Faculty of Pharmacy

Acetylsalicylic Acid

(Aspirin)

Prepared by

Donia Ali Merie Mohammed

1190159
3rd grade

Supervised by

Prof. Ramadan Abdullah Hemeida

Dr. Remon Roshdy

2020/2021
Introduction
Also known as Aspirin, acetylsalicylic acid (ASA) is a commonly
used drug for the treatment of pain and fever due to various
causes. Acetylsalicylic acid has both anti-inflammatory and
antipyretic effects. This drug also inhibits platelet aggregation
and is used in the prevention of blood clots stroke, and myocardial
infarction (MI) .
Interestingly, the results of various studies have demonstrated
that long-term use of acetylsalicylic acid may decrease the risk of
various cancers, including colorectal, esophageal, breast, lung,
prostate, liver and skin cancer . Aspirin is classified as a non-
selective cyclooxygenase (COX) inhibitor and is available in
many doses and forms, including chewable tablets, suppositories,
extended release formulations, and others .
Acetylsalicylic acid is a very common cause of accidental
poisoning in young children. It should be kept out of reach from
young children, toddlers, and infants.
Medical use
Prescription aspirin comes as an extended-release ( long-acting)
tablet. Nonprescription aspirin comes as a regular tablet, a
delayed-release (releases the medication in the intestine to
prevent damage to the stomach) tablet, a chewable tablet, powder,
and a gum to take by mouth and a suppository to use rectally.
Prescription aspirin is usually taken two or more times a day.
Nonprescription aspirin is usually taken once a day to lower the
risk of a heart attack or stroke. Nonprescription aspirin is usually
taken every 4 to 6 hours as needed to treat fever or pain. Follow
the directions on the package or prescription label carefully, and
ask your doctor or pharmacist to explain any part you do not
understand. Take aspirin exactly as directed. Do not take more or
less of it or take it more often than directed by the package label
or prescribed by your doctor.
Swallow the extended-release tablets whole with a full glass of
water. Do not break, crush, or chew them.
Swallow the delayed-release tablets with a full glass of water.
Chewable aspirin tablets may be chewed, crushed, or swallowed
whole. Drink a full glass of water, immediately after taking these
tablets.
Indication
Pain, fever, and inflammation
Acetylsalicylic acid (ASA), in the regular tablet form (immediate-
release), is indicated to relieve pain, fever, and inflammation
associated with many conditions, including the flu, the common cold,
neck and back pain, dysmenorrhea, headache, tooth pain, sprains,
fractures, myositis, neuralgia, synovitis, arthritis, bursitis, burns, and
various injuries. It is also used for symptomatic pain relief after
surgical and dental procedures .
The extra strength formulation of acetylsalicylic acid is also indicated
for the management migraine pain with photophobia (sensitivity to
light) and phonophobia (sensitivity to sound).
Other indications
ASA is also indicated for various other purposes, due to its ability to
inhibit platelet aggregation. These include:
Reducing the risk of cardiovascular death in suspected cases of
myocardial infarction (MI) .
Reducing the risk of a first non-fatal myocardial infarction in patients,
and for reducing the risk of morbidity and mortality in cases of
unstable angina and in those who have had a prior myocardial
infarction .
Pharmacodynamics
Effects on pain and fever
Acetylsalicylic acid disrupts the production of prostaglandins
throughout the body by targeting cyclooxygenase-1 (COX-1) and
cyclooxygenase-2 (COX-2). Prostaglandins are potent, irritating
substances that have been shown to cause headaches and pain upon
injection into humans. Prostaglandins increase the sensitivity of pain
receptors and substances such as histamine and bradykinin. Through
the disruption of the production and prevention of release of
prostaglandins in inflammation, this drug may stop their action at pain
receptors, preventing symptoms of pain. Acetylsalicylic acid is
considered an antipyretic agent because of its ability to interfere with
the production of brain prostaglandin E1. Prostaglandin E1 is known
to be an extremely powerful fever-inducing agent

Mechanism of action
Acetylsalicylic acid (ASA) blocks prostaglandin synthesis. It is non-
selective for COX-1 and COX-2 enzymes. Inhibition of COX-1
results in the inhibition of platelet aggregation for about 7-10 days
(average platelet lifespan). The acetyl group of acetylsalicylic acid
binds with a serine residue of the cyclooxygenase-1 (COX-1) enzyme,
leading to irreversible inhibition. This prevents the production of
pain-causing prostaglandins. This process also stops the conversion of
arachidonic acid to thromboxane A2 (TXA2), which is a potent
inducer of platelet aggregation . Platelet aggregation can result in clots
and harmful venous and arterial thromboembolism, leading to
conditions such as pulmonary embolism and stroke.
It is important to note that there is 60% homology between the protein
structures of COX-1 and COX-2. ASA binds to serine 516 residue on
the active site of COX-2 in the same fashion as its binding to the serine
530 residue located on the active site of COX-1. The active site of
COX-2 is, however, slightly larger than the active site of COX-1, so
that arachidonic acid (which later becomes prostaglandins) manages
to bypass the aspirin molecule inactivating COX-2 . ASA, therefore,
exerts more action on the COX-1 receptor rather than on the COX-2
receptor . A higher dose of acetylsalicylic acid is required for COX-2
inhibition.
What are the side effects of aspirin?
Most patients benefit from aspirin and other NSAIDs with few side
effects. However, serious side effects can occur and generally tend to
be dose-related. Therefore, it is advisable to use the lowest effective
dose to minimize side effects.
The most common side effects of aspirin involve the gastrointestinal
system and ringing in the ears.
Gastrointestinal side effects are
 ulcerations,
  abdominal burning,
 pain,
 cramping,
 nausea,
 gastritis, and
 even serious gastrointestinal bleeding an
What is the dosage for aspirin?
Aspirin should be taken with food. Doses range from 50 mg to 6000
mg daily depending on the use.
 Usual doses for mild to moderate pain are 350 or 650 mg every
4 hours or 500 mg every 6 hours.
 Doses for rheumatoid arthritis include 500 mg every 4-6
hours; 650 mg every 4 hours; 1000 mg every 4-6 hours; 1950
mg twice daily.
 Heart attacks are prevented with 75, 81, 162 or 325 mg daily.
 160 to 325 mg of non-enteric coated aspirin should be chewed
immediately when experiencing symptoms of a heart attack.
 The dose for preventing another stroke is 75 to 100 mg daily.
Contraindications
- Hypersensitivity to salicylic acid compounds or prostaglandin
synthetase inhibitors (e.g. certain asthma patients who may suffer an
attack or faint) or to any of the excipients listed in section 6.1;
- Active, or history of recurrent peptic ulcer and/or gastric/intestinal
haemorrhage, or other kinds of bleeding such as cerebrovascular
haemorrhages;
- Haemorrhagic diathesis; coagulation disorders such as haemophilia
and thrombocytopenia;
- Severe hepatic impairment;
- Severe renal impairment;
- Gout;
- Doses >100 mg/day during the third trimester of pregnancy
- Methotrexate used at doses >15mg/week
Interaction with other medicinal products and other forms of
interaction
Contraindicated combinations
Methotrexate (used at doses >15 mg/week):
The combined drugs, methotrexate and acetylsalicylic acid, enhance
haematological toxicity of methotrexate due to the decreased renal
clearance of methotrexate by acetylsalicylic acid. Therefore, the
concomitant use of methotrexate (at doses >15 mg/week) with Aspirin
Tablets is contraindicated (see section 4.3).
Not recommended combinations
Uricosuric agents, e.g. probenecid
Salicylates reverse the effect of probenecid. The combination should
be avoided.
Combinations requiring precautions for use or to be taken into account
Anticoagulants e.g. coumarin, heparin, warfarin
Increased risk of bleeding due to inhibited thrombocyte function,
injury of the duodenal mucosa and displacement of oral
anticoagulants from their plasma protein binding sites. The bleeding
time should be monitored (see section 4.4).
Anti-platelet agents (e.g clopidogrel and dipyridamole) and selective
serotonin reuptake inhibitors (SSRIs; such as sertraline or
paroxetine)
Increased risk of gastrointestinal bleeding (see section 4.4).
Antidiabetics, e.g. sulfonylureas
Salicylics may increase the hypoglycaemic effect of sulfonylureas.
Overdose
Although considerable inter-individual variations are involved, it can
be considered that the toxic dose is about 200 mg/kg in adults and 100
mg/kg in children. The lethal dose of acetylsalicylic acid is 25-30
grams. Plasma salicylate concentrations above 300 mg/l indicate
intoxication. Plasma concentrations above 500 mg/l in adults and 300
mg/l in children generally cause severe toxicity.
Overdose may be harmful for elderly patients and particularly for
small children (therapeutic overdose or frequent accidental
intoxications may be fatal).