart rate, trouble

concentrating; or

severe skin reaction - fever, sore throat, swelling in your

face or tongue, burning in your eyes, skin pain followed by

a red or purple skin rash that spreads (especially in the face

or upper body) and causes blistering and peeling.

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Common ibuprofen side effects may include:

Upset stomach, mild heartburn, nausea, vomiting;

Bloating, gas, diarrhea, constipation;

Dizziness, headache, nervousness;

Mild itching or rash; or

Ringing in your ears.

Important information of Ibuprofen:

Ibuprofen can increase your risk of fatal heart attack or

stroke, especially if you use it long term or take high doses,

or if you have heart disease. Do not use this medicine just

before or after heart bypass surgery (coronary artery bypass

graft, or CABG).

Ibuprofen may also cause stomach or intestinal bleeding,

which can be fatal. These conditions can occur without

warning while you are using ibuprofen, especially in older

adults.

Do not take more than your recommended dose. An

ibuprofen overdose can damage your stomach or

intestines. Use only the smallest amount of medication

needed to get relief from your pain, swelling, or fever.

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References:

1. "Product Information. Motrin (ibuprofen)." Pharmacia and

Upjohn, Kalamazoo, MI.

2. Cerner Multum, Inc. "Australian Product Information.

3. Cerner Multum, Inc. "UK Summary of Product

Characteristics."

4. "Product Information. Caldolor (ibuprofen)." Cumberland

Pharmaceuticals Inc, Nashville, TN.

5. "Product Information. NeoProfen (ibuprofen)." Ovation

Pharmaceuticals Inc, Deerfield, IL.

6. "Product Information. Ibuprofen (ibuprofen)." Par

Pharmaceutical Inc, Spring Valley, NY.

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