Anti-inflammatory/Antipyretic Agents PDF

ANTIINFLAMMATORY / ANTIPYRETIC AGENTS Actions: Prevent the formation of prostaglandins prevent platelet aggregation and lower body temperature I. SALICYLATES a. Acetylsalicylic acid (aspirin) / (ASA) A nonnarcotic analgesic (reduces pain), antiinflammatory (reduce inflammation), antiplatelet (inc...

ANTIINFLAMMATORY / ANTIPYRETIC AGENTS Actions: Prevent the formation of prostaglandins prevent platelet aggregation and lower body temperature I. SALICYLATES a. Acetylsalicylic acid (aspirin) / (ASA) A nonnarcotic analgesic (reduces pain), antiinflammatory (reduce inflammation), antiplatelet (increase coagulation time), and antipyretic agent (reduce temperature) EXAMPLE: Bayer Aspirin Balsalazide (Colazal, Glazo) Choline Magnesium trisalicylate (Tricosal) Diflunisal Mesalamine (Pentasa and others) Salsalate (Amigesic) Sulfasalazine (Azulfidine) a. Action and Indications Inhibit the synthesis of prostaglandin, an important mediator of the inflammatory reaction The antipyretic effect of salicylates maybe related to blocking of a prostaglandin mediator of pyrogens at the thermoregulatory center of the hypothalamus. At low levels, aspirin affects platelet aggregation by inhibiting the synthesis of thromboxane A2, a potent vasoconstrictor that normally increase platelet aggregation and blood clot formation At higher levels, aspirin inhibits the synthesis of prostacyclin, a vasodilator that inhibits the platelet aggregation. b. Pharmacokinetics Readily absorbed in the stomach. Metabolized in the liver and excreted in the urine. They cross the placenta and enter human milk - not indicated during pregnancy or lactation because of the potential adverse effects on the neonate and associat bleeding risk for the patient. c. Contraindications and Cautions Presence of allergy to salicylates or NSAIDs (with history of nasal polyps, asthma, or chronic urticaria) or tartrazine because of the risk of allergic reaction Bleeding abnormalities Impaired renal function Chickenpox or influenza Surgery or other invasive procedures  scheduled within 1 week -risk for bleeding Pregnancy or lactation Adverse Effects – Gl effect nausea, dyspepsia, heartburn epigasttric discomfort – Clotting system - blood loss, bleeding abnormalities – Salicylism occur with high level of aspirin – Dizziness, ringing of the ears, difficulty hearing, nausea, vomiting, diarrhea, mental confusion, fever, lassitude – Salicylate toxicity include- hyperpnea, tachypnea, hemorrhage, dehydration, excitement, convulsions, pulmonary edema, tetany, metabolic acidosis, electrolyte imbalances, fever, coma and cardiovascular, renal and respiratory collapse e. Drug - Drug Interaction Interact with many other drugs- because of alterations in absorption, effects on the liver, or extension of the therapeutic effects of the salicylates or the interacting drug or both. II. Nonsteroidal antiinflammatory agents (NSAID) – Inhibit the formation of prostaglandins synthesis in the body. – Use to alleviate the inflammation and subsequent discomfort of rheumatoid condition. – Blocks protection of the stomach lining, as well as kidney regulation of water. Examples: 1.ibuprofen (Motrin) 2.Indomethacin (Indocin) 3. Naproxen (Naprosyn) 4. Phenylbutazone (Butazolidin) 5.Piroxicam (Feldene) 6.Propionic Acid 7. Salicylates (ASA) 8. Sulindac (clinorill 9.Fenoprofen 10.Flurbiprofen 11. Ketoprofen 12. Oxaprozin a. Action and Indications 1. Mild to moderate pain 2.Arthritis 3.Dysmenorrhea 4. Fever reduction 5. Minor post operative procedures 6.Decrease inflammation b. Pharmacokinetics – Rapidly absorbed from the G| tract, reaching its peak level in 1-3 hours. They are metabolized in the liver and excreted in the urine. – They cross the placenta and cross into human milk. Not recommended during pregnancy and lactation because of the potential effects on the fetus or neonate c. Contraindications and Cautions – NSAID's are contraindicated in the presence of allergy to any NSAID or salicylates. – Celecoxib is contraindicated in the presence of allergy to sulfonamides – CV dysfuntion or hypertension - because of varying effects of the prostaglandins and increased risk of heart attack and stroke – Peptic ulcer or known GI bleeding – Pregnancy and lactation because of the potential adverse effect on the neonate or mother – Renal or hepatic dysfunction- could alter the metabolism and excretion of these drugs – other known allergies d. Drug - Drug Interaction – An increase chance of bleeding when drugs are used in combination with diseases in which bleeding can occur (ulcers), consumption, or with other medications (anticoagulants). – An increase chance of bleeding when drugs are used in combination with diseases in which bleeding can occur (ulcers), with alcohol consumption, or with other medications (anticoagulants). – Decreased diuretic effect when taken with loop diuretics – Potential for decreased antihypertensive effect of beta blockers if these drugs are combined – Lithium toxicity especially if combined with ibuprofen – Ibuprofen with low dose aspirin decreases the antiplatelet effects of the aspirin e. Major / Adverse Effect – Gl irritation: Heartburn, GI bleeding, nausea, vomiting, dyspepsia, pain, constipation, diarrhea or fatulenc – Hematologic: Bone marrow depression, anemia, , thrombocytopenia – Tinnitus, ototoxicity – (Reye's syndrome with açetylsalicylic acid (aspirin) only, reye's syndrome can occur in clients  – 18 years of age or younger – Headache, dizziness, somnolence and fatigue -related to prostaglandin activity in the CNS – Toxicity in nonnarcotic agents; respiratory alkalosis, increase in rate and depth of respirations, nausea, vomiting, diarrhea, tinnitus, confusion, dizziness – Hypersensitivity to NSAID's; skin rashes urticaria, hypotension, dyspnea, and angioedema (also called angioneurotic edema, acute painless swelling of short duration involving the face, neck, lips, larynx, hands, feet, genitalia, or viscera) – Acute Renal impairment especially with use of ketorolac (should be used 5 days or less) f. Nursing Implication – Give with food or antacid if Gl upset occurs – Monitor CBC and stress compliance with frequent visits for blood monitoring. Older adult clients should be monitored monthly. – Discontinue these products 5 to 7 days before any major procedure or surgery – instruct mothers not to use ASA for children with high fevers – NSAID products can be altenated with acetaminophen (Tylenol |for extremely high or difficult- to-control temperatures. – Teach the clients to report if a temperature does not subside, bleeding occurs, or the swelling and redness do not decrease. – Administer with a full glass of water. – These agents are highly protein bound, Competition with other agents that are protein bound is possible. Example digoxin. Common Drugs 1. Acetylsalicylie acid (Aspirin) (ASA) 2. Ibuprofen (Advil, Motrin, Medipren, Nuprin) 3. Naproxen (Naprosyn, Aleve) 4. Fenoprofen calcium (Nalfon) 5. Flurbiprofen sodium (Ansaid) 6. Indomethacin (Indocin) 7. Tolmetin (Clinoril) 8. Nabumetone (Relafen) 9. Ketorolac (Toradol) Acetaminophen (Tylenol, Ofirmeu) – Use to treat mild to moderate pain and fever. Can be extremely toxic in high doses. Causes severe liver toxicity that can lead to death. a. Therapeutic Action and Indications  – Acts directly on the thermoregulatory cells in the hypothalamus to cause sweating and vasodilation; cause the release of heat and lowers fever. – Indicated for the treatment of pain and fever including influenza common colds or – prophylaxis of children receiving diphtheria-pertussis-tetanus immunizations – for relief of musculoskeletal pain associated with arthritis b. Pharmacokinetics – Rapidly absorbed in the Gl tract, reaching peak level in 0.5-2 hours. Metabolized in the liver and excreted in the urine, with a half life of 3 hours. – Available in IV, in adults and children 2 and over if oral is not possible – Crosses the placenta, enters human milk – Caution for patient with hepatic or renal impairment which could interfere with metabolism and excretion of the drug leading to toxic level. – Should be used cautiously during pregnancy and lactation because of potential adverse efect on the neonate or fetus. c. Contraindications and Cautions – Caution to patients with allergy 19 acetaminophen. because of the hypersensitivity reaction – Use with Caution to pregnant and lactating woman – In hepatic dysfunction – Chronic alcoholism because of toxic effect on the liver – Toxic effects vary withe age, drugs the patient is taking and the underlying hepatic function of the patient. – When Overdose occurs - can be used as an antidote – Acts by restoring glutathione levels so that there is more of it to bind with the toxic metabolite from acetaminophen, which allows for safe excretion of the medication d. Adverse Effects – Rash \ fever – chest pain – liver toxicity and failure – bone marrow suppression e. Drug - Drug Interaction – Toxic effects on the liver with oral coagulants and toxicity with chronic ethanol ingestion – Hepatotoxicity with barbiturates, carbamazepine, hydantoins, or rifampin. – These combination should be avoided: if used appropriate dose adiustments should be made and patient should be monitored closely. f. Nursing Considerations for Parents Receiving NSAIDs Assessment: History and Examination – Assess for contraindications or cautions: known allergies to any salicylates, NSAIDs, tratrazine pregnancy or lactation ^ hepatic and renal disease Assess for baseline status before beginning therapy: – any potential adverse effects – presence of any skin lesions temperature orientation, reflexes and affect – vital signs – perfusion – respirations and adventitious sound – CBC, liver, and renal function tests, urinalyssis, stool, guaiac and serum – electrolytes Drugs Used to Treat Arthritis Antiarthritis Agents – Arthritis is a potentially debilitating inflammatory process in the joints that cause pain and bone deformities Gold Compound – Used only if with antiinflammatory therapies use does not work, or when condition worsen despite weeks or months of standard treatment. – Chrysotherapy - treatment with gold salts (auranofin) -the gold is taken by macrophages, which then inhibits phagocytosis, can be toxic and is reserved for use in patients who are unresponsive to conventional therapy a. Therapeutic Action and Indications – Gold salts are indicated to treat selected cases of rheumatoid and juvenile rheumatoid arthritis and synovitis whose disease has been unresponsive to standard therapy – Action taken up by macrophages which inhibits phagocytosis and release of lysosomal enzymes that cause damage associated with inflammation b. Pharmacokinetics – Gold salts are absorbed in varying routes of administration. – Distributed throughout the body but seem to concentrate in the hypothalamic-pituitary- adrenocortical system and in the adrenal and renal cortices – Gold salts are excreted in the urine and feces. – They crosses the placenta and crosses into human milk - should not be used during pregnancy and lactation. c. Contraindications and Cautions – Gold salts are quite toxic and contraindicated of the presence of known allergy to gold, severe diabetes, congestive heart failure, severe debilitation, renal or hepatic impairment,  hypertension, blood dyscrasias, recent radiation treatments, history of toxic levels of heavy metals and pregnancy or lactation. d. Adverse effects – Stomatitis, glossitis, gingivitis, pharyngitis, colitis, diarrhea, – other GI inflammation; – Gold bronchitis and interstitial pneumonitis – Bone marrow depression – Vaginitis and nephrotic syndrome – Dermatitis, pruritus and exfoliative dermatitis – Allergic reagtions ranging from flushing, fainting and dizziness – anaphylactic shock – Renal toxicity and causing proteinuria Auranofin 1. Bone marrow suppression 2. renal toxicity 3. hepatitis 4. dermatitis 5. nausea 6. vomiting 7. stomatitis 8. Hepatitis 9. rashes e. Drug - Drug Interaction – Should not be combined with penicillamine, antimalarials, cytotoxic drugs, or immunosuppressive agents other than low dose corticosteroids because of the potential for severe toxicity. Disease Modifying Antirheumatic Drugs (DMARDs) 1.For treatment of arthritis and aggresively affect the process of inflammation. 2. Selected during early diagnosis before damage to the joints occurred because they halter the course of the inflammatory process. >> DMARDs are categorized into biologic and non biologic. Tumor Necrosis Factor Blocker (TNF blockers) (Biologic) Often first class used with progressing arthritis. Includes: 1. Adalimumab (Humira) 2.Certolizumab (Cimzia) 3. Etanercept (Embrel) 4.Golimumab (Simponi) a. Therapeutic Action and Indications – TNF Blockers act to decrease the local effect of TNF, a locally released cytokine that can cause the death of tumor cells and stimulate a wide range of pro-inflammatory activities. – The actions of cytokine when inflammation occurs within the joint capsule can lead to the destruction of bone and the malformation of joints, associated with arthritis – TNF Blockers slow the inflammatory response and the joint damage associated with it. – Indicated for the treatment of rheumatoid arthritis – polyarticular juvenile arthritis, psoriatic arthritis, plaque psoriasis, and ankylosing spondylitis. – Adalimumab, certolizumab, and infliximab are used in chron's disease and ulcerative colitis. b. Pharmacokinetics – TNF Blockers are given subcutaneously except infliximab give IV. – Slow onset peaking in 48-72 hours – Primarily excreted in the tissues and have very long half-lives ranging from 115 hours to 2 weeks. – They cross the placenta and may enter the human milk- so is discouraged for use in pregnancy and lactation. c. Contraindications and Cautions – Not use with anyone with an acute infection, cancer, sepsis, tuberculosis, hepatitis, myelosuppression or demyelinating disorders because they block the body's immune/ inflammatory response and serious reactions could occur. – Etanercept cannot be used with history of allergy to medication – Patients who are allergic to hamsters since this drug is made up of chinese hamster ovary products. – Not use for pregnant and lactation because of the potential effects on the neonate or fetus. – Caution for use in patients with renal or hepatic disorders, heart failure, and latex allergies to prevent adverse reaction. – Demyelinating disorders, including multiple sclerosis and various neuritis condition – Myocardial infarction (MI) heart failure, and hypotension – Irritation at the infection site d. Drug to drug interaction – TNF with other immmune suppressant drugs inrease the risk of serious infections and cancer  – Live vaccine should not be given while on these drugs. Other Disease-Modifying Antirheumatic Drugs Example: Anakinra (Kineret) Leflunomide (Arava) Sarilumab (Kevzara) Tofacitinib (Xelijanz) Penicillamine (Depen) Drugs use to directly decrease pain in joints affected by arthritis – hyaluronidase derivatives, (Synvisc) – sodium hyaluronate (Hyalgan) Drugs use to modify disease process in rheumatoid arthritis – antineoplastic drugs methotrexate, cyclophosphamide – cell suppressor abatacept (Orencia) – certain antimalarial drugs – antineoplastic drugs – immune modulators cyclosporine A, – Azathioprine a. Therapeutic Action and Indications – Anakinra - antiarthritic drug is an interleukin-1 receptor antagonist – it blocks the interleukin - 1, which is responsible for the degradation of cartilage in rheumatoid arthritis. – Given each day by subcutaneous injection, often used in combination with other antiarthritic drugs – Hyaluronidase derivatives hyalan G_F 20 and sodium hyaluronate have elastic and viscous properties – injected directly into the joints of patients with severe rheumatoid arthritis of the knee. – seem to cushion and lubricate the joint and relieve the pain associated with degenerative arthritis. – Given for 3-5 weeks – Leflunomide -directly inhibits an enzyme, dihydroorotate dehydrogenase, active in the auto immune process that leads to rheumatic arthritis – relieve signs and symptoms of inflammation – blocking the structural damage this inflammation can cause, showing disease progression. – Sarilumab an interleukin-6 receptor antagonist. Blocking this cause a decrease in  – inflammatory processes systematically and locally within the joint relieving symptoms – reserve for patients who do not respond to other DMARDs. – Penicillamine lowers the immunoglobulin – M-rheumatoid factor levels in patients with acute rheumatoid arthritis relieving signs and symptoms of imflammation. – take 2 to 3 months of therapy before response is noted – Tofacitinib - a kinase inhibitor that blocks signaling pathways within immune cells to prevent their activity. – an oral agent reserved for non responsive patients to traditional therapies. b. Pharmacokinetics Anakinra – slowly absorbed from the subcutaneous tissue – Peak level in 3 to 7 hours – metabolized in the tissues excreted in the urine – Half life of 4-6 hours – Hyaluronidase - not absorbed – systemically – Leflunomide: – slowly abssorbed from the Gl tract – peak level 6 - 12 hours – hepatic metabolism – excreted in the urine – half-life of 14-18 days – Penicillamine oral drug: – peak level 1 - 3 hours after administration – metabolized in the liver – excreted in the urine – half-life of 3 hours c. Contraindications and Cautions – Pregnancy or lactation because of potential for adverse effects on the fetus or neonate – Acute infection because of blocking of normal inflammatory pathways d. Major / Adverse Effect – irritation at injection sites – pain with injection – increase risk of infection \fatal hepatic toxicity and rashes (Leflunomide) – monitoring closely of liver function  – fatal myasthenic syndrome (Penicillamine) – bone marrow depression – Thrombocytopenia – O risk of serious fatal infections, (Tofacitinib, Sarilumab) – tuberculosis – development of lymphomas and other cancers – Toxicity: nephrotoxicity, hepatotoxicity – Metallic taste in mouth, stomatitis, mouth ulcers with gold compounds – Skin changes: rash, dermatitis, changes in pigmentation – Neuropathy: headache and dizziness e. Drug - Drug Interaction – Should not be injected at the same time as local anesthetics – (hyaluronidase derivatives - sodium hyaluronate) – Can cause severe liver dysfunction if combined with other hepatotoxic drugs (Leflunomide) – Decreased absorption of penicillamine if taken with iron salts or antacids – Can cause severe liver dysfunction if combined with other hepatotoxic drugs (Leflunomide) – Decreased absorption of penicillamine if taken with iron salts or antacids – Increased risk of serious infection if used with other immune suppressants (Anakinra & Tofacitinib) Common Drugs 1.NSAID 2.Gold compounds (Chrysotherapy)-bring about phagocytosis in joints a. Gold sodium thiomalate (Myochrysine) b. Aurothioglycose (Solganal) 1. NSAID Propionic Acids: a. fenoprofen (Nalfon) b. Flurbiprofen (Ansaid) c. Ibuprofen (Motrin, Advil, Caldolor IV) d. Ketoprofen (Orudis) e. Naproxen (Naprosyn) f. Oxaprozin (Daypro) 2. 3. Fenamates a. meclofenamate (generic) b. Mefenamic Acid (Pontel) 4. Oxicam Derivatives (Mobic) a. piroxicam (Feldene) Antigout / Hyperuricemia Agents – GOUT DISORDER - characterized by elevated uric acid and urate deposits in kidneys and joints. Extremely painful due to crystal deposits causing local acute inflammation – Control uric acid production with antineoplastic drug therapy a. Therapeutic Action and Indications 1. Control acute inflammation of the attack (Colchicine) a. prevention of actions of neutrophils that facilitate inflammation b. decreases uric acid crystal deposits by inhibiting lactic acid production by leukocytes 2. Increase excretion of uric acid (uricosuric) (Pegloticase) a. lowers uric acid by increasing oxidation to the substance allantoin b. easily eliminated via renal excretion 3. Decrease production of uric acid (Allupurinol, febuxostat & probenecid) a. inhibit xanthine oxidase - an enzyme needed to convert xanthine to uric acid. b. blocks formation of uric acid within the body 4. Pobenecid (Benemid) a. prevents formation of tophi by inhibiting the reabsorption of uric acid by the kidneys. b. Pharmacokinetics Colchicine – absorbed orally takes effect 1-2 hours – crosses the placenta and enters human milk metabolized by the CYP3A4 enzymes in liver Allupurinol – absorbed orally – peak serum level about 1.5 hours – half-life of 1-2 hours – excreted renally and via feces Febuxostat – absorbed orally – max plasma levelin 1-1.5 hours – metabolized in the liver – half life of 5-8 hours – excreted renally and hepatically c. Contraindications and Cautions  – Increased risk of toxicity if used in patients with severe renal and hepatic disease (Colchicine) – Dose adiustments for patients having hemodialysis -medication is not dialyzed out – Allergic reaction -rash -(allupurinol) should be discontinued – Hypersensitivity reaction is higher in patients renal insufficiency and patients receiving thiazide medication. – Cause increase in gouty attack : may be used with colchicine prophylactically – Cardiovascular death (febuxostat) than allupurinol for gout therapy – Pegloticase - anaphylaxis and infusion reaction – Cause increase in gouty attack : may be used with colchicine prophylactically – Cardiovascular death (febuxostat) than allupurinol for gout therapy – should be adminisered in a health care setting – People with G6PD deficiency have a higher risk of hemolysis and methemoglobinemia so screening is needed before starting therapy. – Probenecid - increase acute gout attack-should be given during or recently after an acute attack d. Adverse Effect – Kidney stones – Bone marrow depression, anemia – Nausea, vomiting, diarrhea – Blood dyscrasias – Skin rash and fever – Liver damage – Blood dyscrasias - due to suppressed bone marrow e. Drug - Drug Interaction – Concurrent use of Pgp and CYP3A4 inhibitors with colchicine can cause an overdose enough to cause mortality. all drugs need to be evaluated prior to administration – Allopurinol may slow the metabolism of warfarin an increase risk of bleeding – Febuxostat with azathioprine or mercaptopurine can increase plasma concentration to severe toxic levels f. Nursing Implications 1. Encourage fluid intake of at least 2 to 3 liters per day to prevent kidney stone formation. 2. Stress compliance with treatment, and diet of low -purine foods, limit, beer, wine, shellfish, and legumes to prevent recurrence. 3. Monitor complete blood count (CBC) for decrease in valves agronulocytosis 4. Administer antlinflammatory drugs (Prednisone, Indocin) in addition to drugs that will lower serum uric acid during the acute phase 5. Encourage weight reduction  6. Administer with meals to reduce Gl irritation. Common Drugs a. Allopurinol (Zyloprim) – blocks formation of uric acid within the body b. Colchicine (Novocolchine) – decreases uric acid crystal deposits by inhibiting lactic acid production by leukocytes; used for acute attacks c. Pobenecid (Benemid) – prevents formation of tophi by inhibiting the reabsorption of uric acid by the kidneys. a. Therapeutic Action and Indications – Increased appetite which could lead to weight gain – difficulty sleeping (insomnia) – Changes in mood and behaviour, such as feeling irritable or anxious – An increased risk of infections- especially chickenpox, shingles and measles