October 6 University Faculty of pharmacy

RESEARCH ABOUT :

Aspirin

Under observation : Dr \ Mohammed Abu Elwafa Made by : Asmaa Mohammed Ali Emara Riham Ahmed Hassan Farrag

Aspirin is the most widely used over-the-counter drug in the world. The average tablet contains about 325 milligrams of acetylsalicylic acid with an inert binding material such as starch. Aspirin is used to relieve pain, reduce inflammation, and lower fever. Aspirin originally was derived by boiling the bark of the white willow tree. Felix Hoffman and Arthur Eichengrn first synthesized the active ingredient in aspirin, acetylsalicylic acid, in 1893. Generic Name: aspirin (oral) (AS pir in) Brand Names: Arthritis Pain, Aspergum, Aspir-Low, Aspirin Lite Coat, Bayer Aspirin, Bufferin, Easprin, Ecotrin, Empirin, Fasprin, Genacote, Halfprin, Norwich Aspirin, St. Joseph Aspirin, Stanback Analgesic, Tri-Buffered Aspirin, YSP Aspirin, Zorprin

Aspirin Formula :

CH3

Although the salicin in willow bark has analgesic properties, purified salicylic acid was bitter and irritating when taken orally. Salicylic acid was neutralized with sodium to produce sodium salicylate, which was better-tasting but still irritated the stomach. Salicylic acid could be modified to produce phenylsalicylate, which was better tasting and less irritating, but released the toxic substance phenol when metabolized .

How to make Aspirin :

First gather the chemicals and equipment used to synthesize the aspirin:

Materials

3.0 g salicylic acid 6 mL acetic anhydride* 5-8 drops of 85% phosphoric acid or concentrated sulfuric acid* distilled water (about 50 mL) 10 mL ethanol 1% iron III chloride (optional, to test purity)

*Use extreme caution when handling these chemicals. Phosphoric or sulfuric acid and acetic anhydride can cause severe burns.

Equipment

filter paper (12.5 cm) ring stand with funnel two 400 mL beakers 125 mL Erlenmeyer flask 50 mL buret or measuring pipet 10 mL and 50 mL graduated cylinder fume hood, hot plate, balance dropper stirring rod ice bath wash bottle

*Let's synthesize aspirin... 1. Accurately weigh 3.00 grams of salicylic acid and transfer to a dry Erlenmeyer flask. If you will be calculating actual and theoretical yield, be sure to record how much salicylic acid you actually measured. 2. Add 6 mL of acetic anhydride and 5-8 drops of 85% phosphoric acid to the flask. 3. Gently swirl the flask to mix the solution. Place the flask in a beaker of warm water for ~15 minutes. 4. Add 20 drops of cold water dropwise to the warm solution to destroy the excess acetic anhydride. 5. Add 20 mL of water to the flask. Set the flask in an ice bath to cool the mixture and speed crystallization. 6. When the crystallization process appears complete, pour the mixture through a Buckner funnel. 7. Apply suction filtration through the funnel and wash the crystals with a few milliliters of ice cold water. Be sure the water is near freezing to minimize loss of product. 8. Perform a recrystallization to purify the product. Transfer the crystals to a beaker. Add 10 mL of ethanol. Stir and warm the beaker to dissolve the crystals. 9. After the crystals have dissolved, add 25 mL of warm water to the alcohol solution. Cover the beaker. Crystals will reform as the solution cools. Once crystallization has started, set the beaker in an ice bath to complete the recrystallization. 10. Pour the contents of the beaker into a Buckner funnel and apply suction filtration. 11. Remove the crystals to dry paper to remove excess water. 12. Confirm you have acetylsalicylic acid by verifying a melting point of 135C.

Preparing Aspirin :
In this laboratory exercise, you can prepare aspirin (acetylsalicylic acid) from salicylic acid and acetic anhydride using the following reaction:
Salicylic acid (C7H6O3) + Acetic anhydride (C4H6O3) --> Acetylsalicylic acid (C9H8O4) + Acetic acid (C2H4O2)

Aspirin Oral Uses :

Aspirin is used to reduce fever and relieve mild to moderate pain from conditions such as muscle aches, toothaches, common cold, and headaches. It may also be used to reduce pain and swelling in conditions such as arthritis. Aspirin is known as a salicylate and a nonsteroidal anti-inflammatory drug (NSAID). It works by blocking a certain natural substance in your body to reduce pain and swelling. Consult your doctor before treating a child younger than 12 years. Your doctor may direct you to take a low dose of aspirin to prevent blood clots. This effect reduces the risk of stroke and heart attack. If you have recently had surgery on clogged arteries (such as bypass surgery, carotid endarterectomy, coronary stent), your doctor may direct you to use aspirin in low doses as a "blood thinner" to prevent blood clots.

How to use Aspirin Oral :

If you are taking this medication for self-treatment, follow all directions on the product package. If you are uncertain about any of the information, consult your doctor or pharmacist. If your doctor has directed you to take this medication, take it exactly as prescribed. Take this medication by mouth. Drink a full glass of water (8 ounces/240 milliliters) with it unless your doctor tells you otherwise. Do not lie down for at least 10 minutes after you have taken this drug. If stomach upset occurs while you are taking this medication, you may take it with food or milk. Swallow enteric-coated tablets whole. Do not crush or chew enteric-coated tablets. Doing so can increase stomach upset. Do not crush or chew extended-release tablets or capsules. Doing so can release all of the drug at once, increasing the risk of side effects. Also, do not split extended-release tablets unless they have a score line and your doctor or pharmacist tells you to do so. Swallow the whole or split tablet without crushing or chewing. The dosage and length of treatment are based on your medical condition and response to treatment. Read the product label to find recommendations on how many tablets you can take in a 24-hour period and how long you may self-treat before seeking medical advice. Do not take more medication or take it for longer than recommended unless directed by your doctor. Consult your doctor or pharmacist if you have any questions. If you are taking this medication for self-treatment of headache, seek immediate medical attention if you also have slurred speech, weakness on one side of the body, or sudden vision changes. Before using this drug, consult a doctor or pharmacist if you have headaches caused by head injury, coughing, or bending, or if you have a headache with persistent/severe vomiting, fever, and stiff neck. If you are taking this medication as needed (not on a regular schedule), remember that pain medications work best if they are used as the first signs of pain occur. If you wait until the pain has worsened, the medicine may not work as well. Aspirin with a special coating (enteric coating) or slow release may take longer to stop pain because it is absorbed more slowly. Ask your doctor or pharmacist to help select the best type of aspirin for you. You should not take this medication for self-treatment of pain for longer than 10 days. You should not use this drug to self-treat a fever that lasts longer than 3 days. In these cases, consult a doctor because you may have a more serious condition. Tell your doctor promptly if you develop ringing in the ears or difficulty hearing.

If your condition persists or worsens (such as new or unusual symptoms, redness/swelling of the painful area, pain/fever that does not go away or gets worse) or if you think you may have a serious medical problem, tell your doctor promptly.

Dosage :
Adult aspirin tablets are produced in standardized sizes, which vary slightly from country to country, for example 300 mg in Britain and 325 mg in the USA. Smaller doses are based on these standards; e.g. 75and 81-milligram tablets are used; there is no medical significance in the slight difference. It is of historical interest that in the U.S., a 325 mg dose is equivalent to the historic 5-grain aspirin tablet in use prior to the metric system. In general, for adults, doses are taken four times a day for fever or arthritis, with doses near the maximal daily dose used historically for the treatment of rheumatic fever. For the prevention of myocardial infarction in someone with documented or suspected coronary artery disease, much lower doses are taken once daily. New recommendations from the US Preventive Services Task Force (USPSTF, March, 2009) on the use of aspirin for the primary prevention of coronary heart disease encourage men aged 4579 and women aged 5579 to use aspirin when the potential benefit of a reduction in myocardial infarction (MI) for men or stroke for women outweighs the potential harm of an increase in gastrointestinal hemorrhage. The WHI study said regular low dose (75 or 81 mg) aspirin female users had a 25% lower risk of death from cardiovascular disease and a 14% lower risk of death from any cause. Low dose aspirin use was also associated with a trend toward lower risk of cardiovascular events, and lower aspirin doses (75 or 81 mg/day) may optimize efficacy and safety for patients requiring aspirin for long-term prevention. In children with Kawasaki disease, aspirin is taken at dosages based on body weight, initially four times a day for up to two weeks and then at a lower dose once daily for a further six to eight weeks.

Aspirin side effects :

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using aspirin and call your doctor at once if you have any of these serious side effects:

Black, bloody, or tarry stools. Coughing up blood or vomit that looks like coffee grounds. Severe nausea, vomiting, or stomach pain. Fever lasting longer than 3 days. Swelling, or pain lasting longer than 10 days. Hearing problems, ringing in your ears.

Less serious side effects may include:

Upset stomach, heartburn.

Drowsiness. Headache.

The common aspirin side effects are primarily related to its anti-platelet effects. Serious bleeding, especially gastrointestinal bleeding, is the most common serious side effect. Aspirin also frequently causes gastrointestinal irritation including gastritis, gastric and duodenal ulcers, and esophagitis. These combined with the anti-platelet effect which can cause any bleeding to be more severe make GI bleeding a common aspirin side effect. Especially when used in high doses aspirin causes tinnitus, or ringing in the ears. Irreversible ototoxicity can be an aspirin side effect. The common aspirin side effects related to the anti-platelet effect include bruising and bleeding. Gastrointestinal aspirin side effect symptoms include dyspepsia, nausea, vomiting, constipation, diarrhea and abdominal pain. Aspirin can also lead to reduced excretion of uric acid and hyperuricemia. Dizziness is also common, likely related to the ototoxicity. For an over the counter medication aspirin has a list of serious side effects that rival most medications available only by prescription. Aspirin allergy is reasonably common, and serious aspirin allergic side effects include anaphylaxis, angioedema, and bronchospasm. Gi bleeding can be life-threatening, and the irreversible anti-platelet effect can make this bleeding especially difficult to manage. Bone marrow toxicity can include suppression of any of the lines of blood cells, and manifest as thrombocytopenia, agranulocytosis, and aplastic anemia, or can affect all of the blood elements as pancytopenia. Like all of the NSAIDs aspirin can cause nephrotoxicity, especially with long term high dose use. Tinnitis is among the more unusual and yet common aspirin side effects. Nasal polyps can be caused by aspirin allergy as another unusual aspirin allergy.

Aspirin overdose :
An overdose of aspirin means you have too much aspirin in your body and this can happen in two ways:*If a person accidentally or intentionally takes a very large dose of aspirin at one time, it's called an acute overdose. *If a normal daily dose of aspirin builds up in the body over time and causes symptoms, it's called a chronic overdose. This may happen if your kidneys do not work correctly or when you are dehydrated. Chronic overdoses are usually seen in older patients during hot weather.

Symptoms :
Symptoms of acute overdose may include:

Upset stomach and stomach pain Nausea Vomiting -- may cause an ulcer or irritation of the stomach known as gastritis

Symptoms of chronic overdose may include:

Fatigue Slight fever Confusion Collapse Rapid heart beat Uncontrollable rapid breathing

Large overdoses may also cause:

Ringing in the ears Temporary deafness Hyperactivity Dizziness Drowsiness Hyperactivity Seizures Coma

Missing Aspirin dose :

Since this medication is often used as needed, you may not be on a dosing schedule. If you are using the medication regularly, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and wait until your next regularly scheduled dose. Do not use extra medicine to make up the missed dose.

Before taking Aspirin :

Aspirin should not be given to a child or teenager who has a fever, especially if the child also has flu symptoms or chicken pox. Aspirin can cause a serious and sometimes fatal condition called Reye's syndrome in children. Do not use this medication if you are allergic to aspirin, or if you have: A recent history of stomach or intestinal bleeding; A bleeding disorder such as hemophilia; or An allergy to an NSAID (non-steroidal anti-inflammatory drug) such as Advil, Motrin, Aleve, Orudis, Indocin, Lodine, Voltaren, Toradol, Mobic, Relafen, Feldene, and others. If you have any of these other conditions, you may need a dose adjustment or special tests to safely take aspirin:

Asthma or seasonal allergies. Stomach ulcers. Liver disease. Kidney disease. A bleeding or blood clotting disorder. Heart disease, high blood pressure, or congestive heart failure. Gout.

 Nasal polyps. If you are taking aspirin to prevent heart attack or stroke, avoid also taking ibuprofen (Advil, Motrin). Ibuprofen may make this medication 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). This medication may be harmful to an unborn baby's heart, and may also reduce birth weight or have other dangerous effects. Tell your doctor if you are pregnant or plan to become pregnant while you are taking this medication. Aspirin can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

What should I avoid while taking Aspirin :

Do not use any other over-the-counter medication without first asking your doctor or pharmacist. Aspirin is contained in many medicines available over the counter. If you take certain products together you may accidentally take too much aspirin. Read the label of any other medicine you are using to see if it contains aspirin. Avoid taking an NSAID (non-steroidal anti-inflammatory drug) while you are taking aspirin. NSAIDs include ibuprofen (Motrin, Advil), diclofenac (Voltaren), diflunisal (Dolobid), etodolac (Lodine), flurbiprofen (Ansaid), indomethacin (Indocin), ketoprofen (Orudis), ketorolac (Toradol), mefenamic acid (Ponstel), meloxicam (Mobic), nabumetone (Relafen), naproxen (Aleve, Naprosyn), piroxicam (Feldene), and others. Avoid drinking alcohol while you are taking this medication. Alcohol may increase your risk of stomach bleeding. Avoid taking ibuprofen (Advil, Motrin) if you are taking aspirin to prevent stroke or heart attack. Ibuprofen can make this medication 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).

Interactions :
Tell your doctor if you are taking an antidepressant such as citalopram (Celexa), duloxetine (Cymbalta), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, Symbyax), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft), or venlafaxine (Effexor). Taking any of these drugs with aspirin may cause you to bruise or bleed easily. Before taking this medication, tell your doctor if you are using any of the following drugs:

A blood thinner such as warfarin (Coumadin). Another salicylate such as choline salicylate and/or magnesium salicylate (Magan, Doan's, Bayer Select Backache Pain Formula, Mobidin, Arthropan, Trilisate, Tricosal), or salsalate (Disalcid).

Chemical properties :
Acetylsalicylic acid decomposes rapidly in solutions of ammonium acetate or of the acetate, carbonates, citrates or hydroxides of the alkali metals. Acetylsalicylic acid is stable in dry air, but gradually hydrolyses

in contact with moisture to acetic and salicylic acids. In solution with alkalis, the hydrolysis proceeds rapidly and the clear solutions formed may consist entirely of acetate and salicylate.

Physical properties :
Aspirin, an acetyl derivative of salicylic acid, is a white, crystalline, weakly acidic substance, with a melting point of 135 C (275 F)

History of Aspirin :
The father of modern medicine was Hippocrates, who lived sometime between 460 B.C and 377 B.C. Hippocrates was left historical records of pain relief treatments, including the use of powder made from the bark and leaves of the willow tree to help heal headaches, pains and fevers. By 1829, scientists discovered that it was the compound called salicin in willow plants which gave you the pain relief. According to "From A Miracle Drug" written by Sophie Jourdier for the Royal Society of Chemistry: "It was not long before the active ingredient in willow bark was isolated; in 1828, Johann Buchner, professor of pharmacy at the University of Munich, isolated a tiny amount of bitter tasting yellow, needle-like crystals, which he called salicin. Two Italians, Brugnatelli and Fontana, had in fact already obtained salicin in 1826, but in a highly impure form. By 1829, [French chemist] Henri Leroux had improved the extraction procedure to obtain about 30g from 1.5kg of bark. In 1838, Raffaele Piria [an Italian chemist] then working at the Sorbonne in Paris, split salicin into a sugar and an aromatic component (salicylaldehyde) and converted the latter, by hydrolysis and oxidation, to an acid of crystallized colorless needles, which he named salicylic acid." Henri Leroux had extracted salicin, in crystalline form for the first time, and Raffaele Piria succeeded in obtaining the salicylic acid in its pure state. The problem was that salicylic acid was tough on stomachs and a means of 'buffering' the compound was searched for. The first person to do so was a French chemist named Charles Frederic Gerhardt. In 1853, Gerhardt neutralized salicylic acid by buffering it with sodium (sodium salicylate) and acetyl chloride, creating acetylsalicylic acid. Gerhardt's product worked but he had no desire to market it and abandoned his discovery.

Aspirin Images :

References : www.ncbi.nlm.nih.gov www.webmd.com health.howstuffworks.com www.drugs.com chemistry.about.com inventors.about.com sideeffectz.com www.nlm.nih.gov/medlineplus