Non-opioid analgesics (NSAID)

 

Steroid

• what is steroid?

  Definition: Hormones are endogenous messengers that are produced in glands or single cells. They are responsible for signal transduction and influence the function and metabolic rate of other organs and cells. Complex regulatory circuits normally control their secretion.

  Steroid hormones: derived from cholesterol (e.g., testosterone, progesterone, estrogen, glucocorticoids, mineralocorticoids)

• Glucocorticoid

  Effects

  Anti-inflammatory and immunosuppressive

  • Acute effects (within minutes)
  • Long-term effects (within hours) : Glucocorticoids bind to cytoplasmic glucocorticoid receptors (GRs)
  • Mineralocorticoid properties: e.g., reduced sodium excretion, increased potassium excretion
  • Antiproliferative: triggers cell apoptosis, and inhibits fibroblast proliferation
  • Anabolic-androgenic effects with steroid abuse : increase in muscle mass and strength

• Triamcinolone is a glucocorticoid used to treat certain skin diseases, allergies, and rheumatic disorders among others. It is also used to prevent worsening of asthma and COPD.

• Side Effect

  Systemic glucocorticoids

  Glucocorticoid toxicity depends on the dose that is administered over a certain period of time. Therefore even low doses can have toxic effects if administered long-term. If glucocorticoids are administered once or only briefly (e.g., for treatment of anaphylactic shock), there are usually no significant side effects even in high doses.

  Untitled

• Contraindications

  • General: hypersensitivity
  • Systemic
    • Systemic fungal infections
    • Intrathecal administration
    • Cerebral malaria (dexamethasone)
    • Concomitant live or live attenuated virus vaccination (if glucocorticoids are used in immunosuppressive doses)
    • Idiopathic thrombocytopenic purpura (IM administration)
    • Use in premature infants (formulations containing benzyl alcohol)
  • Topical
    • Dermatological: bacterial, viral or fungal infection of the mouth or throat (triamcinolone)
    • Ophthalmic
      • Systemic fungal infection (triamcinolone)
      • Acute untreated purulent ocular infections (prednisolone)
      • Fungal or mycobacterial ocular infections, viral conjunctivitis, or keratitis (prednisolone, dexamethasone)
  • Inhalation: status asthmaticus or acute asthma episode requiring intensive measures (beclomethasone, budesonide)

• Why corticosteroids should not be stopped suddenly?

  Steroid use cannot be stopped abruptly; tapering the drug gives the adrenal glands time to return to their normal patterns of secretion. Withdrawal symptoms and signs (weakness, fatigue, decreased appetite, weight loss, nausea, vomiting, diarrhea, abdominal pain) can mimic many other medical problems.

Non-steroid analgesics

• include?

  • nonsteroidal anti-inflammatory drugs (NSAIDs),
  • selective COX-2 inhibitors, and
  • acetaminophen.

  

• overview

  NSAIDs inhibit cyclooxygenases (COX-1 and COX-2), thereby disrupting the production of prostaglandin, an important mediator of pain and inflammation.

  Consequently, NSAIDs possess antipyretic, analgesic, and anti-inflammatory effects, and are particularly effective in the management of musculoskeletal pain (e.g., rheumatic disorders, inflammatory joint pain). Side effects include gastrointestinal ulcers and bleeding, increased risk of heart attacks, and renal function impairment. The severity of these side effects is often underestimated because most non-opioid analgesics are easily available OTC.

  Selective COX-2 inhibitors have similar effects to NSAIDs, but show a lower risk for gastrointestinal side effects.

  Acetaminophen possesses antipyretic and analgesic effects and is the most commonly used over-the-counter (OTC) oral analgesic drug. It is generally well tolerated, but overdose can result in significant hepatotoxicity with the risk of acute liver failure.

Nonsteroidal anti-inflammatory drugs

• Agents

  • Ibuprofen, diclofenac, indomethacin, naproxen, aspirin

• Mechanism of action

  • Reversible inhibition of the enzymes cyclooxygenase 1 and 2 (COX-1 and COX-2) → decreased prostaglandin synthesis

• Effects

  • Analgesic
  • Antipyretic
  • Anti-inflammatory (antirheumatic)
  • With the exception of aspirin, only minor antiplatelet function

• Side effects

  • Gastric and duodenal ulcers with the risk of gastrointestinal bleeding and perforation
  • Increased risk of heart attack and stroke (with the exception of aspirin and naproxen)
  • Renal function impairment: prostaglandins normally maintain renal blood flow by inducing vasodilation of the afferent arterioles. NSAIDS inhibit prostaglandin production, which leads to harmful hypoperfusion of the kidneys and reduced GFR.
  • Pseudoallergic reactions
  • For side effects of aspirin, see aspirin.

  The risk of an ulcer is 10–15 times higher if NSAIDS and glucocorticoids are administered simultaneously!

• Indications

  • Acute and chronic pain (particularly musculoskeletal)
  • Fever

• Contraindications

  • Gastroduodenal ulcers
  • Acute hemorrhage (especially aspirin)
  • Renal failure
  • Recent myocardial infarction, unstable angina, heart failure
  • Surgery: discontinue NSAIDs 1–3 days prior to surgery

  Avoid NSAIDs during pregnancy!

Selective COX-2 Inhibitors

• Agent
  • Celecoxib (Celebrex®)
• Effect
  • Analgesic and anti-inflammatory
  • Advantages in comparison to nonselective NSAIDs
• Side effects
  • Increased risk of heart attack and stroke
  • Sulfa drug allergy
  • Renal side effects in at-risk patients
• Indications
  • Acute pain, rheumatoid arthritis, nonrheumatoid joint pain
  • Especially as an alternative to nonselective NSAIDs for patients with a history of peptic ulcer disease and platelet disorders (e.g., Glanzmann thrombasthenia)
• Contraindications'
  • Severe heart failure, recent myocardial infarction, gastrointestinal bleeding

Other non-opioid analgesics

• Agent

  • Acetaminophen/ Paracetamol

  Acetaminophen is the preferred antipyretic during pregnancy but should be avoided in patients with severe hepatic dysfunction.

  NSAIDs are contraindicated in pregnancy and hemorrhagic fevers. They should be used with caution in breastfeeding patients and those with CAD.

• Effect

  • Reversibly inhibits cyclooxygenase in the CNS → antipyretic and analgesic effects
  • Is peripherally inactivated → no anti-inflammatory effect, minimal gastric side effects

• Side effects

  • Hepatotoxicity due to acetaminophen overdose

• Indications

  • Fever and pain

• Contraindications

  • Severe liver impairment

  Maximum daily dose of acetaminophen: 4 g (adults)!

Ibuprofen / Paracetamol? saat radang → mending ibuprofen karena anti inflammatory → tapi karena hambat Prostanglandin 2 (Prostanglandin 2 fungsinya untuk menerunkan gastric) → sakit lambung