Drug Therapy for Pain

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ppt

 

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By: ventilator (28 month(s) ago)

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Presentation Transcript

Drug Therapy for Pain: 

Drug Therapy for Pain Brooke Y. Patterson, PharmD, BCPS/Adjunct Faculty/Rockhurst University

Definitions of Pain: 

Definitions of Pain 'Pain is whatever the experiencing person says it is, existing whenever he/she says it does.' -Mc Caffery 1968 'An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.' - Intl. Assoc. for the study of pain

Food for Thought: 

Food for Thought Costs $100 Billion each year Longer hospitalization Rehospitalizations ER visits Sick days Permanent Disability Only 30% of cancer patients get adequate pain relief 15-20% of Americans have acute pain 25-30% of Americans have chronic pain Leading cause disability for those < 45 y/o

The Mechanisms of Pain: 

The Mechanisms of Pain Transduction Transmission- movement of pain impulses Perception- recognition of pain Modulation- activation

The Mechanisms of Pain: 

The Mechanisms of Pain Transduction- Conversion of mechanical, thermal or chemical stimulus into a neuronal action. Peripheral nerve sites- peripheral afferent nociceptor (PAN) Action Potential causes movement of pain stimulus What causes it? Nociceptive- Release of Chemicals Neuropathic- Abnormal processing of stimuli by the nervous system

The Mechanisms of Pain: 

The Mechanisms of Pain Transmission- movement of pain impulses from the site of transduction to the brain. Transmission along the nociceptor fibers to the level of the spinal cord. Dorsal horn processing. (Dermatomes) Transmission to the thalamus and the cortex.

The Mechanisms of Pain: 

The Mechanisms of Pain Perception- recognition of pain However, there is no precise location where pain perception occurs. Individualized Imagery is a good pain-reduction therapy. Subjective Sensory: Recognition that you have pain. Affective: Emotional responses to pain. Behavioral: How someone expresses or controls pain. Cognitive: Person’s beliefs and attitudes about pain. Sociocultural: Age, Gender, education level, culture and support systems.

The Mechanisms of Pain: 

The Mechanisms of Pain Modulation- activation of descending pathways that either inhibit or facilitate effects on pain transmission.

Types of Pain: 

Types of Pain Nociceptive Pain Normal processing of stimuli that damages or has the potential to damage, normal tissues if prolonged. Different types of origins: Somatic Pain: Arises from bone, joint, muscle, skin or connective tissue. Visceral Pain: Arises from visceral organs, such as pancreas or stomach.

Somatic Pain: 

Somatic Pain Described as 'achy', stabbing, sharp Examples: Bone pain, fractures Muscle tears, sprains Joint pain Soft tissue injury

Visceral Pain: 

Visceral Pain Diffuse and difficult to localize if d/t obstruction of hollow viscus Sharp, aching when due to injury to other visceral structures such as; Pancreatitis Kidney Stones Menstrual Cramps Bowel Obstruction

Neuropathic Pain: 

Neuropathic Pain Multiple Pain Syndromes Often difficult to treat. Believed to be the abnormal firing of the peripheral or central nervous system. Often described as burning, stinging, shooting, traveling, or electric-like. Caused by phantom limb pain, complex regional limb pain complex regional pain syndromes, diabetic neuropathy, post-herpetic neuralgia, or trigeminal neuralgia

Comparing Nociceptive & Neuropathic Pain: 

Comparing Nociceptive and Neuropathic Pain Normal processing of stimuli that damages normal tissue. Responds to opioids or nonopiods. Somatic pain- arises from bone, joint, muscle, skin or connective tissue Visceral pain Tumor involvement that causes aching and is fairly well-localized Obstruction causes intermittent cramping and poor localized pain. Abnormal processing by peripheral or central nervous system. Responds to adjuvant analgesics. Centrally Generated Pain Peripherally Generated Pain- Pain felt along entire nerve pathways. Peripheral nerve injury- pain felt partially along the damaged nerve

Acute VS. Chronic Pain: 

Acute VS. Chronic Pain ACUTE Sudden Short Duration < 3 months Mild--> Severe Can identify specific cause. Predictable prognosis Can be single event or recurrent.  as healing progresses. CHRONIC Continues for more than one month after healing or an acute lesion, or Recurs over a chronic period of time. Pathophysiology may be unclear. Unpredictable prognosis Is associated with a lesion that is not expected to heal. Chronic cancer pain or chronic non-malignant pain.

Sources of Pain: 

Sources of Pain

Acute VS. Chronic Pain Cont’: 

Acute VS. Chronic Pain Cont’ May be associated with sympathetic hyperactivity and anxiety. Usually resolves Treated with short-acting drugs. May be associated with depressed mood, sleep disturbance and disability. Treated with long-acting drugs and adjuvant therapy.

Physiological Effects of Pain: 

Physiological Effects of Pain Increased catabolic demands: poor wound healing, weakness, muscle breakdown Decreased limb movement: increased risk of DVT/PE Respiratory effects: shallow breathing, tachypnea, cough suppression increasing risk of pneumonia and atelectasis Increased sodium and water retention (renal) Decreased gastrointestinal mobility Tachycardia and elevated blood pressure

Psychological Effects of Pain: 

Psychological Effects of Pain Negative emotions: anxiety, depression Sleep deprivation Existential suffering: may lead to patients seeking active end of life.

Immunological effects of Pain: 

Immunological effects of Pain Decrease natural killer cell counts Effects on other lymphocytes not yet defined.

Principles and Goals of Pain Management: 

Principles and Goals of Pain Management Pain is subjective Self-report is the most reliable indicator

Principles of Assessment: 

Principles of Assessment Assess and reassess Use methods appropriate to cognitive status and context Assess intensity, relief, mood, and side effects Use verbal report whenever possible Document in a visible place Expect accountability Include the family

Principles and Goals of Pain Management: 

Principles and Goals of Pain Management Assessment Onset and duration Location Character (sharp, dull, burning, etc…) Intensity – using the 0-10 numerical rating scale, the verbal scale (none, mild, moderate, severe) or the FACES scale for children (cont.)

Principles and Goals of Pain Management: 

Principles and Goals of Pain Management Assessment (cont.) Exacerbating and relieving factors Response to current and past treatments Meaning of pain to patient Cultural responses to pain Emotional state History of chemical dependence

Principles and Goals of Pain Management: 

Principles and Goals of Pain Management Listen to the patient Pain is subjective – there is no pain-o-meter or pain blood test, only what the patient tells us Reassessment After treatment is initiated, pain should be regularly reassessed to determine the efficacy of the intervention Optimal functioning with least side effects The right dose of pain medication is whatever dose it talks to relieve the pain with the fewest side effects Functioning is usually more of a priority in patients who are not end-stage

Patient Pain History: 

Patient Pain History Site(s) of pain? Severity of pain? Date of onset? Duration? What aggravates or relieves pain? Impact on sleep, mood, activity? Effectiveness of previous medication?

What Does Pain Mean to Patients?: 

What Does Pain Mean to Patients? Poor prognosis or impending death Particularly when pain worsens Decreased autonomy Impaired physical and social function Decreased enjoyment and quality of life Challenges to dignity Threat of increased physical suffering

Pharmacologic Treatment of Pain: 

Pharmacologic Treatment of Pain

Pharmacology of Pain Management: 

Pharmacology of Pain Management Individualized- Based on the patient’s medical and pain histories. Multi-modal- Targets multiple sites of action. Optimize effects Minimize adverse effects

Pharmacology of Pain Management Cont’: 

Pharmacology of Pain Management Cont’ Routes of Administration Oral Sublingual Transmucosal (Actiq) Transdermal (Fentanyl duragesic patch) Parenteral: IV, IM, SQ Nebulized Rectal Epidural/Intrathecal (Morphine, Fentanyl)

Pharmacology of Pain Management Cont’: 

Pharmacology of Pain Management Cont’ How do Opioids work? Opioids act on the opioid receptor sites and activate endogenous pain suppression systems in the CNS (Mu receptor sites). Receptor sites are found in: Dorsal horn of the spinal cord Pituitary gland GI tract Endogenous and exogenous opioids control pain by locking onto opioid receptor sites and blocking the release of neurotransmitters.

Pharmacology of Pain Management Cont’: 

Pharmacology of Pain Management Cont’ How NSAID’s and Acetaminophen work? Non-opioids include NSAID’s, Tylenol and Aspirin. They act on the peripheral nerve endings at the site of injury altering the prostaglandin system. NSAID’s have an anti-inflammatory effect. Acetaminophen does NOT have an anti-inflammatory effect. Like ASA, it has analgesic and antipyretic effects. Side effects: NSAID’s: GI irritation, possible nephrotoxicity. Acetaminophen can cause hepatoxicity. Limit 4 grams/24hr

Pharmacology of Pain Management Cont’: 

Pharmacology of Pain Management Cont’ Short Acting Pain Medications Provide analgesia within 30 min. Diluadid, Morphine Actiq-fastest acting oral medication- onset within 5 min. (transmucosal) MSIR oral solution/Roxanol-elixir form of morphine. Helpful for pts. with difficulty swallowing. Titratable. Oxycodone/MSIR tablets- used for short-term therapy or supplemental dosing (breakthrough pain). Compounds: Tylenol #3, Hydrocodone- Lortab/Vicodin, Oxycodone- Percocet. Propoxyphene- Darvon/Darvocet

Pharmacology of Pain Management Cont’: 

Pharmacology of Pain Management Cont’ Long Acting Opioids Usually used for long-term pain. For patients requiring frequent breakthrough dosed of opioids. More predictable serum levels Easier to use; lower dosing intervals, improved compliance

Comparing Long Acting Opioids: 

Comparing Long Acting Opioids MSContin/Oxycontin 8-12 hour duration DO NOT CRUSH TABLETS!!! Reassess and titrate as needed. 12-24 titration Fentanyl/duragesic Transdermal 72 H duration Convenient Reassess and titrate as needed. Effective for patients with chronic pain and intolerance to orals. Do not cut patch. Place above waist and not on bone. 24-48 titration

Pharmacology of Pain Management Cont’: 

Pharmacology of Pain Management Cont’ Meperidine Has a metabolite that is 2x as potent as a convulsant and 1/2 as potent as an analgesic. Breaks down to nomeperidine which has an active metabolite that accumulates w/multiple dosing. Hepatic or renal failure and increases toxicity. Accumulation of active metabolites can produce irritability, tremors, muscle twitching, jerking, agitation or seizures.

Common Nonopiod Analgesics: 

Common Nonopiod Analgesics

Adjuvant Analgesics: 

Adjuvant Analgesics Nontraditional analgesics, most approved for other indications. Multipurpose drugs For muscloskeletal pain Muscle relaxants (Baclofen, Zanaflex) For neuropathic pain Antidepressants- SSRI’s, TCA’s, SSRI's (Pamelor, Cymbalta) Anticonvulsants- Topamax, Gabapentin, Lyrica Approved for post-herpatic neuralgia, diabetic neuropathy.

Modified WHO Analgesic Ladder: 

Modified WHO Analgesic Ladder Proposed 4th Step The WHOLadder Deer, et al., 1999

Optimal Use of AnalgesicsWorld Health Organization Step Ladder: 

Optimal Use of AnalgesicsWorld Health Organization Step Ladder Begin with non-opiate, nonsteroidal antiinflammatory agents (NSAIDS) Add a 'weak' opiate, such as codeine or hydrocodone (with or without an adjuvant) Move to a stronger opiate, such as oxycodone, morphine (with or without an adjuvant) Complementary, non-pharmacologic strategies Interventional strategies

Step 1: Non Opiates: 

Step 1: Non Opiates Acetaminophen No effect of platelet function Avoid in cases of hepatic insufficiency Maximum of 4g/day If one non-opiate is ineffective, switch to a different one. If one NSAID is ineffective, switch to a different class

Step 1: Non Opiates (cont.): 

Step 1: Non Opiates (cont.) NSAIDS Avoid if low albumin level Avoid if low platelets Avoid if renal insufficiency Useful with throbbing, aching pain Administer with food to reduce gastric irritation Salsalate and tolmetin produce less inhibition of platelet aggregation than other NSAIDS Maximum dose of aspirin is 10g/day Use with caution in persons with asthma Indomethacin is available in suppository form

Step 1: Non Opiates (cont.): 

Step 1: Non Opiates (cont.) Cox-2 Inhibitors Rofecoxib (Vioxx) Celebrex (Celebrex) Have no effect on platelet aggregation or bleeding time Less chance of gastric irritation Monitor hepatic functioning

Step 2: Non opiate + Weak Opiate With or Without Adjuvants: 

Step 2: Non opiate + Weak Opiate With or Without Adjuvants Acetaminophen with codeine or hydrocodone Maximum dose related to acetaminophen Adjuvants are those medicines that enhance the efficacy of the opiate and may have independent analgesic activity

Step 2: Non opiate + Weak Opiate With or Without Adjuvants (cont.): 

Step 2: Non opiate + Weak Opiate With or Without Adjuvants (cont.) Types of adjuvants NSAIDS: provide additive analgesia when given to supplement the opiate, often lengthen the duration of opiates Corticosteroids: treats both the cause and resulting pain of aphthous ulcers; also relieves cerebral edema Corticosterioids caution: can cause gastric bleeding, caution with low platelet counts

Step 2: Non opiate + Weak Opiate With or Without Adjuvants (cont.): 

Step 2: Non opiate + Weak Opiate With or Without Adjuvants (cont.) Types of Adjuvants Antidepressants (amitriptyline, desipramine, etc): used for neuropathic pain and post-herpetic neuralgia and additive analgesia with opiates Antidepressants caution: can cause dry mouth, urinary retention and 'hangover effect Antihistamines (hydroxyzine): provides additive analgesia as well as antiemetic and anxiolytic effect Antihistamine Caution: Can cause dry mouth and drowsiness

Step 2: Non opiate + Weak Opiate With or Without Adjuvants (cont.): 

Step 2: Non opiate + Weak Opiate With or Without Adjuvants (cont.) Types of adjuvants Anticonvulsants: gabapentin is the most useful with the fewest side effects and is used to treat neuropathic pain Anticonvulsant Caution: carbamazepine can cause neutropenia Caffeine: drinking a cup of strong coffee along with opiate will increase its effect

Step 3: Opiates With/Without Adjuvants: 

Step 3: Opiates With/Without Adjuvants Dosing schedule and titration Prevent pain with ATC dosing Titrate to pain relief – doses are individualized: the right dose is whatever it takes to relieve the pain with the least amount of side effects/toxicity Long-acting opiates should be used for long-term pain

Step 3: Opiates With/Without Adjuvants (cont.): 

Step 3: Opiates With/Without Adjuvants (cont.) Conversion/equianalgesic dosing Morphine 10 mg sc/im = 20 mg oral solution Hydromorphone 4 mg sc/im = 8 mg oral When switching from one opiate to another, reduce the dose by 1/3 due to incomplete crossover tolerance and titrate from that dose

Step 3: Opiates With/Without Adjuvants (cont.): 

Step 3: Opiates With/Without Adjuvants (cont.) Delivery Formulations Morphine: available in concentrated oral immediate release solutions, suppository, short and long-acting oral pills, iv and im/sc Oxycodone: available with or without aspirin and acetaminophen, long and short-acting formulations (Q12h and Q4h)

Step 3: Opiates With/Without Adjuvants (cont.): 

Step 3: Opiates With/Without Adjuvants (cont.) Delivery formulations Hydromorphone: available in suppository, short-acting pill, iv, im/sc Fentanyl: available in short-acting lollipop and long-acting patch (q48-72h) Meperidine: not recommended when doses of >300 mg/day are needed as can lead to tremors, restlessness and seizures; oral form is equivalent to acetaminophen and should be avoided Propoxphene HVL: limited efficacy, can lead to accumulation of neurotoxic metabilites

Step 3: Opiates With/Without Adjuvants (cont.): 

Step 3: Opiates With/Without Adjuvants (cont.) Tips with long-acting oral opiates Do not crush or break Hydration is important Supplement with short-acting opiates for break-through pain Dolophine (methadone) should be given q6h and titrated very slowly to avoid accumulation due to long half-life

Step 3: Opiates With/Without Adjuvants (cont.): 

Step 3: Opiates With/Without Adjuvants (cont.) Topical fentanyl should be used cautiously if patient is febrile. Do not apply topical fentanyl to broken skin Opioid rotation for chronic pain and long-term therapy When a patient is on opiates for several months, tolerance often develops and improved pain control can be achieved by rotating to an alternate opiate – for example, going from long-acting oxycodone to long-acting morphine and then to the fentanyl patch

Step 4: Complementary and Non-Pharmacological Therapies: 

Step 4: Complementary and Non-Pharmacological Therapies Acupuncture Hypnotherapy Massage Magnet Therapy Nutriceuticals (dietary supplements such as glucosamine chondroitin) Music Therapeutic touch Aromatherapy Heat/ice Distraction (tv, reading) These therapies have research to support that they reduce pain.

Step 5: Interventional Strategies: 

Step 5: Interventional Strategies Plays a small role in pain management in HIV/AIDS Usually done by anesthesiologist Nerve blocks, using anesthetics, corticosteroids or neurolytic drugs Implanted epidural pumps or intraspinal drug delivery – cautious use with persons with AIDS due to risk of infection

Inter-Individual Analgesic Variability/Drug Polymorphism: 

Inter-Individual Analgesic Variability/Drug Polymorphism Environmental Factors Recreational drug-drug interactions Cannabis increase effect of morphone Ritonavir (Norvir) increases Ecstasy levels Alcohol Increases abacavir (Ziagen levels) Other drug-drug interactions Ritonavir increases levels of meperidine, propoxyphene and fentanyl Efavirenz and nevirapine lower methadone levels NSAIDS increase lithium level Phenytoin lowers methadone levels

Inter-Individual Analgesic Variability/Drug Polymorphism (cont.): 

Inter-Individual Analgesic Variability/Drug Polymorphism (cont.) Environmental factors Smoking Smoking shortens half-life of NSAIDS and increases metabolism of meperidine, morphine and propoxyphene Weight and body fat Malnourishment can cause increase toxicities of NSAIDS Diet 7 oz grapefruit juice can effect certain drug metabolism for 24 hours Increases plama levels of busprione, carbamazpeine, triazolam by 4-9 fold

Inter-Individual Analgesic Variability/Drug Polymorphism (cont.): 

Inter-Individual Analgesic Variability/Drug Polymorphism (cont.) Genetic factors Slow metabolizers – will find a drug less effective, build up drug levels and have greater toxicity Rapid metabolizers – may find a drug more effective but shorter length of action

Inter-Individual Analgesic Variability/Drug Polymorphism (cont.): 

Inter-Individual Analgesic Variability/Drug Polymorphism (cont.) Sexual dimorphism Possibility that gender may influence both pain perception and efficacy of pain medications Research is ongoing Cultural factors Beliefs, fears, values affect drug response Expectations regarding pain and pain relief Expectations regarding a drug’s effectiveness

Pain and Chemical Dependence: 

Pain and Chemical Dependence Identification of aberrant behavior Examples include non-prescribed dose escalation and prescription forgery Differential diagnoses of aberrant behavior Somatiform disorder Personality disorder Obsessive compulsive personality

Pain and Chemical Dependence (cont.): 

Pain and Chemical Dependence (cont.) Strategies for managing aberrant behavior Using a team approach Directly address the concern with the patient Oral or written agreements Using long-acting formulations instead of short-acting Encourage participation in recovery programs Limit prescriptions to one provider, one pharmacy, one week supply

Pain and Chemical Dependence (cont.): 

Pain and Chemical Dependence (cont.) General guidelines for management Be consistent Address social, psychological and spiritual effects of pain Methadone maintenance Methadone maintenance does not provide analgesia Phenytoin and rifampin may increase methadone metabolism and cause drug-seeking behavior Patients on methadone need additional medicine for pain control

Questions?: 

Questions? Don’t hesitate to email me: pattersonby@umkc.edu