Medications for Pain, COX & Opioids, Headaches PDF

Medications for Pain Chapter 33, 34, and 36 Non-Opioid Analgesics Chapter 33 Two Types of non-steroidal anti- inflammatory drugs (NSAIDS)  First generation (Classical)  Second-generation (NEW)  Non-selective COX inhibitors  Selective- COX-2 Inhibitors  Asp...

Medications for Pain Chapter 33, 34, and 36 Non-Opioid Analgesics Chapter 33 Two Types of non-steroidal anti- inflammatory drugs (NSAIDS)  First generation (Classical)  Second-generation (NEW)  Non-selective COX inhibitors  Selective- COX-2 Inhibitors  Aspirin  Celecoxib  Ibuprofen  Decrease risk of peptic ulcers  Naproxen  Increase risk of clotting  Inhibit COX-1 & COX-2  Increase of peptic ulcers  Increase of bleeding What is COX? Cyclooxygenase, an enzyme COX 1 & COX 2 Found in all tissues Regulates multiple processes using prostaglandins Stomach  COX-1 protects gastric mucosa Platelets  COX-1 stimulates aggregation Uterus  COX-1 causes contractions for delivery Kidney  COX-1 & 2 maintain renal blood flow Tissue injury  COX-2 promotes inflammation & pain Vessels  COX-2 causes vasodilation Brain  COX-2 mediates fever & perception of pain Colon  COX-2 promotes colorectal cancer COX Inhibitors  Uses: Two major categories:  mild-moderate pain  Anti-inflammatories  inflammation NSAIDs - aspirin,  fever ibuprofen, naproxen,  pre-menstrual celecoxib symptoms  Non anti-inflammatories  protection against acetaminophen colon cancer  Relatively safe, but possible adverse effects First Gen NSAID - Prototype: Aspirin (ASA) Uses: reduction of pain, fever, inflammation, MI prevention MOA: irreversibly inhibits COX-1 and COX-2 Pharmacokinetics  Absorption PO: plain, buffered, enteric-coated  Metabolism Short T1/2, is quickly converted to salicylic acid (SA), an active metabolite SA’s T1/2 is concentration-dependent  Distribution SA is highly bound to albumin, crosses all membranes easily  Excretion SA by kidneys; dependent on pH First Gen NSAID - Prototype: Aspirin (ASA) Adverse Effects  GI – gastric distress, bleeding, ulcers  General excessive bleeding  Renal impairment  Salicylism Syndrome  Hypersensitivity  Do not give ASA to children (Reye’s syndrome) or pregnant women (risk to mom and baby)  Contraindicated in patients with: peptic ulcer disease, bleeding disorders, ASA/NSAID hypersensitivity Interactions  Other anticoagulants (warfarin, heparin)  Alcohol  Other NSAIDs (antiplatelet effect) Aspirin Toxicities  Salicylism Syndrome  develops slowly as ASA levels climb above therapeutic range  s/sx: tinnitus, sweating, headache, dizziness  withhold aspirin until s/sx resolve, then at reduced dose  Acute poisoning  s/sx: respiratory alkalosis  respiratory depression, acidosis, hyperthermia, sweating, dehydration, stupor, coma  an acute medical emergency, death related to respiratory failure  First Gen NSAID – Ibuprofen (Advil, Motrin)  Non-aspirin NSAID  MOA: Reversible inhibition of COX-1 and COX-2  Uses are the same as aspirin except:  does not prevent MIs/CVAs  may increase CV risk  A good choice for dysmenorrhea; is This Photo by Unknown Author is licensed under CC BY-NC-ND selective for COX in the uterine muscle  Less gastric bleeding than aspirin  Risk of renal impairment First Gen NSAID - Naproxen (Aleve, Anaprox)  Another non-aspirin NSAID  Fairly selective for COX-1, less incidence of GI problems and MI/CVA than other non-ASA NSAIDs  T1/2 of 12-17 hours, allows less frequent dosing This Photo by Unknown Author is licensed under CC BY-ND  Otherwise, same as ibuprofen  Second Gen NSAID – Celecoxib (Celebrex)  MOA: inhibits COX-2 only  Uses: arthritis, acute pain, dysmenorrhea  Less GI problems than 1st- generation NSAIDs  Increased risk of MIs and CVAs, can impair kidneys  Use lowest effective dose for shortest possible time  Not a good option for patients with heart disease This Photo by Unknown Author is licensed under CC BY-NC Non-Anti-Inflammatory - Acetaminophen (Tylenol) Uses:  Analgesia (pain reliever)  Antipyretic (fever reducer), preferred for children  NO anti-inflammatory effects MOA: COX inhibition, thought to be limited to the CNS Pharmacokinetics This Photo by Unknown Author is licensed under CC BY-SA  Absorption PO, PR, IV Acetaminophen Metabolism Metabolism - In the liver by two pathways: major and minor  Major pathway  Acetaminophen converted directly into nontoxic metabolites  Minor pathway  CYP450 converts acetaminophen to a toxic metabolite  Glutathione required to then convert toxic metabolite to nontoxic metabolite  24-hour max for acetaminophen in adults: 4g  Watch for acetaminophen in combo medications Acetaminophen and Alcohol (ETOH)  Regular alcohol consumption reduces the liver’s ability to metabolize excessive doses of acetaminophen 1: alcohol induces CYP450 2: alcohol depletes glutathione 3: alcohol causes general liver damage  Recommendation is to have a 2g ( ½ the max limit) in a 24-hr time period for regular users of alcohol Acetaminophen Toxicity  Cause of 50% of acute liver failures  Manifestations of liver injury (hepatic necrosis) appear 48-72 hours after overdose  Early s/sx: N/V/D, sweating, abdominal pain/discomfort are initial signs  Late s/sx: Hepatic failure, coma, death  Antidote: acetylcysteine (Mucomyst)  It substitutes for glutathione  100% effective if given within 8-10 hours References  Assessment Technologies Institute. (2023). Pharmacology Made Easy 4.0  Assessment Technologies Institute. (2023). RN Pharmacology for Nursing Edition 9.0 Drugs for Headaches Chapter 36 Headaches  Very common complaint  Mild, occasional headaches often improved by over-the- counter (OTC) medications  Forms of headache include:  Tension-type  Cluster  Migraine This Photo by Unknown Author is licensed under CC BY-NC-ND  Tension-type Headaches  Most common type  “headband” non-throbbing pain, tightness in head & neck  Abortive: Ibuprofen, naproxen, aspirin- butalbital, acetaminophen  Preventative: coping & relaxation skills, This Photo by Unknown Author is licensed under CC BY-NC amitriptyline Cluster Headaches  Less common, mostly in males (5:1)  Occur in a series of cluster attacks  Lasts 15 min – 2 hrs  Unilateral pain near eye, lacrimation, ptosis, nasal congestion, rhinorrhea  Abortive: Oxygen, sumatriptan  Preventative: This Photo by Unknown Author is licensed under CC BY-SA betamethasone, verapamil, lithium Migraine Headaches  Throbbing, moderate-severe pain that may be unilateral or bilateral  May last for days  Associated with nausea/vomiting, photo/phonophobia  Aura vs. no aura  More common & more severe in females  Very debilitating This Photo by Unknown Author is licensed under CC BY-SA-NC Migraine Headaches Patho  Neurovascular problem  Vasodilation & inflammation of the cranial blood vessels  Many possible triggers  Two neurochemicals are involved:  Calcitoningene-related peptide - CGRP (causes migraines?)  Serotonin/5-HT (suppresses migraines?) Abortive Therapy: Triptans (serotonin receptor agonists) Prototype: Sumatriptan  Uses: Migraines & cluster Adverse Effects headaches  50% experience chest  MOA: “heaviness” – this is not angina pectoris!  bind to and activate specific  Coronary vasospasm – this IS subtypes of serotonin receptors in the brain, causing vasoconstriction angina pectoris! increased risk in patients with Pharmacokinetics CAD risk factors  Absorption  Teratogen PO, SQ, inhalation Interactions  Metabolism  Ergot Alkaloids cause vasospasm hepatic, T ½ = 2.5 hours (wait 24 hrs)   SSRI/SNRI may cause excessive Follow maximum dosing serotonin syndrome instructions Abortive Therapy: Ergot Alkaloids Prototype: Ergotamine  Uses: Migraines & cluster headaches Adverse Effects  MOA – several possibilities  Rare at therapeutic  activation of serotonin receptors doses   Possible nausea/vomiting blockage of cranial inflammation  cranial vasoconstriction  Risk of dependence Pharmacokinetics Interactions  Absorption  Triptans cause vasospastic reactions PO, SL, PR, or inhalation (wait 24 hrs) best absorption/distribution with PR and  inhalation CYP3A4 Inhibitors raise to dangerous levels to  Metabolism cause vasospasm by CYP3A4, T ½ = 2 hours Migraines: Preventative Therapy  In patients who have frequent or severe migraines, ongoing medicine to prevent them may be necessary  Daily dosing Three common options: 1) Beta Blockers – propranolol  May cause tiredness, may exacerbate asthma 2) Antiepileptics – topiramate  May cause fatigue and cognitive dysfunction 3) Tricyclic Antidepressant – amitriptyline  May cause hypotension and anticholinergic effects References  Assessment Technologies Institute. (2023). Pharmacology Made Easy 4.0  Assessment Technologies Institute. (2023). RN Pharmacology for Nursing Edition 9.0 Opioid Medications Chapter 34 Opioid Analgesics  Endogenous opioid peptides:  found in the central nervous system (CNS) and in peripheral tissues  serveas neurotransmitters, neurohormones, and neuromodulators  Opioids: drugs that have actions similar to endogenous opioid peptides, based on morphine  Mu – activation causes analgesia (pain relief), respiratory depression, euphoria, sedation, decreased GI motility, and eventual physical dependence Opioid Kappa – activation causes analgesia, sedation, and decreased GI motility Receptors Delta – no significant effects Classifications of Opioid Drugs Pure Agonists agonists for Mu and Kappa receptors (divide into strong & mod- strong) morphine, fentanyl, codeine, meperidine (Demerol), etc Agonist-Antagonists antagonist for Mu, agonist for Kappa receptors Pentazocine (Talwin), nalbuphine (Nubain) Pure Antagonists antagonists for Mu and Kappa Naloxone (Narcan), naltrexone Strong Opioid Agonists  Common drugs in this class include morphine, hydromorphone, fentanyl, meperidine (Demerol), heroin, methadone  Morphine is the prototype  MOA: mimics endogenous opioids, activating mu and kappa receptors  Clinical uses: relief of moderate to severe pain (postoperative, cancer- related, labor/delivery, MIs) This Photo by Unknown Author is licensed under CC BY-SA Strong Opioid Agonist: morphine Pharmacokinetics Adverse Effects  Absorption / Distribution  Respiratory depression  can be given practically any  onset varies with route, onset and duration differ route  small amount crosses BBB  most serious  scheduled is usually best,  Constipation (common) amount depends on pain  Orthostatic hypotension severity  Metabolism  Urinary retention  affected by first-pass effect  Nausea/vomiting  liver inactivation  Cough suppression  Toxicity: coma, respiratory depression, pinpoint Strong Opioid Agonist: morphine  Drug  Physical Dependence Interactions  Intensity and duration of withdrawal  other CNS syndrome depend on T ½ and depressants degree of dependence on drug  anticholinergics  Morphine has a short half-life:  antihypertensiv withdrawal is intense (7-10 days)  Initial reactions include yawning, es rhinorrhea, and sweating  agonist-  Anorexia, irritability, tremor, antagonists gooseflesh  Violent sneezing, N/V/D, abd  antagonists cramping, bone & muscle pain, kicking movts Strong Opioid Agonist: fentanyl (Duragesic)  Strong opioid, about 100x more potent than morphine  Parenteral administration: for induction and maintenance of anesthesia  Transdermal administration: postoperative pain, chronic pain  usually reserved for persistent severe pain in patients who are opioid This Photo by Unknown Author is licensed under CC BY-SA tolerant  Metabolism is hepatic, by CYP3A4  Adverse effects same as morphine Moderate-Strong Opioid Agonists  Examples: codeine, oxycodone, hydrocodone  MOA is same as strong opioid agonists  Main difference: Less analgesia and respiratory depression  Less abuse potential than strong agonists but tolerance and abuse can occur  Many are co-formulated with APAP This Photo by Unknown Author is licensed under CC BY-SA Moderate-Strong Agonist: Codeine Uses Adverse Effects  relief of mild to moderate pain,  Similar to morphine often co-formulated with  Increase with higher acetaminophen dosages  Cough suppressant  High dosages required for significant pain relief = Pharmacokinetics dangerous side effects Administration/Absorption  PO most common method Metabolism  liver (CYP2D6) metabolizes about 10% of codeine to morphine; this is likely how it produces analgesia  genetic differences in this Agonist-Antagonist Opioids  Activate kappa receptors and block mu receptors  Provide analgesia without as many side effects as pure agonists  Less potential for abuse  If used to replace a long-term opioid agonist, could cause withdrawal symptoms Agonist-Antagonist: Pentazocine (Talwin) MOA Adverse Effects  Activates kappa  Many similar to morphine, but receptors causing less respiratory depression analgesia, sedation, and  Increases cardiac workload; not limited respiratory a good choice for pain related depression to myocardial infarction  Physical dependence can Pharmacokinetics develop but withdrawal is mild Absorption compared to pure opioid  PO administration agonists Metabolism  shortT ½ ; frequent dosing Opioid Antagonists  MOA: block the opioid receptors  Uses: reversal of opioid overdose, relief of opioid-related constipation, and treatment of opioid addiction  No effect on their own; only used in combination with an opioid agonist Opioid Antagonist: Naloxone (Narcan) Pharmacokinetics Adverse Effects  Absorption  None on its own highly affected by first-  If given to a person pass effect physically dependent given parenterally or on opioids, will cause intranasally, longer immediate/severe effects when given withdrawal problems IM/SC  Metabolism hepatic, T1/2 about 2 hours The Opioid Epidemic- Nursing Considerations Nursinggoals to minimize physical dependence and abuse of opioids Assess pain and dosage sufficient to relieve pain Administer lowest effective dose for shortest time need As pain diminishes, opioid dosages should be reduced Switch patient to nonopioid analgesic as soon as possible https://www.aacom.org/reports-programs- initiatives/aacom-initiatives/tackling-the-opioid- epidemic References  Assessment Technologies Institute. (2023). Pharmacology Made Easy 4.0  Assessment Technologies Institute. (2023). RN Pharmacology for Nursing Edition 9.0