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What are analgesic adjunctive agents?

Pharmacological agents which are useful in the management of pain but are not classified as analgesics
--can be used as monotherapy or in combination with non-opioids and opioids


The analgesic adjunctive agents include antidepressants, anticonvulsants, glucocorticoids and other drugs. Antidepresseants and anticonvulsants are the mainstay of treatment for a variety of neuropathic pain. First lets discuss the antidepressants, what are some features?

Serotonin and NE mediate descending inhibition of ascending pain pathways in the brain and spinal cord
--TCAs and SNRIs are used because they enhance both serotonin and NE transmission
SSRIs that enhance only serotonergic transmission are less effective analgesics


Lets discuss a little on the TCAs (tricyclic antidepressants), first off what are they?

(Again these are all SNRIs)


What types of pain can TCAs relieve?

Neuropathic pain including:
--diabetic, postherpetic, polyneuropathy, or nerve injury or fibromyalgia


What are the adverse effects of TCAs?

Constipation, Dry mouth, blurred vision, cognitive changes, tachycardia, urinary hesistation
---all associated with anticholinergic activity
Desipramine and Nortriptyline have fewer anticholinergic and sedative effects (so give to old ppl)


What are the warnings, precautions, and contraindications?

1. Angle-closure glaucoma
2. BPH
3. Urinary retention
4. Constipation
5. CVS (2nd or 3rd degree heart block, arrhythmias)
6. Impaired liver function


In addition to TCAs what are other SNRIs?

Venlafaxine and Duloxetine
--lack potent antihistamine, alpha adrenergic blocking, and anticholinergic effects
--used for several types of neuropathic pain
--better tolerated then TCAs


What are adverse effects of Venlafaxine and Duloxetine (SNRIs)?

Sexual Dysfunction


Moving on to the Anticonvulsants, what are they?

---useful in management of neuropathic pain


First up in the anticonvulsants is Gabapentin and Pregabalin, what are some features?

Gabapentin: postherpetic neuralgia
Pregabalin: neuropathic pain associated with postherpetic neuraligia, diabetic neuropathy and fibromyalgia
---block voltage gated calcium channels (this reduces release of glutamate, NE and substance P)
Adverse Effects:
--Dizziness, Somnolence and Peripheral Edema


Finally Carbamazepine is the third anticonvulsant, what are some features?

Drug of choice for trigeminal neuralgia
--Blockage of voltage gated sodium channels (located in sensory neurons)
Adverse Effects:
--drowsiness, dizziness, nausea, vomiting
--leukopenia but is benign
--aplastic anemia is rare


Next drugs up that can be used as analgesic adjunctive agents are the glucocorticoids. What are some features?

Used in advanced illness
---acute nerve compression, ICP, bone pain, visceral pain, anorexia, nausea and depressed mood
Dexamethasone is the drug of choice: minimal mineralocorticoid effect
(prednisone and methylprednisolone can also be used)


Finally what are the other drugs that can be used as analgesic adjunctive agents?

1. Hydroxyzine: postoperative and cancer pain
2. Clonidine: improve pain and hyperalgesia in sympathetically maintained pain
3. Lidocaine: tx of posterherpatic neuralgia
4. Capsaicin: postherpetic neuralgia
5. Caffeine: enhance analgesic effect of acetaminophen and NSAIDs.

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