7_28 IMMUME 藥學整理.docx

**Chapter 72:** Immunosuppressants **Chapter 73:** Antihistamines **Chapter 74:** Cyclooxygenase Inhibitors: Nonsteroidal Anti-inflammatory Drugs (NSAID)and Acetaminophen （Tylenol） A. **Study Questions for Immunosuppressants 免疫抑制劑（如環孢素和他克莫司）：** 1. **這些藥物常用於器官移...

**Chapter 72:** Immunosuppressants **Chapter 73:** Antihistamines **Chapter 74:** Cyclooxygenase Inhibitors: Nonsteroidal Anti-inflammatory Drugs (NSAID)and Acetaminophen （Tylenol） A. **Study Questions for Immunosuppressants 免疫抑制劑（如環孢素和他克莫司）：** 1. **這些藥物常用於器官移植後，防止身體排斥新器官。還用於治療一些自體免疫疾病，如類風濕性關節炎。** 2. Name the shared MOA pathway between cyclosporine and tacrolimus 3. Know the SE of the immunosuppressants [well] as each one could be asked as an action question ("risk of hypertension" becomes, "check the BP") 4. Tie in your knowledge about glucocorticoids from Endocrine lesson as they are used here, too 5. Be able to identify anaphylactic shock and know appropriate treatment 6. Identify main side effect of methotrexate **B. Study Questions for Antihistamines 組織胺: 抗組胺藥（如苯海拉明和氯雷他定）：** - **這些藥物用於治療過敏反應，如花粉熱、蕁麻疹和過敏性鼻炎。** - **例子：一個人對花粉過敏，使用抗組胺藥可以減輕瘙癢、打噴嚏和流鼻涕。我們需要了解不同代的抗組胺藥，以便選擇不會讓病人感到過度困倦的藥物。** Don't confuse H1 vs H2 receptors with 1^st^ generation H1 blockers and 2^nd^ generation H1 blockers! A. Explain difference between effect at H1 vs H2 receptors B. Explain difference between 1^st^ generation and 2^nd^ generation antihistamines 1. Know: diphenhydramine, hydroxyzine, loratadine, fexofenadine, and cetirizine. **C. Study Questions for** **NSAIDS and Acetaminophen（Tylenol /普拿疼） NSAIDs和對乙醯氨基酚（如阿司匹林和布洛芬）： （Nonsteroidal Anti-inflammatory Drugs，非甾體抗炎藥）** 1. **這些藥物用於1. 緩解疼痛 2. 減少炎症 3.退燒。** 2. **例子：一個人扭傷腳踝，NSAIDs如布洛芬可以幫助減輕腫脹和疼痛。我們需要知道這些藥物的副作用，如胃腸道出血和腎臟問題，以避免對病人造成更大的傷害。** 3. Note similarities and differences between these meds A. For example, why isn't acetaminophen（Tylenol） classified as an NSAID? B. What can aspirin do that acetaminophen can't do? 4. Five meds to know in this unit: aspirin, acetaminophen, ibuprofen, naproxen, and celecoxib 5. Again, SE most important ---\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-- **Immunosuppressants 免疫抑制** - Partial List of Inflammatory Mediators , Histamine & Cytokines 這些導致發炎 什麼是clucocorticoids? how are clucocortic\~\~ (ta sunday) +-----------------------+-----------------------+-----------------------+ | | Cyclosoporine | Tacolimus | | | | | | | po/iv | po | | | | | | | | Has PO IR and ER | | | | formulations, so | | | | careful not to crush! | | | | IV also. | +-----------------------+-----------------------+-----------------------+ | common | common se has 3: | | | | | | | | 1.nephrotoxicity腎毒性 | | | | | | | | | | | | 2.Same for risk of | | | | infection | | | | | | | | 3.Carcinogenic致癌性 | | | | | | | | no gratefruit juice | | +-----------------------+-----------------------+-----------------------+ | | | | +-----------------------+-----------------------+-----------------------+ | different | | | +-----------------------+-----------------------+-----------------------+ **Immunosuppressants （只有這兩個要注意）** - 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 - Also prevent graft vs host disease宿主病 **Cyclosporine** - Discovered in 1970s from a fungus真菌 - Does [not] cause bone marrow suppression 部會造成股隨意至，所以血( - 白血球) 還是一直造。 - 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 (but [not grapefruit!]) **Tacrolimus （會考這個和Cyclosporine的差別）** - 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 **Side Effects for Cyclosporine & Tacrolimus（會考）** - THREE MAIN: **nephrotoxicity腎毒性**, incidence super high, majority of patients **\[T\]** - Will require dose reduction - Keep an eye on BUN and creatinine (監測腎功能) 太高要減量或停藥。 - Same for risk of **infection**, majority of patients - Any flu-like symptoms, fever, chills, malaise不適, sore throat, body aches...etc, they need to report - **Carcinogenic致癌性**: Malignant lymphomas(惡性的淋巴癌) when immunosuppressants combined 🡪 CA (Safe handling!) - Hepatotoxicity (check those LFTs) 肝毒性 - Hypertension (check that BP) **\[C\]** - [Hyperglycemia (check that BG) **\[T\] (可以是考點)** ] - Neurotoxicity: [HA 頭痛,] tremor, insomnia **\[T\]** - GI: N/V, diarrhea **\[T\]** - Hirsutism 多毛症 and gingival hyperplasia牙齦增生 from cyclosporine （ppt的內容貼上） +-----------------------+-----------------------+-----------------------+ | How to idnetify | | | | anaphylactic shock? | | | | | | | | ( 代表histamine | | | | increase, | | | | 導致vasodilation | | | | 所以血壓會下降) | | | +-----------------------+-----------------------+-----------------------+ | cause: | manifestations: | | | | | | | risk factors: | | | +-----------------------+-----------------------+-----------------------+ | | cv: | respiratory | +-----------------------+-----------------------+-----------------------+ | treatment prorities | | | +-----------------------+-----------------------+-----------------------+ | clear airway | skin | dignosis with patient | | | | history & blood | | admin "epinephrine" | | levels: | | | | | | (fluids | | | | | | | | oxygen) | | | +-----------------------+-----------------------+-----------------------+ | | | | +-----------------------+-----------------------+-----------------------+ 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腎毒性 agents like NSAIDS and aminoglycosides (\*\*antibiotic class in Lesson 9) - help prevent infection, avoiding crowds - Both cyclosporine and tacrolimus have narrow therapeutic ranges, [may require drug serum testing要監測血中濃度], and should be given on empty stomach空腹 because food will alter absorption of these meds (especially high fat food) ---\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-- - First used to trea[t CA(癌症)], but found to be effect for autoimmune conditions like [psoriasis] and [rheumatoid arthritis] - Disease-modifying, anti-rheumatic drug (DMARDs), term used to contrast with NSAID - Tablets, subQ auto-injectors - SE: **hepatotoxicity** 肝毒性 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 ------------------------------------------------------------------------ ---------------------------------------------------------------- **B. Antihistamines** **Histamine 可以是一個nt, 不適賀爾蒙，一個分子，主要是讓血管擴張，和組織液不同。若是在支氣管，或讓企管變小，如果再在胃，會讓胃分系胃液。** - Locally-acting, small molecule present in almost all tissue - In blood vessels (BV), dilates small blood vessels and increases capillary permeability - In the bronchi, leads to constriction of smooth muscles - In the stomach, stimulates the secretion of acid - In the central nervous system (CNS), acts as a neurotransmitter (NT) - 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. - **Two types of receptors, therefore, two types of anti-histamine medications** +-----------------------+-----------------------+-----------------------+ | | **[H1 receptors | | | | (若祖安接到h1受體，就會導致血管擴張)] | | | | ** | | +-----------------------+-----------------------+-----------------------+ | | Cause vasodilation of | Acts on parietal | | | small vessels near | cells of stomach to | | | surface of skin, | promote more gastric | | | leading to flushing & | acid release | | | warmth | | | | | \*\* Because this | | | Capillary | H2-blockers only | | | permeability leads to | affect stomach acid, | | | localized edema | we will discuss these | | | 血管裡的東西可能跑到細胞或細胞間導致 | meds in the GI unit. | | | | | | | | Immunological | | | Bronchoconstriction | anti-histamines will | | | 支氣管收縮 | focus on H1-blockers | | | | | | | CNS effect like | | | | memory, cognition, | | | | sleep/wake cycle | | | | 睡眠周期 | | | | | | | | [Itching and pain | | | | ] | | +-----------------------+-----------------------+-----------------------+ | | | | +-----------------------+-----------------------+-----------------------+ +-----------------------------------+-----------------------------------+ | **All H1 blockers treat allergic | | | rxn** | | +-----------------------------------+-----------------------------------+ | | | +-----------------------------------+-----------------------------------+ | **[First generation H1 | **[Second-generation H1 | | antagonists]** | antagonists]** | | | | | **Highly Sedating!! 高度鎮定** | Not sedating | | | | | **MAKE YOU SLEEPING** | selective binding to | | | [perihiphera]l h1 | | ble to cross BBB and bind to | receptors | | histamine receptors in CNS | | | | Lorata**dine** \[Claritin\] | | Diphenhydramine \[Benadryl\] | 用於治療季節性過敏性鼻炎和蕁麻疹。 | | | | | *Sweet "dreams" | | | 經常用於緩解過敏症狀和失眠。因可過bbb* | Fexofena**dine** \[Allegra\] | | | 用於治療過敏性鼻炎和慢性蕁麻疹。([要注意它不適合配所有果汁，會減 | | | 少效果]) | | Hydroxyzine | | | (全身的h1都反映，所以選擇性比較) | Cetiri**zine** \[Zyrtec\] | | 影響認知記憶 | 用於治療季節性過敏、常年性過敏性鼻炎和蕁麻疹。 | | | | | Blocks all the effects at the H1 | | | receptor that were likely | | | triggered by mild allergic rxn | | | 常用於緩解焦慮、過敏反應和手術前的鎮靜 | | +-----------------------------------+-----------------------------------+ | **Additional SE of | | | antihistamines** | | | | | | - - - - - - | | | | | | - - | | +-----------------------------------+-----------------------------------+ **All H1 blockers treat allergic rxn** - - - - **Two classes of antihistamines, both types work at H1 receptors** **[First generation H1 antagonists]** (we often call them by more generic categorization of anti-histamines) - - - - - **[Second-generation H1 antagonists]** - - - - - - - - - - - - - **Cyclooxygenase Inhibitors: (NSAID) Nonsteroidal Anti-inflammatory Drugs and Acetaminophen（Tylenol）** - Triple Effect of COX Inhibitors:\ - NSAIDS do all 3(抗發炎&止痛&解熱)\ - 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? - Cyclooxygenase (COX) Normal Pathway (before we take the drugs to block) +-----------------------+-----------------------+-----------------------+ | | **COX-1 Pathway** | **COX-2 Pathway** | +-----------------------+-----------------------+-----------------------+ | | - Found in almost | - Stimulated by | | | all tissue for | tissue injury | | | various | | | | "housekeeping" | - Causes our pain, | | | needs, including: | fever and | | | | inflammation, | | | - Protects the | which is actually | | | gastric mucosa | helpful when we | | | 保護胃黏膜，防止胃壁被侵蝕 | have an injury | | | | | | | | - NSAID Pathway | | | - Supports renal | **（Nonsteroidal | | | function | Anti-inflammatory | | | | Drugs，非甾體抗炎藥)** | | | - Promotes platelet | | | | aggregation | | | | | - Blocks | | | | prostaglandins前列腺 | | | | 素 | | | | (those are the | | | | PGs) and | | | | thromboxane | | | | 血栓素 (that's | | | | the TX) | | | | | | | | - NSAIDS like | | | | naproxen and | | | | ibuprofen have | | | | less effect on | | | | inhibiting | | | | platelet | | | | aggregation, but | | | | instead have been | | | | linked to | | | | thrombotic events | | | | | | | | - Black Box Warning | | | | for NSAIDS | +-----------------------+-----------------------+-----------------------+ - Do we have to take a fever-reducer? 看圖的例子。 發燒溫度沒有太高。成年人發燒基本上不用吃退燒藥，如果有頭痛，可以吃NASID 他可以止痛加上退燒。 **Aspirin** **三個都有 陣痛發燒解熱** - Acetylsalicylic acid (ASA) - Origins of willow bark from 2000+ BC in Assyria (Iraq) to relieve pain & fever - Therapeutic Use: Antipyretic解熱藥, nonopioid analgesic, anti-inflammatory effect, and [platelet inhibitor] **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 过度换气和抽搐] - 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) 極少會發生暫時性的缺血，導致平血，暈 - Don't forget: any med can cause an allergic reaction and that would look different from SE. Rash, hives, shortness of breath. - Which of the following conditions is a contraindication for the use of aspirin? - 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 **NSAIDS** - Non-steroidal, anti-inflammatory - Work like corticosteroids糖皮質激素 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]) - - - - - - **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. **Acetaminophen（Tylenol） 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=It%20has%20been%20thought%20that,COX%2D1%20and%20%2D2]*](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734311/) **Acetaminophen（Tylenol） vs Aspirin 會考** - 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 **Acetaminophen 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]*](http://tal.fm/505) - What is the maximum dose of acetaminophen for a 24-hour period? - \*\*\*Will need for exam! \_\_\_\_4000 mg or 4g \_\_\_(會考，還會考圖上的數字) p.51 - Also need to know extra strength dose **Who should not take acetaminophen? (tylenol)** 1. **People who drink more than 3 drinks/day**: Avoid use due to increased risk of liver damage. 2. **People with liver disease**: Avoid use, including those with cirrhosis, hepatitis, or fatty liver disease.因為藥會肝毒性，不適合肝不好的人 3. **People taking other medications with acetaminophen**: Avoid mixing, even if within the 4000mg limit. **The nurse reviews a client's list of medications:\ **\ - 2 tablets of extra strength Tylenol every 6 hours PRN for chronic pain, patient takes most days\ - Surgical team prescribes Hydrocodone 10mg/Acetaminophen 300mg (Vicodin) every 4-6 hours as needed following outpatient surgical procedure\ - Arthriten medication from Walmart that contains 250mg acetaminophen and 250mg of aspirin. Dose: take 2 pills every 6 hours as needed. - 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. - A nurse is educating a patient about acetaminophen. Which of the following statements by the patient indicates a need for further teaching? - Answer - **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