Recommendations and guidelines for the use of drugs in the management of cancer pain
Issue of opioid availability
Essential analgesic drug list
Pearls of wisdom
Case report
Reference list
Up to 70% of cancer patients suffer from pain.
Up to 70% of cancer patients suffer from pain.
Most patients can obtain sufficient pain relief with oral analgesics.
Use alternative methods for drugs administration (e.g. intravenous or subcutaneous) only when oral administration is not possible.
Use the Pain Relief Ladder of the World Health Organization (WHO) as a guideline for the use of drugs in the management of pain.
Cancer pain may include different qualities, locations and intensities depending on the type and stage of the cancer.
Cancer pain may include different qualities, locations and intensities depending on the type and stage of the cancer.
The dosage of drugs might require frequent changes during treatment due to progression of the tumour or to side effects.
In the case of new symptoms and pain you should always think of a reasonable alternative and symptomatic treatment.
Pain intensity is influenced not only by somatic findings but also by psychological factors such as fear, depression, sleeplessness
Pain intensity is influenced not only by somatic findings but also by psychological factors such as fear, depression, sleeplessness
In this case you often can reduce analgesics by “treating” the psychosocial factors.
Talk about the problems with your patient and his family.
James Window is a 59 year old policeman, suffering from prostate cancer since 2009. Following surgery, he went into remission for 2 years and continued with his work. However, he then experienced back pain and after undergoing tests, metastases were detected in his spine. He underwent radiotherapy and received ibuprofen 2 x 600mg/day, resulting in reduction of pain for about 3 months.
James Window is a 59 year old policeman, suffering from prostate cancer since 2009. Following surgery, he went into remission for 2 years and continued with his work. However, he then experienced back pain and after undergoing tests, metastases were detected in his spine. He underwent radiotherapy and received ibuprofen 2 x 600mg/day, resulting in reduction of pain for about 3 months.
The local pain increased despite taking more ibuprofen?. As a result, James‘s physician prescribed, tramadol, a low-efficacy opioid. He was started on the lowest dosage of 2 x 50mg/day, with an extended-release formulation. After a short time, the dose was increased to 2 x 100mg and then to 2 x 150mg. At this point, the pain decreased to a tolerable level without side effects.
The local pain increased despite taking more ibuprofen?. As a result, James‘s physician prescribed, tramadol, a low-efficacy opioid. He was started on the lowest dosage of 2 x 50mg/day, with an extended-release formulation. After a short time, the dose was increased to 2 x 100mg and then to 2 x 150mg. At this point, the pain decreased to a tolerable level without side effects.
At this stage, his physician decided to change the treatment to morphine. He started with a dose of 2 x 30mg morphine using an extended-release formula and 10mg morphine with an immediate-release (IR) formula in the event of „break-through pain“. After 3 days of treatment using this regimen, the physician counted the number of IR tablets that James used (6-7 a day) and converted the dose to the extended-release formula. The dosage of morphine prescribed to Richard was then 2 x 100mg / day. w/o leaving the option for IR MO?
At this stage, his physician decided to change the treatment to morphine. He started with a dose of 2 x 30mg morphine using an extended-release formula and 10mg morphine with an immediate-release (IR) formula in the event of „break-through pain“. After 3 days of treatment using this regimen, the physician counted the number of IR tablets that James used (6-7 a day) and converted the dose to the extended-release formula. The dosage of morphine prescribed to Richard was then 2 x 100mg / day. w/o leaving the option for IR MO?
constipation, reduction of the gastrointestinal motility
constipation, reduction of the gastrointestinal motility
nausea, vomiting,
sedation, dizziness
cognitive impairment
respiratory depression, antitussive effects
pruritus
muscle rigidity, urinary retention
Don‘t be afraid of opioid dependency when treating cancer pain
Don‘t be afraid of opioid dependency when treating cancer pain
addiction is exceedingly rare during long-term opioid treatment of cancer pain.
Under-treatment of pain may lead to drug-seeking behavior by the patient (=pseudo-addiction).
Don‘t be afraid of respiratory depression – patients receiving long-term opioid therapy generally develop tolerance to the respiratory-depressant effects of opioids.
Don‘t be afraid of respiratory depression – patients receiving long-term opioid therapy generally develop tolerance to the respiratory-depressant effects of opioids.
Side effects – except for constipation – decrease during prolonged and regular administraiton of opioids.
Opioid-induced-constipation requires that you combine a laxative in nearly all patients treated with an opioid.
How to use opioids in cancer pain?
How to use opioids in cancer pain?
Prefer the extended-release/prolonged-release formulations of oral opioids: onset within 30 - 60 minutes, duration 8 - 12 hours
Treat breakthrough pain with immediate-release formulations: onset within 30 minutes, duration 4 - 6 hours (prescribe 1/5 of the daily opioid dose)
The combination of opioids and non-opioids helps to reduce the dosage and the side effects of the single drug
Tramadol belongs to step II of the WHO ladder, it binds not only to opioid receptors but also to norepinephrone and serotonin reuptake inhibitors
Tramadol belongs to step II of the WHO ladder, it binds not only to opioid receptors but also to norepinephrone and serotonin reuptake inhibitors
It has 0.2 times the analgesic potency of morphine
Decrease the dosage in case of renal or hepatic impairment because of the risk of accumulation and respiratory depression
Morphine is a strong µ-opioid agonist and belongs to step III of the WHO ladder
Morphine is a strong µ-opioid agonist and belongs to step III of the WHO ladder
Commonly used as reference for all other opioids
It can be applied by all routes of administration
The active metabolites accumulate in case of renal impairment and can increase side effects
There are extended- (10, 20, 30, 60, 100, 200mg) and immediate-release (10mg, 20mg) formulations.
Hydromorphone is also a strong µ-opioid agonist
Hydromorphone is also a strong µ-opioid agonist
It has about a 4 - 5 times the analgesic potency of morphine, with a 12h duration of effect
It has an oral and parenteral formulation for s.c., i.m. or i.v. application, an extended- (4mg, 8mg, 12mg 16mg 24mg capsules) and immediate-release formulations (1.3mg, 2.6mg capsules)
Has a low plasma protein binding and therefore, a possibly lower risk of interaction with other drugs
Oxycodone: with 2 times the analgetic potency of morphine and a 8 - 12h duration
Oxycodone: with 2 times the analgetic potency of morphine and a 8 - 12h duration
High oral bioavailability of 60-80%
It is available as an oral extended- (10mg, 20mg, 40mg, 80mg) and immediate-release formula (Oxycodone 5mg, 10mg, 20mg capsules buccal or sublingual) or Oxycodone iv 10mg, 20mg
There is a fixed formula with naloxone to reduce the risk for drug induced constipation (Targin)
Fentanyl: has 80-100 times the analgetic potency of morphine, it is metabolized in the liver, has a rapid onset and a short duration
Fentanyl: has 80-100 times the analgetic potency of morphine, it is metabolized in the liver, has a rapid onset and a short duration
It mainly exists as a parenteral formula but a transdermal application (Fentanyl patches with 12, 25, 50, 75, 100µg/h, change of the patches every 72 hours) is also widely used
For breakthrough pain there are nasal buccal or transmucosal formula (100, 200, 400, 600, 800, 1200, 1600µg)
Oral, rectal
Oral, rectal
Nasal, sublingual, buccal
Transdermal as a patch
Intramuscular via intermittent injection (NOT recommended particularily when long term treatment is planned!)
Subcutaneous - intermittent injections or continuous infusion
Intravenous - intermittent injections or continuous infusion
Spinal epidural
Spinal intrathecal
Richard‘s disease progressed and with it the intensity of his pain and onset of a new type of pain: burning pain which did not respond to the morphine. Also he got a sensitive deficit perineal because of an infiltration of the Pudendal nerve??
Richard‘s disease progressed and with it the intensity of his pain and onset of a new type of pain: burning pain which did not respond to the morphine. Also he got a sensitive deficit perineal because of an infiltration of the Pudendal nerve??
Richard‘s physician prescribed dexamethason 12 mg and gabapentine 3 x 300mg (starting with x mg and increaseing in 100mg steps). As a result, the pain decreased again.
This pain results from a damage to afferent neurons and altered pain transmission and processing in the spinal cord and brain
This pain results from a damage to afferent neurons and altered pain transmission and processing in the spinal cord and brain
Pain characteristics and sensations are different
Neuropathic pain can be difficult to treat, often you need more than opioids: anticonvulsants, antidepressants
Examples for neuropathic pain in cancer pain: neuropathy after chemotherapy or radiotherapy, compression of nerves by the tumor or metastases
The patient‘s description of the pain quality: lancinating, burning, pricking, tender, numb, throbbing, nagging, hot
The patient‘s description of the pain quality: lancinating, burning, pricking, tender, numb, throbbing, nagging, hot
The pain projection and and pain radiation along a course of nerves with segmental or peripheral distribution, a glove-like distribution or attributed to a dermatome
Paresis or muscular weakness and pain in the extremities in the case of a plexopathy
By careful neurological examination:
By careful neurological examination:
Look for somatosensory abnormalities such as dysaesthesias, hyperalgesia, hypaesthesia, dynamic or thermal allodynia
Look for paresis or muskular weakness and pain
For examination use a stub-point needle, a warm or cold spoon, a cottonwool tip
Most commonly used anticonvulsants are gabapentin, pregabalin and carbamazepine
Most commonly used anticonvulsants are gabapentin, pregabalin and carbamazepine
Most commonly used antidepressant: amitriptyline, doxepin
They act as sodium and calcium channel blockers of the neuronal cells
Because of possible side-effects of the central nervous system carefully raise the dosage: „start low, go slow“!
Carbamazepine: initial dose 2 x 100mg/day up to 2 x 800mg/day
Carbamazepine: initial dose 2 x 100mg/day up to 2 x 800mg/day
Gabapentin: initial dose 3 x 100mg/day up to 3 x 800mg/day
Amitriptyline/Doxepin: initial dose 1 x 25mg in the evening up to 1 x 75mg
Possible side effects: constipation, dry mouth, drowsiness, sedation, arrhythmias, induction and elevation of liver enzymes, edema
Corticosteroids such as dexamethason can reduce pain due to nerve structure compression or edema of metastases
Corticosteroids such as dexamethason can reduce pain due to nerve structure compression or edema of metastases
Prescribe initially 1 x 16-24mg/day in the morning or radiotherapy and taper off gradually after pain reduction
Sometimes a combination with opioids will improve pain reduction
James‘s pain was treated sufficiently but he experienced new symptoms: constipation and nausea.
James‘s pain was treated sufficiently but he experienced new symptoms: constipation and nausea.
The constipation was treated with lactulose 3 x 10mg/day and the nausea wtih metoclopramide 4 x 10mg/day
James‘s situation was stable for the next 6 months.
After this time pain increased again because of his progressive disease. He got a new burning pain without reduction of the pain intensity by taking more morphine. Also he got a sensitive deficit perineal because of an infiltration of the plexus pudendus. Under the treatment with dexamethasone 12 mg and gabapentin 3 x 300mg/day (going up in 100mg steps) the pain decreased again.
After this time pain increased again because of his progressive disease. He got a new burning pain without reduction of the pain intensity by taking more morphine. Also he got a sensitive deficit perineal because of an infiltration of the plexus pudendus. Under the treatment with dexamethasone 12 mg and gabapentin 3 x 300mg/day (going up in 100mg steps) the pain decreased again.
Due to his cancer (and possibly a side effect of the medications??), James felt tired and lethargic. He had lost a great deal of strength and energy. Though the quality of his life was good on some days, on other days he was depressed. On the days he was depressed, the pain was more obtrusive than during the ‘good’ days. His family and friends spent time with James and paid him more attention. Consequently, until his death there was no need to increase the doses of the medications he was given.
Due to his cancer (and possibly a side effect of the medications??), James felt tired and lethargic. He had lost a great deal of strength and energy. Though the quality of his life was good on some days, on other days he was depressed. On the days he was depressed, the pain was more obtrusive than during the ‘good’ days. His family and friends spent time with James and paid him more attention. Consequently, until his death there was no need to increase the doses of the medications he was given.
Sometimes it is harder to treat the constipation than pain.
Sometimes it is harder to treat the constipation than pain.
Opioids reduce the gastrointestinal motility, decrease gastrointestinal mucus secretion, increase fluid absorption mainly by binding to peripheral opioid receptors in the mesenteric and submucous plexus and to cerebral and spinal receptors
There is no tolerance to constipation !
Co-administer laxatives such as: lactulose 3 x 10mg to 3 x 40mg/day or macrogol 1-3 sachets/day or non-resorbable oils/paraffines
Co-administer laxatives such as: lactulose 3 x 10mg to 3 x 40mg/day or macrogol 1-3 sachets/day or non-resorbable oils/paraffines
As long as is possible, encourage the patient to be mobile
About 20% of the patients treated with opioids suffer from emesis
About 20% of the patients treated with opioids suffer from emesis
First choice: metoclopramide 4 x 10mg and haloperidol 3 x 0.3-0.5mg orally, subcutaneously or intravenously
It is better to combine opioids and antiemetics at the beginning of the treatment as a prophylaxis
After 7 days of treatment, try to withhold the medication; tolerance to opioid-induced emesis typically developes after this period of time.
Many patients all over the world do not receive adequate relief of pain because of excessive regulatory restrictions on the availability and accessibility of opioids.
Many patients all over the world do not receive adequate relief of pain because of excessive regulatory restrictions on the availability and accessibility of opioids.
There is a reluctance about using opioid analgesics and fear of abuse
Another problem is the lack of knowledge regarding pain relief and opioids among professionals and the public
Ensure opioid availability!
Tramadol
Tramadol
Morphine, Sevredol
Hydromorphine
Oxycodone
Fentanyl
Paracetamol Acetaminophenon
Metamizol, Dipyrone
Ibuprofen, Diclofenac
Sufficient pain reduction can normally be obtained using the principles of the WHO Pain Relief Ladder
Sufficient pain reduction can normally be obtained using the principles of the WHO Pain Relief Ladder
Prefer administration of analgesics using the oral route
