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01 K Module Objectives

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1.1 Describe how a pain signal travels through the nervous system to the brain.
1) Sensory nerve ending in some part of the body is strongly stimulated and sends an electronic message

2) The pain signal travels from the nerve ending to the spinal cord along a single fiber.

3) The sensory nerve releases neurotransmitters across the gap and bind to special receptors located on the second nerve fiber (spinal cord)

4) The nerve fibers connect to a third set of nerve cells located in the brainstem. 5) From there the pain message is transmitted to the conscious brain
1.2 Differentiate acute, chronic benign, and cancer pain.
Acute: pain control is only needed for a few days or perhaps weeks, side effects of medications and other therapies are not a major issue. short-acting PRN meds

Cancer: fairly constant pain that continues for months or years, long acting meds plus short acting/ rescue

Chronic Benign: Diseases or conditions that cause long-term pain, but that are neither fatal nor completely curable, because of the lifelong nature of the condition, avoiding side effects of treatment has a higher priority than it might in Cancer patients.
1.3 Discuss the goals of pain treatment for each type of pain.
Acute pain: provide the patient with effective pain relief that allows them to rest comfortably and to rehabilitate their surgery or injury.

Cancer pain: Provide long-term, effective control of the patient's symptoms, largely free of side effects and to enjoy life as much as is possible.

Chronic benign pain: Restore the patient to the highest degree of function possible
1.4 State the types of physicians who practice pain management.
1) Anesthesiologists (Pain Mgt Specialty)
2) Physical Medicine/Rehabilitation physicians (Pain Mgt Specialty)
3) Neurologists (Pain Mgt Specialty)
4) Psychiatrists
5) Neurosurgeons
6) Orthopedic surgeons
7) Oncologists
8) Rheumatologists
9) Palliative Care (Including Family Practice and Internal Medicine)
1.5 Understand the concept of interdisciplinary pain management.
1) A multidisciplinary team brings a number of diverse diagnostic and therapeutic skills to the management of a patient's pain.
2) The composition of the team, which will vary from one pain treatment center to another, reflects a growing appreciation of the importance of treating the ""whole patient"" rather than just the primary symptom.
3) The ultimate aim of the pain management team is to provide rational, integrated, and consistently effective care for every patient.
1.6 Understand current practice patterns for benign pain and cancer pain.
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1.7 Describe the objectives of palliative care and hospice programs.
Focuses on the treatment of patients near the end of life and in hospice settings.
1.8 Identify patients who are eligible for hospice care.
1. Completion of all active curative treatment.
2. Patient's awareness of the terminal nature of their condition.
3. Patient and family's clear understanding of the goals of hospice care."
1.9 Describe the common reason for undertreatment of pain with opioids.
1. Fear of addiction
2. Lack of education aout pain and pain control
3. Opiod Phobia
4. Fear of legal or regulatory action
1.10.1 Define substance abuse.
A maladaptive pattern of use of a chemical substance that significantly interferes with te person's life

(The American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders)
1.10.2 Define addiction.
A primary, chronic neurobiologic disease, with
genetic, psychosocial and environmental factors characterized by
behaviors that include one or more of the following:
1) impaired control over drug use
2) compulsive use
3) continued use despite harm
4) craving
1.10.3 Define pseudoaddiction.
The following set of behaviors that are exhibited by patients with inadequately treated pain:
⬢ﬠﬠComplaints that pain medication is ineffective.
⬢ﬠﬠHoarding medications, or repetitively counting medications.
⬢ﬠﬠOne or possibly two incidences of running out of medications early.
⬢ﬠﬠObsessing about the duration of time until medication refill.
⬢ﬠﬠA single incidence of obtaining opioids from another source, not repeated after the patient is warned of the consequences
1.11 Describe opioid phobia.
"An irrational fear of using strong opioid analgesics, fairly common cause of undertreatment of pain.
Its end result is unavailability and underutilization of opioids, and its victim is the inadequately treated patient with cancer pain."
2.1 Describe the frequency of both benign and cancer pain
Currently, about 75 million individuals suffer from some form of chronic benign pain, and the total costs of chronic pain are estimated at 90 billion dollars a year.

Almost 10 million persons have a diagnosis of cancer at any one time, most of them suffer
2.2 List at least 6 adverse effects of chronic pain
Chronic pain affects not only bodily functions; it also causes
1) anxiety
2) depression
3) results in numerous unsuccessful medical interventions
4) disrupts family lives
5) causes financial and social problems for the sufferer.
2.3 Describe the basic steps in the initial assessment of a patient in chronic pain
The initial evaluation of pain should include:
1) complete history
2) assessment of the intensity
location, temporal course, and characteristics of the pain
3) some form of psychological assessment
4) a physical examination
5) review of diagnostic tests
2.4 Understand the difference between the intensity and the characteristics of pain
1. A complete assessment of acute pain often consists of little more than some form of pain severity score. The cause of pain is usually obvious severity of pain is usually proportional to the physical damage. While chronic pain severity is assessed in the same way as acute pain, the severity score alone is not a very useful measurement for chronic pain
2. In contrast, there are physiologic, neurological, psychological, socio-environmental, and learned behavior components in every case of chronic benign pain, and in many cases of cancer pain. Assessing these characteristics, or descriptions, of the pain can be quite difficult.
2.5 Understand the reason for psychological assessment of chronic pain patients
Most patients with chronic benign pain, have real, physical causes for their pain. However, most also have some psychological factors that modify their perception of pain to some extent.
2.6 Know the common types of psychological factors that may influence chronic pain
Depression, anxiety, and attention seeking behaviors
2.7 Understand the indication for performing diagnostic tests in chronic pain
1) In cancer patients, the major purpose is to visualize the spread of tumor (or absence of tumor) allowing the oncologist to determine what treatment, in addition to symptom management, is needed.
2) In chronic benign pain, the major purpose of diagnostic testing is to rule out the presence of any diseases for which there is a curative treatment.
2.8 Understand that ongoing evaluation of treatment is necessary
1) Pain treatment rarely results in complete and total pain relief
2) Chronic pain normally waxes and wanes over time. Therefore, it may be difficult to tell if improvement is from a recently started medication, or just the normal change in pain severity that occurs over time
3.1. Describe the general types of pain treatment.
Commonly used therapies include:
1) nerve blocks
2) rehabilitation and physical therapy
3) several different types of medication
4) acupuncture
5) psychotherapy such as stress management
6) neurosurgical procedures, and a number of other treatments.
3.2. Explain the basic principles of pain management.
⬢Proper therapy depends upon recognizing the source(s) of pain and treating each.
⬢Treatments that resolve the painful condition should be explored whenever possible.
⬢If it is not possible to resolve the condition, treatments to relieve the patient's symptoms should be given.
⬢Multimodal therapy (using several different types of therapy) is generally more effective than any single therapy.
⬢Treatment for each patient must be individualized depending on anatomic pathology, the presence of other diseases, age, social and economic status, emotional state and other factors.
⬢Pharmacologic treatment is the primary therapy for a majority of pain patients, especially cancer patients.
⬢The use of nonopioid analgesics and adjuvant agents should always be explored.
⬢The use of opioid analgesics is appropriate in most cases of chronic benign pain and almost all cases of cancer pain.
⬢Pure opioid agonists, such as morphine, should be used in most cases. Mixed agonist-antagonist opioids may induce a withdrawal syndrome in patients tolerant to opioids.
⬢Analgesic drugs should be prescribed in low doses initially, then titrated upwards as necessary.
⬢Oral medications should be used whenever possible. Oral opioids are relatively inexpensive and allow the patient control of their own medication.
⬢When patients have constant, or near constant pain, analgesics should be given "around the clock", not "PRN" (when necessary). Fixed, regular dosing intervals maintain continuous control of pain. "Rescue" medications are allowed, but frequent episodes of breakthrough pain indicate that the regular "around the clock" dose should be increased.
⬢There are no "standard" or set doses of opioids. Individuals vary greatly in their metabolism of opioids; different individuals require different doses of the drug.
⬢Care should be exercised when converting from one analgesic to another, or from one route of administration to another, to avoid overdose or underdose. Conversion tables are notoriously inaccurate and contradictory.
⬢Nonpharmacologic therapies should be investigated and used when appropriate.
3.3. Describe 3 types of nonopioid analgesics.
1) Acetaminophen: is the most widely used nonopioid analgesic, because it has a low incidence of side effects.
2) Aspirin: an analgesic, anti-inflammatory and antipyretic (fever-reducing) drug.
3) The Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): used alone for mild to moderate pain, or in combination with opioids for more severe pain
3.5. Know the most frequently used opioid agents.
1) Morphine (instant release)
2) Fentanyl
3) Hydromorphine
4) Meperidine
5) Methadone
6) Oxycodone
3.6. Understand the advantages and disadvantages of each controlled-release opioid preparation.
See Comp Grid
3.7. Discuss the use of adjuvant drugs to augment opioids.
Medications that are not analgesics, but that may reduce pain or improve other symptoms associated with chronic pain.
3.8. Understand the principle of dose titration.
1) The dose should be gradually increased until pain relief is satisfactory or intolerable side effects occur.
2) The lowest dose that produces analgesia is best, since this is less likely to produce side effects.
3) Usually, the dose, rather than the frequency of dosage, is increased when titrating.
4) Titration of drugs should be carried out as quickly as possible to prevent the patient from experiencing pain or side effects for longer than necessary
3.9.1 Discuss the use of nonpharmacologic interventions for pain control.
While medication alone can effectively control chronic pain in many patients, there are a number of other strategies that may be employed in more difficult cases.
Nonpharmacologic strategies are commonly used in patients with benign chronic pain, and are indicated in cancer patients who continue to have pain in spite of optimal medical management
3.9.2 Give examples of nonpharmacologic treatment of pain
1) Neural Blockade (Regional Analgesia)
2) Physical Therapy
3) Acupuncture
4) Transcutaneous Electrical Nerve Stimulation (TENS)
5) Biofeedback
6) Drug Infusion Pumps
7) Neurostimulation
4.1. Describe general principles of treating cancer pain.
1) The patient must have an informed role in the management of the disease.
2) Involvement of the patient's family is important.
3) A team approach is optimal.
4) Treating the cancer is the first priority
5) All symptoms that cause distress, such as nausea, diarrhea, cough, constipation, insomnia, bedsores, incontinence, etc., should be treated.
6) The patient's environment is important
4.2. Describe the role of anticancer therapies in treating cancer pain.
When the pain is the result of tumor invading the tissues, anticancer therapy is the first priority.
4.3. Describe the four steps of the WHO pain treatment ladder.
1) For mild pain, a nonopioid analgesic is administered and an adjuvant drug added if a specific indication for one exists
2) If a Step One regimen fails to control pain, an oral opioid is administered in combination with a nonopioid analgesic.
3) If steps 1 and 2 do not control the patient's pain, a strong oral opioid is administered, with or without a nonopioid analgesic or adjuvant drug.
4) If the above steps do not control the patient's pain, invasive therapies, such as implanted infusion pumps, destruction of nerves, or spinal cordotomy may be indicated.
4.4. Describe the drugs commonly used in each step of the ladder.
1. Nonopioid analgesics
2. Opioid analgesics
3. Adjuvant medications
4. Invasive therapies
4.5. Discuss the use of potent opioids as step 3 of the WHO ladder.
1) An opioid with flexible routes of administration and wide variation in available doses is used at this level.
2) Long-acting or time-release preparations are suggested, since these medications are taken on a timed schedule, not PRN.
3) A short-acting opioid may be added as rescue medications for breakthrough pain
4.6. Discuss the phenomena of opioid tolerance and dependence.
1) Tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drugs’ effects over time.
2) Dependence is a state of adaptation that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist.
4.8. Discuss the use of nonpharmacologic interventions for cancer pain management
1) Peripheral Neuropathies: Neurostimulation may be beneficial, but is usually reserved for patients with a long life expectancy
2) Postmastectomy Syndrome: the most important therapy is an aggressive physical therapy to restore movement and motion
5.1.1. Understand the differences between cancer and benign pain.
1) Cancer pain: considered more severe, worsenes more rapidly, the underlying cause is in plain sight, the majori
ty of patients succumb to their illnesses within a few years.
2) The causes of CBP, on the other hand, are often difficult to determine, the symptoms do not change rapidly, and the patient usually survives to a normal life expectancy.
5.1.2. Understand the differences between cancer and benign pain treatment goals.
1) Cancer pain: To relieve symptoms and provide comfort.
2) CBP: to restore the person's ability to function, and relief of the pain is only one of the treatments required to restore function
5.2. Name at least 6 common causes of chronic benign pain.
1) Back or Spine
2) Connective Tissue Diseases
3) Peripheral neuropathy and neuralgia
4) Central Pain Syndromes
5) Sympathetically Mediated Pain Syndromes
6) Headaches
5.2.1 Describe Back or Spine problems
1) Most common source of CBP
2) Common Cause:
--"Failed surgery syndrome" or "multiple laminectomy syndrome"
--stenosis
--spondylosis
--spondylolisthesis
5.2.2 Describe Common Connective Tissue Diseases
1) Degenerative arthritis is a common painful connective tissue disease in older adults.
2) Rheumatoid arthritis, lupus erythematosis, and a number of other autoimmune diseases (the immune system attacks the body's tissues)
3) Fibromyalgia (a painful condition of the muscles)
5.2.3 Describe peripheral neuropathy and neuralgia
Results when damage to peripheral nerves causes neuropathic pain.
1) Neuralgia often occurs when nerves are compressed by other structures in the body, as is the case with carpal tunnel syndrome.
2) Peripheral neuropathy results when a disease causes generalized damage to long nerve fibers, resulting in pain of the feet and hands
5.2.4 Describe Central Pain Syndromes
Result from damage to the central nervous system.
This may occur following a stroke, from damage to the spinal cord, or as ""phantom limb pain"", a rare condition that sometimes follows amputation.
Central pain syndromes are considered a form of neuropathic pain.
5.2.5 Describe Sympathetically Mediated Pain Syndromes
- Have a number of names including reflex sympathetic dystrophy, causalgia, and complex regional pain syndrome.
- While these conditions are each fairly rare, they cause extremely severe pain, and are quite difficult to treat.
5.4. Understand the usefulness of opioids in CBP.
1) Effectively reduce the severity of most types of chronic benign pain.
2) They are most effective when the pain is somatic in origin, but are somewhat effective in most cases of neuropathic pain
5.6. State the risks physicians face in prescribing opioids for CBP.
"1) Regulatory agencies review prescribing habits of high dose opioids, should a patient be diverting the medication for illicit resale, the prescribing physician may come under investigation.
2) Should the patient be found to have a substance abuse problem the physician could be sued for failure to diagnose the problem."
5.7. Discuss the techniques used to minimize those risks.
1) Following approved guidelines
2) Avoiding certain opioids that are more likely to be diverted and abused
5.A1 Describe the role of depression and anxiety in CBP
Patients with CBP often suffer depression and anxiety, as severe as that experienced by cancer patients.
However, they often have a history of these problems before they developed chronic pain.
5.A2 What % of patients seek treatment for CBP who don't have a physical problem?
10%
6.1. Know the frequency of substance abuse.
7.5% of the U.S. adult population or 15 million (last 20 years)
6.2. Define substance abuse
Maladaptive pattern of chemical substance use that significantly interferes with the person's life as indicated by at least one of the following:
1. Neglect of work, school, or home obligations
2. Use of the substance in a hazardous situation (driving, operating machinery)
3. Repeated substance related legal problems
4. Continued use of the substance despite recurrent social or interpersonal problems associated with its use
(American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders)
6.2.1 Define Substance Dependence
Substance abuse that is associated with tolerance to the substance’s effect or physical withdrawal symptoms if the substance is discontinued
6.3. Differentiate tolerance and dependence of substance abuse.
Tolerance and withdrawal are considered evidence of substance abuse.
1) In reality, many heavy abusers do not exhibit significant tolerance or withdrawal.
2) Conversely, a perfectly compliant chronic pain patient maintained on long-acting opioids would eventually exhibit both
6.5. Know common signs of substance abuse.
Consistent signs associated with substance abuse include:
1) changes in mental status
2) recent accidents or trauma
3) a history of poor impulse control (legal difficulties, gambling, losing jobs)
4) history of poor or unpredictable responses to standard pain therapies.
5) Patients with a past history or strong family history of substance abuse (including alcohol abuse) are far more likely to have a substance abuse problem than others are
6.6. Differentiate pseudoaddiction from substance abuse.
Pseudoaddiction is a set of behaviors that are often exhibited by patients with inadequately treated pain. They should not be considered signs of abuse in a chronic pain patient unless they are accompanied by other signs of abuse.
1) ﬠﬠComplaints that pain medication is ineffective.
2) ﬠHoarding medications, or repetitively counting medications.
3) ﬠﬠOne or possibly two incidences of running out of medications early especially if the patient states honestly that they took more than prescribed.
4) ﬠﬠObsessing about the duration of time until medication refill.
5) ﬠA single incidence of obtaining opioids from another source, not repeated after the patient is warned of the consequences
6.7. Know factors that are associated with substance abuse.
Chronic pain patients are particularly reluctant to admit to substance abuse, for two reasons.
1) They have developed significant denial and truly believe that no one understands how severe their pain is, justifying (to themselves at least) their overuse of opioids from several sources.
2) Have legitimate fear that admitting to a substance abuse problem means they will have to live in pain for the rest of their lives
6.8. Describe what steps a physician must take if he diagnoses substance abuse.
Standards established by the American Medical Association and the American Society of Addiction Medicine state that referral to a treatment program is the minimal acceptable standard of care once substance abuse is diagnosed.

Discharging a patient with an abuse problem from the practice can place the physician at risk for ""failure to diagnose"" and "failure to treat"" lawsuits.
6.9. Know the documentation guidelines required when physicians prescribe chronic opioids.
Physicians should document:
1) the patient evaluation
2) treatment plan
3) informed consent
4) opioid contract
5) medication list

A periodic chart review should state the patient's benefits of the opioid therapy
6.10. Describe the abuse risks of different categories of opioids.
Any member of the opioid group may be abused, but as a rule
1) short-acting opioids are strongly preferred by abusers
2) Historically, hydrocodone is the most widely abused opioid, probably because as a schedule III medication used for both pain control and cough suppression
3) OxyContin has become arguably the most commonly abused and diverted opioid
4) Truly long-acting agents, such as KADIAN®or Duragesic, are not preferred by abusers because they do not get a ""rush"" from the slow onset of these medications
6.A1 Is it credible to describe some some opiods as "less abusable" or "have lower abuse potential"?
1) No every opioid has at least some abuse potential
2) Statements such as ""has a lower street value"" or ""is more difficult to remove active drug from the matrix"", when accompanied by reprints of factual articles, are much safer and more credible.
7.1. Explain the role of the opioid receptor.
Opioids exert their effects on the body by interacting with specialized macromolecular components in cells called opioid receptors.

Opioid receptors are located in the CNS, pituitary gland, the GI tract, and a few other locations in the body.

They are abundant in the periacqueductal gray matter of the brain and the dorsal horn of the spinal cord, two areas that are very active in pain reduction.

When an opioid binds to one of these receptors as an agonist, it produces analgesia.
7.2. Describe the mechanism of action of morphine and other opioids in analgesia.
1) Endogenous peptides are the primary chemical messengers in the antinociceptive system of the body.
2) Opioid medications attempt to mimic the actions of these endogenous peptides.
3) In the body, endogenous opioids bind to receptors to produce analgesia Opioid medications, such as morphine, bind to receptors and block pain modulating systems in a similar manner as endogenous opioids.
7.2.1 What are the three major types of opioid receptors involved in analgesia?
Mu, Kappa, and Delta
7.2.2 What are the three classes of opiods?
Mu agonists, mixed agonist-antagonist, and partial agonist
7.2.3 Describe and give examples of the mu agonists class of opioids.
1) Most clinically useful opioid analgesics bind primarily to the mu receptor
2) Codeine, Fentanyl, Hydromorphone, Levorphanol, Meperidine, Methadone, Morphine, Oxycodone, and Oxymorphone
7.2.4 Describe and give examples of the mixed agonist-antagonists class of opioids.
1) Bind as agonists at the kappa receptor producing weak analgesia.
Bind as weak antagonists at the mu receptor.
The result is more dysphoria and psychotomimetic effects and less intense respiratory depression
2) Butorphanol, Dezocine, Nalbuphine, Pentazocine"
7.2.5 Describe and give examples of the partial agonist class of opioids.
1) Bind as agonists at mu and kappa but have limited efficacy
2) Buprenorphine
7.3. Discuss the pharmacological effects of morphine and other opioids.
⬢Analgesia.
⬢Depression of central nervous system (sedation, occasionally euphoria, dysphoria).
⬢Respiratory depression.
⬢Suppression of the cough reflex.
⬢Decreased gastrointestinal motility (constipation).
⬢Stimulation of chemoreceptor trigger zone (nausea and vomiting).
⬢Peripheral vasodilation (postural hypotension and fainting).
⬢Pupillary constriction (miosis).
⬢Inhibition of the urine voiding reflex (urinary retention).
⬢Smooth muscle contraction/spasm (constipation and oliguria).
⬢Stimulation of histamine release (sweating, flushing, pruritus, red eyes and postural hypotension).
7.4. Describe the phenomenon of tolerance to morphine.
1) Tolerance develops to analgesia more slowly than other opioid effects.
2) Analgesic tolerance does not occur in every patient and is not addiction.
3) Tolerance to morphine is both dose and time dependent. Large doses of morphine given over a short period will be associated with a more rapid development of tolerance. Conversely, tolerance develops less rapidly when small doses are given.
4) Tolerance occurs to most of the adverse effects of opioids after 2 to 3 weeks of continuous administration. Tolerance does not occur to the constipating effects of opioids
7.5. Describe the phenomenon of dependence to morphine.
Patients using opioid analgesics may continuously develop a physical dependence with or without a psychological dependence
7.6. Explain the basic chemistry of KADIAN®.
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8.1. Describe the types of modified-release morphine preparations.
Extended-release formulation: releases a drug over an extended period.
This allows a reduction in dosing frequency as compared to a drug presented in a conventional dosage form.
Other terms used to describe these dosage formulations include sustained-release, prolonged-action, and controlled-release.
Delayed-release dosage: one that delays the release of a drug until it has passed through the stomach.
According to the US Pharmacopoeia, enteric-coated dosage forms are delayed-release dosage forms
8.2. Describe the mechanism of morphine release in KADIAN®capsules.
The KADIAN capsules consist of a hard gelatin shell containing polymer-coated morphine sulfate pellets. The release of morphine from the pellets is pH dependent, with the rate of release increasing as the pH of the medium around the pellet increases.
1) After ingestion, the gelatin capsule dissolves in the stomach and the pellets are released.
2) In the strongly acidic medium of the stomach, morphine release from the pellets is minimal.
3) As the pellets pass into the more alkaline small intestine, the rate of release increases substantially.
4) Release of morphine increases as the pellet passes through the small intestine into the large intestine, with the rate of release increasing as the pH becomes more alkaline.
5) The pellets are designed to release morphine for up to 24 hours. This is the basis for once a day administration of KADIAN®.
8.3. Describe the absorption of morphine from KADIAN®capsules.
The area under the curve (AUC) is comparable for both KADIAN®and morphine sulfate solution, indicating that similar amounts of drug are absorbed from either preparation.
8.4. Describe the bioavailability of morphine from KADIAN®capsules.
Cmax produced by KADIAN®is lower than that produced by morphine sulfate solution, meaning the peak drug concentration is not as high with KADIAN®as with morphine sulfate solution
8.5. Describe the major findings of the single-dose KADIAN research.
?
8.6. Describe the major findings of the steady-state KADIAN research.
?
8.7. Describe the pharmacokinetics of KADIAN®.
⬢Slow rate of drug release in the gastrointestinal tract and therefore slow rate of absorption.
⬢Extent of absorption similar to that of morphine sulfate solution.
⬢Bioavailability is not significantly affected by food.
⬢Rate of absorption slowed marginally by food but is not clinically relevant.
⬢Provides adequate plasma morphine concentrations, which may permit once a day dosing.
⬢The unique pharmacokinetic profile of KADIAN®indicates that it has sustained-release properties that provide the option of 24-hour pain control with a single daily dose.
However, a patient's response to morphine is highly individualized and there is no demonstrated correlation between blood plasma levels and the degree of pain relief that each patient will experience
8.8. Discuss the metabolism and excretion of KADIAN®and the clinical implications.
1) The major metabolic pathway of morphine involves glucuronidation, which occurs predominantly in the liver.
2) Thus, the effects of morphine may be increased in patients with hepatic disease.
3) Because morphine is excreted primarily via the kidneys, renal impairment slows the clearance of morphine conjugates, resulting in accumulation of the active metabolite morphine-6-glucuronide (M6G).
4)For this reason, dosage reduction may be advisable in the presence of clinically significant hepatic or renal impairment
9.1. Describe the factors to be considered in selecting the initial dose of KADIAN®.
1) Patients who do not have a proven tolerance to opioids should preferably be treated to clinical response using an immediate-release morphine formulation and then be converted to a long-acting product.
2) KADIAN®is chosen as the initial opioid, patients should be started only on the 20mg strength.
3) The dose may be increased by 20mg every other day
9.2. Describe the key factors in switching a patient from another opioid to KADIAN®.
"In opioid tolerant patients:
1) KADIAN®should be started by administering one-half of the estimated total daily oral morphine dose every 12 hours or 24 hours.
2) The dose should be titrated no more than every-other-day to allow the patients to stabilize before escalating the dose.
3) The first dose of may be given with the last dose of conventional oral morphine due to the long delay until the peak effect after administration of KADIAN®."
9.3. Describe the potential adverse interactions of KADIAN®with other medications.
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9.4. Describe the key information to be provided to patients on KADIAN®.
"⬢The dose of KADIAN should not be adjusted without consulting the medical practitioner.
⬢KADIAN capsules should be swallowed whole.
The pellets in KADIAN capsules should not be chewed, crushed, or dissolved due to risk of overdose. Taking chewed or crushed KADIAN capsules or pellets will lead to the rapid release and absorption of a potentially toxic dose of morphine.
⬢KADIAN®may impair mental or physical ability required for the performance of potentially hazardous tasks such as driving a motor vehicle or operating machinery. Patients started on KADIAN®or whose dose has been changed should refrain from dangerous activity until it is established that they are not adversely affected.
⬢Morphine should not be taken with alcohol or other central nervous system depressants (sleeping medications, tranquilizers) because additive effects, including central nervous system depression, may occur. A medical practitioner should be consulted if other prescription medications are currently being used or are prescribed for future use.
⬢Women of childbearing potential, who become or are planning to become pregnant, should consult a medical practitioner regarding analgesic and other drug use.
10.2. Describe the potential serious adverse effects of KADIAN®and other opioids.
1) The adverse effects of morphine, and therefore KADIAN®, are essentially the same as those observed with other opioid analgesics.

2) Serious adverse reactions that may be associated with KADIAN®include respiratory depression, respiratory arrest, circulatory depression, cardiac arrest, hypotension, and/or shock
10.3. Discuss the abstinence syndrome that may be seen when chronic opioids are discontinued.
1) Physical dependence develops to morphine with chronic use.
2) Thus, the patient may experience withdrawal/abstinence syndrome if morphine is abruptly discontinued.
3) This is usually mild and is characterized by rhinitis, myalgia (muscle aches), abdominal cramping, and occasional diarrhea.
4) Most observable symptoms disappear in 5-14 days without treatment. However, there may be a phase of chronic abstinence that lasts for 2-6 months characterized by insomnia, irritability, and muscle aches.
10.4. Discuss the clinical manifestations of opioid overdose.
Acute overdose with morphine is manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, sometimes, pulmonary edema, bradycardia, hypotension, and death.
10.5. Understand the use of opioids in pregnancy, labor and delivery, and breastfeeding.
1) Pregnant patients should be given KADIAN®only when the benefits clearly outweigh the potential risks to the fetus.
2) KADIAN®is not recommended for use in women during and immediately before labor, and women should not breast-feed their infants when taking KADIAN®.
10.6.1 Identify the contraindications of KADIAN
1) Patients with known hypersensitivity to morphine, morphine salts, or any of the capsule components of KADIAN® because of the risk of anaphylaxis.
2) Patients with acute or severe bronchial asthma and those with respiratory depression. In these patients, KADIAN® would further compromise respiratory function through its depressant effects on respiration.
3) Patients with obstruction of the gastrointestinal tract, especially a condition of the intestine known as paralytic ileus. The concern is that obstructions to the flow of material along the gastrointestinal tract could lead to retention of the drug in the stomach for an extended period, with subsequent release of a bolus morphine dose into the small intestine.
10.6.2 Identify the precautions of KADIAN
1) Patients with central nervous system depression, toxic psychosis, acute alcoholism, and those with biliary disease.
2) Patients should be warned that morphine may impair the mental and/or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery
3) The potential combined effects of morphine with other central nervous system depressants, including other opioids, phenothiazines,
sedatives/hypnotics, and alcohol.
10.7. Discuss potential drug interactions involving KADIAN®
Because of the risk of interactions, KADIAN® should not be administered to patients receiving
1) monoamine oxidase inhibitors
2) mixed opioid antagonists/agonists
3) should be administered with caution in patients taking other central nervous system depressants or diuretics
12.2. Describe the anatomy of a clinical research paper and the importance of each part.
1) Abstract
2) Introduction
3) Methods
4) Results
5) Discussion
6) References

Deck Info

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