Analgesic and anti inflammatory drug dosage action side effect uses all detail
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Analgesic and Anti-Inflammatory Drugs — Complete Overview
Sources: Katzung's Basic and Clinical Pharmacology, 16th Ed.; ROSEN's Emergency Medicine; Miller's Anesthesia, 10th Ed.
CLASSIFICATION
| Category | Examples |
|---|---|
| Non-opioid analgesics / NSAIDs | Aspirin, Ibuprofen, Naproxen, Diclofenac, Indomethacin, Ketorolac, Piroxicam, Meloxicam, Celecoxib, Paracetamol |
| Opioid analgesics | Morphine, Codeine, Tramadol, Fentanyl, Oxycodone, Buprenorphine |
| Disease-modifying / other | Corticosteroids, DMARDs (for chronic inflammatory disease) |
PART I — NSAIDs (NON-STEROIDAL ANTI-INFLAMMATORY DRUGS)
Mechanism of Action
All NSAIDs work by inhibiting cyclooxygenase (COX) enzymes — COX-1 and COX-2 — which catalyze the conversion of arachidonic acid to prostaglandins, thromboxanes, and prostacyclin. The resulting decrease in prostaglandin synthesis produces:
- Analgesia — reduced peripheral and central pain sensitization
- Antipyresis — reduced hypothalamic prostaglandin E₂
- Anti-inflammation — decreased vascular permeability, leukocyte chemotaxis, and edema
COX-1 is constitutively expressed in the stomach, kidneys, and platelets.
COX-2 is induced at sites of inflammation; also expressed in CNS, kidneys, and vascular endothelium.
- Non-selective NSAIDs inhibit both COX-1 and COX-2
- Selective COX-2 inhibitors (coxibs) spare COX-1, reducing GI ulceration risk but increasing cardiovascular risk
INDIVIDUAL NSAID DRUG PROFILES
1. ASPIRIN (Acetylsalicylic Acid)
| Parameter | Details |
|---|---|
| Class | Salicylate |
| Half-life | 0.25 hr (aspirin); salicylate 1.9–12 hr (dose-dependent) |
| Mechanism | Irreversibly acetylates and inhibits COX-1 and COX-2 |
| Analgesic/antipyretic dose | 325–650 mg every 4–6 hr (max 4 g/day) |
| Anti-inflammatory dose | 1200–1500 mg three times daily |
| Antiplatelet dose | 75–100 mg/day |
| Uses | Pain, fever, headache, arthritis (OA, RA), prevention of MI and stroke, Kawasaki disease |
| Side effects | GI irritation, peptic ulceration, bleeding (antiplatelet), tinnitus and hearing loss (high doses/toxicity), hypersensitivity (aspirin-exacerbated respiratory disease), Reye syndrome (children with viral illness), metabolic acidosis in overdose |
| Contraindications | Children with viral illness, peptic ulcer, bleeding disorders, NSAID hypersensitivity |
2. IBUPROFEN
| Parameter | Details |
|---|---|
| Class | Propionic acid derivative |
| Half-life | 2 hr |
| Mechanism | Non-selective, reversible COX-1 and COX-2 inhibitor |
| Dosage | 400–600 mg every 6–8 hr (max 3200 mg/day); OTC: 200–400 mg every 4–6 hr |
| Uses | Mild-to-moderate pain, fever, OA, RA, dysmenorrhea, headache |
| Side effects | GI upset, peptic ulcer, renal impairment, fluid retention, cardiovascular events (with long-term use), hypersensitivity |
| Notes | Ibuprofen has a relatively favorable GI and CV profile at low OTC doses. The free fraction is higher in women than men |
3. NAPROXEN
| Parameter | Details |
|---|---|
| Class | Propionic acid derivative (naphthylpropionic acid) |
| Half-life | ~13 hr |
| Mechanism | Non-selective COX inhibitor; only NSAID marketed as a single enantiomer |
| Dosage | 250–500 mg twice daily; OTC 220 mg every 8–12 hr |
| Uses | OA, RA, ankylosing spondylitis, acute gout, dysmenorrhea, migraine, bursitis/tendonitis, juvenile idiopathic arthritis |
| Side effects | Nausea, dizziness, somnolence, GI bleeding (higher than OTC ibuprofen), rare allergic pneumonitis, leukocytoclastic vasculitis, pseudoporphyria |
| Contraindications | Hepatic impairment |
| Notes | Naproxen has a more favorable cardiovascular risk profile than ibuprofen — Katzung 16th Ed., p. 1008 |
4. DICLOFENAC
| Parameter | Details |
|---|---|
| Class | Acetic acid derivative (phenylacetic acid) |
| Half-life | 1.9–2.3 hr |
| Mechanism | Non-selective COX inhibitor; also decreases arachidonic acid release and inhibits lipoxygenase |
| Dosage | 50–75 mg twice daily (oral); topical gel and transdermal patch also available |
| Uses | OA, RA, ankylosing spondylitis, dysmenorrhea, post-operative pain, actinic keratosis (topical) |
| Side effects | GI ulceration, hepatotoxicity (elevated LFTs), CV events, renal impairment; cardiovascular risk may be higher than with other NSAIDs |
| Notes | Available as oral, ophthalmic, topical, and IV/IM formulations |
5. INDOMETHACIN
| Parameter | Details |
|---|---|
| Class | Indole acetic acid derivative |
| Half-life | 4–5 hr |
| Mechanism | Potent non-selective COX inhibitor; also inhibits phospholipase A, platelet aggregation, and neutrophil motility |
| Dosage | 25–50 mg three times daily; 75 mg SR formulation available |
| Uses | Acute gout, ankylosing spondylitis, moderate-to-severe RA, closure of patent ductus arteriosus (IV), Bartter syndrome, pericarditis |
| Side effects | High frequency of GI side effects (20–50%), severe headache, dizziness, depression, psychosis, bone marrow depression (rare), platelet dysfunction |
| Notes | One of the most potent NSAIDs but has the highest CNS side effect rate — limited to conditions where other NSAIDs fail |
6. KETOROLAC
| Parameter | Details |
|---|---|
| Class | Pyrrolizine carboxylic acid (acetic acid group) |
| Half-life | ~5–6 hr |
| Mechanism | Potent, non-selective COX inhibitor |
| Dosage | 15–30 mg IM/IV every 6 hr; 10 mg oral every 4–6 hr; max duration: 5 days |
| Uses | Short-term management of moderate-to-severe acute pain (post-operative, renal colic); can replace opioids in many settings |
| Side effects | GI ulceration and bleeding (risk increases beyond 5 days), renal impairment, inhibition of platelet aggregation |
| Notes | Parenteral NSAID — very useful for acute pain without sedation or respiratory depression |
7. MELOXICAM
| Parameter | Details |
|---|---|
| Class | Oxicam (enolcarboxamide) |
| Half-life | 20 hr — allows once-daily dosing |
| Mechanism | Preferential COX-2 inhibitor (not fully selective) |
| Dosage | 7.5–15 mg once daily |
| Uses | OA, RA, juvenile idiopathic arthritis |
| Side effects | Similar to other NSAIDs; lower GI risk than indomethacin; may increase CV risk at high doses |
8. PIROXICAM
| Parameter | Details |
|---|---|
| Class | Oxicam |
| Half-life | 57 hr (enterohepatic cycling) — once daily dosing |
| Mechanism | Non-selective COX inhibitor; also inhibits PMN migration, oxygen radical production, and lymphocyte function at high concentrations |
| Dosage | 20 mg once daily |
| Uses | OA, RA |
| Side effects | At doses >20 mg/day: peptic ulcer and GI bleeding risk increases markedly (relative risk up to 9.5); standard NSAID adverse effects |
9. CELECOXIB
| Parameter | Details |
|---|---|
| Class | Coxib — selective COX-2 inhibitor |
| Half-life | 11.2 hr |
| Mechanism | Selectively inhibits COX-2; spares COX-1 (platelet and gastric mucosal protection preserved) |
| Dosage | 100–200 mg twice daily |
| Uses | OA, RA, ankylosing spondylitis, acute pain, familial adenomatous polyposis (FAP), dysmenorrhea |
| Side effects | Reduced GI ulceration compared to non-selective NSAIDs; increased cardiovascular risk (thrombotic events — MI, stroke) due to loss of prostacyclin without loss of thromboxane; sulfonamide allergy cross-reactivity |
| Notes | Contraindicated in patients with established cardiovascular disease or high CV risk |
10. PARACETAMOL (Acetaminophen)
| Parameter | Details |
|---|---|
| Class | Para-aminophenol derivative |
| Half-life | 2–3 hr |
| Mechanism | Central COX inhibitor (weak peripheral effect); may act on endocannabinoid system; no significant anti-inflammatory action |
| Dosage | 500–1000 mg every 4–6 hr (max 4 g/day in healthy adults; 2 g/day in liver disease or heavy drinkers) |
| Uses | Mild-to-moderate pain, fever, OA (preferred over NSAIDs in patients with GI or CV risk), headache |
| Side effects | Hepatotoxicity in overdose (via toxic NAPQI metabolite) — antidote: N-acetylcysteine; minimal GI or CV risk at therapeutic doses |
| Contraindications | Hepatic impairment, active alcoholism |
COMMON ADVERSE EFFECTS OF NSAIDs (Class Effects)
| System | Effects |
|---|---|
| GI | Peptic ulceration, GI bleeding, dyspepsia, nausea; risk reduced by misoprostol or proton pump inhibitors |
| Renal | Acute kidney injury, sodium and water retention, reduced GFR (especially in volume-depleted patients), hyperkalemia, interstitial nephritis |
| Cardiovascular | Hypertension, fluid retention, increased risk of MI and stroke (especially COX-2 selective and high-dose non-selective NSAIDs) |
| Platelet | Inhibition of thromboxane A₂ → anti-aggregation (reversible except aspirin which is irreversible) |
| Respiratory | Aspirin-exacerbated respiratory disease (aspirin triad: asthma, nasal polyps, NSAID sensitivity) |
| Hepatic | Elevated transaminases (especially diclofenac) |
| Pregnancy | Premature closure of ductus arteriosus; avoid in third trimester |
PART II — OPIOID ANALGESICS
Mechanism of Action
Opioids bind to μ (mu), κ (kappa), and δ (delta) opioid receptors in the CNS and peripheral tissues. Activation causes:
- Analgesia (supraspinal and spinal)
- Euphoria/sedation
- Decreased GI motility
- Respiratory depression
- Cough suppression
INDIVIDUAL OPIOID DRUG PROFILES
1. MORPHINE
| Parameter | Details |
|---|---|
| Receptor | Primarily μ-opioid agonist |
| Half-life | 2–4 hr |
| Dosage | IV: 2–4 mg (up to 0.1 mg/kg) every 5–30 min; oral: 5–30 mg every 4 hr |
| Uses | Severe pain (cancer, MI, post-operative, trauma), acute pulmonary edema, dyspnea in palliative care |
| Side effects | Respiratory depression, hypotension (histamine release + vasodilation), nausea/vomiting, constipation, sedation, pruritus, urinary retention, miosis |
| Antidote | Naloxone (competitive antagonist) |
| Notes | Active metabolite morphine-6-glucuronide accumulates in renal failure — use with caution; causes significant histamine release — ROSEN's Emergency Medicine |
2. CODEINE
| Parameter | Details |
|---|---|
| Mechanism | Prodrug → converted to morphine by CYP2D6 |
| Dosage | 30–60 mg every 4–6 hr (oral/IM) |
| Uses | Mild-to-moderate pain, antitussive (cough suppression) |
| Side effects | Constipation, nausea, sedation; ultra-rapid metabolizers at risk of morphine toxicity; poor metabolizers get no analgesia |
| Notes | Contraindicated in children after tonsillectomy/adenoidectomy; CYP2D6 polymorphisms affect response |
3. TRAMADOL
| Parameter | Details |
|---|---|
| Mechanism | Weak μ-opioid agonist + inhibits serotonin and norepinephrine reuptake |
| Dosage | 50–100 mg every 4–6 hr (max 400 mg/day) |
| Uses | Moderate pain, neuropathic pain, fibromyalgia |
| Side effects | Nausea, dizziness, seizures (at high doses or with serotonergic drugs), serotonin syndrome, constipation, less respiratory depression than full opioids |
| Contraindications | Epilepsy, concurrent MAOIs or SSRIs (serotonin syndrome risk) |
4. FENTANYL
| Parameter | Details |
|---|---|
| Potency | 80–100× more potent than morphine |
| Half-life | 30–60 min (IV); 17–27 hr (transdermal patch) |
| Dosage | IV: 12.5–50 mcg every 5–30 min; transdermal: 25–100 mcg/hr patches |
| Uses | Intraoperative analgesia, procedural sedation, severe chronic pain (transdermal), ACS |
| Side effects | Respiratory depression, chest wall rigidity (at high IV doses), minimal histamine release (advantage over morphine), bradycardia |
| Notes | Preferred in hemodynamically unstable patients and those with morphine allergy — ROSEN's Emergency Medicine |
5. BUPRENORPHINE
| Parameter | Details |
|---|---|
| Mechanism | Partial μ-agonist + κ-antagonist; high receptor affinity |
| Dosage | Sublingual: 0.2–0.4 mg every 6–8 hr; for addiction: 4–24 mg/day (Suboxone with naloxone) |
| Uses | Moderate-to-severe pain, opioid use disorder (OUD) treatment |
| Side effects | Respiratory depression (ceiling effect — safer than full agonists), nausea, headache, withdrawal precipitation if given to opioid-dependent patients |
| Notes | Ceiling effect on respiratory depression makes it safer; displaces other opioids from receptors |
OPIOID SIDE EFFECTS SUMMARY
| System | Effects |
|---|---|
| CNS | Analgesia, sedation, euphoria, miosis, confusion |
| Respiratory | Dose-dependent respiratory depression (most serious adverse effect) |
| GI | Constipation (most common; tolerance does not develop), nausea, vomiting, delayed gastric emptying |
| CVS | Hypotension, bradycardia |
| Other | Pruritus (especially intraspinal), urinary retention, physical dependence, tolerance |
WHO ANALGESIC LADDER
For pain management (especially cancer pain):
| Step | Pain Level | Drug Class |
|---|---|---|
| Step 1 | Mild | Non-opioid (Paracetamol, NSAIDs) ± adjuvants |
| Step 2 | Mild-to-moderate | Weak opioid (Codeine, Tramadol) + non-opioid ± adjuvants |
| Step 3 | Moderate-to-severe | Strong opioid (Morphine, Fentanyl, Oxycodone) + non-opioid ± adjuvants |
QUICK REFERENCE DOSAGE TABLE
| Drug | Standard Dose | Route | Frequency |
|---|---|---|---|
| Aspirin (anti-inflammatory) | 1200–1500 mg | Oral | TID |
| Aspirin (antiplatelet) | 75–100 mg | Oral | OD |
| Ibuprofen | 400–600 mg | Oral | Q6–8H |
| Naproxen | 250–500 mg | Oral | BID |
| Diclofenac | 50–75 mg | Oral/IM | BID |
| Indomethacin | 25–50 mg | Oral | TID |
| Ketorolac | 15–30 mg | IM/IV | Q6H (max 5 days) |
| Meloxicam | 7.5–15 mg | Oral | OD |
| Piroxicam | 20 mg | Oral | OD |
| Celecoxib | 100–200 mg | Oral | BID |
| Paracetamol | 500–1000 mg | Oral/IV | Q4–6H |
| Morphine | 2–4 mg IV; 5–30 mg oral | IV/Oral | Q4–6H (titrate) |
| Codeine | 30–60 mg | Oral | Q4–6H |
| Tramadol | 50–100 mg | Oral | Q4–6H |
| Fentanyl | 12.5–50 mcg IV | IV | Q5–30 min |
| Buprenorphine | 0.2–0.4 mg | Sublingual | Q6–8H |
KEY CLINICAL POINTS
- GI protection: Use a PPI (omeprazole) with NSAIDs in high-risk patients (elderly, history of ulcer, concurrent corticosteroids/anticoagulants)
- Renal risk: NSAIDs should be avoided in patients with CKD, dehydration, or heart failure
- CV risk: COX-2 inhibitors and high-dose NSAIDs increase thrombotic cardiovascular risk — naproxen has the most favorable CV profile
- Paracetamol is the preferred analgesic in patients with GI or CV contraindications to NSAIDs
- Opioids: Always consider constipation prophylaxis (laxatives); monitor for respiratory depression
- Antidote for opioid overdose: Naloxone 0.4–2 mg IV/IM/SC, repeat every 2–3 min as needed
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