Pain Relievers, Antipyretics, and Anti-inflammatory Drugs: An Overview

Pain Relievers, Antipyretics, and Anti-inflammatory Drugs: An Overview

1. Pharmacokinetic Properties

• Absorption: Weak acids, so they are well absorbed through the gastrointestinal tract.

• Protein binding: They bind strongly to plasma proteins (95-99%), leading to drug interactions.

• Distribution: Widely distributed, including joints and synovial fluid. Drug concentration in synovial fluid is usually half the concentration in plasma.

• Metabolism: Metabolized in the liver (oxidation, hydrolysis, conjugation), excreted in the urine.

• Half-life (T1/2): Varies greatly depending on the drug type.

2. Mechanism of Action

• Antipyretic: Inhibit prostaglandin synthetase, reducing the synthesis of prostaglandin E1 and E2.

• Analgesic: Provide mild to moderate pain relief, acting on peripheral sensory receptors.

• Analgesic: Reduce the synthesis of prostaglandin F2.

• Anti-inflammatory:

• Inhibit cyclooxygenase (COX) enzyme, blocking prostaglandin synthesis.

• Stabilize lysosomal membranes and inhibit leukocyte chemotaxis, suppressing leukocyte migration to the site of inflammation.

• Antiplatelet: Inhibit thromboxane synthetase enzyme, reducing the synthesis of thromboxane A2.

3. Location and Function of COX

• COX1:

• Located in tissues, kidneys, stomach, platelets, uterus, and testicles.

• Protects and maintains physiological functions.

• Involved in the production of protective prostaglandins, known as the “housekeeping enzyme.”

• COX2:

• Located in some parts of the central nervous system, inflammatory tissues, and activated tissues.

• Involved in inflammation and cell division.

• Its synthesis rate increases 20-80 times when induced by damage or ischemia.

4. Selective COX Inhibition Properties

• Drugs that inhibit COX1 more strongly than COX2: May cause gastrointestinal side effects.

• Drugs that inhibit COX2 more strongly than COX1: Fewer gastrointestinal side effects, but may not necessarily inhibit COX1.

5. Indications

• Mild and moderate pain, especially pain accompanied by inflammation.

• Fever from any cause.

• Acute and chronic inflammatory conditions (rheumatoid arthritis, acute gout, ankylosing spondylitis).

• Secondary prevention of myocardial infarction and stroke (aspirin).

6. Adverse Effects

• Gastrointestinal: Irritation, epigastric pain, peptic ulcers, gastrointestinal bleeding (due to inhibition of prostaglandin E2).

• Obstetrics: Can cause fetal malformations, prolonged pregnancy and labor, postpartum hemorrhage (due to inhibition of prostaglandin F2?).

• Renal: Reduced renal blood flow, decreased glomerular filtration rate, fluid retention, hyperkalemia, and interstitial nephritis (due to inhibition of prostaglandin E2 and I2).

• Respiratory: Can induce pseudo-asthma or exacerbate asthma attacks (due to cyclooxygenase inhibition, increasing leukotrienes).

• Blood: Prolonged bleeding time, thrombocytopenia, reduced prothrombin (due to inhibition of platelet aggregation).

• Liver: Hepatitis, liver necrosis, cholestatic jaundice, increased liver enzymes.

• Skin: Photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis.

• CNS: Headache, dizziness, tinnitus, deafness, drowsiness, confusion, anxiety, aseptic meningitis.

• Eye: Blurred vision, retinal disorders.

7. Contraindications and Precautions

• Peptic ulcer disease, gastrointestinal bleeding.

• Individuals with prolonged bleeding time or a tendency to bleed easily.

• Severe liver or kidney impairment.

• Asthma.

• Drug hypersensitivity.

• Pregnant women and breastfeeding mothers.

8. Drug Interactions

• Pharmacodynamic:

• Reduced combined drug effect: Diuretics, beta-blockers, ACE inhibitors.

• Increased risk of side effects: Anticoagulants, sulfonylureas (blood glucose lowering), alcohol, cyclosporine, corticosteroids.

• Pharmacokinetic:

• Inhibition of metabolism, competition for plasma protein binding: Oral anticoagulants, sulfonylureas, phenytoin, valproate.

• Reduced renal excretion: Digoxin, lithium, aminoglycosides, methotrexate.

9. Aspirin

• Antiplatelet effect: Irreversibly inhibits COX-1 on platelet membranes.

• Low dose: Inhibits thromboxane A2, preventing platelet aggregation.

• High dose: Inhibits prostacyclin, promoting platelet aggregation.

• Uric acid effect/excretion:

• Low dose (1-2g/day): Reduces uric acid excretion.

• High dose (>3g/day): Increases uric acid excretion.

• Indications:

• …

• Kawasaki syndrome treatment.

• Adverse effects:

• General adverse effects.

• Reye’s syndrome (contraindicated in children).

• Hypersensitivity.

• Overdose (tinnitus, vomiting, double vision, confusion, coma…).

• Pregnancy: Inhibits uterine contractions, delaying labor, increasing the risk of bleeding in the mother and fetus.

• Drug interactions: Competition for plasma protein binding, reduced uric acid excretion.

10. Diclofenac

• Indications: Treatment of dysmenorrhea, post-cataract surgery inflammation, temporary pain relief and photophobia after refractive corneal surgery.

• Pregnancy: Contraindicated in the last trimester of pregnancy (risk of inhibiting uterine contractions and premature closure of the ductus arteriosus, leading to irreversible pulmonary hypertension, renal failure in the fetus).

11. Ibuprofen

• Indications: Antipyretic in children, patent ductus arteriosus in premature infants, dysmenorrhea.

• Adverse effects:

• Premature closure of the ductus arteriosus in utero.

• Inhibition of uterine contractions and delayed labor.

12. Paracetamol (Acetaminophen)

• Effects: Analgesic, antipyretic, with little to no anti-inflammatory effects.

• Hepatotoxicity at high doses:

• Toxic dose > 10g/day.

• Dose > 20g can be fatal.

• Antidote: N-acetylcysteine, methionine.

Note: This information is for informational purposes only. Please consult with a physician for specific advice on your health condition.