Aspirin

Aspirin (the active chemical is acetylsalicylic acid) is a well-known non-steroidal anti-inflammatory drug (NSAID) that has been used in medicine since the late 19th century. Aspirin has antipyretic, analgesic (pain relieving) and anti-inflammatory properties, and is one of the most commonly used medicines in the world.

Pharmacological properties

1. Anti-inflammatory action: Aspirin reduces inflammation by blocking the production of prostaglandins, substances that play a key role in the development of inflammation, pain and fever in the body. This is achieved by inhibiting the enzyme cyclooxygenase (COX), which is necessary for the synthesis of prostaglandins.
2. Analgesic Action: Effective for mild to moderate pain such as headache, toothache, muscle pain, menstrual pain and other types of pain.
3. Antipyretic action: Aspirin is effective in reducing fever by affecting the hypothalamic center of thermoregulation, dilating peripheral vessels and increasing sweating.

Utilization

• As an analgesic: to reduce pain of various etiologies.
• As an antipyretic: to reduce high body temperature.
• Asan antiaggregant: low doses of aspirin are used to prevent blood clots, which is useful in the prevention of myocardial infarction and stroke. Aspirin prevents platelet aggregation (sticking of blood platelets together), thereby reducing the risk of thrombosis.

Indications Aspirin.

1. Analgesic action (analgesic):

   • Treatment of headaches, including migraine.
   • Reduction of toothache, muscle and joint pain.
   • Reduction of menstrual pain.

2. Antipyretic action (antipyretic):

   • Reduction of high body temperature associated with colds and other infectious diseases.

3. Anti-inflammatory action:

   • Use in various inflammatory diseases such as rheumatoid arthritis and osteoarthritis.
   • Treatment of inflammatory processes, e.g. Tendonitis or bursitis.

4. Antiaggregant action:

   • Prevention of thrombosis and embolism, including reducing the risk of myocardial infarction and stroke in individuals at high risk of developing them.
   • Prevention of recurrent myocardial infarction and postoperative thrombosis.
   • As a prophylactic agent for thromboembolism and ischemic stroke.

5. Other Specific Uses:

   • Treatment of Kawasaki syndrome, a disease that affects the blood vessels in children.
   • Prevention of colorectal

Release form

1. Pills

• Regular tablets: This is the most common form, containing 100 to 500 mg of acetylsalicylic acid. Tablets are taken orally and are intended to relieve pain, reduce fever, or as an antiaggregant.
• Chewable tablets: These contain aspirin in a smaller dosage, often around 81 mg, and are used mainly to prevent heart attacks or strokes. The chewable form speeds up the onset of action of the drug.
• Coatedtablets (enterosoluble): The coating prevents aspirin from breaking down in the acidic environment of the stomach, reducing the risk of irritation and ulcerogenic action on the gastrointestinal tract. Such tablets dissolve already in the intestine.

2. Capsules

• Liquid capsules: These capsules contain aspirin in liquid form, allowing it to be absorbed faster and relieve symptoms more quickly.

3. Powders

• Solution powders: Aspirin in powder can be dissolved in water for oral intake. This form is especially convenient for those who have difficulty swallowing tablets.

4. Rectal suppositories

• Suppositories: Used to administer aspirin rectally, which may be necessary for vomiting or other conditions where oral administration is not possible.

5. Effervescent (effervescent) tablets

• Effervescent tablets: Tablets that dissolve in water to form aneffervescent drink. This form improves the absorption of aspirin and reduces its negative effects on the gastrointestinal tract.

Pharmacodynamics

1. Antiaggregant action:

   • Aspirin irreversibly inhibits the enzyme cyclooxygenase (COX), which is essential for the synthesis of thromboxanes and prostaglandins.
   • Inhibition of COX-1 leads to a decrease in the formation of thromboxane A2 in platelets, which reduces their ability to aggregate and reduces the risk of blood clots. This property is used for the prevention and treatment of coronary heart disease and other vascular diseases.

2. Analgesic and antipyretic actions:

   • Aspirin also inhibits the synthesis of prostaglandins, which play a key role in causing inflammation, pain and fever.
   • Reducing the level of prostaglandins in the central nervous system and in the focus of inflammation leads to a decrease in pain sensitivity and normalization of body temperature in febrile conditions.

3. Anti-inflammatory action:

   • Aspirin reduces the severity of inflammation by blocking the synthesis of prostaglandins and thromboxanes, which are involved in the development of inflammation, causing redness, swelling and pain.
   • Aspirin's effectiveness as an anti-inflammatory agent makes it suitable for treating conditions such as rheumatoid arthritis and osteoarthritis.

4. Other effects:

   • Aspirin can increase blood urea levels by decreasing blood flow through the kidneys, which is the result of inhibiting prostaglandins that maintain adequate blood flow.
   • It can also irritate the gastric mucosa, leading to gastritis and peptic ulcers due to the blockade of protective prostaglandins in the stomach.

Pharmacokinetics

1. Aspirin is rapidly absorbed from the gastrointestinal tract, with effervescent tablet forms, granules in suspension, and fast dissolving tablets showing faster absorption rates than other forms (Kanani, Voelker, & Gatoulis, 2015).
2. After absorption, ASC is rapidly converted to salicylic acid (SA), its active metabolite. The conversion occurs predominantly during the first passage through the liver (Brune, 1974).
3. Pharmacokinetic parameters such as maximum plasma concentration (Cmax) and time to reach maximum concentration (Tmax) vary significantly depending on the formulation used, which affects the onset and duration of action (Kanani, Voelker, & Gatoulis, 2015).
4. In certain populations, such as gastrectomy patients, aspirin shows reduced systemic clearance and prolonged half-life, emphasizing the need for dose adjustment for these individuals (Mineshita, Fukami, & Ooi, 1984).
5. Genetic factors may influence the pharmacokinetics and pharmacodynamics of aspirin, affecting its efficacy as an antiaggregant agent. Variants in genes related to cyclooxygenases and glycoproteins are associated with differences in the antiaggregant effects of aspirin (Würtz, Kristensen, Hvas, & Grove, 2012).

Dosing and administration

Analgesic and antipyretic action:

• Adult dosage: Usually 500 mg to 1000 mg every 4 to 6 hours as needed and depending on symptoms. Should not exceed 4000 mg per day.
• Dosage for children: The use of aspirin in children to treat cold or fever symptoms can be dangerous and is associated with a risk of Reye's syndrome. The dosage should be closely monitored by a doctor.

Prevention of cardiovascular disease:

• Dosage: Low-dose aspirin, usually 75 mg to 325 mg per day. The generally accepted dose for the prevention of heart attack or stroke is 81 mg per day (low-dose tablet).

Prevention and treatment of coronary heart disease:

• Dosage: 75-325 mg daily, depending on the doctor's recommendation.

Colorectal cancer prevention:

• Adult Dosage: Low doses (usually 81-325 mg daily) may be recommended for some patients at high risk for colorectal cancer, but only under the supervision of a physician.

Methods of admission:

• Aspirin should be taken with meals or after meals with plenty of water to minimize gastrointestinal irritation.
• Enterosolubil coated tablets are designed to reduce gastric irritation, so they should not be broken or chewed.

Important Precautions:

• Alcohol should be avoided when taking aspirin as it may increase the risk of stomach bleeding.
• Aspirin may interact with other medications, including ibuprofen, warfarin, some antidepressants, and many others, so you should check with your doctor before starting to take it.
• Aspirin is not recommended for people with peptic ulcers, asthma, or bleeding disorders without first consulting a doctor.

Use Aspirin. during pregnancy

Effect on pregnancy:

1. First trimester:

   • Some studies suggest a possible association between aspirin use in the first trimester and an increased risk of birth defects such as heart defects and cleft palate, although the evidence may be mixed. Therefore, it is recommended that aspirin use in the first trimester be avoided unless the potential benefits outweigh the risks.

2. Second trimester:

   • The use of low-dose aspirin for certain medical purposes, such as the prevention of pre-eclampsia, may be allowed, but only under medical supervision.

3. Third trimester:

   • Aspirin use is particularly dangerous because of the risk of premature closure of the arterial duct in the fetus, which can lead to serious circulatory problems in the newborn.
   • Aspirin may also increase the risk of bleeding in both mother and fetus, decrease uterine contractility, which may result in prolonged labor and increase the likelihood of bleeding in the postpartum period.

The use of aspirin for the prevention of preeclampsia:

• Low-dose aspirin (60-150 mg daily) is sometimes prescribed to pregnant women to prevent pre-eclampsia, a condition characterized by high blood pressure and protein in the urine. This is especially important for women at high risk of developing this condition.
• It is recommended to start taking it from the 12th week of gestation (second trimester) and continue until delivery, but only after a thorough examination and under strict medical supervision.

Contraindications

1. Allergy to aspirin or other NSAIDs (nonsteroidal anti-inflammatory drugs):

   • People with an allergic reaction to aspirin or other drugs from the group of NSAIDs should avoid aspirin. Allergy may manifest as bronchospasm, angioedema, urticaria or anaphylaxis.

2. Pepticulcer disease:

   • Aspirin can aggravate the condition by causing bleeding or perforation of the gastrointestinal tract. It inhibits the production of prostaglandins, which protect the gastric mucosa.

3. Hemorrhagic disorders:

   • As an antiaggregant, aspirin increases the risk of bleeding, making its use contraindicated in conditions such as hemophilia or vitamin K deficiency.

4. Asthma associated with the use of NSAIDs:

   • Some people with asthma may experience an increase in symptoms when taking aspirin or other NSAIDs, known as "aspirin-induced asthma."

5. Severe kidney disease:

   • Aspirin can worsen kidney failure by reducing blood flow through the kidneys, which is important for their function.

6. Severe liver disease:

   • In severe liver dysfunction, the use of aspirin may cause further deterioration of the condition.

7. Pregnancy (especially the third trimester):

   • Aspirin can cause fetal arterial duct closure, increased bleeding during labor, delayed labor, and other serious effects.

8. Lactation period:

   • Aspirin may be excreted with breast milk and may have adverse effects on the baby.

9. Children under 12 years of age:

   • Aspirin use in children for viral infections is associated with a risk of developing Reye's syndrome, a rare but dangerous condition that can cause severe liver and brain damage.

Side effects Aspirin.

1. Digestive system: Aspirin can cause gastrointestinal irritation, including gastritis, ulcers, and even bleeding. These risks increase with higher doses and with long-term use (Li et al., 2020).
2. Allergic reactions: Aspirin can cause a variety of allergic reactions including skin rash, angioedema, and bronchospasm, especially in people with asthma or those with chronic urticaria (Stevenson, 1984).
3. Renal impairment: Prolonged aspirin use may affect renal function, causing renal failure, especially in patients with existing renal disease or in elderly patients (Karsh, 1990).
4. Interaction with other drugs: Aspirin may interact with anticoagulants, sulfonylureas, diuretics, methotrexate, and antacids, which may enhance their effects or increase the risk of side effects (Karsh, 1990).
5. CNS Toxicity: High doses of aspirin can cause toxic effects on the central nervous system, manifested by tinnitus (ringing in the ears), dizziness, and even seizures (Ingelfinger, 1974).

Overdose

Symptoms of aspirin overdose:

1. Mild to moderate overdose:

   • Headache
   • Dizziness
   • Tinnitus (tinnitus )
   • Nausea and vomiting
   • Confusion of consciousness
   • Hyperventilation (increased and rapid breathing)

2. Severe overdose:

   • Severe acid-base imbalance: electrolyte imbalance and acidosis.
   • Hyperthermia (high body temperature)
   • Tachypnea.
   • Tachycardia (rapid heartbeat).
   • Coma
   • Seizures
   • Nephrotoxicity: renal failure due to toxic effects on the kidneys.
   • Respiratory alkalosis followed by metabolic acidosis.
   • Electrolyte disorders such as hypokalemia (low blood potassium levels).
   • Hemorrhagic diathesis: increased risk of bleeding.

Mechanisms of toxic action:

Aspirin in high doses disrupts the normal functioning of cellular mitochondria and acid-base homeostasis, which leads to metabolic acidosis. Aspirin also irreversibly inhibits the enzyme cyclooxygenase, which leads to decreased synthesis of protective prostaglandins and increased formation of lactate and pyrogens in the body at toxic doses.

Treatment of aspirin overdose:

1. Symptomatic treatment:

   • Ensuring airway patency, maintaining breathing and circulation.
   • Correction of electrolyte and acid-base balance.

2. Medical Procedures:

   • Gastric lavage to remove unabsorbed aspirin (especially if ingestion was less than 2-4 hours ago).
   • Activated charcoal to reduce absorption of aspirin from the gastrointestinal tract.
   • Forced alkaline diuresis to accelerate aspirin excretion.
   • Hemodialysis in cases of severe poisoning to rapidly remove aspirin from the blood.

3. Maintaining normal hydration to maintain adequate renal function and prevent the development of renal failure.

Prevention of overdose:

• Strict adherence to recommended dosages.
• Avoid taking aspirin concurrently with other NSAIDs or alcohol, which may increase its side effects.
• Consult with your doctor before starting aspirin, especially in individuals with chronic conditions or taking multiple medications.

Interactions with other drugs

1. Anticoagulants: Co-administration of aspirin with anticoagulants (e.g. Warfarin) increases the risk of bleeding due to synergistic enhancement of antithrombotic effects (Karsh, 1990).
2. Nonsteroidal anti-inflammatory drugs (NSAIDs): NSAIDs such as ibuprofen or naproxen may reduce the cardioprotective effects of aspirin by competing for binding to cyclooxygenase-1 in platelets, potentially reducing its antiaggregant effect (Russo, Petrucci, & Rocca, 2016).
3. ACE inhibitors: Aspirin may reduce the effectiveness of ACE inhibitors (e.g., enalapril) due to aspirin's inhibition of prostaglandin synthesis, which is necessary for the full vasodilatory action of ACE inhibitors (Spaulding et al., 1998).
4. Diuretics: Co-administration of aspirin with diuretics may reduce their diuretic and antihypertensive effects, also due to interaction with prostaglandins (Karsh, 1990).
5. Serotonin reabsorption inhibitors (SSRIs): Aspirin in combination with SSRIs may increase the risk of gastrointestinal bleeding due to synergism in their effects on platelets (Russo, Petrucci, & Rocca, 2016).
6. Methotrexate: Aspirin may increase the toxicity of methotrexate by delaying its excretion through competition for tubule secretion in the kidneys (Hayes, 1981).