[2.2] Pain Meds and Joint Disorders Part 2 (Opioids until OA and RA)

Narcotic analgesics

Opium derivatives

Primary use of narcotic analgesics

Relieve intense pain and the accompanying anxiety

Classification of most narcotics

Schedule II controlled substances

Yellow prescription required

Possible effects of schedule II controlled substances

Dependence, tolerance, and addiction

Opioid vs opiate?

Opioids are synthetic

Opiates are natural

MOA of endogenous site of action of opioids

Body self-pain relieving mechanisms

Natural opioids of endogenous site

Endorphins, enkephalins, and dynorphins

MOA of exogenous site of action of opioids

Bind to specific opioid receptors in CNS

• mu (μ)

• delta (δ)

• kappa (κ)

• sigma (σ)

Mimics action of endogenous opioids

Clinical effects of μ1 receptor

Inhibit transmission of pain

Clinical effects of μ2 receptor

Respiratory depression, euphoria, constipation, physical dependence

Clinical effects of δ receptor

Inhibit transmission of pain

Clinical effects of σ receptor

Autonomic effects, dysphoria, hallucinations

List the narcotic analgesics

• Codeine

• Hydrocodone

• Hydromorphone

• Meperidine

• Methadone

• Morphine

• Oxycodone

• Propoxyphene

List the strong agonists under narcotic analgesics

• Fentanyl

• Alfentanil

• Remifentanil

• Morphine

• Meperidine (a.k.a. Pethidine)

• Methadone

• Sufentanil

List the moderate agonists under narcotic analgesics

• Propoxyphene

• Codeine

• Oxycodone

List the mixed agonist-antagonists under narcotic analgesics

• Pentazocine

• Buprenorphine

• Nalbuphine

• Butorphanol

List the antagonists under narcotic analgesics

• Naloxone

• Naltrexone

What narcotic analgesic used to be present in cough syrup?

Codeine

Codeine undergoes what process?

Glucuronidation

Codeine causes a “high” feeling due to

10% of codeine is broken down into morphine

What narcotic analgesic is 5x more potent than morphine?

Hydromorphone

Hydromorphone is available in these dosage forms:

• Oral pill and liquid

• Pills

• Parenteral preparation

Hydromorphone has ___ onset and ___ half life

rapid onset; shorter half life

Hydromorphone undergoes:

Extensive glucuronidation

What narcotic analgesic is 1.5-2x more potent than morphine?

Oxycodone

Oxycodone targets what receptor(s)?

Mu and kappa

Oxycodone has little practical difference in relieving pain with what?

Hydrocodone

Hydrocodone (Vicodin) is how many times more potent than codeine?

6x

(hence the VI in the proprietor name)

What narcotic analgesic is 80-100x more potent than morphine?

Fentanyl

Fentanyl targets what receptor(s)?

Mu and delta

Fentanyl has ___ onset and ___ half life

rapid onset; very short half life

Fentanyl is available as:

Fentanyl patch for stable pain

The onset of analgesia for fentanyl takes how many hours?

12 hours

How long does it take for fentanyl to reach maximum effect?

24 hours

What narcotic analgesic is 10x more potent than fentanyl?

Sufentanil

Sufentanil can be absorbed through the buccal/sublingual mucosa because it is:

Lipophilic

Onset of sufentanil takes

5-10 minutes

Sufentanil lasts for how long?

30 minutes

Sufentanil is excellent for what kind of pain? Provide example.

For incident or breakthrough pain

Usually taken by cancer patients or roadside incident patients

What centrally acting analgesic is taken orally and has weak opioid activity?

Tramadol

Tramadol serves as an agonist for what receptor?

Mu

TRUE or FALSE: Tramadol has been placed in controlled drug schedule.

FALSE

Unlike the other analgesics mentioned, tramadol has not been placed in controlled drug schedule.

Tramadol is usually combined with:

Paracetamol

Tramadol is used for:

Moderate to moderately severe pain

Tramadol recommended dose

50-100 mg every 4-6 hours, max. of 400 mg/day

A miscellaneous pain medication that is repeatedly applied locally to inhibit pain

Capsaicin

Topical capsaicin cream is used for:

Joint pain and tenderness in arthritis patients

What do you call drugs used primarily for conditions other than pain but can be used as analgesics?

Adjuvant pain medications or analgesic adjuncts

TRUE or FALSE: Analgesic adjuncts enhance the effects of analgesics.

TRUE

Tricyclic antidepressants can be used for:

Chronic pain complicated by depression or insomnia, or neurogenic pain

Anticonvulsants can be used for what pain? Provide examples of anticonvulsants.

Neurogenic pain

Lamotrigine, Carbamazepine

Corticosteroids can be used for what pain?

Pain associated with bony metastases

Neuroleptics can be used for what pain?

Pain complicated by delirium or nausea

Antihistamines can be used for what pain?

Pain complicated by anxiety or nausea

Examples of topical anesthetics

• EMLA

• Tetracaine

• Lidocaine

• Betacaine

• Lignocaine

Calcitonin can be used for what pain?

For osteoporotic back pain and neuropathic pain

Calcitonin analgesic MOA

Mediated by restoration of serotonin receptors that control selective glutamate release from C-afferent fibers

Bisphosphonates are the Standard of Care (SOC) for what condition?

Skeletal events associated with bone metastases

Examples of bisphosphonates

• Pamidronate IV

• Zoledronic Acid IV

(Remember: ‘dron’ = bisphosphonates)

Bisphosphonates MOA

Stimulate osteoclast apoptosis

Inhibit cholesterol synthesis pathway to:

• ↓ bone resorption

• ↑ bone density

Benzodiazepines are used for what kind of pain?

Pain complicated by anxiety or muscle spasms

TRUE or FALSE: Rheumatoid arthritis is characterized as an immune-mediated, chronic and progressive inflammatory disease.

TRUE

TRUE or FALSE: Rheumatoid arthritis occurs more frequently in men than in women.

FALSE

Occurs more frequently in women

Rheumatoid arthritis involves what types of joints?

Symmetric joints and smaller joints

TRUE or FALSE: Rayuma and rheumatoid arthritis (RA) are equivalent terms.

FALSE

Rayuma is a general term for joint pain or body aches.

RA is a specific immune-mediated inflammatory disease.

Outline the general pathogenesis of RA

1. Synovial inflammation

2. Macrophage activation

3. MMP and RANK ligand production

4. Joint destruction

How does synovial inflammation in RA occur?

An unknown trigger initiates the process

Leukocytes are recruited to the site of inflammation (synovial tissue)

How does macrophage activation in RA occur?

Autoimmune response by CD4 T cells activate macrophages

They then produce pro-inflammatory cytokines

B cells differentiate into plasma cells → antibody production

Immune complexes containing the antibodies interact with macrophages → activation (positive feedback)

How does MMP and RANK ligand production in RA occur?

Pro-inflammatory cytokines produced in Step 2 are:

• IL-1

• IL-6

• IL-17

• TNF-𝛼

They induce production of matrix metalloproteinases (MMP) and RANK ligand (RANKL) by fibroblasts

How does joint destruction in RA occur?

MMP → cartilage degradation

RANKL → osteoclast differentiation and activation

Differentiate osteoarthritis (OA) and rheumatoid arthritis (RA) in terms of cause

OA happens due to wear and tear of joints over time

RA is an autoimmune disorder that attacks joints

Differentiate OA and RA in terms of onset

OA happens gradually

RA can occur gradually or suddenly

TRUE or FALSE: OA affects joints asymmetrically while RA affects joints symmetrically.

TRUE

In OA, one side is more affected

In RA, both sides are equally affected.

List the joints commonly affected in OA

• Knees

• Hips

• Spine

• Hands

List the joints commonly affected in RA

• Hands

• Wrists

• Feet

• Knees

Fill in the blanks: With rest,

OA ___ [worsens/improves]

RA ___ [worsens/improves]

OA improves

RA worsens

Fill in the blanks: With activity,

OA ___ [worsens/improves]

RA ___ [worsens/improves]

OA worsens

RA improves