Pain and Chemical Dependency Fathy Nasr

Transcription

1 Pain and Chemical Dependency Fathy Nasr WEB SITE: profathynasr.com

2 Opioid Receptors Adenosine Guanosine Inositol

3 PHAMACOTHERAPY, Step ladder Analgesic pyramids WHO Nociceptive Neuropathic Simple analgesics + Strong opioids Simple Analgesics + Weak opioids Simple Analgesics Adjuvant + Simple analgesics + Strong opioids Adjuvant + Simple Analgesics + Weak opioids Adjuvant + Simple Analgesics

4 WHO 3-Step Ladder 1 Mild Acetaminophen NSAIDs, ASA ± Adjuvants 2 Moderate Codeine Hydrocodone Oxycodone Dihydrocodeine Tramadol ± Adjuvants 3 Severe Morphine Hydromorphone Methadone Levorphanol Fentanyl Oxycodone ± Adjuvants

5 Mechanism of action in vitro The lower the K i value, the higher the affinity mu delta kappa NE 5-HT Tramadol M Morphine Tramadol has a much lower affinity for Opioids receptors than morphine, but, in contrast, additionally inhibits monoamine reuptake. Adapted from: Raffa RB. Am J Med 1996

6 Structural modifications of the morphine skeleton Objective: To separate analgesic activity and side effects by modification of the morphine N N N N N HO HO O O OH OH HO O CO 2 Et O HO N HO

7 Opioids insensitive pain 1. Consider Opioids for all patients with moderate or severe chronic pain but weigh the influences 2. Have no analgesic ceiling effect. 3. Problem of addiction: Presence of pain protects against addiction. Pain that does not respond progressively to increasing opioids dose: 1. Nerve compression or nerve destruction 2. Skeletal pain 3. Neuropathic pain

8 PAIN TREATMENT Analgesic Guideline: Stabilize with short-acting before longacting Utilize least invasive route possible: Oral route preferable; concentrate sublingually Trans cutaneous > subcutaneous > intravenous Converting from one opioid to another: Calculate equi analgesic dose Reduce by 30-50%(Renal, hepatic disease, Geriatric patients) 10% total daily dose as prn If >2 prn s /24 hours, increase baseline by 25-50% to calculate new baseline. 1-2 h for oral; min for parenteral,

9 Adverse effects Side effects are mainly: Constipation. 41% Nausea / vomiting. 32% Sedation / dizziness., mental clouding 29% Rash. Respiratory depression. Less common Sweating, Myoclonus Amenorrhea Itch Sexual dysfunction Urinary retention Headache

10 PAIN TREATMENT Anticipate Opioid Side Effects Constipation Prophylactic treatment better than prn Stool softener: Colace (docusate) Bowel Stimulants: Senokot (senna) Dulcolax (bisacodyl) Hyperosmolar: Lactulose, Miralax Oral naloxone,naltrexone (enteric opioid antagonist) Avoid bulk laxatives

11 PAIN TREATMENT Anticipate Opioids Side Effects Sedation, most common in opioid naïve Tolerance usually develops in hours Appears well before respiratory depression Decrease dose or increase interval Consider amphetamines Avoid naloxone if possible (withdrawal)

12 PAIN TREATMENT Special Situations Anxiety and depression Don t over-normalize or over-pathologize Usual treatments work Special role of dextro amphetamine Neuropathic pain Tricyclic antidepressants >> SSRI s Anticonvulsants Gabapentin, Pregabalin Mexiletine

13 Opioids rotation Respiratory depression Addiction 1].Change route of administration not drug. Oral and trans dermal preferred Oral transmucosal available for fentanyl, used for breakthrough pain Rectal route limited use Par enteral SQ and IV preferred and feasible for long-term therapy Epidural intra thecal generally preferred for long-term use 2].Change the drug PO/PR (mg) Analgesic SC/IV/IM (mg) 30 Morphine Hydromorphone Oxycodone - 20 Methadone 10 3].Active metabolites may contribute more to the analgesic effect of repeated doses than a single dose (Pethadine, Morphine, Methadone)

14 Acute pain: very unlikely Cancer pain : very unlikely Chronic nonmalignant pain: Opioid Therapy: Standard of Care 30-80% of cancer patients depending on stage 24-37% of addicts complains of chronic severe pain (Rosenblum et al, JAMA, 2003) Populations with advanced illness Cancer HIV/AIDS Others Moderate to severe pain Populations with acute illness, injury, or surgery 2-40% of general population (Gureje et al, JAMA, 1998; Verhaak et al, Pain, 1998) 30-40% overall, at least partially disabling in about 30% (Portenoy et al, J Pain, 2004)\ Short-term or long-term opioid therapy

15 Tolerance Is the need for higher dose( or increased plasma concentration) to achieve the same pharmacological effect.? Progress of disease rather than tolerance Declining effect with drug exposure Tolerance to side effects is desirable; tolerance to analgesia may be a problem Large clinical experience is reassuring Theoretical connection to the genesis of addiction/relapse, but neither necessary nor sufficient Should never be labeled addiction Problem of tolerance: Tolerance can be prevented or delayed if dosing is properly scheduled.

16 The 0pioid paradox The smart balance Sufficient Analgesia Tolerance Hypoventilation Reduced GIT motility (Ward,2002)

17 Opioid for Chronic Pain: The Need for Balance Opioids are essential drugs. Patients with pain, including those with addiction, must have access to treatment Opioids are abusable, particularly by those with addiction. Regulators and law enforcement must stem diversion and abuse

18 Opioids for Chronic Pain: Historical Context War on drugs Tragedy of needless pain

19 Definitions Abstinence Addiction Cross-addiction Neuroadaptation Opiophobia Physical dependence Poly substance related disorder Pseudo addiction Recovery Remission Substance abuse Substance dependence Withdrawal syndrome

20 Physical Dependence Potential for abstinence on abrupt discontinuation or dose reduction, or administration of an antagonist Highly variable phenomenology Tachycardia, tachypnea Nausea/vomiting, diarrhea, abdominal cramps Sweating, rhino rhea, piloerection Myalgias and arthralgias Anxiety, insomnia Not a problem if abstinence is avoided Theoretical connection to the genesis of addiction/relapse, but neither necessary nor sufficient Should never be labeled addiction

21 Substance abuse A maladaptive pattern of drug use that results in harm or places the individual at risk Using street drugs, non-medical sources, self escalation, use pain medication for other reason than to control pain Loss of control over drugs Drug use outside of socially accepted norms Includes any use of an illicit drug and some degree of aberrant use of prescription drugs DSM IV: Psychoactive Substance Abuse

22 Addiction Is a primary, chronic, neurobiological disease with genetic, psychosocial and environmental factors influencing its development and manifestation. Presence of pain protects against addiction. It is characterized by behaviors that include one or more of the following: 4C impaired control over drug use compulsive use continued use despite harm craving 3-26% general population 19-25% hospitalized patients 40-60% after major trauma 3-16% chronic pain patient( opiates) 70% 0f pain patient on Opioids

23 Pseudo addiction 1. Aberrant drug-related behavior in patients reacting to under treatment of pain. 2. Diagnostic challenge: May co-exist with addiction or other psychiatric disorders multiple providers, repeatedly requesting more medication Behavior disappears with proper treatment

24 Aberrant Drug-Related Behavior Problematic behaviors or red flags for clinicians Assessment: 1. History and physical examination 2. Diagnostic, therapeutic and laboratory results 3. Evaluations and consultations 4. Discussion of risks and benefits 5. Frequent visits. 6. Informed consent Treatment objectives: 1. Medications (including date, type, dose and quantity) 2. Prescription of long-acting drug only 3. Small prescription (one-week or two-week supply) Periodic reviews 1. Instructions and agreements, 2. Written agreement, perhaps a formal contract

25 Aberrant Drug-Related Behavior cont d Reporting unintended psychic effects Selling prescription drugs Prescription forgery Stealing or borrowing drug from another person Injecting oral formulation Obtaining prescriptions from non-medical source Multiple episodes of prescription loss Concurrent abuse of related illicit drugs Multiple dose escalations despite warnings Repeated gross impairment or dishevelment

26 Initial Structuring of Therapy to Reduce Risk Role of urine/blood drug screen Advantages Can confirm that prescribed drug is taken and that other drugs are not Makes a strong statement potentially useful in monitoring ( trust but verify ) Disadvantages Cannot confirm that the proper dose is taken Can be misinterpreted Can be stigmatizing

27 Opioid Therapy: Laws and Regulations International laws and treaties International Narcotics Control Board No direct influence on prescribers Federal laws and regulations FDA assesses safety and efficacy DEA monitors and addresses abuse/diversion State laws and regulations Medical boards and law enforcement Variable from state to state

28 Managing the patient Avoid IV, inhaled opiate( replace), prefer oral, rectal, topical, T. mucosal, T. dermal and long acting, implanted, intra thecal. Control over conc., dose, type of medication Methadone should be initiated, Continue methadone and document follow-up. Stigma of drug abuse 21% taking psychotropic drugs from their physician

29 Opioid Therapy: Monitoring Outcomes Assess the Seven A s over time 1. Assessment 2. Analgesia (pain relief) 3. Activities of daily living (physical and psychosocial functioning) 4. Adverse effects (side effects) 5. Aberrant drug-related behavior 6. Adherent to diagnosis 7. Action( managements)

30 CAGE questionnaire 2-4 positive answer of 4 Ought to cut People criticize you, annoyed Feel guilty Morning drink (eye opener)

31 PAIN TREATMENT, CONCLUSION Patients are expert about their own pain Pain can almost always be relieved For unrelieved moderate or severe pain: Follow WHO Pain Guidelines Baseline dose at proper interval PRN for breakthrough at 10-15% total dose Get help for difficult cases Pain or palliative care specialists

32 Pain and Chemical Dependency: Conclusions The complex interface between pain and chemical dependency extends from molecular biology to public policy From the clinical perspective, the issues surrounding long-term Opioid therapy are most significant Opioid therapy can be considered in all populations, including those with addictive disease Ability to treat problematic patients is seen as a continuum of skills

33 Pain and Chemical Dependency: Conclusions Safe and effective Opioid therapy requires Assessment and reassessment Skillful drug administration Knowledge of addiction medicine principles Documentation and communication

34 CASE PRESENTATION 75 year old woman with metastatic ovarian cancer Admitted for experimental chemotherapy Not ready for hospice Usual pain severe rated 8/10 Current medication, Percocet (5/325) 2 tabs q4h Why not just increase the dose of Percocet?

35 Using the Equi analgesic Table, calculate an equivalent amount of oral morphine to 2 Percocet (5/325) /4h; select a new baseline. A. 10 mg MS /4h atc B. 15 mg MS /4h at c C. 20 mg MS /6h atc D. 30 mg MS /6h atc E. I am not sure; I need help.

36 Using the Equi analgesic Table, calculate an equivalent amount of oral morphine to 2 Percocet (5/325) /4h; select a new baseline. 2 tabs Percocet /4h = 12 tabs/day 12 tabs x 5 mg oxycodone /tab = 60 mg/day 60 mg oxycodone = 90 mg oral morphine Increase baseline by ~1/3 (poorly controlled) but decrease by ~1/3 with med change 90 mg / 6 doses = 15 mg /4h oral morphine

37 Now, based on the 15 mg MS /4h atc dose, calculate the appropriate prn dose. A. 5 mg MS /1h prn B. 10 mg MS /1h prn C. 15 mg MS /2h prn D. 20 mg MS /4h prn E. I am not sure

38 Now, based on the 15 mg MS /4h atc dose, calculate the appropriate prn dose. 15 mg MS /4h = 90 mg MS per day PRN dose is 10% of total daily dose PRN interval for oral is /1-2h PRN is 10 mg /1h

39 Based on your intervention (15mg /4h atc), her average pain is down to 6/10. She has taken 6 additional prn doses of 10 mg each in 24 hours. Calculate a new baseline and prn. Baseline A. 20 mg MS /4h atc B. 25 mg MS /4h atc C. 30 mg MS /6h atc D. 40 mg MS /6h atc E. I still don t get it

40 Based on your intervention (15mg /4h atc), her average pain is down to 6/10. She has taken 6 additional prn doses of 10 mg each in 24 hours. Calculate a new baseline and prn. PRN A. 10 mg MS /1h prn B. 15 mg MS /1h pr n C. 20 mg MS /4h prn D. 25 mg MS /4h prn

41 Total daily dose is 90 mg + 60 prn = 150 mg New baseline is 150 / 6 doses = 25 mg /4h New prn is 10% of 150 mg = 15 mg q1h prn

42 On 25 mg MS /4h, her pain is now 3/10 on average. She has taken only 1 prn. Choose a long-acting morphine dose and prn. Total 24 hour atc dose is 150 mg MS Baseline 75 mg MS Contin bid (1-60 mg tab and 1-15 mg tab bid) PRN remains the same - 15 mg MSIR /1h prn (3cc of 5 mg/cc liquid or 15 mg MSIR tablet)

43 After 2 months of good pain control, enrolled in hospice, she develops acute back pain (10/10) and vomiting. Calculate an equal amount of parenteral morphine (increased by 1/3) and an hourly rate. A. 1 mg/hr B. 3 mg/h r C. 5 mg/hr D. 7 mg/hr E. I am not sure

44 Hospice, she develops acute back pain (10/10) and vomiting. Calculate an equal amount of parenteral morphine (increased by 1/3) and an hourly rate. 30 mg oral morphine = 10 mg of IV morphine Total dose of 150 mg po = 50 mg IV Increase by ~1/3 = total daily dose of 70 mg Divide by 24 to get an hourly rate = 3 mg/hr

45 Assuming a 3 mg/hour rate, now calculate a new prn morphine dose A. 3 mg /30 minutes prn B. 7 mg /30 minutes pr n C. 10 mg /2h prn D. 20 mg /2h prn E. This seems like too much medicine

46 Assuming a 3 mg/hour rate, now calculate a new prn morphine dose 3 mg/hr = 72 mg per day New PRN is 10% daily dose = 7 mg Parenteral interval is / minutes

47 SOME ADDITONAL QUESTIONS How frequently to re-evaluate the baseline? Are there upper limits to morphine dose? Additional diagnostic issues for her pain? Does the fact she is on hospice limit her treatment options for pain?

48 After several dose adjustments, and radiation therapy, her pain is 3-4 on average. Her morphine infusion is at 5 mg per hour, and she has taken one prn of 12 mg in the last 24 hours. She wants to go home off IV s. Calculate an equivalent dose of morphine concentrate (20 mg/cc). A. 1cc /2h atc B. 2cc /2h at c C. 3cc /4h atc D. 4cc /4h atc E. Lost again

49 Calculate an equivalent dose of morphine concentrate (20mg/cc). 5 mg/hr = 120 mg/day IV morphine 10 mg IV = 30 mg po morphine 120 mg IV = 360 mg po morphine 360 mg / 6 doses = 60 mg q4h 20 mg/cc ms concentrate = 3 cc q4h 10% of 360 = 36 mg /1h prn 36 mg = ~ 2 cc ms concentrate /1h prn

50 Summary Treat moderate to severe pain aggressively Baseline meds around the clock 10% total daily dose prn (/1-2h po/30-60 min IV) Adjust baseline upward daily, adding prn total Oral > trans cutaneous > subcutaneous > IV Reduce by 1/3 when changing meds Elderly, renal or hepatic disease: reduce doses! Under-treated pain has adverse consequences Get help if you need it!

51 Quinsy, Addiction

52 Thank you very much for you attention