Pain Management

Categories:

NSAIDs
- Salicylates
  - Aspirin (ASA)
    - Slows the bd of oral hypoglycemics (decrease hypoglycemic dose)
    - Monitor when used with Lithium
- Acetic Acid Derivatives
  - Blocks COX1 and COX2
  - Bromfenac (Prolensa, Bromday)
  - Diclofenac (Voltaren)
  - Indomethacin
  - Ketorolac (Toradol)
- Oxicams
  - Meloxicam (Mobic)
  - Piroxicam (Feldene)
- Propionic Acid Derivatives
  - Ibuprofen
    - SE: Hyperkalemia, Hyponatremia, Hypokalemia + RTA (hyperchloremic metabolic acidosis, low urine anion gap)
  - Naproxen
- Coxibs
  - Celecoxib (Celebrex)
    - COX1 completely, COX2 some
  - Etodolac
    - COX1 completely, COX2 some
  - Parecoxib (Dynastat)
- Other
  - Nabumetone (Relafen, Relifex)
Neuropathic Pain
- Orders of loss:
  - 1) Pain
  - 2) Temperature
  - 3) Touch
  - 4) Pressure
- TCAs (Amitriptyline/Nortriptyline)
  - Decrease reuptake of serotonin and norepinephrine
  - Inhibition of pain signals
  - Can be used in patients with Depression + Neuropathy
  - CI: ≥65, pre-existing Cardiac disease
- Anticonvulsants
  - Gabapentin Enacarbil (Horizant)
    - Not FDA approved
    - Influence synthesis/uptake of GABA
      - Does not Bind GABA-A/GABA-B
    - Restless leg, neuropathy, anxiety
  - Gabapentin (Neurotin)
    - Not FDA approved
    - Antiepileptic, migraine prevention, diabetic neuropathy, RLS
  - Pregabalin (Lyrica)
    - Dose: 50mg BID to TID
    - MOA: Decreased depolarization of neurons in CNS
      - Inhibits the release of excitatory neurotransmitters by binding voltage gated calcium modulators on nerve endings
      - 6x binding affinity of gabapentin
      - May potentiate opioids/benzos
    - Use: FDA for fibromyalgia
    - SE: drowsiness, weight gain, fluid retention
- Dual SNRIs (Duloxetine)
  - In painful diabetic neuropathy
- Opioids (Oxycodone)
  - Activation of central opioid receptors
- Capsaicin (Topical)
  - Loss of membrane potential in nociceptive fibers
- Lidocaine (Topical)
  - Decreased depolarization of neurons in peripheral nerves
- Milnacipran (Savella)
  - SNRI
- Medical Cannabis
  - Some efficacy in the treatment of chronic non-cancer pain
Chronic inflammatory Demyelinating neuropathy
- Distal paresthesias and numbness
- Motor weakness in upper and lower extremities
Somatic Pain
- Joint pain
- NSAIDs (Ketorolac)
DMARDs
- Pts on prednisone ≥20mg/day, methotrexate ≥25mg/week, and azathioprine ≥3mg/kg/day should avoid live vaccines
- Nonbiologic agents (sDMARDs):
  - Methotrexate (MTX, Rheumatrex, Trexall)
    - MOA: Purine Antimetabolite, inhibits dihydrofolate reductase
    - Most predictable benefit and well tolerated in RA
    - Give with Folic Acid
    - May continue through surgery w/o stopping
    - SE: Hypersensitivity Pneumonitis, cytopenias even at low doses, abnormal LFTs, Infections, mucosal ulcers, GI, Abortifacient, alopecia, skin nodules, nephrotoxicity, macrocytic anemia, hepatotoxicity, stomatitis
      - May activate hepB or C, myelosuppression
    - CI: pregnancy, moderate to advanced renal disease, chronic liver disease, heavy alcohol use, parenchymal disease
    - Cycle off for ≥1 ovulatory cycle prior to pregnancy, 3 months for males
    - Methotrexate Pneumonitis
      - CXR w/interstitial infiltrates
      - Not dose related
      - Usually within 1st year
      - Subacute w/cough, dyspnea, fever
      - Bronchoscopy with BAL usually needed to R/O infection
      - TX: Stop MTX, taper with glucocorticoids
    - Get CXR, CBC and CMP, Viral HepB/HepC titers
      - CMP/CMP every 4 weeks for 3m, then every 3m
      - PFTs if COPD or dyspnea
    - PCN/sulfa decrease renal excretion
    - Folate supplementation
  - Azathioprine (AZA)
    - Thiopurine
    - First metabolized to 6-MP by the liver
    - Then metabolized by 3 pathways
      - 1) TPMT converts 6-MP to 6-MMP
        
        Main pathway, inactive in 11% of population
      - 2) HPRT states conversion of 6-MP to 6-TG
        
        Bone marrow suppression if high or on XO inhibitors, monitor CBC/LFTs
        
        Hepatotoxic levels of 6-MMP if defective
      - 3) XO converts 6-MP to 6-TU
    - More commonly used for SLE and IBD
    - Test for TPMT (Thiopurine methyltransferase) prior to initiation of 6-mp or aza
    - SE: Cytopenias, hepatotoxicity, GI
      - Increases risk of bone marrow toxicity
      - Dose-dependent diarrhea, leukopenia, hepatotoxicity
  - Cyclosporine A (CYA)
    - Calcineurin Inhibitor, inhibits T-cell production of IL-2
    - Synergistic with MTX
    - SE: Renal toxicity, hypertension
  - Cyclophosphamide (CYP)
    - Alkylating agent, disrupts DNA replication
    - SE: malignancy, infertility, infections, cytopenia, hemorrhagic cystitis
  - Hydroxychloroquine (HCQ, Plaquenil)
    - MOA: TNF & IL-1 suppressor
    - Antimalarial
    - Safe in pregnancy
    - May continue through surgery w/o stopping
    - SE: Retinal toxicity, neuromyopathy, hyperpigmentation
      - Annual eye exam after 5 years of continuous use
      - Increased retinal tox risk:
        
        Retinopathy more likely with renal or liver disease
        
        ≥60 y/o, ≥400mg/day, use ≥5 years, underlying retinal or macular disease
      - May exacerbate psoriasis
      - CBC/CMP every 3-6m
      - Initiation has an increased risk of MACE/CV mortality/MI vs. Methotrexate in HF patients
    - CI: G6PD deficiency
  - Leflunomide (LEF, Arava)
    - MOA: Antimetabolite, pyrimidine synthesis inhibitor
    - Initial DMARD in patients unable to take MTX
    - Same baseline studies as MTX
    - May continue through surgery w/o stopping if minor, stop 1-2 days before major surgeries, restart 1-2 weeks after
    - SE: Pneumonitis, cytopenias, hepatotoxicity, Infections, GI
    - CI: pregnancy, lactation, teratogenic
      - Give cholestyramine 8g PO TID for 11 days to eliminate drug (want leflunomide <0.02mg/L for 2 tests 14 days apart)
      - Extremely teratogenic
  - Mycophenolate Mofetil (MMF)
    - Reversibly inhibits IMP Dehydrogenase, preventing purine synthesis of B and T cells
    - SE: GI upset, pancytopenia, hypertension, hyperglycemia, less nephrotoxic and neurotoxic
      - Teratogenic
      - Associated with invasive CMV infection
  - Sulfasalazine (SSZ, Azulfidine)
    - Antibiotic/Anti-inflammatory
    - RA and IBD
      - Sulfapyridine produces effects for RA
      - 5-ASA produces effects for IBD
    - SE: Cytopenias (check G6PD prior), Hepatotoxicity, oligospermia in 80% but reversible, rash, N/V/D/Ab pain, hemolytic anemia
    - Give folic acid supplements
    - May continue through surgery w/o stopping
    - Reyes syndrome in pts given varicella vaccine
    - Relatively safe during pregnancy
    - CI: G6PD deficiency
  - Tofacitinib (Xeljanz)
    - Small-molecule JAK-1/3 inhibitor
      - Inhibits intracellular signaling involved in T-cell activation, proinflammatory cytokine production, cytokine signaling
    - Refractory RA
    - SE: Infections (shingles particularly), Hyperlipidemia, cytopenias, TB reactivation, Abnormal LFTs if used with MTX
- Biologic Agents (bDMARDs):
  - Screening: HepB, HepC, TB
    - Vaccinate with flu, pna, other vaccines
    - Avoid live attenuated vaccines (nasal flu, MMR, shingles)
    - Suspend biologic therapy during perioperative period
  - Anti-TNF Biologics:
    - Monoclonal antibodies that bind and inactivate TNF
    - Best used with MTX to halt and possibly reverse disease
    - Use: IBD, Rheumatoid Arthritis
      - Moderate to High risk patients: <30, extensive involvement, perianal +/- rectal disease, deep ulcer, prior surgery, structuring +/- penetrating behavior
    - SE: drug induced lupus, CNS demyelination, worsening HF, malignancy, infection
    - CI: HF class III/IV, no live vaccines
      - TNFi + Thiopurine (azathioprine or 6-MCP) = increased risk for hepatosplenic T-cell lymphoma
    - Adalimumab (Humira)
      - Humanized Monoclonal Antibody
      - Soluble TNF-alpha inhibitor
      - Subcutaneous
    - Certolizumab (Cimzia)
      - Fab’ segment of humanized monoclonal antibody attached to polyethylene glycol strands
      - Soluble TNF-alpha inhibitor
      - Subcutaneous
    - Etanercept (Enbrel)
      - Fusion protein made of two p75 TNF-alpha receptors linked to IgG Fc segment, Soluble TNF receptor linked to IgG1 (not a monoclonal antibody)
    - Golimumab (Simponi)
      - Humanized Monoclonal Antibody
      - Soluble TNF-alpha inhibitor
      - Subcutaneous
    - Infliximab (Remicade)
      - Chimeric (mouse-human) Monoclonal Antibody
      - Soluble TNF-alpha inhibitor
      - SE: Arthralgias (MC)
  - Non-TNF Biologics:
    - Abatacept (Orencia)
      - Soluble CTLA-4 receptor/IgG Fc segment chimera co-stimulation inhibitor (CD80 and CD86)
        
        Blocks communication
        
        Inhibits T-cells
        
        Does not block TNF-alpha
      - SE: COPDE, infections, Nausea, Sinus infection, pneumonia, TB, Hyperglycemia
        
        Associated with COPD exacerbations in vivo
        
        Can’t be used with biologics
    - Anakinra (Kineret)
      - Recombinant receptor antagonist
      - IL-1 antagonist
      - Less efficacious than other biologics
      - Requires daily injection
      - Continue for minor procedures, stop 1-2 days before major surgeries, restart 10 days later
      - SE: Neutropenia, infections, injections site reaction
    - Belimumab
      - Humanized Monoclonal Antibody
    - Canakinumab
      - Humanized Monoclonal Antibody
    - Rilonacept
      - Dual IL-1B receptors chimerically attached to IgG Fc segment
    - Rituximab (Rituxan)
      - MOA: Chimeric (mouse-human) Monoclonal Antibody to CD20 surface Ig of B cells
      - Stop 7 months before major surgery
      - Use: CD 20+ NHL, CLL, ITP, RA
        
        Used with MTX, when refractory to TNFi
      - SE: Serious infections (increased risk of PML), SJS/TEN, HepB reactivation, serious infusion reactions, pulmonary toxicity
    - Secukinumab
      - Humanized Monoclonal Antibody
    - Tocilizumab (Actemra)
      - Humanized Monoclonal Antibody
      - IL-6 receptor antagonist
      - Refractory to DMARDs +/- TNFi
      - SE: infections, hyperlipidemia, cytopenias, Diverticulitis/perforation, abnormal LFTs
        
        Increases risk of bowel perforation in pts w/history of diverticulitis
        
        Decreases efficiency of oral contraceptives
    - Tofacitinib
      - Oral targeted Synthetic Janus Kinase inhibitor
      - SE: Increased risk of thrombotic events
    - Ustekinumab (Stelera)
      - Humanized Monoclonal Antibody
      - Anti-IL-12/23 antibody
      - Used in high risk resistant crohns for induction and maintenance
      - Stop 1 week before procedure, restart ≥14 days later
Acetaminophen (Tylenol)
- Metabolized within hepatic microsomes, predominantly by phase II reactions
  - 90% by Glucouronidation and Sulfination to nontoxic conjugates
  - 5% by P450 oxidation to NAPQI
    - Hepatotoxic metabolite, usually conjugates to glutathione
  - 5% by Direct urinary excretion
- Toxicity
  - RF: Malnutrition (decreased GSH), fasting, P450 induction
- Poisoning
  - Stage I (30 minutes to 4 hours)
    - Asymptomatic to GI upset
    - LFTs normal
  - Stage II (24 hours to 72 hours)
    - Initial symptoms resolve
    - RUQ pain, hepatomegaly
    - Increased LFTs, PT/INR, Total Bilirubin
  - Stage III (72 hours to 96 hours)
    - GII upset, jaundice
    - CNS dysfunction (hepatic encephalopathy)
    - Bleeding diathesis
    - +/- Acute renal failure
    - LFTs ≥10k, PT/INR increase, Total Bilirubin ≥4.0, Hyperammonemia, Hypoglycemia
    - MC time of death (MSOF)
  - Stage IV (4 days to 2 weeks)
    - Recovery
    - Labs normalize
- W/U: Measure Acetaminophen concentrations at 4 and 8 hours post ingestion
- Treatment
  - Rumack-Matthew Nomogram
    - To predict toxicity and need for N-acetylcysteine for acute overdoses
  - Activated Charcoal if within 4 hours (1g/kg)
  - N-acetylcysteine if within 8 hours
    - Regenerates hepatic glutathione stores (IV ≥ oral in failure, prior to LFTs)
    - Death and hepatotoxicity uncommon if NAC given within 8hrs
Triptans
- General
  - CI: Brainstem or hemiplegic Auras
- Sumatriptan (Imitrex)
  - 3 methods of delivery (injection, intranasal, oral)
  - Combo: Sumatriptan + Naproxen
    - Works better than either alone
- Zolmitriptan (Zomig)
- Rizatriptan (Maxalt)
  - Works the fastest
  - Propranolol increases blood levels (downward titrate)
- Almotriptan (Axert)
- Eletriptan (Relpax)
- Fovatriptan (Frova)
- Naratriptan (Amerge)
- CI: complicated or basilar migraines, CHD or Prinzmetal angina, Stroke history, uncontrolled BP, pregnancy, MAOIs within 24hrs

Pain Management

results matching ""

No results matching ""