aspirin introduction and important things should know as in medical field

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ASPIRIN
Synonyms :salicylic acid acetate
IUPAC NAME:2-acetoxybenzoic acid
STRUCTURE:
FORMULA : C9H8O4
BACKGROUND : 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

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PHYSIOCHEMICAL PROPERTIES . melting point 130-140 0
C
Boiling point 140 0
C
Water solubility 10 mg/mL
PKa 3.5
.
PHARMACOLOGY : 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
For reducing the risk of transient ischemic attacks (TIA) and to prevent
atherothrombotic cerebral infarction (in conjunction with other
treatments)

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For the prevention of thromboembolism after hip replacement surgery
For decreasing platelet to platelet adhesion following carotid
endarterectomy, aiding in the prevention of transient ischemic attacks
(TIA)
Used for patients undergoing hemodialysis with a silicone rubber
arteriovenous cannula inserted to prevent thrombosis at the insertion
site
Important note regarding use of the extended-release formulation
In the setting of acute myocardial infarction, or before percutaneous
interventions, the extended-release form of acetylsalicylic acid should
not be used. Use immediate-release formulations in scenarios requiring
rapid onset of action The extended-release form is taken to decrease
the incidence of mortality and myocardial infarction (MI) for individuals
diagnosed with chronic coronary artery disease (CAD), including
patients with previous myocardial infarction (MI) or unstable angina or
with chronic stable angina. Additionally, the extended-release form is
used to decrease the risk of death and recurrent episodes of stroke in
patients with a history of stroke or TIA
CONTRAINDICATION:
Aspirin is contraindicated in patients with known allergy to NSAIDs and in
patients with asthma, rhinitis, and nasal polyps. It may cause anaphylaxis,
laryngeal edema, severe urticaria, angioedema, or bronchospasm (asthma)
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

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(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
Effects on platelet aggregation
The inhibition of platelet aggregation by ASA occurs because of its
interference with thromboxane A2 in platelets, caused by COX-1
inhibition. Thromboxane A2 is an important lipid responsible for platelet
aggregation, which can lead to clot formation and future risk of heart
attack or stroke
A note on cancer prevention
ASA has been studied in recent years to determine its effect on the
prevention of various malignancies . In general, acetylsalicylic acid is
involved in the interference of various cancer signaling pathways,
sometimes inducing or upregulating tumor suppressor genes Results of
various studies suggest that there are beneficial effects of long-term
ASA use in the prevention of several types of cancer, including
stomach, colorectal, pancreatic, and liver cancers . Research is
ongoing.
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

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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
Absorption
Absorption is generally rapid and complete following oral administration
but absorption may be variable depending on the route, dosage form,
and other factors including but not limited to the rate of tablet
dissolution, gastric contents, gastric emptying time, and gastric pH
Detailed absorption information
When ingested orally, acetylsalicylic acid is rapidly absorbed in both the
stomach and proximal small intestine. The non-ionized acetylsalicylic
acid passes through the stomach lining by passive diffusion. Ideal
absorption of salicylate in the stomach occurs in the pH range of 2.15 -
4.10. Intestinal absorption of acetylsalicylic acid occurs at a much faster
rate. At least half of the ingested dose is hydrolyzed to salicylic acid in
the first-hour post-ingestion by esterases found in the gastrointestinal

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tract. Peak plasma salicylate concentrations occur between 1-2 hours
post-administration
Volume of distribution
This drug is distributed to body tissues shortly after administration. It is
known to cross the placenta. The plasma contains high levels of
salicylate, as well as tissues such as spinal, peritoneal and synovial
fluids, saliva and milk. The kidney, liver, heart, and lungs are also found
to be rich in salicylate concentration after dosing. Low concentrations of
salicylate are usually low, and minimal concentrations are found in
feces, bile, and sweat
Protein binding
50% to 90% of a normal therapeutic concentration salicylate (a main
metabolite of acetylsalicylic acid ) binds plasma proteins, particularly
albumin, while acetylsalicylic acid itself binds negligibly . Acetylsalicylic
acid has the ability to bind to and acetylate many proteins, hormones,
DNA, platelets, and hemoglobin .
Metabolism
Acetylsalicylic acid is hydrolyzed in the plasma to salicylic acid. Plasma
concentrations of aspirin following after administration of the extended-
release form are mostly undetectable 4-8 hours after ingestion of a
single dose. Salicylic acid was measured at 24 hours following a single
dose of extended-release acetylsalicylic acid .
Salicylate is mainly metabolized in the liver, although other tissues may
also be involved in this process . The major metabolites of
acetylsalicylic acid are salicylic acid, salicyluric acid, the ether or
phenolic glucuronide and the ester or acyl glucuronide. A small portion
is converted to gentisic acid and other hydroxybenzoic acids
Half-life
The half-life of ASA in the circulation ranges from 13 - 19 minutes.
Blood concentrations drop rapidly after complete absorption. The half-
life of the salicylate ranges between 3.5 and 4.5 hours
ADVERSE EFFECT
 rash

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 gastrointestinal ulcerations,
 abdominal pain,
 upset stomach,
 heartburn,
 drowsiness,
 headache,
 cramping
 Toxicity
 Lethal doses
 Acute oral LD50 values have been reported as over 1.0 g/kg in
humans, cats, and dogs, 0.92 g/kg - 1.48 g/kg in albino rats, 1.19 g/kg
in guinea pigs, 1.1 g/kg in mice, and 1.8 g/kg in rabbit models
 Acute toxicity
 Salicylate toxicity is a problem that may develop with both acute and
chronic salicylate exposure 7. Multiple organ systems may be affected
by salicylate toxicity, including the central nervous system, the
pulmonary system, and the gastrointestinal system. Severe bleeding
may occur. In the majority of cases, patients suffering from salicylate
toxicity are volume-depleted at the time of presentation for medical
attention. Fluid resuscitation should occur immediately and volume
status should be monitored closely. Disruptions in acid-base balance
are frequent in ASA toxicity 7.
 The acute toxicity of acetylsalicylic in animals has been widely studied.
The signs of poisoning in rats from lethal doses are mild to severe
gastroenteritis, hepatitis, nephritis, pulmonary edema,
encephalopathy, shock and some toxic effects on other organs and
tissues. Mortality has been observed following convulsions or
cardiovascular shock. An important differentiating property between
various animal species is the ability to vomit toxic doses. Humans,
cats and dogs have this ability, but rodents or rabbits do not
 Chronic toxicity and carcinogenesis
 Chronic ASA toxicity is frequently accompanied by atypical clinical
presentations that may be similar to diabetic ketoacidosis, delirium,
cerebrovascular accident (CVA), myocardial infarction (MI) or cardiac
failure. Plasma salicylate concentrations should be measured if
salicylate intoxication is suspected, even if there no documentation
available to suggest ASA was ingested. In older age, nephrotoxicity
from salicylates increases, and the risk of upper gastrointestinal
hemorrhage is increased, with higher rates of mortality . It is also

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important to note that ASA toxicity may occur even with close to
normal serum concentrations. Prevention of chronic ASA includes the
administration of smallest possible doses, avoidance of concurrent use
of salicylate drugs, and therapeutic drug monitoring. Renal function
should be regularly monitored and screening for gastrointestinal
bleeding should be done at regular intervals
 Chronic toxicity studies were performed in rodents. ASA was
administered at doses measured to be 2 to 20 times the maximum
tolerated clinical dose to mice for up to one year. Negative dose-
related effects were seen. These include decreased mean survival
time, decreased number of births and progeny reaching an appropriate
age for weaning. No evidence of carcinogenesis was found in 1-year
studies At daily doses of 0.24 g/kg/day given for 100 days to albino
rats, ASA led to signs to excessive thirst, aciduria, diuresis,
drowsiness, hyperreflexia, piloerection, changes in respiration,
tachycardia, followed by soft stools, epistaxis, sialorrhea, dacryorrhea
and mortality during hypothermic coma in the second study month
 Use in pregnancy and lactation
 While teratogenic effects were observed in animals nearly lethal
doses, no evidence suggests that this drug is teratogenic in humans .
It is advisable, however, to avoid ASA use the first and second
trimester of pregnancy, unless it is clearly required. If acetylsalicylic
acid containing drugs are ingested by a patient attempting to conceive,
or during the first and second trimester of pregnancy, the lowest
possible dose at the shortest possible duration should be taken This
drug is contraindicated in the 3rd trimester of pregnancy
DRUG-DRUG INTERACTIONS
if you are taking aspirin to prevent heart attack or stroke, avoid also
taking ibuprofen (Advil, Motrin). Ibuprofen can make aspirin less effective in
protecting your heart and blood vessels. If you must use both medications,
ask your doctor how far apart your doses should be.
Food Interactions

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 Avoid alcohol. Alcohol increases the risk of gastrointestinal
bleeding.
 Avoid herbs and supplements with anticoagulant/antiplatelet
activity. Examples include garlic, ginger, bilberry, danshen,
piracetam, and ginkgo biloba.
 Take after a meal. This reduces irritating gastrointestinal effects.
 Take with a full glass of water.
ASPIRIN
Aspirin is prepared by chemical synthesis from salicylic
acid, through acetylationwith acetic anhydride.The molecular
weight of aspirin is 180.16g/mol.
THERAPEUTIC APPLICATION
 Acute Coronary Syndrome (ACS)
 Anxiety
 Arthritis
 Atherothrombotic cerebral infarction
 Cardiovascular Disease (CVD)
 Cardiovascular Events
 Cardiovascular Mortality
 Colorectal Adenomas
 Colorectal Cancers
 Common Cold
 Coronary artery reocclusion
 Death
 Dyspeptic signs and symptoms
 Fever
 Flu Like Symptom
 Flu caused by Influenza
 Headache
 Heterozygous Familial Hypercholesterolemia
 Inflammation
 Juvenile Idiopathic Arthritis (JIA)
 Kawasaki Syndrome

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 Major Adverse Cardiovascular and Cerebrovascular Events
(MACCE)
 Migraine
 Morbidity
 Mucocutaneous Lymph Node Syndrome
 Muscle Contraction
 Myocardial Infarction
 Myocardial Infarction (MI), first occurrence
 Neuralgia
 Pain
 Pain caused by Common Cold
 Pain, Menstrual
 Pericarditis
 Polycythemia Vera (PV)
 Preeclampsia
 Rheumatic Pain
 Rheumatism
 Rheumatoid Arthritis
 Rhinosinusitis
 Severe Pain
 Soreness, Muscle
 Spondyloarthropathies
 Stroke
 Systemic Lupus Erythematosus (SLE)
 Tension Headache
 Thromboembolism
 Toothache
 Transient Ischemic Attack
 Venous Thromboembolism
 Acute Inflammation
 Atherothrombotic events
 Death by myocardial infarction
 Moderate Pain
 Thrombotic events
Associated Therapies
 Antiplatelet Therapy
 Hemodialysis Treatment
 Secondary Prevention.

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