Analgesic adjuvant explained

An analgesic adjuvant is a medication that is typically used for indications other than pain control but provides control of pain (analgesia) in some painful diseases. This is often part of multimodal analgesia, where one of the intentions is to minimize the need for opioids.[1] [2] [3]

Rationale

Multimodal analgesia refers to the use of multiple classes of medications in order to treat pain from different molecular mechanisms at once. Prolonged use of higher doses of opioids is associated with increased risk of tolerance and opioid use disorder, so there is a growing trend in the use of multimodal analgesia to treat pain.[4] [5] [6]

Types

Anticonvulsants

Anticonvulsants work through blockade of sodium and calcium ion channels to reduce glutamate (excitatory neurotransmitter) release.[7] Nociceptor hyper-excitability, due to damage to pain-transmitting neurons, results in chronic neuropathic pain. Common anticonvulsants used to treat neuropathic are gabapentinoids (calcium channel blockers) and carbamazapine (sodium channel blocker).[8] There is some evidence that anticonvulsants may also help with inflammatory pain through reduction of nociceptor hyper-excitability originally due to damage to surrounding tissue.[9]

Antidepressants

Antidepressants act (as treatment for both depression and pain) by modulating serotonin and norepinephrine neurotransmitter metabolism. Descending serotonin pathways in the spinal cord are implicated in modulation of pain perception, especially in chronic pain. Common agents used are serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs). Duloxetine, venlafaxine, and amitriptyline are all FDA-approved for chronic musculoskeletal pain, peripheral neuropathy, and fibromyalgia).[11] [12] [13]

Muscle relaxants

Over-excitation of skeletal muscle can result in spasticity (increased muscle tone) and/or muscle spasms (involuntary muscle contractions) which may contribute to pain.[14] There are several different types of muscle relaxants used for pain with different mechanisms of action. Muscle relaxants often have sedating effect that contributes to analgesia and improved relaxation. Experts disagree over whether muscle relaxants are useful for acute musculoskeletal pain.[15]

Alpha-2 adrenergic agonists

Alpha-2 adrenergic agonists such as clonidine are traditionally used to treat hypertension via inhibition of norepinephrine release.[16] Central alpha-2 adrenergic activation in the locus ceruleus and spinal cord induce sedation and pain modulation respectively. Clonidine has been shown to have some efficacy when treating both acute and chronic pain.[17]

External links

Notes and References

  1. Portenoy . Russell K. . April 2020 . A Practical Approach to Using Adjuvant Analgesics in Older Adults . Journal of the American Geriatrics Society . 68 . 4 . 691–698 . 10.1111/jgs.16340 . 1532-5415 . 32216151. 214683328 .
  2. Wheeler . Kathleen E. . Grilli . Ryan . Centofanti . John E. . Martin . Janet . Gelinas . Celine . Szumita . Paul M. . Devlin . John W. . Chanques . Gerald . Alhazzani . Waleed . Skrobik . Yoanna . Kho . Michelle E. . Nunnally . Mark E. . Gagarine . Andre . Ergan . Begum A. . Fernando . Shannon . July 2020 . Adjuvant Analgesic Use in the Critically Ill: A Systematic Review and Meta-Analysis . Critical Care Explorations . en-US . 2 . 7 . e0157 . 10.1097/CCE.0000000000000157 . 7340332 . 32696016.
  3. Hamburger . J. . Beilin . Y. . 2019-11-01 . Systemic adjunct analgesics for cesarean delivery: a narrative review . International Journal of Obstetric Anesthesia . 40 . 101–118 . 10.1016/j.ijoa.2019.06.009 . 31350096 . 198378073 . 0959-289X.
  4. Morgan . Michael M . Christie . MacDonald J . October 2011 . Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human . British Journal of Pharmacology . en . 164 . 4 . 1322–1334 . 10.1111/j.1476-5381.2011.01335.x . 0007-1188 . 3229764 . 21434879.
  5. Kaye . AlanDavid . Urman . RichardD . Rappaport . Yury . Siddaiah . Harish . Cornett . ElyseM . Belani . Kumar . Salinas . OrlandoJ . Fox . CharlesJ . 2019 . Multimodal analgesia as an essential part of enhanced recovery protocols in the ambulatory settings . Journal of Anaesthesiology Clinical Pharmacology . en . 35 . 5 . S40–S45 . 10.4103/joacp.JOACP_51_18 . 0970-9185 . 6515722 . 31142958 . free .
  6. Olmos . Andrea V. . Steen . Sasha . Boscardin . Christy K. . Chang . Joyce M. . Manahan . Genevieve . Little . Anthony R. . Lee . Man-Cheung . Liu . Linda L. . 2021-07-01 . Increasing the use of multimodal analgesia during adult surgery in a tertiary academic anaesthesia department . BMJ Open Quality . en . 10 . 3 . e001320 . 10.1136/bmjoq-2020-001320 . 2399-6641 . 34281910. 8291327 .
  7. Kammerer . M. . Rassner . M. P. . Freiman . T. M. . Feuerstein . T. J. . July 2011 . Effects of antiepileptic drugs on GABA release from rat and human neocortical synaptosomes . Naunyn-Schmiedeberg's Archives of Pharmacology . en . 384 . 1 . 47–57 . 10.1007/s00210-011-0636-8 . 0028-1298 . 21533993 . 1388805.
  8. Sidhu . Harpreet S. . Sadhotra . Akshay . 2016 . Current Status of the New Antiepileptic Drugs in Chronic Pain . Frontiers in Pharmacology . 7 . 276 . 10.3389/fphar.2016.00276 . 1663-9812 . 4996999 . 27610084 . free.
  9. Tomić . Maja . Pecikoza . Uroš . Micov . Ana . Vučković . Sonja . Stepanović-Petrović . Radica . 2018-12-01 . Antiepileptic drugs as analgesics/adjuvants in inflammatory pain: current preclinical evidence . Pharmacology & Therapeutics . 192 . 42–64 . 10.1016/j.pharmthera.2018.06.002 . 0163-7258 . 29909236 . 49291532.
  10. Web site: DailyMed - TEGRETOL- carbamazepine suspension TEGRETOL- carbamazepine tablet TEGRETOL XR- carbamazepine tablet, extended release . 2023-11-08 . dailymed.nlm.nih.gov.
  11. Web site: 2010 . Cymbalta (duloxetine hydrochloride) capsules . FDA Highlights of Drug Prescribing Information.
  12. Web site: 2017 . EFFEXOR XR® (venlafaxine Extended-Release) Capsules . FDA Highlights of Prescribing Information.
  13. Web site: Amitriptyline Hydrochloride Tablets, USP . 2023-11-08 . www.accessdata.fda.gov.
  14. Fudin . Jeffrey . Mena . Raouf . A Review of Skeletal Muscle Relaxants for Pain Management . Practical Pain Management . 11 April 2017 . 16 . 5.
  15. Schoonover . Julie . Rubin . Susan E. . March 2022 . Should Muscle Relaxants Be Used as Adjuvants in Patients With Acute Low Back Pain? . American Family Physician . en-US . 105 . 3 . 221 . 1532-0650 . 35289585.
  16. Giovannitti . Joseph A. . Thoms . Sean M. . Crawford . James J. . 2015 . Alpha-2 Adrenergic Receptor Agonists: A Review of Current Clinical Applications . Anesthesia Progress . 62 . 1 . 31–38 . 10.2344/0003-3006-62.1.31 . 0003-3006 . 4389556 . 25849473.
  17. Kumar . Anil . Maitra . Souvik . Khanna . Puneet . Baidya . Dalim Kumar . 2014 . Clonidine for management of chronic pain: A brief review of the current evidences . Saudi Journal of Anaesthesia . 8 . 1 . 92–96 . 10.4103/1658-354X.125955 . 1658-354X . 3950462 . 24665248 . free.

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