Aspirin

CHEMISTRY:
  • Aspirin is Acetyl salicylic Acid. 
PHARMACOKINETICS:
  • Absorption: Well from stomach & upper small intestine 
  • Distribution: wide , crosses placental barrier PPL: In 1-2hrs. t1/2: 15 min. 
  • Metabolism: Rapid hydrolysis by Esterases in blood & tissues in to Salicylate & Acetic Acid. 
  • Salicylate is 80-90-% PPB 20
MOA:
  1. Anti-inflammatory: Aspirin irreversibly acetylates both isoforms of cyclooxygenase enzyme , COX-1 & COX-2 & inactivates them.
  2. Anti-inflammatory dose of aspirin is 3 - 6 g/d
  • Analgesic: 
  1. Aspirin & Other NSAIDs inhibit cyclo-oxygenase enzyme , reduce production of PGs in injured tissue. PGE2 is thought to sensitize the nerve ending (pain receptors)to action of bradykinin , Histamine & other mediators released by the inflammatory process.
  2. Inhibit pain stimuli at subcortical sites -Thalamus & Hypothalamus. 
  • As Antipyretic: 
  1. Aspirin lowers raised body temperature , no effect on normal temperature 
  2. Cytokine is released from WBCs, activated by infection, malignancy or inflammation.
  3. Because of inhibition of PGE2 synthesis , the thermostat is reset towards normal & rapidly lowers body temperature by increasing heat dissipation due to peripheral vasodilation & sweating.
  • Antiplatelet: 
  1. TXA2 normally promotes platelet aggregation
  2. Prostacyclin –PGI 2 normally inhibit platelet aggregation.
  3. In low doses Inhibit Platelet Aggregation due to irreversible acetylation of COX-1 enzyme in platelets. 
  4. Low doses 81-100mg/ d inhibit TXA2 synthesis in platelets , higher doses inhibit prostacyclin –PGI2 also.
  5. Aspirin should be stopped 7-10 prior to operations, to avoid risk of bleeding. Prolonged BT
  • Aspirin + Low molecular weight Heparin is recommended in a woman with Antiphospholipid Antibodies and history of prior abortions / still birth.
INDICATIONS:
  • It is used to ease pain, swelling, and fever.
  • It is used to treat arthritis. Efficacy greater than acetaminophen as an anti-inflammatory agent
  • It is used to treat rheumatic fever.
  • It is used to protect bypass grafts and stents in the heart.Aspirin reduces risk of TIA
  • It is used to lower the chance of heart attack, stroke, and death in some people.
  • Low dose aspirin therapy markedly decreases thromboxane production but only partially blocks prostocyclin and prostaglandin E2 production.
  1. Pre-ecalmpsia: In preeclamptic woman, thromboxane is increased and prostaglandin E2 and prostacyclin are decreased, resulting in vasoconstriction and sensitivity to infused angiotensin II.Low dose aspirin as explained above enhances concentration of vasodilating prostanoids and restores refractoriness to infused angitensin II.
  2. Post MI: No confusions on this one. Low dose aspirin is advised to such patients.
  3. IUGR: Early antiplatelet therapy with low dose aspirin may prevent uteroplacental thrombosis, placental infarction, and idiopathic fetal growth retardation in women with a history of recurrent severe fetal growth restriction
CONTRAINDICATIONS:
  • Peptic ulcer
  • Prostaglandin has cytoprotective function for gastric mucosa by inhibiting acid secretion and promoting secretion of mucus.
  • Aspirin inhibits synthesis of cytoprotective PG -3 bleeding & perforation may occur.
  • Children with chicken pox & influenza
  • Aspirin can cause Reye's syndrome (hepatic encephalopathy).
  • Acknowledging this aspirin should not be given to children < 12 years, e.g. in JRA.
  • Bleeding tendencies
  • By its antiplatelet action, aspirin can exacerbate bleeding.
  • Chronic liver disease
  • Long-term therapy with high dose aspirin can cause insidious onset hepatic injury.
  • Aspirin is contraindicated in a case who is on treatment with Warfarin.
ADVERSE EFFCETS:
  • Common side effects of aspirin tablet:
  • Conditions Of Excess Stomach Acid Secretion
  • Feel Like Throwing Up
  • In aspirin poisoning most important step is Fluids
  • Heartburn
  • Irritation Of The Stomach Or Intestines
  • Stomach Cramps
  • Throwing Up
  • Samter's triad consists of Nasal polyp, bronchial asthma and aspirin sensitivity.
Rare side effects of aspirin tablet:
  • A Rupture In The Wall Of The Stomach Or Intestine
  • Anemia
  • Bleeding
  • Bleeding Of The Stomach Or Intestines
  • Blood Coming From Anus
  • Bronchospasm
  • Decrease In The Ability Of Platelet Cells To Clot
  • Decreased Blood Platelet
  • Decreased White Blood Cells
  • Drowsiness
  • Giant Hives
  • Hemolytic Anemia
  • Hemorrhage Within The Skull
  • Hepatitis Caused By Drugs
  • Hives
  • Inflammation Of Skin Caused By An Allergy
  • Interstitial Nephritis
  • Itching
  • Large Purple Or Brown Skin Blotches
  • Life Threatening Allergic Reaction
  • Ringing In The Ears
  • Seizures
  • Small Skin Blister
  • Stomach Or Intestinal Ulcer
  • Trouble Breathing
  • Wheezing
  • Abnormal Liver Function Tests
  • Burning Stomach
  • Collection Of Clotted Blood In An Organ, Space Or Tissue
  • Loss Of Appetite
  • Rash
  • Redness Of Skin
  • Aspirin and non-steroidal antiinflammatory drugs (NSAIDs) may cause anaphylactic or anaphylactoid reactions
PRECAUTIONS:
  • In CHF & low cardiac reserve patients
  • Aspirin reduces renal blood flow by inhibiting synthesis of vasodilator PGs fluid & salt retention worsening of CHF and renal failure may occur.
  • Aspirin should be stopped 1 week before elective surgery so that platelet function becomes normal.
  • In G-6-PD deficiency
  • High doses can cause hemolysis.
  • In diabetics
  • Aspirin causes increased utilization of glucose by increasing cellular metabolism, especially in skeletal muscle, due to uncoupling of oxidative phosphorylation blood sugar may decrease and liver glycogen may be depleted, especially in diabitics → dangerous hypoglycemia may occur
Exam Question
  • At usual therapeutic doses (blood levels), expected effects of aspirin include efficacy greater than acetaminophen as an anti-inflammatory agent
  • Aspirin is contraindicated in Warfarin
  • In low doses, aspirin inhibits cyclo-oxygenase 
  • Important effects of aspirin include reduction of fever, prostaglandin synthesis in inflammed tissues & Respiratory stimulation
  • Aspirin irreversibly inhibits platelets 
  • Aspirin is useful in prevention of heart attack and stroke 
  • Aspirin is contraindicated in Peptic ulcer
  • In aspirin poisoning most important step is Fluids
  • Aspirin and NSAIDS are most commonly involved in Anaphylactoid reaction
  • Aspirin hypersenstitivity is seen along with Nasal Polyposis
  • Mechanism of action of Aspirin in MI is Thromboxane A2 synthesis inhibition
  • Low doses of aspirin used in myocardial infarction act by Inhibiting cyclooxygenase
  • Antiplatelet action of aspirin is due to Decrease thromboxane A2 synthesis
  • Aspirin is associated with Reye's Syndrome
  • An elective surgery is to be done in a patient taking heavy doses of Aspirin. Management consists of Stopping aspirin for 7 days and then do surgery
  • A patient is on aspirin shows Prolonged BT
  • Aspirin + Low molecular weight Heparin is recommended in a woman with Antiphospholipid Antibodies and history of prior abortions / still birth.
  • Low doses of aspirin therapy is essentially advised for IUGR, Post myocardinal infarction & Pre ecclampsia
  • Aspirin reduces risk of TIA 
  • Anti-inflammatory dose of aspirin is 3 - 6 g/d
  • Chemically aspirin is Acetyl salicylic acid
Don't Forget to Solve all the previous Year Question asked on Aspirin