Anti-Inflammatory, Antipyretic & Analgesic Pharmacology.pdf

Anti-Inflammatory, Antipyretic & Analgesic Pharmacology DONE BY: MOHAMMAD ALLAHIB Inflammation  Inflammation is the body's protective response to injury, infection, or harmful stimuli  It involves immune cells, blood vessels, and molecular mediators  Signs of Inflammation:  Redness...

Anti-Inflammatory, Antipyretic & Analgesic Pharmacology DONE BY: MOHAMMAD ALLAHIB Inflammation  Inflammation is the body's protective response to injury, infection, or harmful stimuli  It involves immune cells, blood vessels, and molecular mediators  Signs of Inflammation:  Redness (Rubor): Due to increased blood flow  Heat (Calor): From increased blood flow and metabolic activity  Swelling (Tumor): Due to fluid accumulation  Pain (Dolor): From pressure on nerves and release of inflammatory mediators  Loss of Function (Functio Laesa): Result of pain and swelling Phases of Inflammation Acute Inflammation Chronic Inflammation  Rapid onset, short duration  Characteristics: Prolonged duration, ongoing tissue destruction and repair  Eliminate the initial cause of cell injury, remove dead cells, and initiate tissue  Purpose: Persistent inflammation due to repair an ongoing stimulus or unresolved acute inflammation  Vascular Changes: Increased blood flow (vasodilation) and increased  Cellular Infiltration: Predominantly vascular permeability macrophages, lymphocytes, and plasma cells  Cellular Events: Migration of leukocytes, primarily neutrophils, to the  Tissue Destruction: By inflammatory cells site of injury  Repair: Attempted by connective tissue replacement and angiogenesis Molecular Mediators of Inflammation Histamine Cytokines ► Source:  Examples: ► Mast cells  IL-1 ► Basophils  TNF-α ► Platelets  Effect: ► Effect:  Modulate immune response ► Vasodilation  Promote leukocyte recruitment ► Increased vascular permeability Molecular Mediators of Inflammation Prostaglandins  Source: Arachidonic acid metabolism  Effect:  Vasodilation  Fever  Pain Molecular Mediators of Inflammation Chemokines Complement System  Effect: Attract leukocytes to the  Effect: site of inflammation  Enhances phagocytosis  Recruits immune cells  Directly lyses pathogens Pathways of Inflammation 1. Vascular Response:  Vasodilation: Increases blood flow to the area  Increased Permeability: Allows plasma proteins and leukocytes to enter the tissue 2. Cellular Response:  Leukocyte Recruitment: Neutrophils and later macrophages migrate to the site of injury  Phagocytosis: Engulfment and destruction of pathogens and debris by leukocytes Outcomes of Inflammation  Resolution: Clearance of the injurious stimuli, removal of inflammatory cells, and repair of tissue  Chronic Inflammation: If the injurious stimulus persists, leading to ongoing tissue damage and repair  Fibrosis: Excessive connective tissue deposition leading to scar formation  Abscess Formation: Localized collection of pus due to infection Introduction  Anti-Inflammatory Agents: Drugs that reduce inflammation  Types of Anti-Inflammatory Agents:  Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)  Corticosteroids  Disease-Modifying Anti-Rheumatic Drugs (DMARDs)  Analgesic Agents: Drugs that relieve pain Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)  Mechanism of Action:  Inhibition of Cyclooxygenase (COX) Enzymes:  COX-1: Found in most tissues; involved in maintaining gastric mucosa, renal blood flow, and platelet aggregation  COX-2: Induced during inflammation; responsible for the synthesis of inflammatory prostaglandins  Effect: Reduces the synthesis of prostaglandins and thromboxanes, leading to decreased inflammation, pain, and fever Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Ibuprofen  Brand Names: Advil, Profinal, Captain, Brufen  Uses: Pain relief for mild to moderate pain, inflammation, fever  Dosage: Typically 200-800 mg every 6-8 hours  Side Effects: GI irritation, nausea, dizziness, renal impairment Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Naproxen  Brand Names: Napreben, Nopain DS & Proxen  Uses: Longer-lasting relief for arthritis, gout, menstrual pain  Dosage: 250-500 mg every 8-12 hours  Side Effects: Similar to ibuprofen; increased cardiovascular risk with long-term use Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Aspirin  Brand Names: Aspicor, Aspicot  Uses: Pain relief, anti-inflammatory, antipyretic, anti-platelet for cardiovascular protection  Dosage: 325-650 mg every 4-6 hours for pain; low dose (81-325 mg) daily for heart protection  Side Effects: GI bleeding, Reye's syndrome in children, tinnitus at high doses Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Diclofenac  Brand Names: Voltaren, Cataflam, Voltfast, Dicloftil, Diclogesic, Voldic-K  Uses: Pain relief, anti-inflammatory, osteoarthritis, rheumatoid arthritis, dysmenorrhea & acute migraine  Dosage:  Pain/Arthritis: 50 mg 2-3 times daily or 75 mg twice daily  Menstrual Pain: 50 mg 3 times daily  Migraine: 50 mg at onset  Side Effects:  Common: Stomach pain, nausea, indigestion  Serious: GI bleeding, heart risks, liver damage, kidney issues Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Celecoxib  Brand Names: Celebrex  Uses: Selective COX-2 inhibitor; used for osteoarthritis, rheumatoid arthritis, acute pain  Dosage: 100-200 mg once or twice daily  Side Effects: Lower GI risk but potential cardiovascular risk; contraindicated in patients with sulfa allergy Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Rofecoxib  Brand Names: Vioxx  Uses: Selective COX-2 inhibitor; used for osteoarthritis, rheumatoid arthritis, acute pain, dysmenorrhea  Dosage:  Osteoarthritis: 12.5-25 mg once daily  Rheumatoid Arthritis: 25 mg once daily  Acute Pain: 50 mg once daily as needed  Menstrual Pain: 25-50 mg once daily  Side Effects:  Common: Stomach pain, nausea, headache  Serious: Increased risk of heart attack and stroke, GI bleeding, kidney issues Corticosteroids  Mechanism: Mimic cortisol, suppressing inflammation and immune response  Effects:  Bind to Glucocorticoid Receptors: Corticosteroids enter cells and bind to glucocorticoid receptors in the cytoplasm  Regulate Gene Expression: The corticosteroid-receptor complex moves to the nucleus and influences the transcription of anti-inflammatory genes and suppression of pro- inflammatory genes  Membrane Stabilization: Corticosteroids stabilize lysosomal and cell membranes, reducing the release of inflammatory mediators.  Decrease Capillary Permeability: This reduces edema and swelling  Side Effects: Weight gain, osteoporosis, hypertension, diabetes, immunosuppression Corticosteroids Prednisone Hydrocortisone Dexamethasone ► Commonly used for ► Used for adrenal ► Potent anti-inflammatory effects, used inflammatory and insufficiency and in severe inflammatory conditions and autoimmune inflammatory skin as an adjunct in cancer therapy conditions conditions Disease-Modifying Anti-Rheumatic Drugs (DMARDs)  Mechanism: Modify the underlying disease process, not just symptoms  Examples: Methotrexate, Sulfasalazine, Hydroxychloroquine, Biologics (e.g., Etanercept, Infliximab)  Uses: Rheumatoid arthritis, other autoimmune diseases  Side Effects: Immunosuppression, liver toxicity, risk of infections Traditional DMARDs Methotrexate  Examples: Ebetrexat, Methotrexate Ebewe & Metoject  Mechanism: Inhibits dihydrofolate reductase, reducing DNA synthesis and cell replication  Uses: First-line treatment for rheumatoid arthritis (RA).Side Effects: Liver toxicity, bone marrow suppression, gastrointestinal upset  Monitoring: Regular blood tests to monitor liver function and blood cell counts Traditional DMARDs Sulfasalazine  Examples: Azulfidine, Azulfidine EN- Tabs  Mechanism: Suppresses inflammatory responses by inhibiting prostaglandin and leukotriene synthesis  Uses: RA and inflammatory bowel disease (IBD).Side Effects: Rash, gastrointestinal issues, liver toxicity  Monitoring: Regular blood tests for liver and kidney function Traditional DMARDs Hydroxychloroquine  Examples: Corvaquine & Dolquine  Mechanism: Modulates immune system activity and has anti- inflammatory properties  Uses: Mild RA, lupus  Side Effects: Retinal toxicity, gastrointestinal upset  Monitoring: Regular eye exams to monitor for retinal damage Biologic DMARDs Tumor Necrosis Factor (TNF) Inhibitors  Examples: Etanercept, Infliximab, Adalimumab  Mechanism: Bind to and neutralize TNF-alpha, a pro-inflammatory cytokine  Uses: Moderate to severe RA, psoriasis, ankylosing spondylitis  Side Effects: Increased risk of infections, injection site reactions  Monitoring: Regular screening for infections, including tuberculosis Tumor Necrosis Factor (TNF) Inhibitors Etanercept Infliximab Adalimumab Biologic DMARDs Interleukin Inhibitors  Examples: Tocilizumab (IL-6 inhibitor), Anakinra (IL-1 receptor antagonist)  Mechanism: Block specific interleukins involved in the inflammatory process  Uses: RA, juvenile idiopathic arthritis  Side Effects: Increased risk of infections, elevated liver enzymes  Monitoring: Regular blood tests for liver function and signs of infection. Biologic DMARDs B-Cell and T-Cell Targeting Agents  Examples: Rituximab (targets B-cells), Abatacept (modulates T-cell activity)  Mechanism: Rituximab depletes B- cells; Abatacept inhibits T-cell activation  Uses: RA, particularly in patients unresponsive to TNF inhibitors  Side Effects: Infusion reactions, increased risk of infections  Monitoring: Screening for infections, regular monitoring during infusion. Antipyretic Agents Fever  Fever is an elevation in body temperature often due to infection, inflammation, or other medical conditions  Common Causes:  Bacterial Infections: Examples include pneumonia, urinary tract infections, and sepsis  Viral Infections: Examples include influenza, common cold, COVID-19  Inflammatory Diseases: Autoimmune diseases such as rheumatoid arthritis, lupus  Other Causes: Cancer, heatstroke, certain medications, and immunizations Antipyretic Agents  Drugs that reduce fever  Target hypothalamus, the body’s thermostat  Mechanism: Reduce the production of prostaglandins in the hypothalamus, lowering the set point of body temperature  Main Agents: Acetaminophen (Paracetamol) and Non-Steroidal Anti- Inflammatory Drugs (NSAIDs) Antipyretic Agents 1. Acetaminophen (Paracetamol):  Central Action: Inhibits cyclooxygenase (COX) enzymes in the brain, particularly COX-3, leading to a decrease in prostaglandin E2 (PGE2) in the hypothalamus  Effect: Reduces the hypothalamic set point for temperature control, leading to heat dissipation (sweating, vasodilation) 2. NSAIDs (e.g., Ibuprofen, Aspirin):  Peripheral and Central Action: Inhibit COX-1 and COX-2 enzymes, reducing the synthesis of prostaglandins which are involved in fever production  Effect: Decrease the production of pyrogenic cytokines that act on the hypothalamus, lowering the set point temperature Acetaminophen (Paracetamol)  Common Brands: Tylenol, Panadol  Use: Safe for use in all ages, including infants, children, and pregnant women  Dosage: 500-1000 mg every 4-6 hours (maximum 4 grams per day for adults)  Onset of Action: 30-60 minutes  Duration of Action: 3-4 hours  Side Effects: Generally well-tolerated; potential for hepatotoxicity at high doses or with chronic use  Special Considerations: Safe in pregnancy and breastfeeding; caution in patients with liver disease Ibuprofen  Common Brands: Advil, Profinal, Captain, Brufen  Uses: Effective for reducing fever, especially in conditions accompanied by inflammation (e.g., arthritis)  Dosage: 200-400 mg every 4-6 hours (maximum 1200 mg per day for over-the-counter use)  Onset of Action: 30 minutes  Duration of Action: 4-6 hours  Side Effects: Gastrointestinal irritation, renal impairment, increased bleeding tendency  Special Considerations: Avoid in patients with peptic ulcer disease, chronic kidney disease, or aspirin allergy Aspirin  Common Brands: Bayer, Aspicot, Aspicor  Uses: Used less frequently as an antipyretic due to side effects and risk of Reye's syndrome in children  Dosage: 325-650 mg every 4-6 hours (maximum 4 grams per day)  Onset of Action: 1-2 hours  Duration of Action: 4-6 hours  Side Effects: Gastrointestinal bleeding, tinnitus, Reye's syndrome in children  Special Considerations: Not recommended for children or teenagers with viral infections; caution in patients with bleeding disorders or asthma Antipyretic Agents Pediatrics Geriatrics Pregnancy ► Preferred Antipyretic: ► Considerations: ► Preferred Antipyretic: Acetaminophen Acetaminophen and Monitor for renal is considered safe; NSAIDs are ibuprofen are function and generally avoided in the third trimester preferred; avoid gastrointestinal due to risk of premature closure of the aspirin due to risk of tolerance; lower ductus arteriosus Reye's syndrome doses may be needed ► Dosage Adjustments: Dosages must be adjusted according to weight and age Analgesic Agents Pain  Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage  Types of Pain:  Acute Pain  Chronic Pain  Pain Pathways:  Nociceptive Pain  Neuropathic Pain Types of Pain Acute Pain Chronic Pain  Short duration  Lasts longer than 3-6 months  Sudden onset  Persistent or recurrent  Often linked to a specific injury or  Examples: illness  Arthritis  Examples:  Back pain  Post-surgical pain  Neuropathic pain (e.g.,  Fractures diabetic neuropathy)  Burns Pain Pathways Nociceptive Pain Neuropathic Pain  Caused by damage to body tissue  Caused by damage to the nervous system  Activation of nociceptors (pain receptors)  Often described as burning or shooting pain  https://www.ypo.education/neuro logy/neuropathic-pain- t458/video/ Assessment of Pain Pain Scales  Numeric Rating Scale (NRS): 0 (no pain) to 10 (worst pain)  Visual Analog Scale (VAS): Line scale where patients mark their pain level  Faces Pain Scale: Used for children or those with communication difficulties Analgesic Agents Non-Opoid Paracetamol Analgesics Naproxen NSAIDs Ibuprofen Aspirin Morphine Opoid Analgesics Oxycodone Fentanyl Adjuvant Antidepressants Analgesic Anticonvulsants Non-Opioid Analgesics (Strongest to Weakest) Lower risk of gastrointestinal irritation compared to nonselective NSAIDs Celecoxib 100-200 mg once or twice daily, Maximum daily dose: 400 mg Diclofenac Effective for more severe inflammatory conditions 50-75 mg two to three times daily, Maximum daily dose: 150 mg Naproxen Longer duration of action compared to Ibuprofen 250-500 mg every 12 hours, Maximum daily dose: 1000-1250 mg Ibuprofen Effective and widely used NSAID 200-400 mg every 4-6 hours, Maximum daily dose 1200-2400 mg Aspirin Effective for pain & inflammation, cardiovascular protection at low doses 325-650 mg every 4-6 hours, 81-325 mg daily for antiplatelet effect Paracetamol Well-tolerated, minimal gastrointestinal effect 325-1000 mg every 4-6 hours, Maximum daily dose: 1000-4000 mg Opioid Analgesics Morphine  Mechanism: Binds to mu-opioid receptors in the CNS, altering the perception and response to pain  Uses: Moderate to severe pain, particularly post-operative and cancer pain  Benefits: Effective for severe pain  Side Effects: Sedation, constipation, respiratory depression, risk of dependence and overdose  Dosing: Typically 5-30 mg every 4 hours for immediate release; long-acting formulations available. Opioid Analgesics Oxycodone  Mechanism: Similar to morphine, binds to mu-opioid receptors  Uses: Moderate to severe pain  Benefits: Available in immediate and extended-release formulations  Side Effects: Similar to morphine, with high potential for abuse  Dosing: Typically 5-15 mg every 4-6 hours for immediate release; extended-release formulations dosed every 12 hours Opioid Analgesics Fentanyl  Mechanism: Binds to mu-opioid receptors; highly potent  Uses: Severe pain, often used in chronic pain management and anesthesia  Benefits: Rapid onset, available in various formulations (transdermal patches, lozenges)  Side Effects: Similar to other opioids, but with increased potency and risk of overdose  Dosing: Transdermal patches typically applied every 72 hours. Adjuvant Analgesics Antidepressants  Examples: Amitriptyline (tricyclic antidepressant), Duloxetine (SNRI)  Mechanism: Modulate neurotransmitters (serotonin and norepinephrine) involved in pain pathways  Uses: Neuropathic pain, fibromyalgia, chronic pain conditions  Benefits: Can improve pain and associated mood disorders  Side Effects: Sedation, dry mouth, weight gain (TCAs); nausea, insomnia (SNRIs).Dosing: Amitriptyline typically 10-50 mg at bedtime; Duloxetine 30-60 mg daily. Adjuvant Analgesics Anticonvulsants  Examples: Gabapentin, Pregabalin  Mechanism: Modulate calcium channels, reducing neuronal excitability  Uses: Neuropathic pain, postherpetic neuralgia, fibromyalgia  Benefits: Effective for certain types of chronic pain  Side Effects: Dizziness, sedation, peripheral edema  Dosing: Gabapentin typically 300-600 mg three times daily; Pregabalin 75-150 mg twice daily Combining Therapies Combining Therapies  Enhanced Efficacy: Combining drugs with different mechanisms can provide better symptom control  Reduced Side Effects: Lower doses of each drug can be used, minimizing the risk of side effects associated with higher doses of a single drug  Broader Coverage: Address multiple pathways involved in pain, inflammation, or fever Special Considerations in Specific Populations Patients with Elderly Patients Comorbidities Pediatric Patients ► Increased sensitivity ► Consider impact on ► Adjust dosages based to drug effects and existing conditions on age and weight higher risk of side (e.g., cardiovascular, ► Consider effects renal, hepatic) developmental ► Careful dose ► Comprehensive factors in drug adjustments and approach to minimize metabolism and monitoring risks and maximize excretion benefits NSAIDs + Acetaminophen  Mechanism:  NSAIDs: Inhibit COX enzymes, reducing prostaglandin synthesis and inflammation  Acetaminophen: Inhibits central COX enzymes, reducing pain and fever  Benefits:  Synergistic pain relief  Reduced inflammation with NSAIDs  Enhanced overall pain management  Considerations:  Monitor for gastrointestinal issues from NSAIDs  Avoid excessive acetaminophen to prevent liver toxicity  Example: Combining ibuprofen with acetaminophen for acute pain relief, such as dental pain or musculoskeletal injuries Corticosteroids + DMARDs  Mechanism:  Corticosteroids: Suppress the immune response and reduce inflammation  DMARDs: Slow disease progression by targeting underlying mechanisms of autoimmune diseases  Benefits:  Rapid symptom relief from corticosteroids  Long-term disease control with DMARDs  Considerations:  Corticosteroids for short-term use to avoid severe side effects  Regular monitoring of blood counts, liver function, and infection signs due to DMARDs  Example: Prednisone combined with methotrexate for rheumatoid arthritis management. Opioids + Non-Opioids  Mechanism:  Opioids: Bind to opioid receptors in the CNS, altering pain perception  Non-Opioids (NSAIDs/Acetaminophen): Reduce peripheral inflammation and pain signaling  Benefits:  Enhanced pain relief for severe pain  Lower doses of opioids required, reducing the risk of dependence and side effects  Considerations:  Monitor for sedation, respiratory depression, and constipation from opioids  Use multimodal analgesia to minimize opioid dosage  Example: Combining oxycodone with acetaminophen (Percocet) for postoperative pain management Clinical Applications: Inflammatory Conditions Arthritis Osteoarthritis 1. Symptoms: Joint pain, stiffness, reduced mobility. 2. Treatment:  NSAIDs: Ibuprofen, Naproxen, Diclofenac  Mechanism: Reduce inflammation and pain by inhibiting COX enzymes  Benefits: Effective in reducing pain and inflammation  Side Effects: Gastrointestinal irritation, renal impairment  Topical Analgesics: Diclofenac gel  Mechanism: Localized COX inhibition  Benefits: Fewer systemic side effects  Acetaminophen: For pain management, especially in patients with contraindications to NSAIDs  Mechanism: Central inhibition of COX enzymes  Benefits: Good safety profile for long-term use  Side Effects: Hepatotoxicity at high doses  Rheumatoid Arthritis 1. Symptoms: Symmetrical joint inflammation, pain, swelling, morning stiffness 2. Treatment:  NSAIDs: To manage pain and inflammation  Examples: Ibuprofen, Diclofenac  Corticosteroids: Prednisone, Dexamethasone  Mechanism: Potent anti-inflammatory effects  Benefits: Rapid relief of symptoms  Side Effects: Long-term use can cause osteoporosis, hyperglycemia, and adrenal suppression  Rheumatoid Arthritis 2. Treatment:  DMARDs: Methotrexate, Sulfasalazin  Mechanism: Modulate the immune response to prevent joint damage  Benefits: Slow disease progression  Side Effects: Liver toxicity, bone marrow suppression  Biologics: Etanercept, Infliximab  Mechanism: Target specific components of the immune system (e.g., TNF-alpha).Benefits: Effective in patients not responding to traditional DMARDs  Side Effects: Increased risk of infections, injection site reactions Tendonitis 1. Symptoms: Pain, swelling, tenderness around tendons 2. Treatment:  NSAIDs: Oral (Ibuprofen, Naproxen, Diclofenac) or topical (Diclofenac gel)  Mechanism: Reduce inflammation and pain  Benefits: Effective relief of symptoms  Side Effects: GI irritation (oral NSAIDs), skin irritation (topical NSAIDs)  Corticosteroid Injections: For severe cases  Mechanism: Potent local anti-inflammatory effect  Benefits: Rapid symptom relief  Side Effects: Tendon weakening, risk of rupture with repeated use Bursitis 1. Symptoms: Pain, swelling, warmth around affected bursae (fluid-filled sacs cushioning joints) 2. Treatment:  NSAIDs: Ibuprofen, Naproxen, Diclofenac  Mechanism: Reduce inflammation and pain  Benefits: Alleviate symptoms  Side Effects: GI irritation, renal issues with prolonged use  Corticosteroid Injections: For persistent inflammation  Mechanism: Strong local anti-inflammatory effect  Benefits: Effective in reducing swelling and pain  Side Effects: Risk of infection at the injection site, weakening of surrounding tissues  Rest and Physical Therapy: To prevent recurrence and promote healing.  Benefits: Reduces strain on the affected area and enhances recovery Rhinitis 1. Symptoms: Runny nose, Nasal congestion, Sneezing, Itchy nose, eyes, or throat, Postnasal drip 2. Treatments:  Antihistamines (Loratadine, Cetirizine):  Benefits: Relieve sneezing, itching, runny nose  Side Effects: Drowsiness (depends on type)  Corticosteroid Nasal Sprays (Fluticasone, Mometasone):  Benefits: Decrease congestion, sneezing  Side Effects: Nasal irritation, nosebleeds  Decongestants (Pseudoephedrine, Phenylephrine):  Benefits: Alleviate congestion  Side Effects: Increased BP, insomnia Sinusitis 1. Symptoms: Pain, swelling, tenderness around sinuses, Nasal congestion, Thick nasal discharge, Headache, Reduced smell and taste, Fever, Cough 2. Treatment:  NSAIDs (Ibuprofen, Naproxen, Diclofenac):  Benefits: Alleviate symptoms  Side Effects: GI irritation, renal issues  Corticosteroid Nasal Sprays (Fluticasone, Budesonide):  Benefits: Decrease swelling, relieve congestion  Side Effects: Nasal irritation, nosebleeds Sinusitis  Antibiotics (Amoxicillin, Doxycycline):  Benefits: Resolve infection  Side Effects: GI upset, allergic reactions  Decongestants (Pseudoephedrine, Phenylephrine):  Benefits: Alleviate congestion  Side Effects: Increased BP, insomnia  Rest and Hydration:  Benefits: Enhance recovery  Side Effects: None Clinical Applications: Pain Conditions Postoperative Pain Management  NSAIDs:  Examples: Ibuprofen, Naproxen, Diclofenac, Aspirin  Mechanism: Inhibit COX enzymes, reducing prostaglandin synthesis  Benefits: Effective in reducing mild to moderate pain and inflammation  Considerations: Can cause gastrointestinal irritation and increased bleeding risk  Opioids:  Examples: Morphine, Oxycodone.  Mechanism: Bind to opioid receptors in the central nervous system (CNS), altering the perception of pain  Benefits: Effective for moderate to severe pain  Side Effects: Sedation, constipation, risk of dependence and respiratory depression  Administration: Often given intravenously or orally in the postoperative setting  Multimodal Analgesia:  Strategy: Combining different types of pain medications to enhance pain relief and reduce opioid requirements  Examples: NSAIDs or acetaminophen combined with opioids  Benefits: Improved pain control, reduced opioid side effects Chronic Pain Conditions 1. Non-Opioid Analgesics:  Examples: Acetaminophen, NSAIDs.  Uses: First-line treatment for conditions like osteoarthritis and chronic low back pain.  Benefits: Generally well-tolerated, especially acetaminophen. 2. Opioids:  Examples: Long-acting formulations like Oxycodone CR (controlled release), Fentanyl patches.  Uses: Reserved for severe chronic pain not responsive to other treatments.  Considerations: Risk of tolerance, dependence, and side effects necessitate careful monitoring Chronic Pain Conditions 3. Adjuvant Analgesics:  Antidepressants:  Examples: Amitriptyline, Duloxetine.  Mechanism: Enhance pain relief through modulation of serotonin and norepinephrine.  Uses: Effective for neuropathic pain, fibromyalgia.  Side Effects: Sedation, dry mouth, weight gain.  Anticonvulsants:  Examples: Gabapentin, Pregabalin.  Mechanism: Stabilize nerve membranes, reducing neuropathic pain.  Uses: Diabetic neuropathy, postherpetic neuralgia.  Side Effects: Dizziness, somnolence. 4. Topical Analgesics:  Examples: Lidocaine patches, Capsaicin cream.  Uses: Localized pain, especially neuropathic pain.  Benefits: Minimal systemic side effects. Cancer Pain Management 1. Strong Opioids:  Examples: Morphine, Hydromorphone.  Mechanism: Bind to opioid receptors in the CNS.  Benefits: Effective for severe pain, commonly used in palliative care.  Administration: Oral, intravenous, subcutaneous, or transdermal. 2. Adjuvant Therapies:  Examples: Bisphosphonates for bone pain, corticosteroids for inflammation-related pain.  Mechanism: Target specific pain pathways and underlying causes of pain.  Benefits: Enhances overall pain management and patient quality of life. 3. Non-Pharmacological Interventions:  Examples: Physical therapy, psychological support, nerve blocks.  Uses: Complementary approaches to reduce pain and improve function.  Benefits: Holistic approach to pain management, addressing physical and emotional aspects of pain. Clinical Applications: Fever Reduction Fever Acetaminophen (Paracetamol) NSAIDs  Uses: First-line treatment for fever in  Common Examples: Ibuprofen, Aspirin, Naproxen, children and adults Diclofenac  Dosage:  Uses: Effective in reducing fever and providing  Adults: Typically 500-1000 mg every 4-6 additional anti-inflammatory and analgesic benefits hours, not exceeding 4000 mg per day  Dosage:  Children: Dosed based on weight,  Ibuprofen: typically 10-15 mg/kg every 4-6 hours  Adults: 200-400 mg every 4-6 hours, not exceeding  Side Effects: Generally well-tolerated, but 3200 mg per day high doses can cause hepatotoxicity  Children: 5-10 mg/kg every 6-8 hours (liver damage)  Aspirin:  Liver Function: Monitor in patients using high doses of acetaminophen or with  Adults: 325-650 mg every 4-6 hours, not exceeding preexisting liver conditions 4000 mg per day. Not recommended for children due to the risk of Reye’s syndrome Fever NSAIDs  Side Effects: Gastrointestinal irritation, risk of bleeding, renal impairment  Renal Function: Monitor in patients using NSAIDs, especially long-term use  Drug Interactions: Be aware of potential interactions with other medications, such as anticoagulants with NSAIDs Clinical Applications: Autoimmune Disorders Systemic Lupus Erythematosus (SLE) 1. Anti-Malarial Drugs:  Hydroxychloroquine:  Mechanism: Modulates immune system activity  Uses: Reduces flares, improves long-term outcomes, and reduces cardiovascular risk  Side Effects: Retinal toxicity (requires regular eye exams), gastrointestinal issues 2. Corticosteroids:  Mechanism: Powerful anti-inflammatory effects  Uses: Acute management of severe disease flares  Examples: Prednisone, Methylprednisolone  Side Effects: Same as in rheumatoid arthritis; long-term use should be minimized Systemic Lupus Erythematosus (SLE) 3. Immunosuppressants:  Azathioprine:  Mechanism: Inhibits purine synthesis, reducing immune cell proliferation  Uses: Maintenance therapy to reduce disease activity  Side Effects: Bone marrow suppression, liver toxicity, increased infection risk  Mycophenolate Mofetil:  Mechanism: Inhibits inosine monophosphate dehydrogenase, affecting lymphocyte proliferation  Uses: Severe lupus nephritis and other severe manifestations  Side Effects: Gastrointestinal disturbances, increased infection risk, teratogenicity 4. Biologics:  Belimumab:  Mechanism: Inhibits B-cell activating factor (BAFF), reducing B-cell survival  Uses: Active, autoantibody-positive lupus with inadequate response to standard therapies  Side Effects: Nausea, diarrhea, fever, increased risk of infections Inflammatory Bowel Disease (IBD) 1. Corticosteroids:  Mechanism: Reduce inflammation by suppressing immune response.  Uses: Induction of remission in moderate to severe IBD (Crohn's disease and ulcerative colitis).  Examples: Prednisone, Budesonide, Dexamethasone  Side Effects: Similar to other autoimmune uses; focus on minimizing long-term use. 2. Aminosalicylates:  Examples: Mesalamine, Sulfasalazine.  Mechanism: Anti-inflammatory effects in the gastrointestinal tract.  Uses: Induction and maintenance of remission in mild to moderate ulcerative colitis.  Side Effects: Headache, nausea, rash, rare nephrotoxicity Inflammatory Bowel Disease (IBD) 3. Immunosuppressants:  Thiopurines (e.g., Azathioprine, 6-Mercaptopurine):  Mechanism: Inhibit purine synthesis, reducing immune cell proliferation.  Uses: Maintenance therapy in IBD.  Side Effects: Bone marrow suppression, liver toxicity, increased infection risk. 4. Biologics:  TNF Inhibitors (e.g., Infliximab, Adalimumab):  Mechanism: Inhibit TNF, reducing inflammation.  Uses: Moderate to severe Crohn's disease and ulcerative colitis not responding to other treatments.  Side Effects: Increased infection risk, potential risk of malignancies