ADJUVANT ANALGESIC THERAPY

Definisi :

Obat yang fungsi awalnya bukan untuk anti nyeri, tapi jika diberikan dengan antinyeri dapat
meningkatkan kualitas pasien terhadap nyeri.

An analgesic adjuvant is a medication that is typically used for indications other than pain control

but provides control of pain in some painful diseases.

An adjuvant analgesic, or coanalgesic, is a medication that is not primarily designed to control pain but
can be used for this purpose

1. Kapan pakenya
Bisa akut dan kronik, paling sering pada kasus kronis ( kronis non cancer pain )

Chronic pain is defined by the International Association for the Study of Pain (IASP) as persistent or
recurrent pain lasting more than 3 months or beyond the normal tissue healing period. Biasa terapi
adjuvant untuk penyakit2 kronik. 5 CNCP refers to any chronic pain that is not due to a malignancy. CNCP
can be classified as neuropathic pain or nociceptive pain. 6 It is a globally encountered problem in the
healthcare field and often triggers physiological, social, and psychological responses, which may
consequently seriously harm people’s health, functioning, and well-being. 7 It is a significant health
concern with negative consequences for individuals, families, and society as a whole. Because it is a
multidimensional morbid condition with both objective and subjective characteristics, CNCP is difficult to
assess and manage in clinical practice. However, despite limited scientific evidence to suggest efficacy,
the use of opioid medication for CNCP has been increasing substantially. 8,9 Though less than 5% of the
global population,

Sumber : https://www.dovepress.com/the-modified-who-analgesic-ladder-is-it-appropriate-for-chronic-
non-ca-peer-reviewed-fulltext-article-JPR

Paling terakhir, epidural analgesic / intratekal contohnya

2. Untuk diagnosis apa aja dan jenisnya

Adjuvant analgesics tend to be less effective for musculoskeletal pain, such as back pain or joint
pain.1 However, they can work well for neuropathic pain and pain syndromes such as
fibromyalgia. They also have a role in treating cancer pain.

Unlike many other non-opioid analgesics, adjuvant analgesics are not available over the counter.

Depending on the kind of pain you have, you may be able to choose from several different types
of adjuvant analgesics. The ideal combination of medications varies greatly from one person to
the next, even among people with the same condition.

A. Antidepressants

While antidepressants are not often thought of as pain medication, some can effectively treat
chronic pain conditions.

Antidepressants are thought to control the way pain messages are sent and processed between the
spinal cord and the brain. In addition, these drugs may decrease anxiety (which is common in
some pain conditions) and help regulate sleep. Better sleep can, in turn, help lower pain levels.

ANTIDEPRESSANTS FOR CHRONIC PAIN

Condition Tricyclics SSRIs/SNRIs Atypical

Arthritis X X X  

Neuropathy  X X X
 ANTIDEPRESSANTS FOR CHRONIC PAIN

Condition Tricyclics SSRIs/SNRIs Atypical

Postherpetic neuralgia
X    
(nerve damage from shingles)

Fibromyalgia X X X

Chronic fatigue syndrome (ME/CFS) X X  

Irritable bowel syndrome (IBS) X X  

Migraine X    

Complex regional pain syndrome (CRPS) X    

Tricyclic antidepressants (TCAs) can include:

 Elavil (amitriptyline)
 Norpramin (desipramine)
 Pamelor (nortriptyline)

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake

inhibitors (SNRIs) can include:

 Cymbalta (duloxetine)
 Savella (milnacipran)
 Effexor (venlafaxine)

Some atypical antidepressants are also commonly used to treat both chronic pain syndromes
and nerve pain, such as:

 Serzone (nefazodone)
 Desyrel (trazodone)

Monoamine oxidase inhibitors (MAOIs) are not often prescribed for chronic pain because newer
drugs are considered safer, have fewer dangerous drug interactions, and don't require a restricted
diet like MAOIs do.2

B. Anticonvulsants

Anticonvulsants can also be used to treat chronic pain. Anticonvulsants work by not allowing
certain types of nerve transmissions. They can also decrease neuropathic pain, such as that
caused by trigeminal neuralgia, diabetic neuropathy, CRPS, and fibromyalgia (which may
involve small-fiber neuropathy and other types of nerve pain).
Anticonvulsants commonly used to manage chronic pain include:

 Neurontin (gabapentin): The most common adjuvant analgesic

 Lyrica (pregabalin): Similar to Neurontin, but some people respond differently to it3
 Tegretol (carbamazepine): The first-line treatment for trigeminal neuralgia
 Dilantin (phenytoin): Considered a second-line drug

C. Corticosteroids

Oral corticosteroids, also called glucocorticoids, lower pain by inhibiting some mechanisms of
inflammation and reducing blood flow to alleviate edema (fluid retention). They can also reduce
neuropathic pain by lessening signals from injured nerve. These drugs are also commonly used
for treating CRPS and cancer pain.

Side effects are more likely with long-term use, so corticosteroids are generally recommended
for short-term treatment. When they are used for long-term therapy, doctors should monitor
patients closely.

Corticosteroids are also available via injection and for topical use.

Common corticosteroids are:

 Cortone (cortisone)
 Cortef (hyrdrocortisone)
 Medrol (methylprednisolone)
 Decadron (dexamethasone)
 Deltasone (prednisone)
 Prelone (prednisolone)

D. Antispasmodics

This class of drugs is also known as muscle relaxants. They come in two forms: one to treat
smooth muscles (such as those in the gastrointestinal tract) and another to treat skeletal muscle
spasms.

Antispasmodics for smooth muscles are most often used for treating the intestinal spasms of IBS
but they can also be effective against stomach or bladder spasticity.

Smooth-muscle relaxants include:

 Bentyl (dicyclomine)
 Levsin (hyoscyamine)
 Buscopan (hyoscine butylbromide)
A growing body of research suggests that the long-time traditional remedy peppermint oil may
have antispasmotic properties that can be beneficial for people with IBS—and that it may
possibly be even better than antispasmotic drugs.5 The American College of Gastroenterology
even recommends it as a first-line treatment.6

Skeletal muscle antispasmotics are a common choice for musculoskeletal conditions, especially
if physical therapy hasn't been successful. Drugs in this class may also be used to treat spasms
associated with neurological conditions, such as:

 Cerebral palsy
 Multiple sclerosis
 Spinal cord disease

Common musculoskeletal antispasmotics include:

 Flexeril (cyclobenzaprine)
 Zanaflex (tizanidine)
 Soma (carisoprodol)

The antispasmotic/antineuralgic drug Lioresal (baclofen) is sometimes used to treat a condition

called trigeminal neuralgia that causes facial pain.

 Muscle Relaxants. Skeletal muscle relaxants are used to ‘relax muscles,’ relieve
stiffness, and decrease pain and discomfort caused by strains, sprains, or other injury to
muscles or joints. However, they do not take the place of rest, exercise, physical therapy,
or other modalities. Commonly used drugs in this class include: baclofen (Lioresal),
carisoprodol (Soma), cyclobenzaprine (Flexeril), diazepam (Valium), methocarbamol
(Robaxin), orphenadine (Norflex), metaxalone (Skelaxin), and tizanidine (Zanaflex).
They all act on the central nervous system (CNS) to produce their depressant effect. It is
important to note that, since muscle relaxants act centrally, they indiscriminately relax all
muscles and leave the injured area exposed to reinjury if used for long term. It is strongly
recommended they be used for a short-term basis only. Note that sudden cessation of the
use of baclofen has been associated with withdrawal symptoms and signs.

Tizanidine (Zanaflex) is a centrally acting agent and also is an alpha2-adrenergic agonistic that
may contribute some analgesic properties. It is used for acute low back pain, acute
musculoskeletal neck pain, and chronic tension headache. This agent has a reversible liver
toxicity and should be used with caution. Cari-sporodol (Soma) is a popular muscle relaxant with
an active byproduct metabolite, meprobamate—a barbiturate—that is potentially addictive. The
use of alprazolam (Xanax) as a muscle relaxant is not clinically warranted.
Topical Agents

Topical agents are popular adjuvant choices for neuropathic pain, arthritis, fibromyalgia, CRPS,
and other conditions that cause muscle or nerve pain. They're also used for injuries such as
sprains.

These medications are applied directly to the skin and absorbed into the bloodstream. They may
be available as creams, ointments, or patches. Both over-the-counter and prescription forms are
available.

Lidoderm (lidocaine) is a local anesthetic that works by preventing nerves from sending pain
signals to your brain.

Capsaicin cream, which is made from the "hot" component of chili peppers, is a counter-
irritant. Essentially, topicals containing capsaicin stimulate nerve endings when you put them on
your skin, and those signals interfere with your body's pain signals.

Mentholated products, which may make your skin feel hot, cold, or a combination of the two,
are counterirritants. Simply put, they purposefully irritate the skin as a means of distracting your
brain from focussing on your pain.

Common brand names include:

 Tiger Balm
 Icy Hot
 Biofreeze

More on Topical Analgesics

Other Adjuvants

Some drugs have more limited uses as adjuvant painkillers, but may be considered.

Bisphosphonates

Bisphosphonates are used for pain from CRPS and cancer that has spread to the bone. Originally
used to counter bone loss, they've also been found to have a direct impact on these types of pain.

Common bisphosphonates include high-dose Fosamax (alendronate) and the intravenous drug
Aredia (pamidronate).

Side Effects of Bisphosphonates

NMDA Receptor Antagonists

N-mthyl-D-aspartate (NMDA) receptor antagonists are injectable anesthetics that can help
alleviate pain from cancer (especially in cases where morphine is not longer effective), CRPS,
and in emergency settings.

Examples of these drugs are ketamine and dextramethorphan (a liquid form of which is used as a
cough syrup).

Botox

Botulinum toxin (Botox) injections can be used to treat muscle stiffness, spasticity, some types
of neuropathic pain, post-stroke pain, and CRPS

https://www.verywellhealth.com/what-are-adjuvant-analgesics-2564529

https://www.practicalpainmanagement.com/treatments/pharmacological/adjuvant-analgesia-
management-chronic-pain

Vitamin B complex sebagai analgesic adjuvant  degenerative spinal diseases, rheumatologic

diseases, polyneuropathies and in different postoperative situations

 Antiarrhythmics. Current research supports the use of mexiletine as an effective treatment for
neuropathic pain.41,42 In one double-blind crossover study, mexiletine not only decreased pain
but also the accompanying parasthesias and dysesthesias. 43 Another study found mexiletine
decreased pain and sleep disturbances associated with painful diabetic neuropathy. 44 This agent
is not free of side effects and should be used carefully.
 Calcium channel blockers. Verapamil is a calcium channel blocker commonly used to treat
chronic pain and has been successfully used to treat migraine and cluster headaches. 45 It is
unclear whether the mechanism of action is primarily related to cerebral artery vasodilatation or
interaction with serotonergic systems.
 Ketamine. Ketamine is an ideal anesthetic agent that works on the NMDA receptors. It can be
used to treat cancer and non-cancer pain and may be indicated for long term palliative care
situations as well. A starting dose of 150 mg/day for subcutaneous infusion or 1 mg every 12
hours intrathecally has been suggested. 46 More clinical trials are needed to justify more routine
use in the management of chronic pain. The topical form of this medication is clinically used. In
the authors’ experience, Ketamine can be used in highly opioid-dependent patients undergoing
major surgeries.
 Lidocaine. Systemic administration of lidocaine can produce sodium channel blocking activity
leading to analgesia. Pain with a more central mechanism, such as neuropathic pain and
phantom pain, seems to respond better. Low rate infusions have been used as a third or fourth
line of treatment especially in opioid–tolerant patients. Incremental rate infusions over 20 to 30
minutes can be used as a therapeutic test before starting mexiletine in patients where anti-
epileptic drugs have not been effective. 47 Cardiac monitoring is mandatory when using this
medication. The idocaine (Lidoderm) 5% patch is a transdermal method of delivery for this local
 anesthetic. Each adhesive patch contains lidocaine 700 mg (50 mg per gram adhesive) in an
aqueous base. It also contains methyparaben and propylparaben as preservatives. The patch is
applied once for up to 12 hours in a 24 hours period.
 Capsaicin. Capsaicin can be used as a topical ointment against neuropathic pain. It acts by
inhibiting substance P formation at the skin. It is effective in only 50% to 60% of patients. 48 This
agent can take up to a week to start working and the patient should be advised of this lag time.
 Tramadol. Tramadol is a synthetic analog of codeine. It binds weakly to mu-opioid receptors and
inhibits serotonin and norepinephrine reuptake. It has been used to treat restless leg syndrome.
It has less abuse and addiction potential than other opioids but seizures have been reported
with its use.
 Botulinum toxin. This drug blocks pre-synaptic release of acetylcholine. The neurotoxin type A is
used clinically while the type B is still in development. Therapeutic effects last 3-4 months and
are achieved through the sprouting of new nerve terminals.
 Miscellaneous Drugs. Certain radiopharmaceuticals (Strontium 89, Sumarium) have been used,
with success, in advanced and palliative cancer pain patients. Recent studies have also
concluded that Pamidronate (Aredia) or other bisphosphonates should be used routinely for
metastatic bone disease, especially in breast cancer.

“To the extent that emotional states can affect pain experience, interventions aimed at altering such
states—or aimed at teaching patients to alter such states—can have analgesic effects.”

Non-pharmacological Adjuvant Analgesics

To the extent that emotional states can affect pain experience, interventions aimed at altering
such states—or aimed at teaching patients to alter such states—can have analgesic effects.
Psychological therapies such as cognitive behavioral therapy, stress, anxiety, and anger
management would fall under this rubric. It is not the purpose of this paper to cover these
therapies which have been well discussed elsewhere.49 Similarly, nerve blocks used by
anesthesiologist and modalities used in physical medicine and rehabilitation are discussed in
their respective texts. Selected modalities are described in this paper because of their popularity
and to enhance and update the reader’s knowledge of these modalities.

 Electrical Stimulation. Spinal Cord Stimulation. Electrical stimulation of the spinal cord
and peripheral nerves and receptors is a direct outgrowth of the gate control theory.
Long-term electrical stimulation of the spinal cord produces substantial analgesia below
the stimulated spinal cord segments in some patients with chronic pain. It is postulated
that analgesia results from both stimulation of large ascending tracts and blockade of
spinothalamic pathways.50 This procedure has good short-term efficacy but long-term
efficacy has yet to be demonstrated. Its high cost would likely limit its use as other less
intrusive and less costly alternative management tools become available.

Transcutaneous electrical nerve stimulation (TENS). TENS has been widely used in the
management of chronic pain and is well accepted by patients and physicians. While
spinal cord stimulation is an invasive and costly procedure, TENS is less intrusive and
involves only surface stimulation. Typically, electrodes are placed on the site of the most
severe pain and moved around as needed to optimize pain relief. The use of high
frequency TENS was originally based on the gate control theory, which suggested that
 counter-stimulation of the nervous system would modify pain perception. Later studies
suggested that with low frequency, high amplitude (“acupuncture-like”) stimulation,
TENS could also raise endorphin levels in the spinal fluid.51 Despite its wide use, there is
meager evidence from controlled clinical trials of the efficacy for treating chronic pain. A
controlled trial at the Seattle Veterans Affairs Medical Center concluded that, for patients
with low back pain, TENS is no more efficacious than placebo, and does not add any
benefit to exercise alone.52

Cranial Electrical Stimulation (CES). Another form of electrical stimulation is the use of
micro-current therapy, also known as cranial electrical stimulation (CES). This procedure
has a solid history of research in its application to sleep by Russian scientists. It is
purported to have a different mechanism of action than TENS. Researchers have claimed
success in treating diverse disorders, including depression; anxiety, insomnia, and
psychosis.53 A recent review concluded that CES is highly effective in the treatment of
chronic pain.54 Efficacy for treating pain has been documented for headaches,55 as well
as intractable pain conditions not responsive to other treatments.56 It has been used to
increase potency of nitrous oxide in dental procedures,57 and to decrease narcotic
requirements during neuroleptic analgesia and surgery.58 Although a recent double-blind
controlled study, using veterans who suffer from long-term, severe, intractable pain, has
failed to support the efficacy of this procedure,59 another double-blind control study of
patients with fibromyalgia reported that three weeks of CES treatment resulted in 28%
reduction in tender point scores and a 27% reduction in self reported pain scores. The
researchers concluded that it is as effective as drug therapies.60 Thus, CES appears
promising as a non-pharmacological treatment for chronic pain in clinical practice.

 Biofeedback. Biofeedback is a procedure that has been widely used in the management
and rehabilitation of patients with chronic pain. It is the treatment of choice for Raynaud
disease. In myofascial pain syndromes, surface EMG offers an objective way of
documenting the presence of trigger points, and of re-regulating the dys-regulated
muscle. It has been widely used to treat tension and migraine headaches. EMG electrodes
are placed on the involved muscle and the patient is taught to reduce muscle contractions
thru a feedback procedure. Biofeedback for migraines involves learning to control blood
flow in the hands or the temple area as a way of impacting pain. Numerous studies have
documented improvement rates of 45-55 percent for migraines and 46-57 percent for
tension-type headaches.61 It has been used in other pain related disorders where there is a
muscle component (e.g., TMJ, back pain), a vascular component (e.g., diabetic
neuropathy), anxiety, and stress component (many pain conditions fall in this category).

 EEG Biofeedback. EEG biofeedback is a new addition and, therefore, much fewer
research studies have been done on its application and efficacy in pain management. Case
reports have accrued on its effectiveness for fibromyalgia62 and phantom limb pain.63 A
combination EMG-EEG biofeedback protocol has resulted in significant improvements in
self reported pain and associated physical and psychological symptoms among
fibromyalgia patients. One EEG biofeedback protocol—the alpha-theta protocol—trains
patients to go into a deep meditative-hypnotic state. It is well known that a deep hypnotic
or meditative state can significantly alter pain experience. To the extent that EEG reflects
 the experience of pain in the brain, this modality has potential application. The
applicability of biofeedback also extends beyond the specific focus on pain reduction.
Many chronic pain patients are depressed, angry, anxious, and exhibit other psychiatric
symptoms that, in turn, may exacerbate pain. Biofeedback can train patients to reduce
bracing of posture and improve self-regulation of body physiology that impacts pain. The
drawback is that biofeedback often requires multiple sessions and trained personnel to
administer.

 Hypnosis. Hypnotic analgesia has been widely studied.64 Although the specific
mechanism of action is still being debated, increased susceptibility to hypnotic suggestion
in a hypnotic state has been repeatedly observed and accepted as a legitimate phenomena.
Hypnotic analgesia is complex and research to date indicates that there are probably
multiple factors and mechanisms involved, including selective reduction of pain-related
affect, reductions in sensory pain, and inhibition of pain signal at the spinal level of
processing. It is beyond the scope of this paper to discuss hypnotic analgesia in detail.
The reader is referred to an excellent text entitled “Hypnosis and suggestion in the
treatment of pain” by Joseph Barber.64

 Relaxation therapy.Relaxation therapy is a systematic approach to teaching patients to

gain awareness of their physiological responses and achieve both a cognitive and a
physiological sense of tranquility without the use of machinery employed in biofeedback.
The most commonly used include progressive muscle relaxation, meditation, autogenic
training, and guided imagery. Relaxation therapy has been most widely tested with
chronic tension headaches, chronic vascular headache, and low back pain. Unlike
biofeedback and hypnosis that require specialized training, relaxation therapy can be
easily learned and taught to patients. For more information, the reader is referred to
Blanchard’s section of the text “Psychological Approaches to Pain Management.”65

Tentang NSAID

inflamasi akan menginduced asam arachidonat , membuat cox 1 dan cox 2

cox 1 hasilin tromboxan dan prostaglandin, cox 2 Cuma prostaglandin

NSAID fungsinya menghambat enzim COX 1 dan COX 2

COX 1 fungsi buat hasilin tromboxan, prostaglandin, prostasiklin  lindungin mukosa gaster
dari lingkungan yg acid ( prostaglandin dan prostasiklin ) dan agregasi platelet ( tromboxan a 2)

Contoh inhibitor cox 1 : ketorolac, aspirin

Jadi kalo pake obat2 an ini fr buat terjadi ulkus peptikum + GI bleeding, bkin risk of bleeding

Conventional NSAIDs, like diclofenac, ibuprofen, and naproxen, are non-selective COX inhibitors,
blocking the production of both physiologic and inflammatory prostaglandins.
Inhibitor cox 2 :meloxicam, diclofenac, celecoxib

Prostasiklin vs tromboxan a 2 dia dominan prostasiklin yg bisa induced vasodilatasi pembuluh

darah jantung. Kalo pake obat ini risk nya adalah infark miokard.