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Presentation 1.pptx

  1. Role of Anti-depressants and Anti- epileptics in chronic pain management
  2. • Chronic and acute pain are different. • Require different treatment approaches. • Acute pain is a protective response to injury. • Chronic pain may be a maladaptive response. • Acute pain most often is nociceptive. • Chronic pain may be nociceptive or neuropathic (i.e., resulting from neuronal maintenance of pain either peripherally or in the central nervous system). • Nociceptive pain usually is treated with anti-inflammatory or analgesic medications. • Neuropathic pain typically is treated with medications that influence neurotransmitters Background
  3. Peripheral neuropathic pain Central neuropathic pain Non-neuropathic pain* Complex regional pain syndrome Multiple sclerosis Arthritis Human immunodeficiency virus sensory neuropathy Myelopathies Inflammatory arthritis Idiopathic peripheral neuropathy Parkinson's disease Osteoarthritis Infection Poststroke pain Chronic low back pain Metabolic disorders Chronic neck pain Alcohol and other toxins Fibromyalgia Diabetic neuropathy Post-traumatic pain Nutritional deficiencies Nerve compression or entrapment Phantom limb pain
  4. The Special Interest Group on Neuropathic Pain (NeuPSIG) proposal: Tricyclic antidepressants (TCAs), Gabapentinoids, and selective serotonin– norepinephrine reuptake inhibitors (SNRI) as the first-line drugs for neuropathic pain. Lidocaine, Capsaicin, and Tramadol as the second-line treatment. Strong opioids (Morphine and Oxycodone) and botulinum toxin-A (BTX-A) as third-line treatments for neuropathic pain.
  5. Tricyclic Anti-depressants
  6. The Special Interest Group on Neuropathic Pain (NeuPSIG) proposal: Tricyclic antidepressants (TCAs), Gabapentinoids, and selective serotonin– norepinephrine reuptake inhibitors (SNRI) as the first-line drugs for neuropathic pain. Lidocaine, Capsaicin, and Tramadol as the second-line treatment. Strong opioids (Morphine and Oxycodone) and botulinum toxin-A (BTX-A) as third-line treatments for neuropathic pain.
  7. Independent analgesic action Pain relief in depressed and non-depressed patients with chronic pain Secondary and Tertiary amines. Desipramine, amitriptyline and its metabolite, nortriptyline, and imipramine.
  8. Amitriptyline can act as a local anesthetic by blocking voltage-gated sodium channels. Antidepressants may have additional mechanisms of action by modulating the immune system, which is heavily involved in neuropathic pain. TCAs may directly interfere with central sensitization by blocking NMDA receptors in the spinal cord .
  9. "Dirty drugs” that affect multiple targets. Anticholinergic effects are a major concern because of the risk of cardiotoxicity, limiting the dosage to less than 100 mg/day. Also include dry mouth, orthostatic hypotension, constipation, and urinary retention. In order to overcome these problems, selective SNRIs, in particular duloxetine, have been introduced in the treatment of neuropathic pain.
  10. Duloxetine has shown consistent efficacy in painful diabetic neuropathy and low back pain. Dosing of duloxetine is simple with 60 mg once or twice daily appearing to be equally effective. Nausea is the most common adverse effect of duloxetine, which appears to be reduced by lowering the dosage to 30 mg once daily for 1 week before increasing to 60 mg once daily.
  11. Anti-epileptics.
  12. Pregabalin and gabapentin are both derived from GABA, but they have no effect on the GABAergic system. Their mechanism of action includes binding to the alpha-2/delta-1 subunit of the voltage-gated calcium channels in several areas of the central nervous system (CNS) and spinal cord in which these channels are expressed. This explain their analgesic, anxiolytic, and anticonvulsant pharmacological properties. Brainstem structures, from which descending modulatory fibers originate, may be a key target of the analgesic action of gabapentinoids, because alpha-2/delta-1 expression is very high in these areas.
  13. Pregabalin has greater binding affinity for the alpha-2/delta-1 subunit. Analgesic potency in neuropathic pain is six times higher compared with gabapentin. The system-L protein family [L-type amino acid transporters (LAT)] enables the transport of large neutral amino acids, including phenylalanine, leucine, isoleucine, and valine; intestinal absorption of gabapentin and pregabalin is also facilitated by this protein family. Results from preclinical studies suggest that gabapentin is transported exclusively by the LAT1 transporter. This results in dose-limited absorption, which may be due to saturation of the facilitated transport process. An additional pathway also appears to mediate the absorption of pregabalin, resulting in a high level of absorption into the bloodstream
  14. Both drugs do not undergo metabolism by phase I or phase II enzymes and are excreted unmodified by the kidneys. Not prone to pharmacokinetic drug–drug interactions and, specifically, are not substrates of the cytochrome P450 (CYP) system, which is involved in the metabolism of many other drugs. This is of significant clinical value, because the two drugs can be safely used in comorbid patients on pharmacological polytherapy. Gabapentin and pregabalin can be safely used in combination with other analgesic drugs used in the treatment of neuropathic pain.
  15. Pregabalin and gabapentin are well tolerated drugs. The most commonly reported adverse effect of...... pregabalin is dizziness, followed by somnolence, dry mouth, edema, and blurred vision, with treatment discontinuation due to somnolence occurring in 4% of patients. For....... gabapentin, dizziness and somnolence occur in more than 20% of patients and are the most commonly reported adverse effects; other adverse effects include confusion and peripheral edema. For both drugs, adverse effects are dose-dependent and reversible.
  16. Gabapentin and pregabalin may be initiated in the emergency department but the onset of pain relief is not typically seen immediately. These agents require a slow titration to effect over several weeks. As a result, they should be started at a low dose and titrated based upon clinical effect. Additionally, neither gabapentin nor pregabalin should be administered with opioids as both may potentiate the euphoric effects of opioids when taken concomitantly, increasing susceptibility to abuse and a worsening respiratory and CNS depression.
  17. Dosing/Titration/Therapeutic switch of Pregabalin Dosing in diabetic peripheral neuropathy Begin at 50 mg PO three times daily and increase to 100 mg three times daily within 1 week based on efficacy and tolerability. Dosing in postherpetic neuralgia Begin at 75 mg PO twice a day or 50 mg three times daily and increase to 100mg three times daily within 1 week based on efficacy and tolerability. Dosing may be further escalated over 2–4 weeks to a maximum of 300 mg twice a day, or 200 mg three times daily. Converting to Pregabalin: Gabapentin should be discontinued over a minimum of 1 week before starting pregabalin at a dose of 50 mg three times daily.
  18. Treatment Strategy
  19. Use of a pain scale facilitates clinical evaluation of the patient's response to a therapeutic drug trial. An assessment of quality of life and activities of daily living should be incorporated into the clinical evaluation of the therapeutic drug trial. Identification of psychiatric comorbidity may suggest the use of an antidepressant for nonpain indications.
  20. Neuropathic pain A tricyclic antidepressant is the preferred initial therapy if the patient has coexisting insomnia, anxiety, or depression. (cost effective also) An antiepileptic drug (e.g., gabapentin is preferred if the patient cannot tolerate the side effects of tricyclic antidepressants, has cardiac contraindications to the use of tricyclic antidepressants (e.g., conduction abnormalities, recent cardiac event), or is a “frail elder.” Titrate the selected medication to achieve clinical effect or to the maximum tolerated dosage. With gabapentin, if no effect is seen at a dosage of 1,800 mg per day, discontinue the drug; if a partial effect occurs, titrate the drug to a dosage of 2,400 to 3,600 mg per day. Monitor response to treatment.
  21. If monotherapy is tolerated but only partially effective, combine an antidepressant with an antiepileptic drug. If monotherapy is poorly tolerated or ineffective, choose a first-line agent from a different medication class or use a second-line agent. If pain relief remains inadequate, consider use of a short-acting or long-acting opioid or tramadol.
  22. Non-neuropathic pain Exercise is the primary therapy for chronic low back pain and fibromyalgia. Begin treatment of low back pain with a nonsteroidal anti-inflammatory drug (not effective in the treatment of fibromyalgia). Consider use of a tricyclic antidepressant as a pain adjuvant to promote sleep and alleviate muscle spasm. In appropriately selected patients, consider use of a short- or long-acting opioid or tramadol. Empiric use of antiepileptic drugs such as gabapentin is not justified by the current literature but is common practice in pain clinics.
  23. Conclusion The pharmacotherapy of neuropathic pain is challenging and for many patients effective treatment is lacking. Neuropathic pain is also associated with interference with sleep, depression, and anxiety that, if not properly treated, will negatively influence the responses to analgesic drugs. When choosing a drug, consider comorbidity, prioritizing the use of those drugs that can satisfy more than one medical need, as for instance gabapentinoids in the case of interference of pain with sleep, or SNRI in the case of associated depression.
  24. Consider patients comorbidities taking are at higher risk of drug–drug interactions that may be responsible for adverse drug reactions or therapeutic failure. Since a large number of drug–drug interactions involve metabolism by the CYP enzymes, drugs which do not undergo metabolism by CYP or do not undergo liver metabolism at all, as in the case of gabapentinoids, are preferable to other drugs. This holds true in the case of combination pharmacotherapy, in which two or more analgesic drugs are co-administered when one is not enough, a therapeutic strategy that seems to have evident advantages.
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