Pharmacotherapy adjuvant analgesics /certified fixed orthodontic courses by Indian dental academy
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Pharmacotherapy adjuvant analgesics /certified fixed orthodontic courses by Indian dental academy
- 1. Pharmacotherapy of Pain: Adjuvant Analgesics INDIAN DENTAL ACADEMY Leader in continuing dental education www.indiandentalacademy.com
- 2. Adjuvant Analgesics • Defined as drugs with other indications that may be analgesic in specific circumstances • Numerous drugs in diverse classes • Sequential trials are often needed
- 3. Adjuvant Analgesics • • • • • Multipurpose analgesics Drugs used for neuropathic pain Drugs used for musculoskeletal pain Drugs used for cancer pain Drugs used for headache
- 4. Multipurpose Adjuvant Analgesics Class Examples Antidepressants amitriptyline, desipramine, nortriptyline, paroxetine, venlafaxine, citalopram, others Alpha-2 adrenergic agonists tizanidine, clonidine Corticosteroids prednisone, dexamethasone
- 5. Multipurpose Adjuvant Analgesics Antidepressants • Best evidence: 30 amine TCAs (eg, amitriptyline) • 20 amine TCAs (desipramine, nortriptyline) better • tolerated and also analgesic Some evidence for SSRI/SSNRIs/atypical antidepressants (eg, paroxetine, venlafaxine, maprotiline, bupropion, others) and these are better tolerated yet
- 6. Multipurpose Adjuvant Analgesics Alpha-2 adrenergic agonists • Clonidine and tizanidine used for chronic pain of • • any type Tizanidine usually better tolerated Tizanidine starting dose 1–2 mg/d; usual maximum dose up to 40 mg/d
- 7. Adjuvant Analgesics for Neuropathic Pain Class Examples Anticonvulsants gabapentin, valproate, phenytoin, carbamazepine, clonazepam, topiramate, lamotrigine, tiagabine, oxcarbazepine, zonisamide, levetiracetam Local anesthetics mexiletine, tocainide
- 8. Adjuvant Analgesics for Neuropathic Pain Class Examples NMDA receptor dextromethorphan, ketamine Antagonists amantadine Miscellaneous baclofen, calcitonin Topical lidocaine, lidocaine/prilocaine, capsaicin, NSAIDs
- 9. Adjuvant Analgesics for Neuropathic Pain Anticonvulsants • Gabapentin commonly used – Favorable safety profile and positive RCTs in PHN/diabetic neuropathy – Usual effective dose: 600–3600 mg/d and sometimes higher • Analgesic effects established for phenytoin, • carbamazepine, valproate, clonazepam, and lamotrigine Limited experience with other drugs
- 10. Adjuvant Analgesics for Neuropathic Pain • Local anesthetics • Oral therapy with mexiletine, tocainide, flecainide • IV/SQ lidocaine also useful • Useful for any type of neuropathic pain
- 11. Adjuvant Analgesics for Neuropathic Pain Miscellaneous drugs • Calcitonin – RCTs in CRPS and phantom pain – Limited experience • Baclofen – RCT in trigeminal neuralgia – 30–200 mg/d or higher – Taper before discontinuation
- 12. Adjuvant Analgesics for Neuropathic Pain NMDA-receptor antagonists • N-methyl-D-aspartate receptor involved in • neuropathic pain Commercially-available drugs are analgesic: ketamine, dextromethorpan, amantadine
- 13. Topical Adjuvant Analgesics • Used for neuropathic pain – Local anesthetics • Lidocaine patch • Cream, eg, lidocaine 5%, EMLA • Capsaicin • Used for musculoskeletal pains • NSAIDs
- 14. Adjuvant Analgesics for Musculoskeletal Pain “Muscle relaxants” • Refers to numerous drugs, eg, cyclobenzaprine, carisoprodol, orphenadrine, methocarbamol, chlorzoxazone, metaxalone • Centrally-acting analgesics • Do not relax skeletal muscle
- 15. Adjuvant Analgesics for Chronic Headache • • • • • • • Beta blockers Anticonvulsants Calcium channel blockers Alpha-2 adrenergic agonists Antidepressants Vasoactive drugs ACE inhibitors
- 16. Adjuvant Analgesics for Cancer Pain • For bone pain – Bisphosphonates (eg, pamidronate, clodronate), calcitonin, radiopharmaceuticals (eg, Sr89, Sm153) • For bowel obstruction pain – Anticholinergics, octreotide
- 17. Adjuvant Analgesics With Opioid Interactions • NMDA antagonists (eg, dextromethorphan, ketamine, amantadine) • Cholecystokinin-B antagonists (eg, proglumide) • Ultra-low doses of opioid antagonists
- 18. Thank you For more details please visit www.indiandentalacademy.com
Notas do Editor
- The adjuvant analgesic drugs include many drugs in diverse classes. All of these drugs are available for indications other than analgesia, but they may be analgesic in select circumstances. The term “adjuvant” applies in the management of pain associated with advanced medical illness, in which case they are typically added to an opioid regimen. Overall, the term is a misnomer because these drugs now are commonly used as primary analgesics in many painful disorders.
- Based on clinical observations, the adjuvant analgesics can be divided into a group that would be appropriate to consider for any type of pain, a group used generally for neuropathic pain, a group used for musculoskeletal pains, a group used for cancer pain, and a group used for headache prophylaxis.
- Several classes of drugs have analgesic effects established in diverse pain syndromes and, on this basis, may be considered nonspecific analgesics. The antidepressants and the alpha-2 adrenergic agonists may be considered in this context. Corticosteroids probably are nonspecific analgesics also, but they are generally reserved for select patients because of their long-term toxicity.
- Extensive evidence demonstrates the analgesic efficacy of antidepressant drugs. Evidence is best for the tricyclic drugs, but some of the newer drugs have been studied, may be analgesic, and are better tolerated.
- Alpha-2 adrenergic agonists appear to have analgesic potential in all types of chronic pain. Tizanidine is available commercially as an antispasticity agent and may be better tolerated. For both tizanidine and clonidine, initial doses should be low, and the dose should be slowly titrated to judge analgesic effects.
- In addition to the antidepressants and alpha-2 adrenergic agonists, a variety of other drug classes have been used for neuropathic pain. These include anticonvulsants, local anesthetics, and others.
- Other drugs for neuropathic pain include the NMDA receptor antagonists and a variety of topical agents.
- Anticonvulsants may be used to treat all types of neuropathic pain. Experience with gabapentin is extensive and favorable. Many other drugs with diverse mechanisms also are used. Patients with refractory neuropathic pain are candidates for sequential trials of these drugs, as an effort is made to identify the most favorable one.
- Systemic local anesthetics can have an analgesic effect on all types of neuropathic pain. Both oral therapy and brief infusions of parenteral anesthetics have been used for pain.
- Calcitonin, usually tried via the intranasal route, has been demonstrated to be analgesic in small studies of patients with complex regional pain syndrome (reflex sympathetic dystrophy) and acute phantom pain. On this basis, a trial may be indicated in refractory neuropathic pain. Baclofen is established as an analgesic for trigeminal neuralgia and also is tried for other types of neuropathic pain. The effective dose range is very broad. The potential for seizures upon drug withdrawal mandates dose tapering prior to discontinuation.
- The NMDA receptor is involved in mechanisms responsible for some types of neuropathic pain. The NMDA antagonists are analgesic, but the extent of these favorable effects has yet to be defined and clinical utility has been limited by the lack of adequate formulations and toxicity. These drugs usually are considered for very refractory cases.
- Topical analgesics are less likely than systemic analgesics to produce side effects and should be considered in a variety of painful disorders. A lidocaine impregnated patch is approved in the United States for treatment of postherpetic neuralgia and, like local anesthetic creams, can be used for neuropathic pain of diverse types. A eutectic mixture of lidocaine and prilocaine penetrates the epidermis and can produce dense cutaneous anesthesia. Topical capsaicin continues to be tried for both neuropathic and musculoskeletal pains, notwithstanding mixed results in clinical trials. Topical NSAIDs may have analgesic effects in arthritic and musculoskeletal pains.
- Numerous compounds have been studied in acute musculoskeletal pain syndromes, such as acute low back pain, and have been found to be analgesic. These drugs are centrally-acting analgesics; their analgesic mode of action is unknown. They do not relax skeletal muscle in the clinical setting. For more information, please see Myofascial Pain.
- A large number of adjuvant analgesics are used in the prophylaxis of frequent vascular headache or in the management of chronic daily headache syndrome. In addition to the NSAIDs and opioids, beta blockers (eg, propranolol), anticonvulsants (eg, valproate, gabapentin), calcium channel blockers (eg, verapamil), alpha-2 adrenergic agonists (eg, tizanidine), antidepressants (eg, amitriptyline), vasoactive drugs (isometheptene) and angiotensin-converting-enzyme inhibitors (eg, lisinopril) may be tried. For more information, please see Headache.
- Adjuvant analgesics may be extremely useful in the management of some cancer pain syndromes. The multipurpose drugs and the drugs used for neuropathic pain often are used. Osteoclast inhibitors, including the bisphosphonates and calcitonin, and several radiopharmaceuticals may be helpful for multifocal bone pain. Anticholinergic drugs, such as scopolamine, and the somatostatin analogue, octreotide, are used for pain related to bowel obstruction.
- NMDA receptors are important in the central mechanisms of hyperalgesia and chronic pain. Ketamine and oral dextromethorphan are NMDA antagonists that may be used in conjunction with opioids to manage severe neuropathic states. Methadone, a pure opioid agonist, has an intrinsic NMDA antagonistic action, which may add an adjuvant effect for neuropathic pain to the opioid analgesia. Cholecystokinin (CCK), a major neuropeptide in the CNS, has a role in both endogenous and exogenous pain transmission. CCK-B antagonists, such as proglumide, have been evaluated in clinical trials as adjuncts to opioid therapy in patients with chronic pain. Thus far, results pertaining to efficacy in these trials have been conflicting. Ultra-low dose opioid antagonists appear to potentiate opioid effects and reverse opioid tolerance. They also are being investigated for clinical use.