N5375 Lesson 8A Immune.pptx

Week 8A: Immune+ (Immunosuppressants, Antihistamines, NSAIDS, and Acetaminophen) N5375: Pharmacology Columbia University School of Nursing Dr. Ana Maria Kelly 1 Summer 2024 Chapters Chapter 72: Immunosuppressants Chapter 73: Antihistamines Chapter 74:...

Week 8A: Immune+ (Immunosuppressants, Antihistamines, NSAIDS, and Acetaminophen) N5375: Pharmacology Columbia University School of Nursing Dr. Ana Maria Kelly 1 Summer 2024 Chapters Chapter 72: Immunosuppressants Chapter 73: Antihistamines Chapter 74: Cyclooxygenase Inhibitors: Nonsteroidal Anti- inflammatory Drugs and Acetaminophen 2 Study Questions for Immunosuppressants 1. Name the shared MOA pathway between cyclosporine and tacrolimus 2. Know the SE of the immunosuppressants well as each one could be asked as an action question (“risk of hypertension” becomes, “check the BP”) 3. Tie in your knowledge about glucocorticoids from Endocrine lesson as they are used here, too 4. Be able to identify anaphylactic shock and know appropriate treatment 5. Identify main side effect of methotrexate 3 Study Questions for Antihistamines 1. Don’t confuse H1 vs H2 receptors with 1st generation H1 blockers and 2nd generation H1 blockers! A. Explain difference between effect at H1 vs H2 receptors B. Explain difference between 1st generation and 2nd generation antihistamines 2. Know: diphenhydramine, hydroxyzine, loratadine, fexofenadine, and cetirizine. 4 Study Questions for NSAIDS and Acetaminophen 1. Note similarities and differences between these meds A. For example, why isn’t acetaminophen classified as an NSAID? B. What can aspirin do that acetaminophen can’t do? 2. Five meds to know in this unit: aspirin, acetaminophen, ibuprofen, naproxen, and celecoxib 3. Again, SE most important 5 Immunosuppressant s Chapter 72 6  Histamine Cytokines Tumor necrosis factor (TNF) Partial List of Interleukins Inflammator y Mediators Prostaglandins Nitric Oxide Bradykinin 7  Immunosuppress ants Cyclosporine and tacrolimus are the most effective immunosuppressant meds available MOA for both: inhibits the enzyme calcineurin that normally would promote synthesis of interleukin-2 (IL-2) and other inflammatory cytokines. But by blocking the enzyme, these meds suppress the production of these mediators. Blocks subsequent proliferation of white blood cells and immune response. Principle therapeutic use? Prevention of organ rejection for transplant patients 8 Cyclosporine Discovered in 1970s from a fungus Does not cause bone marrow suppression Often given for kidney, liver and heart transplants Often combined with tacrolimus and a glucocorticoid like prednisone Both cyclosporine and tacrolimus are metabolized hepatically and excreted through feces, but still very high risk of nephrotoxicity Dosing: PO capsules or liquid preferred, IV if they have issue swallowing Can mix with juice to be more tasty 9 (but not grapefruit!) Tacrolimus Takro-LEE-mus Has PO IR and ER formulations, so careful not to crush! IV also. Newer & slightly more effective than cyclosporine, but more toxic 10  Side Effects for Cyclosporine & Tacrolimus THREE MAIN: nephrotoxicity, incidence super high, majority of patients [T] Will require dose reduction Keep an eye on BUN and creatinine Same for risk of infection, majority of patients Any flu-like symptoms, fever, chills, malaise, sore throat, body aches…etc, they need to report Carcinogenic: Malignant lymphomas when immunosuppressants combined  CA (Safe handling!) Hepatotoxicity (check those LFTs) Hypertension (check that BP) [C] Hyperglycemia (check that BG) [T] Neurotoxicity: HA, tremor, insomnia [T] GI: N/V, diarrhea [T] 11 Hirsutism and gingival hyperplasia from cyclosporine 12 Pause: Anaphylactic Reaction to any med S/sx: Flushing (or other derm effects like rash, hives, itching, etc), respiratory distress (often wheezing, may include swelling of tongue), hypotension (BP drops out) and tachycardia (heart starts to race) It’s a sudden vasodilatory, bronchoconstriction effect Treatment: stop treatment, administer fluids and epinephrine to vasoconstrict and bronchodilate 13  Nursing Education How long do patients need to take immunosuppressants meds for s/p transplant surgery? Since we know that very high risk of renal damage and infection, what do you think you need to teach patients? Try to avoid other nephrotoxic agents like NSAIDS and aminoglycosides (**antibiotic class in Lesson 9) Both cyclosporine and tacrolimus have narrow therapeutic ranges, may require drug serum testing, and should be given on empty stomach because food will alter absorption of these meds (especially high fat 14 food)  Methotrexate Disease-modifying, anti- rheumatic drug (DMARDs), term used to contrast with NSAID First used to treat CA, but found to be effect for autoimmune conditions like psoriasis and rheumatoid arthritis Tablets, subQ auto-injectors SE: hepatotoxicity 15 A patient on immunosuppressant therapy with tacrolimus is scheduled for laboratory tests. Which of the following tests is most important to monitor for potential adverse effects? A) Serum glucose B) Serum creatinine C) Serum calcium D) Serum sodium 16 Answer If this was a SATA Q, this would also be correct. When else would it be important to check glucose? Review from Endocrine Part II: When giving corticosteroid Answer B: We check creatinine because it’s one of the renal labs and nephrotoxicity is very common and very dangerous. Calcium unrelated When would it be important to check sodium? Review from Endocrine Part II: If someone has SIADH or if they receiving desmopressin treatment for DI 17 Antihistamines Chapter 73 18 Histamine Locally-acting, small molecule that is presents in almost all tissue. In BV, dilates small blood vessels and increases capillary permeability In the bronchi, it leads to constriction of smooth muscles In the stomach, it stimulates the secretion of acid In the CNS, it acts as a NT 19 Release of histamine Histamine can be released from Mast Cells by an allergic reaction (shown here with Immunoglobulin antibodies activating the Mast Cell) But also possible that non- allergen effects can also cause release of histamine, like cell injury or certain fluids or dyes. 20  H1 H2  GI Two types H1 receptors Cause vasodilation of H2 receptors Acts on parietal cells of of small vessels near stomach to promote more gastric acid receptors, surface of skin, leading to flushing & warmth release therefore, Capillary permeability two types leads to localized edema ** Because this H2- of anti- Bronchoconstriction blockers only affect stomach acid, we will histamine CNS effect like discuss these meds in the GI unit. memory, cognition, medications sleep/wake cycle Immunological anti- histamines will focus on Itching and pain H1-blockers 21 All H1 blockers treat allergic rxn Med term for hives? Urticaria Sometimes, it’s even more mild, like rhinitis or rhinorrhea. What does that mean? Inflamed mucus membranes in the nose and runny nose. Make sure to study all derm conditions on skin with different levels of melanin If antihistamines can block all these effects, why don’t they fully solve the problem? Don’t forget the other inflammatory mediators, like cytokines. 22  Both H1 Two classes First generation H1 antagonists (we often Second-generation H1 antagonists of call them by more generic categorization of anti- Not sedating Why? Unlikely to cross antihistami histamines) Highly Sedating!! BBB Loratadine [Claritin] nes, both Why? Able to cross BBB and bind to Fexofenadine [Allegra] types work histamine receptors in CNS Cetirizine [Zyrtec] We’re up dine-ing, no at H1 Diphenhydramine sleeping! Unique issue: don’t receptors [Benadryl] Sweet “drams” take with fruit juice, impedes digestion Hydroxyzine Blocks all the effects at the H1 receptor that were 23 likely triggered by mild Additional SE of antihistamines Dry mouth, blurry vision, urinary retention Especially the first-gens Do these sound familiar? Anticholinergic effects are back! 🥳 Antihistamines sometimes bind at Ach receptors and block Ach, causing anticholinergic SE Here’s a positive: not too hard on either kidneys or liver 24  So you don’t have to run back to Week 2 PPT… 25 A patient reports taking diphenhydramine for insomnia. The nurse should educate the patient about which potential side effect of long-term use? A) Liver toxicity B) Dependence C) Cognitive impairment D) Cardiac arrhythmias 26 Answer Long-term use of diphenhydramine, especially in older adults, can lead to cognitive impairment, including memory issues and confusion. Patients should use this medication only as directed and for short-term relief. 27 A patient with a history of asthma is prescribed an antihistamine. Which antihistamine should be used with caution in this patient? A) Cetirizine B) Fexofenadine C) Hydroxyzine D) Loratadine 28 Answer Hydroxyzine, a first-generation antihistamine, can cause drying of the respiratory secretions, which might exacerbate asthma symptoms. Second-generation antihistamines like cetirizine, fexofenadine, and loratadine are generally safer options. 29 Which of the following instructions should the nurse provide to a patient taking fexofenadine for allergies? A) "Take this medication on an empty stomach for best results." B) "Avoid taking this medication with fruit juice." C) "This medication may cause drowsiness; avoid driving." D) "You can take this medication as needed for symptoms." 30 Answer Fruit juices, particularly apple, orange, and grapefruit juice, can reduce the absorption of fexofenadine, decreasing its effectiveness. Patients should be advised to avoid consuming fruit juice around the time of taking this medication. Optional info: why? Many fruit juices such as grapefruit, orange and apple juice are organic anion transporting peptide (OATP) 1A2 inhibitors. OATP1A2 transporters are involved in the absorption of fexofenadine from the gastrointestinal tract. Inhibition of the activity of intestinal OATP1A2 reduces serum concentrations of fexofenadine by up to 70%, possibly reducing its effectiveness.2 Patients can avoid this interaction by not drinking fruit juice within 4 hours before or 1-2 hours after taking fexofenadine. 31 A patient is prescribed A) Drowsiness diphenhydramin e for allergic rhinitis. Which of B) Hypertension the following side effects should the nurse C) Tachycardia include in the patient D) Diarrhea teaching? 32 Answer Nothing fancy here, just remember that diphenhydramine [Benadryl] makes you sleepy, that’s why many people prefer the second – generation H1antagonists This will come up often in clinicals and in MDE (sedating vs non-sedating antihistamines) 33  Cyclooxygenase Inhibitors: Nonsteroidal Anti-inflammatory Drugs and Acetaminophen Chapter 74 34  Triple Effect of COX Inhibitors: - NSAIDS do all 3 - Acetaminophen only does 2. Which ones? That is why acetaminophen is not considered an NSAID - Aspirin does all 3, plus one additional effect. What is it? Suppress inflammation Relieve pain Reduce fever (anti- (analgesic) (antipyretic) inflammatory) 35 Cyclooxygenase (COX) Normal Pathway (before we take the drugs to block) COX-1 Pathway COX-2 Pathway Found in almost all tissue Stimulated by tissue injury for various Causes our pain, fever “housekeeping” needs, and inflammation, which including: is actually helpful when Protects the gastric we have an injury mucosa Supports renal function Promotes platelet aggregation 36 NSAID Pathway Blocks prostaglandins (those are the PGs) and thromboxane (that’s the TX) NSAIDS like naproxen and ibuprofen have less effect on inhibiting platelet aggregation, but instead have been linked to thrombotic events 37 Black Box Warning for NSAIDS A nurse is caring for a patient with a history of cardiovascular disease who is prescribed naproxen. Which adverse effect is the nurse most concerned about? A) Renal failure B) Gastrointestinal bleeding C) Increased risk of thrombotic events D) Hepatotoxicity This question is difficult. A, B and D are all true for NSAIDS, but for a cardiac patient, C is the greatest risk. NSAIDs are associated with an increased risk of thrombotic events such as myocardial infarction and stroke. This is particularly concerning in patients with a history of cardiovascular disease. Not fully understood. 38 You will need to know the 5 meds underlined in orange 39  Do we have to take a fever- reducer? 40  Aspirin Acetylsalicylic acid (ASA) Origins of willow bark from 2000+ BC in Assyria (Iraq) to relieve pain & fever Therapeutic Use: Antipyretic, nonopioid analgesic, anti- inflammatory effect, and platelet inhibitor 41  SE ASA #1 concern: GI bleeding In fact, aspirin makes the Beers List! But only at doses above >325mg, hence the development of baby aspirin (81 mg) Overall, same dosing as acetaminophen, we will review N/V More toxic effect: tinnitus is an early sign of ASA toxicity  report! Can progress to: Salicylate poisoning: hyperventilation and convulsions Long term use can cause hepatic damage Look for signs of jaundice & elevated LFTs Long term, high dose use can also lead to renal impairment Also used for transient ischemic attacks (TIA) What about for pediatric patients? No, risk of Reye’s Syndrome, swelling of brain and liver Don’t forget: any med can cause an allergic reaction and that would look different from SE. Rash, hives, shortness of breath. 42  A) Hypertension Which of the following conditions is B) Diabetes mellitus a contraindicat C) Peptic ulcer ion for the disease use of aspirin? D) Hyperlipidemia 43 Answer Low dose ASA is considered cardioprotective. Three of these conditions place the patient at increased risk for chronic, cardiac disease. Gastric bleeding is the main SE of ASA due to direct effect on gastric mucosa, but also that it stops platelet aggregation, so answer is C 44 NSAIDS Non-steroidal, anti-inflammatory Work like corticosteroids without the steroid side effects First generational (conventional) are all the NSAIDS except celecoxib. Additionally, all the NSAIDS are nonselective except celecoxib. NSAIDS (including aspirin) also considered ototoxic (tie this with aminoglycosides + furosemide + age >65 for biggest increase risk) 45 A patient with osteoarthritis is A) "Take this medication on an empty stomach." prescribed ibuprofen for pain B) "Monitor for signs of bleeding, such as black, management. tarry stools." Which instruction C) "Limit fluid intake while should the nurse taking this medication." include in the D) "This medication may patient teaching? cause hypoglycemia." 46 Answer NSAIDs, including ibuprofen, can cause gastrointestinal bleeding. Patients should be instructed to monitor for signs of bleeding, such as black, tarry stools, and report them immediately to their healthcare provider. Low Hgb blood test is another sign Blood may also head backwards instead of forward (meaning vomit with bright red blood in it) Even just strong abd pain should be taken seriously 47 Celecoxib [Celebrex] Selective COX-2 Inhibitor (all the other NSAIDS we mentioned are nonselective, inhibit both COX 1 and 2) Of all NSAIDS, poses greatest risk for cardiovascular harm because selective to COX-2 and that is where the thrombotic effect is hypothesized to originate from Also hepatotoxic and also risk of thrombotic event like other NSAIDS Interestingly, although selective to COX-2, still is some risk of GI bleeding and renal toxicity Can you take ASA or NSAID with Celecoxib? No. Same pathway. Is it okay to take NSAIDS and acetaminophen together? Yes, as long as you pay attention to total mg/day for both. Practice calculating for 24-hour period. 4000mg for acetaminophen. But best practice is alternate dosing, taking one med during the window period of the other. 48 Acetaminophen MOA Overall: Decreases prostaglandin synthesis in CNS Been in use since late 1800s and pathway still not fully understood “It is now considered that the inhibition of COX activity is not the main analgesic mechanism of acetaminophen” (Ohashi and Kohno, 2020) https://www.ncbi.nlm.nih.gov/pmc /articles/PMC7734311/#:~:text=I t%20has%20been%20thought%2 0that,COX%2D1%20and%20%2D 49 Acetaminophen vs Aspirin Therapeutic use? Analgesic and antipyretic In that respect, same as aspirin Most commonly used analgesic in US So, what’s different? Good different: 1. Does not suppress platelet aggregation, so no risk of bleeding 2. Does not cause gastric ulceration 3. Does not cause reduced renal blood flow or cause renal impairment Bad different: 1. Devoid of clinically useful anti-inflammatory or antirheumatic actions 2. Overdose may cause severe liver injury 50 Acetaminoph en Dosing The most common drug ingredient in the US Great podcast episode! This American Life “Use Only as Directed” 9.20.13 http://tal.fm/505 What is the maximum dose of acetaminophen for a 24-hour period? ***Will need for exam! _____________ Also need to know extra strength dose 51  Who should not take acetaminophen? Someone who drinks more than 3 drinks/day Someone with liver disease, but this isn’t only chronic cirrhosis, this includes hepatitis from infectious disease or fatty liver disease that is connected to nutrition and lifestyle Anyone taking another medication with acetaminophen, best 52 practice, not to mix even if The nurse reviews a client’s list of medications: A. No action needed. - 2 tablets of extra strength Tylenol every 6 hours PRN for chronic pain, B. The nurse will need to notify the client and the provider that the patient takes most days prescribed daily dose places the - Surgical team prescribes client over the maximum safe dose Hydrocodone 10mg/Acetaminophen of acetaminophen. 300mg (Vicodin) every 4-6 hours as C. The nurse will need to notify the needed following outpatient client and the provider that the daily surgical procedure use of the PRN medications may - Arthriten medication from Walmart place the client over the maximum that contains 250mg safe dose of acetaminophen. acetaminophen and 250mg of aspirin. Dose: take 2 pills every 6 D. The nurse will need to contact the hours as needed. pharmacist about possible drug interactions. 53 Acetaminophen Reversal Agent For OD: acetylcysteine, which is a drug that is usually used for respiratory secretions, but when given orally, can prevent uptake of acetaminophen in liver, but one unfortunate issue: smells like rotten eggs. 54 A nurse is educating a patient about acetaminophen. Which of the following statements by the patient indicates a need for further teaching? 01 02 03 04 A) "I can take B) "I should C) "I can use D) "I should acetaminophe avoid alcohol this medication report any n with or while taking for long-term signs of without food." this pain jaundice to my medication." management." healthcare provider." 55  Answer Aspirin or other NSAIDS are best taken with food because of stomach upset It is recommended to limit alcohol while taking acetaminophen because of extra stress on liver Acetaminophen is not recommended for long term, chronic use due to risk of liver toxicity. Correct answer C And it would be correct for a patient to report signs of jaundice, which would indicate liver toxicity. 56 The Beers Criteria for Potentially Inappropriate Medication Use in Older Adults American Geriatrics Society updates list q3y What is considered elderly? Retirement age: 65 Almost 100 meds on list, but let’s touch on few main classes Meds where side effects outweigh benefits