Analgesic Adjunctive Agents (Coanalgesics)

Question 1

What are analgesic adjunctive agents?

Answer 1

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

Question 2

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?

Answer 2

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

Question 3

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

Answer 3

Imipramine
Amitriptyline 
Desipramine 
Nortriptyline 
(Again these are all SNRIs)

Question 4

What types of pain can TCAs relieve?

Answer 4

Neuropathic pain including:

–diabetic, postherpetic, polyneuropathy, or nerve injury or fibromyalgia

Question 5

What are the adverse effects of TCAs?

Answer 5

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)

Question 6

What are the warnings, precautions, and contraindications?

Answer 6

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

Question 7

In addition to TCAs what are other SNRIs?

Answer 7

Venlafaxine and Duloxetine

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

Question 8

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

Answer 8

Nausea
Sexual Dysfunction
Somnolence

Question 9

Moving on to the Anticonvulsants, what are they?

Answer 9

Gabapentin
Pregabalin
Carbamazepine
—useful in management of neuropathic pain

Question 10

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

Answer 10

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

Question 11

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

Answer 11

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

Question 12

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

Answer 12

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)

Question 13

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

Answer 13

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.