Anti-Inflammatory Drugs Class - PDF

Anti-Inflammatory Drugs: NSAIDs & Acetaminophen Chapter 75 Objectives  Discuss the role of inflammation in pain  Understand the role of anti-inflammatory, anti-rheumatoid and other related medications in pain reduction  Differentiate the above classification and understand the...

Anti-Inflammatory Drugs: NSAIDs & Acetaminophen Chapter 75 Objectives  Discuss the role of inflammation in pain  Understand the role of anti-inflammatory, anti-rheumatoid and other related medications in pain reduction  Differentiate the above classification and understand their mechanism of action, significant interactions, indications, adverse effects and contraindication  Identify maximum recommended doses for the prototype medications  Identify sign of toxicity The Inflammatory Response Signs of Inflammation? Mechanisms? The Inflammatory Response Tissue injury causes the release of: Prostaglandins bradykinin histamine leukotriennes serotonin Release of Autacoids Local mediators cause vasodilation, increased vascular permeability, chemotaxis, pain Gastrointestinal tract Renal Platelet function Blood vessels Non-Steroidal Anti-inflammatory Drugs NSAIDs or Cyclooxygenase Inhibitors (except acetaminophen) NSAIDs X NSAIDs: Mechanism of Action Blocking either or both cyclooxygenase (COX) enzymes COX-1 & COX-2  COX is the enzyme that converts arachidonic acid into prostanoids (prostaglandins and related compounds) Limits the undesirable inflammatory effect of PGs and related substances Non-Steroidal Anti-inflammatory Drugs (NSAIDs) Large and chemically diverse group of drugs with the following properties: analgesic anti-inflammatory antipyretic NSAIDs: Indications Relief of mild to moderate pain Osteoarthritis, rheumatoid arthritis and juvenile rheumatoid arthritis Acute gout (a form of arthritis) Various bone, joint, and muscle pain Dysmenorrhea Fever Many other conditions Non-Selective NSAIDs Inhibit COX-1 and COX-2 alleviate mild to moderate pain inflammatory disorders (rheumatoid arthritis, osteoarthritis, bursitis) Suppress inflammation but pose risk of serious harm Non-Selective NSAIDs acetylsalicylic acid (ASA) – Aspirin ketorolac (Toradol) sodium salicylate ibuprofen (Motrin, Advil) naproxen (Aleve) diclofenac sodium (Voltaren) Lots more Combination Medications Combinations eg ASA with caffeine and pseudoephedrine NSAIDs and mild opioids Codeine – 222s Acetylsalicylic acid (ASA, Aspirin) Standard NSAID against which all others are compared  Salicylic acid prepared from willow bark, other plants  Bayer Pharmaceuticals (1899) made acetylsalicylic acid  ‘Aspirin’ from acetalation spiraea  Acetyl group Salicylic acid Acetlysalicylic acid ASA Acetylsalicylic acid (ASA, Aspirin) Anti-inflammatory – where and how? Analgesic – where and how? Antipyretic - where and how? Antiplatelet – lasts about 8 days  Why? Acetylsalicylic acid (ASA, Aspirin) ASA is different to other NSAIDs Irreversibly inhibits COX All other NSAIDs reversibly inhibit COX ASA (Aspirin) Antiplatelet MI, stroke and other thromboembolic events(see antiplatelet class) dose 80 – 160 mg daily prophylactic ONLY NSAID used for this purpose ASA (Aspirin) – Contraindications and Cautions Pregnancy in late trimester connected with low weight, intracranial bleed, and even death Almost all bleeding disorders, hemophilia Why? Discontinue 1 week before operation Caution in renal dysfunction What is the BIG problem with ASA? All NSAIDs – Adverse Effects Gastrointestinal Gastric ulceration (erosions)  dyspepsia, heartburn, epigastric distress, nausea GI bleeding Protect GI ASA (Aspirin) – Adverse Effects Influenza and chickenpox in kids/teens due to possibility of Reye’s syndrome Vomiting Liver damage CNS problems (encephalopathy)  Confusion, seizures, coma All NSAIDs – Adverse Effects Renal reductions in creatinine clearance  what does this mean? acute tubular necrosis with renal failure NSAIDs - Salicylate Toxicity ASA, Na salicylate, Mg salicylate Adults tinnitus and hearing loss Children Hyperventilation (CNS stimulation) ASA (Aspirin) - Interactions Increased bleeding with anticoagulants Glucocorticoids gastric ulcers Non-ASA NSAIDs reduce antiplatelet effects of ASA do not mix NSAIDs if ASA used for antiplatelet effect Non-ASA NSAIDs Non-ASA NSAIDs ASA-like drugs with fewer GI, renal, and hemorrhagic effects than ASA (aspirin) 20+ non-ASA NSAIDs available (all similar, but for unknown reasons, patients tend to do better on one drug or another) Inhibit COX-1 and COX-2: Inhibition is reversible (unlike with ASA) Do not protect against MI and stroke Summary of NSAID Adverse Effects Gastrointestinal ulceration Blockade of platelet aggregation (*) bleeding problems  but IM/stroke prevention with ASA (ie not AE) Inhibition of prostaglandin-mediated renal function Hypersensitivity reactions Summary of Contraindications Conditions with bleeding as a risk Vitamin K deficiency – Why? (see later class) peptic ulcer disease Severe renal or hepatic disease Breastfeeding Selective COX-2 Inhibitors Gastrointestinal tract Renal Platelet function Blood vessels  Selective NSAIDs X Gastrointestinal tract Renal Platelet function Blood vessels Possible Solution of GI Problem? Not really! NSAIDs: Selective COX-2 Inhibitors COX-2 Responsible for inflammatory mediators COX-2 Inhibitors celecoxib (Celebrex)  “sulfa” drug – allergies? rofecoxib (Vioxx) – withdrawn 2004 (Merck) NSAIDs: Selective COX-2 Inhibitors Just as effective as traditional NSAIDs in suppressing inflammation and pain Perhaps lower risk for GI adverse effects  But higher than not taking the drug Can impair renal function and cause hypertension and edema Increased risk of MI and stroke Reduction of NSAID- induced GI Problem? Protect GI  NSAIDs X NSAIDs X Gastrointestinal tract Renal Platelet function misoprostol Blood vessels NSAIDs and GI Ulceration Reduce GI ulceration misoprostol (Cytotec)  synthetic prostaglandin  used in combination with NSAIDs to reduce ulceration NSAIDs - Antipyretic Antipyretic (reduce fever) inhibit prostaglandin E2 production within the area of the brain that controls temperature NSAIDs: Client Implications Before beginning therapy, assess for conditions that may be contraindications to therapy, especially: GI lesions or peptic ulcer disease Bleeding disorders NSAIDs: Client Implications Notify if GI pain occurs or evidence of GI bleeding Clients should watch closely for the occurrence of any unusual bleeding, such as in stool dark or black color, tarry Enteric-coated tablets should not be crushed or chewed NSAIDs: Client Implications Salicylates are NOT to be given to children under age 12 Reye’s syndrome - ABSOLUTELY CRITICAL Acetaminophen Chapter 75 NON-opioid Analgesics Acetaminophen (eg Tylenol) analgesic antipyretic Little to no anti-inflammatory effects  Not a NSAID No antiplatelet effect Alternative for those who cannot take NSAID products Acetaminophen Mechanism? Where does it act? Acetaminophen Inhibits COX but only a COX present in CNS  analgesic effect? No peripheral therapeutic sites of action Absence of adverse effects associated with NSAIDs no GI ulceration, excessive bleeds Acetaminophen Antipyretic (reduce fever) inhibit prostaglandin E2 production within the area of the brain that controls temperature Acetaminophen Maximum 4000 mg per day for adult 2400 mg for 11-12 years  sliding scale based on age/weight extreme caution in alcohol abusers Acetaminophen Single ingredient tabs are 325mg, 500mg, 650mg  maximum reached quickly Tylenol 1,2,3,or 4 (combination) codiene (8,15, 30, 60 mg)  all have 300 mg acetaminophen  possible unintentional use Acetaminophen Contraindications severe hepatic disease severe renal disease alcoholism drug allergy Acetaminophen: Toxicity OTC and prescription Can be lethal in overdose Overdose whether intentional or due to chronic unintentional misuse (how?) hepatic necrosis (drug-induced hepatitis) Long-term ingestion of large doses also causes nephropathy  Acetaminophen  Tylenol Products: Tablets, Gelcaps, Geltabs, Caplets, Liquid, Arthritis Pain Extended Relief Caplets, Extended Release Geltabs, Sore Throat Adult Liquid, Allergy Sinus Nighttime Caplets, Severe Allergy Caplets, Allergy Sinus Day Time Caplets, Gelcaps and Geltabs, Multi-Symptom Cold Non- Drowsy Caplets and Gelcaps, Multi-Symptom Cold Nighttime Complete Formula Caplets, Multi-Symptom Cold Severe Congestion Non-Drowsy Caplets, Flu Day Non-Drowsy Gelcaps, Flu Nighttime Gelcaps and Liquid, PM Caplets, Geltabs and Gelcaps, Sinus Day Non-Drowsy Geltabs, Gelcaps and Caplets, Sinus Nighttime Caplets, Women’s Menstrual Relief Caplets  Alka-Seltzer Plus Products: Cold Medicine LiquiGels and Effervescent Tablets, Cold & Sinus Medicine Liqui-Gels, Effervescent Tablets, Night-Time Cold Medicine Liqui- Gels, Cold & Cough Medicine Liqui-Gels, Flu Medicine Liqui- Gels, Nose & Throat Cold Medicine Effervescent Tablets.  Benadryl Products: Allergy & Cold Caplets, Allergy & Sinus Headache Caplets and Gelcaps, Severe Allergy & Sinus Headache Caplets.   Contac Products: Severe Cold and Flu Caplets, Severe Cold and Flu Caplets Non-Drowsy.  Excedrin Products: Tablets, Caplets and Geltabs, Aspirin- Free Tension Headache Caplets and Geltabs, Migraine Tablets, Caplets and Geltabs, PM Tablets, Caplets and Geltabs, QuickTabs Tablets.  Goody’s Products: Body Pain Formula Powder, Headache Powder, Pain Relief Tablets, PM Powder. Midol Products: Menstrual Caplets and Singlet Caplets  Sudafed Products: Non-Drowsy Cold & Cough Liquid Caps, Severe Cold Caplets and Tablets, Sinus & Cold Liquid Caps, Sinus Headache Caplets and Tablets, Sinus Nighttime Plus Pain Relief Caplets.  TheraFlu Products: All Regular and Maximum Strength Hot Liquid.  Triaminic Products: Flu, Cough & Fever Liquid, Cough & Sore Throat Liquid and Softchews.  Vanquish Products: Vanquish Caplets  Vicks Products: 44M Cough, Cold & Flu Relief Liquid, DayQuil LiquiCaps/Liquid, NyQuil LiquiCaps/Liquid 2 Gelcaps, PMS Caplets and Gelcaps.  Robitussin Products: Multi- Symptoms Cold & Flu Caplets and Softgels, Flu Liquid, Multi- Symptom Honey Flu Liquid, Sinus &Congestion Caplets Acetaminophen Warnings Next 4 slides highlight recent acetaminophen information and warnings Not needed for exams Acetaminophen Warnings More than 700 different acetaminophen products licensed for sale  > 50% of acetaminophen use in combination products 4,000 hospitalizations in Canada each year for acetaminophen overdose  20% unintentional ~250 cases of serious liver injury each year in Canada involving acetaminophen  >50% involved accidental overdose 2014 Acetaminophen Report http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/acetamino-eng.php Acetaminophen Warnings ~20% of acetaminophen-related liver injuries due less than 4 g/day In many of these cases, patients had identifiable risk factors for acetaminophen liver injury alcoholism viral liver disease (hepatitis A, B or C) Sept 2016 Acetaminophen Label Warnings DO NOT USE with other drugs containing acetaminophen Liver warning This product contains acetaminophen. Severe or possibly fatal liver damage may occur if you take:  more than the recommended dose in 24 hours  with other drugs containing acetaminophen  while drinking three (3) or more alcoholic drinks every day (for adult use products only) Acetaminophen Label Warnings Symptoms of liver damage may include: yellowing of the skin/eyes, dark urine sweating, nausea, vomiting, stomach pain unusual tiredness, and/or loss of appetite Acetaminophen: Toxicity acetylcysteine Acetaminophen: Overdose Recommended antidote acetylcysteine (Mucomyst)  mucolytic used usually to decreased viscosity of bronchial secretion Protects liver from acetaminophen- induced damage max protection within 8-10 hours (IV or PO) give even in late presentation @24h Acetaminophen Dangerous interactions may occur if taken with alcohol Acetaminophen should not be taken in the presence of: liver dysfunction, chronic alcoholism possible liver failure or severe renal disease when taking other hepatotoxic drugs