1. NEW ANALGESIC IN THE MANAGEMENT OF PAIN
IN 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

2. 2
Presentation Points
Being ignorant is not so much a shame as being unwilling to learn

3. 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

4. 4
Presentation 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. 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. 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. 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. 8
Management
1. Anti-inflammatory drugs
2. Skeletal muscle relaxants
3. Physiotherapy
4. Back exercises
5. Support belt
6. Surgery for severe cases
A open foe may prove a curse ; but a pretended friend is worse

9. 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. 10
Low Back Pain
Frequently due to minor problems
1.Poor posture
2.Mild cases of PID
3.Muscular strain (lumbago)
You are what you think and not what you think you are

11. 11
Periarticular Pain
1. Bursitis
2. Tendonitis (tennis elbow)
Discipline Weighs ounces; Regret weighs Tons

12. 12
Frozen Shoulder
Inflammation of tissues surrounding shoulder
joint
1. Degenerative process
2. Muscle tear
3. Bursitis
Also called scapulohumeral periarthritis
A great many people think they are thinking when they are merely re
arranging their prejudices
W. James

13. 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 complications
Many Ideas grow better when transplanted into another mind than in
the one where they sprang UP
O.W. Holmos

14. 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, 2003
A woman’s desire for revenge outlasts all her other emotions

15. 15
Presentation Points
Every discovery contains an irrational element or
4 creative intuition

16. 16
Nociceptive Pain Pathways
I have never let my Medical schooling interfere with my education
Mark Twain

17. 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 muscles
We learn by thinking and the quality of the learning outcome is determined
by the quality of our thoughts
R.B. Schmeck

18. 18
Mediators involved in pain mechanisms
When they tell you to grow up, they mean stop growing
Piccaso

19. 19
Different target sites for analgesics
A medical school should not be a preparation for life.
A school should be life

20. 20
Limitations of Opioids and NSAIDs
Opioids Drugs
NSAIDs
“Social Isolation is in itself a pathogenic
Factor for disease production”

21. 21
Presentation Points
Through Action You Create your Own Education - D.B. ELLIS

22. 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, 1996
Serious, sincere, systematic study surely secures supreme success

23. 23
Flupirtine: Mechanisms are different from opioids
I. Flupirtine does not show any relevent affinity for opiate receptors
• Structurally different from morphine
• Analgesic activity is not altered by opiate antagonist naloxone
II. Flupirtine does not show any relevent influence on 5HT receptors
• Analgesic activity is not altered by 5HT receptor antagonist cyproheptadine
III. Does not influence the BDZ receptors or the α-1 or α-2 adrenergic receptors or nicotinic or
muscarinic receptors
IV.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. 24
Flupirtine indirectly influences NMDA receptors
Mechanism of action has yet to be fully explained: evidence that flupirtine interacts with
glutamatergic N-Methyl-D-Aspartate (NMDA) receptor1,2.3,4,5
Not possible to demonstrate direct effect on NMDA receptor: all findings point to indirect influence
on 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. 25
Glutamate Receptors
Glutamate receptors
Glutamate receptors
Ionotropic receptors Metabotropic receptors
NMDA AMPA Kainate Gr I Gr II Gr III
The secret of walking on water is Knowing where the stones are

26. 26
NMDA Receptors
Memory, the daughter of attention, is the teeming mother
of knowledge - Martin Tupper

27. 27
NMDA Receptors
Science is below the mind; Spirituality is beyond the mind

28. 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)1
1
Kornhuber J, et al. J Neural Transm 1999; 106: 857-867
Science is below the mind; Spirituality is beyond the mind

29. 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, 1987
Success 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. 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. 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 excretion
Memory, Pity and Beauty are short lived in life;
But tinged with emotion persist in life

32. 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. 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. 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. 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 formulation
Every thing should be made as simple as possible; but not simpler

36. 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. 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

38. 38
Flupirtine Adverse Effects
Rare
↑ in liver
enzymes,
hepatitis
Knowledge without action is useless;
Action without knowledge is foolish

39. 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 min
1
Hummel T, et al. Dose-related analgesic effects of flupirtine. Br Journal of Clin Pharmacol. 32; 69-76; 1991
2
Kobal G, et al. Effects of flupirtine on pain-related evoked potential and spontaneous EEG. Agents and Actions. 23: 117-19; 1988
3
Bromm B. Assessment of analgesia by evoked cerebral potential measurements in humans. Postgrad Med J. 63: 9-13; 1987
4
Gatto R. et al. Study on the analgesic effect of flupirtine in dentistry. Quadeni di Odontostomatologia. 3: 71-82: 1986

40. 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 intensity
percent
Borgognone A, et al. A new non-opioid analgesic (flupirtine) in the treatment of postoperative pain. Therapeutika 1986; 86: 1-

41. 41
Post-op pain in orthopedic setting
Analgesic efficacy of flupirtine versus codeine in 66 patients undergoing hip replacement Sx
Pain 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 d4
Galasko CSB, et al. Current Medical Research and Opinion, 1985, vol 9: 594-601

42. 42
Post-op pain in orthopedic setting
FLU group: time taken for pain relief gradually decreased from 52 min to 32 min
PENTAZOCIN group: small progressive increase from 42 to 48 min
No 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. 43
Post-op pain in orthopedic setting
Higher 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

44. 44
Post-op pain in orthopedic setting
Galasko CSB, et al. Current Medical Research and Opinion, 1985, vol 9: 594-601
Teachers are reservoirs from which, through the process
of education, the students draw the water of life

45. 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: 338-348
It is not your position that makes you happy or unhappy
It is your disposition

46. 46
Post-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. 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: 338-348
Learn to adapt, adjust and accommodate
Learn to give, not to take and learn to serve not to rule

48. 48
Post-op pain in orthopedic Sx setting
Mastronardi P, et al. J Int Med Res, 1988; 16: 338-348
Hate screeches, fear squeals; conceits trumpets
but love since lullabies

49. 49
Post-op pain in gynecological Sx setting
Analgesic efficacy of flupirtine versus dihyrdrocodeine for post-op patients with abdominal
hysterectomy (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 = 25
Assessments 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 interventions
Moore RA ,et al. Br J Anaesth. 1983; 55: 429-432

50. 50
Post-op pain in gynecological Sx setting
Moore RA ,et al. Br J Anaesth. 1983; 55: 429-432
Reputation is made in a moment; character is built in a life time

51. 51
Clinical experience with flupirtine in US
1300 pts evaluated (episiotomy, surgical or dental procedures) at 26 study sites
Placebo evaluations or versus paracetamol 650 mg, codeine 60 mg, pentazocin 50 mg or oxycodone
10/paracetamol 650 mg
FLU 100-300 mg (max 600 mg/d)
Total Pain Relief (TOPAR) scores
Total Pain Relief (TOPAR) scores
McMahon FG, et al. Postgrad Med Journal , 1987; 63: 81-85

52. 52
Clinical experience with flupirtine in US
McMahon FG, et al. Postgrad Med Journal , 1987; 63: 81-85
Character gets you out of bed commitment moves you to
action faith, hope and Discipline follow through to

53. 53
Phase IV study in 869
patients
Max dose 600 mg/d
Duration: 2-90 days
VAS 10 pt scale:
0 = none
10 = maximum pain relief

54. 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 knowledge
54

55. 55
Efficacy of flupirtine in osteoporosis pain
Ringe, et al. Arzneim Forschung, 2003
Opinion is ultimately determined by the feelings
and not by the intellect

56. 56
Low Back Pain: Comparison with Tramadol
209 patients with moderate-severe subacute LBP randomized to either flupirtine or tramadol
Flupirtine 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 Rates
Li C, et al. Current Medical Research and Opinion 2008, 24(12): 3523-3530

57. 57
Low 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 < 0.001
Li 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

58. 58
Low Back Pain: Comparison with Tramadol
Li 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. 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.11-18
A true commitment is a heart felt promise to yourself from
which you will not back down -
D. Mcnally

60. 60
Efficacy 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 Rx
G.Mueller-Schwefe. Progress of Medicine 121 Jg.- Original No.1/2003, Pg.11-18
Serious, sincere, systematic
studies,
surely secure supreme success

61. 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.11-18
God is a comedian performing before an audience
that is afraid to laugh

62. 62
Clinical experience in migraine
47 pts with migraine evaluated
Flupirtine (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 5
Million R, et al. Current Medical Research and Opinion, 1984; vol 9 (no 3): 204-212

63. 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 5
Million R, et al. Current Medical Research and Opinion, 1984; vol 9 (no 3): 204-212

64. 64
Clinical experience in migraine
Million 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

65. 65
10 patients with tumor/chemoRx/radioRx-related neuropathic pain not controlled with opioid drugs
Flupirtine 100 mg x 4 times/d x 8 d (max dose 300 mg x 4 times/d)
Opioid Rx was continued during trial
Assessment 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

66. 66
The word shall perish not for lack of wonders but lack of wonder

67. 67
71 patients with cancer-related pain not controlled with opioid drugs
Flupirtine 100 mg x 4 times/d x 4 wks (max dose 100 mg x 6 times/d); n = 35
Tramadol 50 mg x 4 times/d x 4wks (max dose 50 mg x 6 times/d); n = 36
Assessment 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. 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

69. 69
Presentation Points
“Men of Genius Admired:
Men of Wealth envied
women of power feared but only
women of character are trusted”
A- Friedman

70. 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 pain
1
Scheef W. Analgesic efficacy and safety of oral flupirtine in the treatment of cancer pain. J Postgrad Med 1987;63(suppl 3):67–
70
2
Galasko CS, et al. Trial of oral flupirtine maleate in the treatment of pain after orthopaedic surgery. Curr Med Res Opin
1985;9(9):594–601
3
Heusinger JH. Efficacy and tolerance of flupirtine and pentazocine in 2 multicentre trials. J Postgrad Med 1987;63(suppl 3):71–9
4
Riethmuller-Winzen H. Flupirtine in the treatment of post-operative pain. Postgrad Med J 1987; 63(suppl 3):61–5
5
Scheef W, Wolf-Gruber D. [Flupirtine in patients with cancer pain]. Arzneimittelforschung 1985; 35(1):75–7

72. Dedicated to my family for
making everything worthwhile

73. READ not to contradict or confute
Nor to Believe and Take for Granted
but TO WEIGH AND CONSIDER
THANK YOU
My sincere thanks to SUN-SOLARIS