Opioids in practice

Question 1

What is the pathophysiology of chronic pain?

Answer 1

Physical Component
Psychological Component
Environmental Component
Sensitisation
-Allodynia
-Hyperalgesia

Question 2

Opioid classifications

Answer 2

Naturally occuring compounds
Semi-synthetic compounds
Synthetic compounds

Question 3

Naturally occuring compound opioids

Answer 3

Morphine
Codeine
Thebaine
Papaverine

Question 4

Semi - synthetic compound opioids

Answer 4

Diamorphine
Dihydromorphine
Buprenorphine
Oxycodone

Question 5

Synthetic compound opioid

Answer 5

Pethidine
Fentanyl
Methadone
Alfentanil
Remifentanil

Question 6

What is the mechanism of action of opioids?

Answer 6

There are three opioid receptors, MOR (µ), KOR(κ) and DOR(δ).
Opioid receptors are distributed throughout the central nervous system, to a lesser extent in the periphery, and also occupying sites within the vas deferens, knee joint, gastrointestinal tract, heart and immune system.
The presynaptic action of opioids inhibiting neurotransmitter release is considered to be their major effect in the nervous system.

Question 7

What are the positive effects of opioids?

Answer 7

We reviewed 26 studies with 27 treatment groups that enrolled a total of 4893 participants.
Opioids were administered orally, transdermally or intrathecally.
All three modes of administration were associated with clinically significant reductions in pain, but the amount of pain relief varied among studies.

Question 8

Guidance on prescribing opioids

Answer 8

Chou et al. concluded that the ‘Evidence is insufficient to determine the effectiveness of long-term opioid therapy for improving chronic pain and function. Evidence supports a dose-dependent risk for serious harms.’

Question 9

Gastrointestinal system effects of opioids

Answer 9

The pathophysiology of this process results from stimulation of κ and μ opioid receptors in the gastrointestinal tract. Multiple studies report that 40%–45% of patients on opiate therapy experience constipation, while 25% experience nausea.

Question 10

Respiratory effects of opioid use

Answer 10

Chronic opiate use has been shown to be associated with multiple features of sleep-disordered breathing, including central sleep apnea, ataxic breathing, hypoxemia, and carbon dioxide retention. Among patients on around-the-clock opioid therapy for at least 6 months, the prevalence of sleep-disordered breathing (ranging from mild to severe central and/or obstructive apnea) has been found to be as high as 75%.

Question 11

Cardiovascular system effects

Answer 11

This is area requires further research but patients with arthritis found that when opioid therapy was compared with NSAIDs and selective cyclooxygenase-2 (COX-2) inhibitors, opioid therapy was associated with a 77% increased risk of cardiovascular events (eg, myocardial infarction, heart failure).

Question 12

CNS system effects of opioids

Answer 12

Dizziness and sedation are also central nervous system effects that can lead to unintended consequences among those receiving long-term opioid therapy, such as falls, fractures, and respiratory depression.
Hyperalgesia associated with excessive sensitivity to pain has been reported in patients on chronic opioid therapy.

Question 13

MSK system effects

Answer 13

Recent meta-analyses have reported a relative risk of fractures of around 1.4 for elderly patients on opiate therapy.
Recent studies have found that doses of propoxyphene and morphine over 50 mg doubled the risk of fractures in the elderly, with an annual fracture rate of 9.95%.
While the primary mechanism of this increased risk is poorly understood, the prevailing theory is that opiate use leads to an increased risk of falls through its central nervous system effects such as dizziness and reduced alertness.

Question 14

Negative effects of opioids

Answer 14

The mechanism of these effects is believed to occur through opiate interaction with the hypothalamic-pituitary-adrenal axis in humans. Opiates have been shown to affect the release of every hormone from the anterior pituitary including growth hormone, prolactin, thyroid-stimulating hormone, adrenocorticotropic hormone, and lutein-stimulating hormone.
……decrease in gonadotropin-releasing hormone can manifest clinically in males as hypogonadism, also known as opiate-induced androgen deficiency, sexual dysfunction, infertility, fatigue, and decreased levels of testosterone. The decrease in testosterone is of special concern because preliminary studies have suggested increased risk of metabolic syndrome and insulin resistance.
…..decreased pulsatile release of gonadotropin-releasing hormone and subsequent decrease in luteinizing and follicle-stimulating hormones may have dramatic clinical consequences in women as well. Decreased circulating levels of estrogen, low follicle-stimulating hormone, and increased prolactin can lead to osteoporosis, oligomenorrhea, and galactorrhea.

Question 15

Immune system effects of opioids

Answer 15

It is believed that these opioids directly affect the μ-opioid receptor on all immune cells. They may also modulate the immune function indirectly through glucocorticoids released by the hypothalamic-pituitary-adrenal axis and norepinephrine released by the sympathetic nervous system. Recent literature has shown an increase in pneumonia in elderly patients on chronic opioid therapy.

Question 16

Addiction and misuse of opioids

Answer 16

Opioid dependence and misuse includes a range of drug-taking behaviors such as increasing dose without prescription, obtaining additional opioids from other doctors, purposeful sedation, use for purposes other than pain relief, and hoarding pain medications.
Current literature remains inconclusive on the overall risk of opioid addiction; however, opioid misuse has been found to be relatively common in a thorough study of general practice patients. With this finding in mind, it has been found that long-term opioid treatment is associated with an 87% increase in all-cause mortality.[2]
the 2-year risk of opioid-related mortality among those prescribed 200 to 400 mg/d of morphine (or equivalent) was 0.8%, and the risk among those prescribed more than 400 mg/d of morphine (or equivalent) was 1.0%. Although these absolute risks may seem small, it bears reiterating that the outcome is mortality, and preventing any number of avoidable deaths should be a major public health priority.[3].

Question 17

Guidance on prescribing opioids

Answer 17

Key points for strong opioids The following key points should be noted with regards to prescription of strong opioids.
It is crucial that the potential benefits and potential risks are discussed with the patient.
Side effects resulting from continuing use of opioids may include tolerance, withdrawal, weight gain, reduced fertility and irregular periods, erectile dysfunction, hyperalgesia, depression, dependence, addiction, reduced immunity, osteoporosis and constipation.
There is a variety of evidence regarding misuse of these medicines and this should be considered particularly when prescribing to at risk patients.

Question 18

Treating non-pharmacological chronic pain

Answer 18

Physical: Weight loss, smoking cessation, exercise – stretching, physiotherapy, yoga, pilates, joint injections.
Psychological: Counselling, CBT, music, meditation, relaxation.
Complementary Therapy: Massage, reflexology.
Occupational: Work place based review.

Question 19

Pharmacological treating chronic pain

Answer 19

Non Opioid Analgesics: NSAIDs, Cox- 2 inhibitors, paracetamol.

Opioid Analgesics: Intermittent usage / slow and low.

Adjuvant Analgesics: Anti-convulsants, antidepressants, lidocaine patches.

Question 20

What are the signs of abuse and dependency

Answer 20

Use of pain medications other than for pain treatment
Impaired control (of self or of medication use)
Compulsive use of medication
Continued use of medication despite harm (or lack of benefit)
Craving or escalation of medication use
Selling or altering prescriptions
Stealing or diverting medications
Calls for early refills / losing prescriptions
Reluctance to try nonpharmacologic interventions.

Question 21

Key associations with opioid dependency

Answer 21

Gender : No statistically significant association.
Age : High in younger and then decreases with age increases.
Marital Status : Highest in those cohabiting but not married.
Education : Not statistically significant.
Employment : Highest dependency in the unemployed.
Ethnicity : Highest rates in non white population.
General Health : Very bad health has a strong association.
Alcohol : No significant association
Smoking : Association between smokers and never smoked.
Internet Pharmacy : High association between buying on the internet and dependency.