Anti inflammatory

• Inflammation


  • Process by which the body's white blood cells and chemicals protect us from infection and foreign substances such as bacteria and viruses
  • The protective action of the body as a response to trauma, infection, injury and a chronic medical problem like arthritis
  • Triggered by the release of chemical mediators from injured tissues and migrating cells
• Chemical mediators of inflammation


  • Histamines
  • Kinins
  • Prostaglandins
• Histamines


  Substance found in some body cells; cause more blood and lymph fluid flow to the site of injury
• Kinins


  Blood plasma proteins that influence smooth muscle contraction; increase blood flow, increase the permeability of small capillaries, and stimulate pain receptors
• Prostaglandins


  Chemical messengers synthesized at the site in response to the WBCs that flow to the area of injured tissue; activate the inflammatory response, and produce pain and fever
• Goal of inflammation


  • To remove the initial cause of injury
  • To remove the consequences of injury
• Five cardinal signs of inflammation


  • Rubor (redness)
  • Calor (warmth)
  • Tumor (swelling)
  • Dolor (pain)
  • Functio laesa (loss of normal function)
• The first four signs were described by Roman encyclopedist Aulus Cornelius Celsus
• The fifth cardinal sign was added by Rudolph Virchow
• Phases of inflammation


  1. Vascular phase

  2. Delayed phase
• Vascular phase


  Occurs 10-15 minutes after tissue injury; during vasodilation, fluid and WBCs leave the plasma and flow to the injured tissue
• Delayed phase


  Occurs when WBCs infiltrate injured tissues to defend against infectious disease and foreign material
• Anti-inflammatory drugs


  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Steroidal anti-inflammatory drugs (SAIDs)
• Routes of administration for anti-inflammatory drugs


  • By mouth (tablets, capsules or medicines)
  • As injections
  • By suppositories
  • As creams, gels, and foams
• NSAIDs


  • Medicines that relieve pain, swelling, stiffness and inflammation without exposing the patient to adverse side effects that occur when using corticosteroid medication
  • One of the most widely used groups of pharmacologic agents
  • No undesirable side effects unlike steroidal drugs
  • Available at the counter without prescription
  • Very effective in the treatment of many inflammatory disorders including rheumatoid arthritis, somatic pain, and gynecological disorders
  • Inhibit two forms of COX: COX-1 and COX-2
  • COX-1 is involved in maintaining membrane integrity of mucosal cells in the gastrointestinal tract
  • COX-2 is involved in the inflammatory process
• Contraindications for NSAIDs


  • Nursing and pregnancy
  • Serious bleeding
  • Allergy, asthma, angioedema
  • Impaired renal function
  • Drugs (Anticoagulant)
• Conditions where NSAIDs should be used only under close physician supervision


  • You have asthma
  • You are breastfeeding
  • You have heart problems
  • You have kidney problem
• NSAIDs cannot be used in the following cases: allergy to aspirin, aspirin should not be used under the age of 16, during pregnancy, on blood thinning agent, active peptic ulcer, history of stomach ulcer
• Salicylates


  • Aspirin (acetylsalicylic acid) is the first discovered NSAIDs and is the prototype of traditional NSAIDs
  • Made from salicylic acid found in willow tree bark with bitter taste and irritates the stomach
  • Overuse can lead to respiratory alkalosis that may result in subsequent metabolic acidosis
  • Used as an analgesic, an antipyretic, in larger doses, an antiinflammatory agent, and in lower doses, an antiplatelet by inhibiting cyclooxygenase and platelets
  • Small intestine is the primary site of aspirin absorption
  • Before entering the systemic circulation, aspirin is rapidly hydrolyzed to acetic acid and salicylic acid, which occurs partially by plasma esterase and partially by the liver
• Categories of aspirin


  • Analgesic (relieves pain)
  • Antipyretic (reduces fever)
  • Anticoagulant (aggregation)
• Aspirin


  • Peak level: 1-2 hours after oral dose
  • Adverse effects: Gastrointestinal bleeding, acid-base disturbances, allergic reactions, tinnitus, and Reye's syndrome
• Propionic acid derivatives


  • Reversible inhibitors of the cyclooxygenase
  • Used in the treatment of chronic rheumatoid arthritis and osteoarthritis
  • Adverse effects: gastrointestinal disturbances, headache and tinnitus
• Propionic acid derivatives


  • Ibuprofen
  • Naproxen
  • Fenoprofen
  • Ketoprofen
  • Flurbiprofen
  • Oxaprozin
• Ibuprofen


  • Reduces inflammation, fever, and the sensation of pain
  • Acts as an anticoagulant, suppressing the formation of blood clots
  • Prevents the body from excreting salt and water properly and it should be used with caution by people who suffer from kidney disease, liver disease and high blood pressure
• Naproxen


  • One of the safest NSAIDs
  • Used for relief of pain and inflammation associated with adult and adolescent rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, bursitis, tendinitis, and gout
  • Used in treating headaches and menstrual cramps
  • Can cause increased sensitivity to sunlight
• COX-2-selective NSAIDs


  Directly targets COX-2 which reduces the risk for peptic ulceration but results shown an increased risk for renal failure, heart attack, thrombosis and stroke due to a relative increase in thromboxane
• COX-2-selective NSAIDs


  • Celecoxib
  • Rofecoxib
• Acetic acid derivatives


  Acts by reversibly inhibiting cyclooxygenase
• Acetic acid derivatives


  • Indomethacin
  • Etodolac
• Indomethacin


  • Used in the treatment of acute gouty arthritis, ankylosing spondylitis and osteoarthritis
  • Adverse effects: peptic ulcer and gastrointestinal disturbances
• Etodolac


  • For mild analgesic, inflammation and pain, relieving swelling and stiffness
  • Available only by prescription
  • Capsules or tablets are taken orally every 6-8 hours (200-400 mg)
  • Total daily dosage should not exceed 1200 mg
• Oxicam derivatives


  • Used in the treatment of rheumatoid arthritis, ankylosing spondylitis and osteoarthritis
  • Piroxicam and its metabolites are excreted in urine while meloxicam occurs in both urine and feces
  • Adverse effect: gastrointestinal disturbances
• Oxicam derivatives


  • Piroxicam
  • Meloxicam
• Fenamates


  Used to treat pain, including menstrual pain
• Fenamates


  • Mefenamic acids
  • Meclifenamate
• Acetaminophen/Paracetamol


  • N-acetyl-p-aminophenol
  • Brand names: Tylenol, Panadol, Excedrin, Calpol, Tempra
  • Available in a tablet, capsule, liquid suspension, suppository, intravenous, and intramuscular form
  • Suitable substitute for aspirin as it is as effective as aspirin in its analgesic and antipyretic actions and is preferred over aspirin in patients with a bleeding/coagulation disorder or in children requiring only antipyretics or analgesics, because no association between acetaminophen and Reye's syndrome has been demonstrated
  • This is NOT considered as NSAID since it has MINOR antiinflammatory effects
• Acetaminophen/Paracetamol


  • Peak level: 5 to 20 μg/mL occurring in 30 to 60 minutes
  • Half life: Approximately 2 hours
  • Major metabolites: glucuronide and sulfate conjugates (5% of the major metabolites are converted to N-acetyl-p-amino benzoquinoneimine (NAPQI) which is hepatotoxic in high concentrations; acetylcysteine is administered in cases of toxicity to NAPQI
  • Minor metabolites: deacetylated and hydroxylated derivatives
  • Toxic dose: 140 mg/kg
  • Adverse effects: Skin rashes, hepatotoxicity, cyanosis of the skin, mucosa, and fingernails due to methemoglobinemia, vascular collapse, shock, and total seizures
• Steroidal anti-inflammatory drugs (SAIDs)


  • Often referred to as corticosteroids or glucocorticoids
  • Powerful medications which are based on hormonal substances
  • Have stronger anti-inflammatory response than non-steroidal medicines
  • Can cause mental changes and have more side-effects
  • Can be taken as pills, given through your veins, or injected directly into a joint space
• Steroidal anti-inflammatory drugs


  • Cortisol
  • Cortisone
  • Prednisone
  • Prednisolone
  • Betamethasone
  • Budesonide
  • Triamcinolone
  • Dexamethasone
  • Methylprednisone
• Corticosteroids


  • Hormones produced in the adrenal cortex and regulate inflammation, electrolyte levels, stress response, carbohydrate metabolism, and other physiological responses
  • Typically prescribed for short-term treatment
  • Utilization must be tapered off, otherwise the patient is at risk to have adrenal crisis
  • Long-term use can produce adverse side effects: risk of infection (corticosteroids suppress the immune system), increased appetite and weight gain, edema (since Na and H2O are retained), increased blood pressure