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New analgesic in the management of pain in this millennium recent perspectives-flupirtine
 

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  • NMDA receptor is one of the main mediators of excitatory neurotransmission. The binding of both glutamate and glycine activates this receptor. The receptor is a ligand gated ion channel, which permits the movement of calcium, sodium and potassium across the post-synaptic membrane
  • NMDA receptor is one of the main mediators of excitatory neurotransmission. The binding of both glutamate and glycine activates this receptor. The receptor is a ligand gated ion channel, which permits the movement of calcium, sodium and potassium across the post-synaptic membrane
  • NMDA receptor is one of the main mediators of excitatory neurotransmission. The binding of both glutamate and glycine activates this receptor. The receptor is a ligand gated ion channel, which permits the movement of calcium, sodium and potassium across the post-synaptic membrane
  • NMDA receptor is one of the main mediators of excitatory neurotransmission. The binding of both glutamate and glycine activates this receptor. The receptor is a ligand gated ion channel, which permits the movement of calcium, sodium and potassium across the post-synaptic membrane
  • NMDA receptor is one of the main mediators of excitatory neurotransmission. The binding of both glutamate and glycine activates this receptor. The receptor is a ligand gated ion channel, which permits the movement of calcium, sodium and potassium across the post-synaptic membrane
  • NMDA receptor is one of the main mediators of excitatory neurotransmission. The binding of both glutamate and glycine activates this receptor. The receptor is a ligand gated ion channel, which permits the movement of calcium, sodium and potassium across the post-synaptic membrane
  • PPID = peak pain intensity difference SPID = sum of pain intensity difference
  • NRS numerical rating scale
  • NRS numerical rating scale
  • NRS numerical rating scale

New analgesic in the management of pain in this millennium recent perspectives-flupirtine New analgesic in the management of pain in this millennium recent perspectives-flupirtine Presentation Transcript

  • NEW ANALGESIC IN THE MANAGEMENT OF PAININ THIS MILLANEUM – RECENT PERSPECTIVES -FLUPIRTINE Prof. A.V. SRINIVASAN, MD, DM, Ph.D, F.A.A.N, F.I.A.N. Emeritus Professor The Tamilnadu Dr. M.G.R. Medical University Former Head Institute of Neurology, Madras Medical College
  • 2Presentation PointsBeing ignorant is not so much a shame as being unwilling to learn
  • 3 Rationale Analgesics are used in clinical practice for a variety of painful conditions NSAIDs are the most commonly used analgesic-anti-inflammatory drugs, but have GI ADRs Opioid analgesics are also used in moderate-severe painful conditions, but have their own limitations due to unwanted side effects Flupirtine is an amino-substituted pyridine derivative, centrally-acting, but non-opioid analgesic Molecular structure and mechanisms do not resemble any other currently available analgesic agent “The True Art of Memory is The Art of Attention” - S.Johnson
  • 4Presentation Points “ We Sometimes think we have forgotten something when in fact we never really learned it in the first place” Imp.Your Memory Skills
  • 5 Pain Sensation Pain is an unpleasant sensation that originates from ongoing or impending tissue damage Management of different types of pain (acute, postoperative, inflammatory, neuropathic, cancer- related and chronic) is the most frequent problem encountered by clinicians Drug therapy is the first line of approach for the treatment of pain Through Action You Create your Own Education - D.B. ELLIS
  • 6 Pain Sensation Acute pain >> normal and predictable physiologic response to adverse chemical, thermal, or mechanical stimulus; it is associated with surgery, trauma, or acute illness and is usually experienced for a limited and defined period of time Chronic pain usually present for a period exceeding 3 weeks and usually associated with neuropathic pain, cancer-related pain and certain types of arthritis (OA and RA) Thought is the labour of the intellect Reverie is its pleasure
  • 7 Pain classified according to underlying mechanisms Nociceptive caused by tissue injuries and damage Inflammatory pain Neuropathic caused by nerve injuries Imagination is more Important than Knowledge
  • 8 Management1. Anti-inflammatory drugs2. Skeletal muscle relaxants3. Physiotherapy4. Back exercises5. Support belt6. Surgery for severe cases A open foe may prove a curse ; but a pretended friend is worse
  • 9 Low Back Pain Annually 15-45% of adults suffer from low back pain Lifetime prevalence is at least 70% Most prevalent among adults 35-55 yrs old Associated with substantial disability Economic impact  Absenteeism  Increased utilization of health care resources It is a great misfortune not to possess sufficient wit to speak well
  • 10 Low Back PainFrequently due to minor problems1.Poor posture2.Mild cases of PID3.Muscular strain (lumbago) You are what you think and not what you think you are
  • 11 Periarticular Pain1. Bursitis2. Tendonitis (tennis elbow) Discipline Weighs ounces; Regret weighs Tons
  • 12 Frozen ShoulderInflammation of tissues surrounding shoulder joint 1. Degenerative process 2. Muscle tear 3. BursitisAlso called scapulohumeral periarthritis A great many people think they are thinking when they are merely re arranging their prejudices W. James
  • 13 Post-operative Pain Millions of surgeries are performed on an annual basis, necessitating the frequent use of acute postoperative pain management There are many types of surgery and, with few exceptions, all are painful More than 80% of patients experience post-operative pain Important issues in managing post-operative pain  Optimizing pain management for the individual patient  Ensuring safety  Minimizing side effects  Maintaining ease of use for staff and patients  Reducing complicationsMany Ideas grow better when transplanted into another mind than inthe one where they sprang UP O.W. Holmos
  • 14 Post-operative pain still undermanaged 1 Apfelbaum JL, et al. Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg, 2003A woman’s desire for revenge outlasts all her other emotions
  • 15Presentation Points Every discovery contains an irrational element or 4 creative intuition
  • 16 Nociceptive Pain PathwaysI have never let my Medical schooling interfere with my education Mark Twain
  • 17 Low Back Pain Lifting even smaller weights in the wrong way can cause low back pain Sitting for long hours with poor postures places strain on back musclesWe learn by thinking and the quality of the learning outcome is determinedby the quality of our thoughts R.B. Schmeck
  • 18Mediators involved in pain mechanisms When they tell you to grow up, they mean stop growing Piccaso
  • 19Different target sites for analgesics A medical school should not be a preparation for life. A school should be life
  • 20Limitations of Opioids and NSAIDsOpioids DrugsNSAIDs “Social Isolation is in itself a pathogenic Factor for disease production”
  • 21 Presentation PointsThrough Action You Create your Own Education - D.B. ELLIS
  • 22 Flupiritine Spectrum of Activity 1 Friedel and Fittion, Drugs 1993/ 2Schuster, CNS Drugs 1999/3Sheridan et al. Neurology 1986/4Schwarz, et al. J Neurol Transm, 1996Serious, sincere, systematic study surely secures supreme success
  • 23 Flupirtine: Mechanisms are different from opioidsI. Flupirtine does not show any relevent affinity for opiate receptors• Structurally different from morphine• Analgesic activity is not altered by opiate antagonist naloxoneII. Flupirtine does not show any relevent influence on 5HT receptors• Analgesic activity is not altered by 5HT receptor antagonist cyproheptadineIII. Does not influence the BDZ receptors or the α-1 or α-2 adrenergic receptors or nicotinic or muscarinic receptorsIV.Low potential for drug abuse, drug dependence, tolerance or withdrawal symptoms1 Ringe JD, et al. Analgesic Efficacy of Flupirtine in primary care of patients with osteoporosis related pain. Arzneim.-Forsch./Drug Res. 53, No. 7, 496−502 (2003) Discipline Weighs ounces Regret weighs Tons
  • 24 Flupirtine indirectly influences NMDA receptorsMechanism of action has yet to be fully explained: evidence that flupirtine interacts withglutamatergic N-Methyl-D-Aspartate (NMDA) receptor1,2.3,4,5Not possible to demonstrate direct effect on NMDA receptor: all findings point to indirect influenceon NMDA receptor (functional NMDA antagonism) 1 Block F, et al. NeuroReport 1994/2Rupalla K, et al. Eur J Pharmacol 1995/3Perovil S, et al. Neurodegeneration 1995/4Osborne NN et al. Brain Research 1994/ 5Schwarz M, et al. NeuroReport 1994 Experience can be defined as yesterday’s answer to today’s problems
  • 25 Glutamate Receptors Glutamate receptors Glutamate receptors Ionotropic receptors Metabotropic receptors NMDA AMPA Kainate Gr I Gr II Gr IIIThe secret of walking on water is Knowing where the stones are
  • 26NMDA ReceptorsMemory, the daughter of attention, is the teeming motherof knowledge - Martin Tupper
  • 27NMDA ReceptorsScience is below the mind; Spirituality is beyond the mind
  • 28 Flupirtine as a SNEPCO Flupirtine KCNQ Stabilizes membrane: inhibits incoming pain signals G-protein NMDA-receptor with Mg+2 block K+ ↓ Ca+2 increase after excitotoxic stimulation Interaction with G-protein-activated inwardly rectifying K+ channels (GIRK) >> opening of which leads to stabilization of RMP of neuronal cells >> causes an indirect inhibition of NMDA receptor. At therapeutically relevant concentration, flupirtine is a selective neuronal potassium channel opener (SNEPCO)11 Kornhuber J, et al. J Neural Transm 1999; 106: 857-867 Science is below the mind; Spirituality is beyond the mind
  • 29 Analgesic Activity: Animal Studies Methadone Methadone Flupirtine Flupirtine Dextroproxyphene Dextroproxyphene Buprenorphine Buprenorphine > > Codeine Codeine Morphine Morphine Pentazocine Pentazocine Phenacetin Phenacetin Paracetamol Paracetamol • Max analgesia reached at 30 min post-dose • Duration of effects: at least 75 min • Flupirtine classified as medium to strong analgesic with onset/duration similar to codeine Jakovlev V, et al. Arzneimittel-Forschnug 35: 30-43; 1985 Nickel B. The antinociceptive activity of flupirtine: a structurally new analgesic. Postgrad Med Journal 63(Suppl 3),19-28, 1987Success is a prize to be won. Action is the road to it.Chance is what may lurk in the shadows at the road side.
  • 30 Flupirtine Indications Available as 100 mg capsules Indicated for use in acute and chronic pain conditions such as  painful musculoskeletal conditions with or without spasm  pains after traumatic/orthopedic/general surgical/gynecological operations and injuries  stress headaches  cancer-related pain  dysmenhorrhea  neuropathic pain NATURE, TIME AND PATIENCE are the 3 great physicians
  • 31 Pharmacokinetic Data • Studies included both young and elderly healthy volunteers • Studies included patients with mild/mod renal impairment, liver disease and epilepsy Parameter Data (200 mg flupirtine maleate orally) Bioavailability 90% (Freely soulble in water and undergoes rapid gastric absorption and appears in plasma in 15-30 min) Cmax 1.98 mg/L (Plasma concentrations are linearly related over the dose range from 50-300 mg) Tmax 2 hr Half-life ~ 9.6 hr (Drug accumulation not observed after oral admin of 100 mg) Vd 1.16 L/kg Protein binding ~84 % Metabolism Hepatic [2 active metabolites with 20-30% of analgesic activity of parent compound] Excretion 72% renal and 18% fecal excretionMemory, Pity and Beauty are short lived in life;But tinged with emotion persist in life
  • Pharmacokinetic Data in Special 32 Populations Parameter Data (100 mg flupirtine maleate orally) Healthy volunteers Hepatic Impairment Renally impaired 18-35 yrs 66-83 yrs ClCr = 44-99 ml/min Cmax 0.77 mg/L 1.12 mg/L 1 mg/L 0.72 mg/L Tmax 1.6 hr 1.8 hr 2.5 hr 1.8 hr Half-life 6.5 hr 14 hr Not reported 9.8 hr Total body clearance 16.5 L/hr 9.7 L/hr Not reported 15.8 L/hr Mean elimination half-life of flupirtine was higher in elderly patients than in younger normal subjects, and this was associated with an increased maximum serum concentration and reduced clearance Abrams SM, et al. Pharmacokinetics of flupirtine in elderly volunteers and in patients with moderate renal impairment. Postgrad Med J. 1988 May;64(751):361-3.It is the disease of not listening, the malady of not marking, that I am troubled withal - Shakespeare
  • 33 Flupirtine Dosage 100 mg, three to four times daily For severe pain, 200 mg three times daily (daily dose exceeding 600 mg not advisable) The sign wasn’t placed there By the Big Printer in the sky
  • 34 Flupirtine Dosage in Special Populations For elderly patients: 100 mg twice daily initially, increased to thrice daily if needed For patients with impaired renal function: 100 mg thrice daily (with careful monitoring) For patients with impaired hepatic function: use carefully with monitoring of liver enzymes Pediatric patients: adequate trials have not been conducted in these patients Pregnancy and Lactation: safety and efficacy studies have not been conducted Flupirtine can be excreted into breast mik in lactating mothers The art of medicine is caring for the heart of the patient
  • 35 Flupirtine Contraindications  Patients with a risk of a hepatic encephalopathy  Patients with cholestasis  Patients with myasthenia gravis  Patients with pre-existing liver disease and alcohol abuse  In patients with hypersensitivity to flupirtine maleate or any other ingredient of this formulationEvery thing should be made as simple as possible; but not simpler
  • 36 Flupirtine Precautions May cause sedation: patients should not undertake driving vehicles or operation machinery More care if alcohol is also consumed Speak obligingly even if you cannot oblige
  • 37 Flupirtine Drug Interactions Flupirtine can intensify the action of alcohol and medicines which exhibit sedative or muscle- relaxing properties Flupirtine may displace warfarin from its protein binding and thus increase the anticoagulant effect necessitating dosage changes of warfarin Flupirtine with paracetamol or carbamazepine should not be used Develop the heart; art comes automatically
  • 38Flupirtine Adverse Effects Rare ↑ in liver enzymes, hepatitis Knowledge without action is useless; Action without knowledge is foolish
  • 39 Analgesic Activity: Human Studies Author Dose Test Results Hummel 50-100 CO2 application to Linear dose-related reduction in (1991)1 mg nasal mucosa pain intensity Kobal (1988)2 200 mg CO2 application to Pain threshold ↑ within 30-60 min nasal mucosa with max effect 1.5-2 hr postdose Bromm (1987)3 IV 80 mg Evoked cerebral Equivalent analgesia with flupirtine potentials in response and pentazocine to phasic pain stimuli Gatto (1886)4 Thermal stimulation of Flupirtine superior to placebo tooth pulp producing ↑ pain threshold within 15 min and lasting up to 45 min1 Hummel T, et al. Dose-related analgesic effects of flupirtine. Br Journal of Clin Pharmacol. 32; 69-76; 19912 Kobal G, et al. Effects of flupirtine on pain-related evoked potential and spontaneous EEG. Agents and Actions. 23: 117-19; 19883 Bromm B. Assessment of analgesia by evoked cerebral potential measurements in humans. Postgrad Med J. 63: 9-13; 19874 Gatto R. et al. Study on the analgesic effect of flupirtine in dentistry. Quadeni di Odontostomatologia. 3: 71-82: 1986
  • 40 Post-op pain in general Sx setting Analgesic efficacy of flupirtine versus placebo in 28 patients undergoing general surgical procedures Pain intensity measured on a 5-point scale (no pain – unbearable pain) Dose used: 100 mg orally single dose Assessments at baseline and 3 and 6 hr post-dose Reduction in pain intensity Reduction in pain intensitypercentBorgognone A, et al. A new non-opioid analgesic (flupirtine) in the treatment of postoperative pain. Therapeutika 1986; 86: 1-
  • 41 Post-op pain in orthopedic settingAnalgesic efficacy of flupirtine versus codeine in 66 patients undergoing hip replacement SxPain relief measured on 5-point scale (0 = none and 4 = unbearable)Dose used: FLU 100-200 mg orally as required (min interval of 4 hrs between doses) PENTAZOCIN 50-100 mg orally as required (min interval of 4 hrs between doses) Patients (n) in each severity grade on d1 Patients (n) in each severity grade on d1 Patients (n) in each severity grade on d4 Patients (n) in each severity grade on d4Galasko CSB, et al. Current Medical Research and Opinion, 1985, vol 9: 594-601
  • 42 Post-op pain in orthopedic settingFLU group: time taken for pain relief gradually decreased from 52 min to 32 minPENTAZOCIN group: small progressive increase from 42 to 48 minNo significant differences between groups Time taken for pain relief after drug administration (min) Time taken for pain relief after drug administration (min) Complete pain relief after drug administration (%) Complete pain relief after drug administration (%)Galasko CSB, et al. Current Medical Research and Opinion, 1985, vol 9: 594-601
  • 43 Post-op pain in orthopedic settingHigher proportion of patients reported being satisfied with flupirtine than with pentazocin Patients satisfied with analgesia (%) Patients satisfied with analgesia (%)Galasko CSB, et al. Current Medical Research and Opinion, 1985, vol 9: 594-601
  • 44Post-op pain in orthopedic settingGalasko CSB, et al. Current Medical Research and Opinion, 1985, vol 9: 594-601Teachers are reservoirs from which, through the processof education, the students draw the water of life
  • 45 Post-op pain in orthopedic Sx setting Analgesic efficacy of flupirtine versus diclofenac sodium for post-op patients in elective orthopedic Sx settings (n = 40) Dose used: 100 mg orally single dose (FLU) x 4 doses (max/day); n = 20 50 mg orally single dose (DIC) x 4 doses (max/day); n = 20 Assessments made 30 and 60 min post-dose and 1 hrly for 6 hrs on 100 mm VAS (0 = no pain and 100 = max conceivable pain) Pain relief measured on 100 mm VAS (0 = no pain relief and 100 = total relief) Overall Clinical Assessment (values = number of patients) Therapy Excellent Good Moderate Useless Flupirtine (n = 20) 4 2 8 6 Diclofenac (n = 20) 1 4 4 11 Mastronardi P, et al. J Int Med Res, 1988; 16: 338-348It is not your position that makes you happy or unhappyIt is your disposition
  • 46Post-op pain in orthopedic Sx setting Analgesic effect of first administration of FLU or DIC (mean VAS scores)Mastronardi P, et al. J Int Med Res, 1988; 16: 338-348 A good teacher is a perpetual learner
  • 47 Post-op pain in orthopedic Sx setting Analgesic effect of third administration of FLU or DIC (mean VAS scores) * * * * * * * * Statistically significant between groups Mastronardi P, et al. J Int Med Res, 1988; 16: 338-348Learn to adapt, adjust and accommodateLearn to give, not to take and learn to serve not to rule
  • 48 Post-op pain in orthopedic Sx setting Mastronardi P, et al. J Int Med Res, 1988; 16: 338-348Hate screeches, fear squeals; conceits trumpetsbut love since lullabies
  • 49 Post-op pain in gynecological Sx settingAnalgesic efficacy of flupirtine versus dihyrdrocodeine for post-op patients with abdominalhysterectomy (n = 50)Pain intensity measured on a 4-point scale (0= no pain – 3 = severe pain)Dose used: 100 mg orally single dose (FLU); n = 25 60 mg orally single dose (Dihydrocodeine); n = 25Assessments made twice daily x 3 days post-op Pain intensity and relief scores Pain intensity and relief scores Total analgesic and antiemetics interventions Total analgesic and antiemetics interventionsMoore RA ,et al. Br J Anaesth. 1983; 55: 429-432
  • 50 Post-op pain in gynecological Sx setting Moore RA ,et al. Br J Anaesth. 1983; 55: 429-432Reputation is made in a moment; character is built in a life time
  • 51 Clinical experience with flupirtine in US1300 pts evaluated (episiotomy, surgical or dental procedures) at 26 study sitesPlacebo evaluations or versus paracetamol 650 mg, codeine 60 mg, pentazocin 50 mg or oxycodone10/paracetamol 650 mgFLU 100-300 mg (max 600 mg/d) Total Pain Relief (TOPAR) scores Total Pain Relief (TOPAR) scoresMcMahon FG, et al. Postgrad Med Journal , 1987; 63: 81-85
  • 52 Clinical experience with flupirtine in US McMahon FG, et al. Postgrad Med Journal , 1987; 63: 81-85Character gets you out of bed commitment moves you toaction faith, hope and Discipline follow through to
  • 53Phase IV study in 869patientsMax dose 600 mg/dDuration: 2-90 daysVAS 10 pt scale:0 = none10 = maximum pain relief
  • 20 patients had 29 AEs (2.4%) 20 patients had 29 AEs (2.4%) 19 AEs rated as drug-related 19 AEs rated as drug-related 10 AEs rated possibly not drug-related 10 AEs rated possibly not drug-related 1.3% CNS related 1.3% CNS related 1.1% GI related 1.1% GI related no drug dependency no drug dependency no tolerance no tolerance no withdrawal symptoms no withdrawal symptoms 25 of 29 AEs resolved by study end 25 of 29 AEs resolved by study end wisdom to listen - Hodly’s to speak and it is the privilege of the It is the providence of the knowledge54
  • 55Efficacy of flupirtine in osteoporosis pain Ringe, et al. Arzneim Forschung, 2003Opinion is ultimately determined by the feelingsand not by the intellect
  • 56 Low Back Pain: Comparison with Tramadol209 patients with moderate-severe subacute LBP randomized to either flupirtine or tramadolFlupirtine 100 mg x 3 times/d x 5-7 d (n = 105)Tramadol 50 mg x 3 times/d x 5-7d (n = 104)Assessment on Numerical Rating Scale 0 = no pain to 10 = worst pain imaginable Pain Relief Rates Pain Relief RatesLi C, et al. Current Medical Research and Opinion 2008, 24(12): 3523-3530
  • 57Low Back Pain: Comparison with Tramadol Mean LBP Intensity Scores Mean LBP Intensity Scores ADR events and ADR related dropouts (%) ADR events and ADR related dropouts (%) p = 0.02 59% 56% p < 0.001Li C, et al. Current Medical Research and Opinion 2008, 24(12): 3523-3530 A great many people think they are thinking when they are merely re arranging their prejudices W. James
  • 58Low Back Pain: Comparison with TramadolLi C, et al. Current Medical Research and Opinion 2008, 24(12): 3523-3530 The Truth is fear and immorality are two of the greatest inhibitors of Performance to progress
  • 59 Efficacy in Musculo-Skeletal Disorders 7,806 pts with musclo-skeletal disorders (cervical/lumbar spine pain, myofascial pain, tension headache, muscle spasm associated with arthritis) evaluated Flupirtine 100 mg (2-3 doses/d) max dose 600 mg/d Assessment on pain scale: 0 = no pain to 4 = very severe pain G.Mueller-Schwefe. Progress of Medicine 121 Jg.- Original No.1/2003, Pg.11-18A true commitment is a heart felt promise to yourself fromwhich you will not back down - D. Mcnally
  • 60Efficacy in Musculo-Skeletal Disorders % patients with response (improvement by at % patients with response (improvement by at % patients with continuous pain at beginning % patients with continuous pain at beginning least 1 step) at end of 1 wk least 1 step) at end of 1 wk and end of 4 wks Rx and end of 4 wks RxG.Mueller-Schwefe. Progress of Medicine 121 Jg.- Original No.1/2003, Pg.11-18 Serious, sincere, systematic studies, surely secure supreme success
  • 61 Efficacy in Musculo-Skeletal Disorders % patients with response (improvement by at least 1 % patients with response (improvement by at least 1 % patients with response (improvement by at least 1 % patients with response (improvement by at least 1 step): reduction of muscle spasm step): reduction of muscle spasm step): restriction of daily activities step): restriction of daily activities G.Mueller-Schwefe. Progress of Medicine 121 Jg.- Original No.1/2003, Pg.11-18God is a comedian performing before an audiencethat is afraid to laugh
  • 62 Clinical experience in migraine47 pts with migraine evaluatedFlupirtine (n = 24) 100 mg (up to 4 doses/d x 5 d)Paracetamol (n = 23) 1 gm (up to 4 doses/d x 5 d) 60 % patients unable to work 20 % patients confined to bed 50 PAR PAR 40% pts % pts 10 30 FLU 20 10 FLU 0 0 1 2 3 4 5 1 2 3 4 5Million R, et al. Current Medical Research and Opinion, 1984; vol 9 (no 3): 204-212
  • 63 Clinical experience in migraine Mean VAS scores of pain severity during migraine attack 70 60 50 40 Score 30 PAR 20 FLU 10 0 Time (d) 1 2 3 4 5Million R, et al. Current Medical Research and Opinion, 1984; vol 9 (no 3): 204-212
  • 64Clinical experience in migraineMillion R, et al. Current Medical Research and Opinion, 1984; vol 9 (no 3): 204-212 Man is made by his beliefs; as he beliefs, so he is
  • 6510 patients with tumor/chemoRx/radioRx-related neuropathic pain not controlled with opioid drugsFlupirtine 100 mg x 4 times/d x 8 d (max dose 300 mg x 4 times/d)Opioid Rx was continued during trialAssessment of pain relief by Wisconsin Brief Pain Questionnaire (0 = no pain to 10 = worst pain) * * * Patient # 1 and 10 could not understand the questionnaire and hence values are not available
  • 66The word shall perish not for lack of wonders but lack of wonder
  • 6771 patients with cancer-related pain not controlled with opioid drugsFlupirtine 100 mg x 4 times/d x 4 wks (max dose 100 mg x 6 times/d); n = 35Tramadol 50 mg x 4 times/d x 4wks (max dose 50 mg x 6 times/d); n = 36Assessment of pain relief by scale (1 = pain free to 5 = severe pain) Pain Intensity Differences after 4 wks Pain Intensity Differences after 4 wks No Pre-Rx Successful Pre-Rx Not successful Pre-Rx All patients In any field, find the strangest thing and explore it
  • 68 % pts with pain alleviation after 4 wks % pts with pain alleviation after 4 wks 54 % 36 %There are sixty trillion cells in the human body
  • 69Presentation Points“Men of Genius Admired:Men of Wealth enviedwomen of power feared but onlywomen of character are trusted” A- Friedman
  • 70 Summary Flupirtine is a centrally acting,non-opioid analgesic that exhibits additionally muscle relaxing activity Has been used in Europe for 20 years in treatment of pain states such as post-Sx, arthritis, and muscular pain syndromes Flupirtine has been found in clinical trials to be safe and well tolerated 1,2,3,4 Free of the opioid-related respiratory depression, dependence potential, and constipation4,5 Devoid of cardiac effects in humans during prolonged exposure5 Useful adddition alone and in combination with NSAIDs to control pain1 Scheef W. Analgesic efficacy and safety of oral flupirtine in the treatment of cancer pain. J Postgrad Med 1987;63(suppl 3):67–702 Galasko CS, et al. Trial of oral flupirtine maleate in the treatment of pain after orthopaedic surgery. Curr Med Res Opin1985;9(9):594–6013 Heusinger JH. Efficacy and tolerance of flupirtine and pentazocine in 2 multicentre trials. J Postgrad Med 1987;63(suppl 3):71–94 Riethmuller-Winzen H. Flupirtine in the treatment of post-operative pain. Postgrad Med J 1987; 63(suppl 3):61–55 Scheef W, Wolf-Gruber D. [Flupirtine in patients with cancer pain]. Arzneimittelforschung 1985; 35(1):75–7
  • Dedicated to my family formaking everything worthwhile
  • READ not to contradict or confuteNor to Believe and Take for Grantedbut TO WEIGH AND CONSIDERTHANK YOUMy sincere thanks to SUN-SOLARIS