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

NEW ANALGESIC IN THE MANAGEMENT OF NEW ANALGESIC IN THE MANAGEMENT OF PAIN IN THIS MILLANEUM – PAIN IN THIS MILLANEUM – RECENT RECENT PERSPECTIVES - FLUPIRTINEPERSPECTIVES - 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

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

Presentation PointsPresentation Points2

Being ignorant is not so much a shame as being unwilling to learn

RationaleRationale3

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


“ We Sometimes think we have forgotten something when in fact we never really learned it in the first place”Imp.Your Memory Skills

Pain SensationPain Sensation5

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

Pain SensationPain Sensation6

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

Pain classified according to underlying Pain classified according to underlying mechanismsmechanisms

7

Nociceptive caused by tissue injuries and damage

Inflammatory pain

Neuropathic caused by nerve injuries

Imagination is more Important than KnowledgeImagination is more Important than Knowledge

ManagementManagement8

1. 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

Low Back PainLow Back Pain9

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 nor sufficient judgment to keep silent - La Broyers character


Frequently due to minor problems

1.Poor posture2.Mild cases of PID3.Muscular strain (lumbago)

You are what you think and not what you think you areYou are what you think and not what you think you are

Periarticular PainPeriarticular Pain11

1. Bursitis

2. Tendonitis (tennis elbow)

Discipline Weighs ounces; Regret weighs Tons

Frozen ShoulderFrozen Shoulder12

Inflammation of tissues surrounding shoulder joint

1. Degenerative process2. Muscle tear3. Bursitis

Also called scapulohumeral periarthritis

A great many people think they are thinking when they are merely re A great many people think they are thinking when they are merely re arranging their prejudicesarranging their prejudices

W. JamesW. James

Post-operative PainPost-operative Pain13

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 Many Ideas grow better when transplanted into another mind than in the one where they sprang UPthe one where they sprang UP

O.W. HolmosO.W. Holmos

Post-operative pain still undermanagedPost-operative pain still undermanaged14

1Apfelbaum 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


Every discovery contains an irrational element or Every discovery contains an irrational element or 4 creative intuition4 creative intuition

Nociceptive Pain PathwaysNociceptive Pain Pathways16

I have never let my Medical schooling interfere with my education I have never let my Medical schooling interfere with my education Mark TwainMark Twain


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 We learn by thinking and the quality of the learning outcome is determined by the quality of our thoughtsby the quality of our thoughts

R.B. SchmeckR.B. Schmeck

Mediators involved in pain mechanismsMediators involved in pain mechanisms18

When they tell you to grow up, they mean stop growing When they tell you to grow up, they mean stop growing PiccasoPiccaso

Different target sites for analgesicsDifferent target sites for analgesics19

A medical school should not be a preparation for life. A medical school should not be a preparation for life. A school should be lifeA school should be life

Limitations of Opioids and NSAIDsLimitations of Opioids and NSAIDs20

Opioids Drugs

NSAIDs

“Social Isolation is in itself a pathogenicFactor for disease production”


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

Flupiritine Spectrum of ActivityFlupiritine Spectrum of Activity22

1Friedel 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

Flupirtine: Mechanisms are different from Flupirtine: Mechanisms are different from opioidsopioids

23

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

Flupirtine indirectly influences NMDA Flupirtine indirectly influences NMDA receptorsreceptors

24

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)

1Block 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

Glutamate ReceptorsGlutamate Receptors25

Glutamate receptorsGlutamate receptors

Ionotropic receptors Metabotropic receptors

AMPANMDA Kainate Gr IIGr I Gr III

The secret of walking on water is Knowing where the stones are

NMDA ReceptorsNMDA Receptors26

Memory, the daughter of attention, is the teeming mother of knowledge - Martin Tupper

NMDA ReceptorsNMDA Receptors27

Science is below the mind; Spirituality is beyond the mind

Flupirtine as a SNEPCOFlupirtine as a SNEPCO28

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

G-protein

K+

Flupirtine

NMDA-receptor with Mg+2 block

↓ Ca+2 increase after excitotoxic stimulation

1Kornhuber J, et al. J Neural Transm 1999; 106: 857-867

Stabilizes membrane: inhibits incoming pain signals

KCNQ

Science is below the mind; Spirituality is beyond the mind

Analgesic Activity: Animal StudiesAnalgesic Activity: Animal Studies29

MethadoneBuprenorphine

Morphine

MethadoneBuprenorphine

Morphine

FlupirtineFlupirtine

PentazocinePentazocine

DextroproxypheneCodeine

PhenacetinParacetamol

DextroproxypheneCodeine

PhenacetinParacetamol

>>

Jakovlev V, et al. Arzneimittel-Forschnug 35: 30-43; 1985Nickel B. The antinociceptive activity of flupirtine: a structurally new analgesic. Postgrad Med Journal 63(Suppl 3),19-28, 1987

• 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

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.

Flupirtine IndicationsFlupirtine Indications30

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

Pharmacokinetic DataPharmacokinetic Data31

• Studies included both young and elderly healthy volunteers• Studies included patients with mild/mod renal impairment, liver disease and epilepsy

ParameteParameterr

Data (200 mg flupirtine maleate orally)Data (200 mg flupirtine maleate orally)

BioavailabilitBioavailabilityy

90% (Freely soulble in water and undergoes rapid gastric absorption 90% (Freely soulble in water and undergoes rapid gastric absorption and appears in plasma in 15-30 min)and appears in plasma in 15-30 min)

CmaxCmax 1.98 mg/L (Plasma concentrations are linearly related over the dose 1.98 mg/L (Plasma concentrations are linearly related over the dose range from 50-300 mg)range from 50-300 mg)

TmaxTmax 2 hr2 hr

Half-lifeHalf-life ~ 9.6 hr (Drug accumulation not observed after oral admin of 100 mg)~ 9.6 hr (Drug accumulation not observed after oral admin of 100 mg)

VdVd 1.16 L/kg1.16 L/kg

Protein Protein bindingbinding

~84 %~84 %

MetabolismMetabolism Hepatic [2 active metabolites with 20-30% of analgesic activity of Hepatic [2 active metabolites with 20-30% of analgesic activity of parent compound]parent compound]

ExcretionExcretion 72% renal and 18% fecal excretion72% renal and 18% fecal excretionMemory, Pity and Beauty are short lived in life; But tinged with emotion persist in life

Pharmacokinetic Data in Special Pharmacokinetic Data in Special PopulationsPopulations

32

ParameterParameter Data (100 mg flupirtine maleate orally)Data (100 mg flupirtine maleate orally)

Healthy volunteersHealthy volunteers Hepatic Hepatic ImpairmentImpairment

Renally impairedRenally impaired

18-35 yrs18-35 yrs 66-83 yrs66-83 yrs ClCr = 44-99 ClCr = 44-99 ml/minml/min

CmaxCmax 0.77 mg/L0.77 mg/L 1.12 mg/L1.12 mg/L 1 mg/L1 mg/L 0.72 mg/L0.72 mg/L

TmaxTmax 1.6 hr1.6 hr 1.8 hr1.8 hr 2.5 hr2.5 hr 1.8 hr1.8 hr

Half-lifeHalf-life 6.5 hr6.5 hr 14 hr14 hr Not reportedNot reported 9.8 hr9.8 hr

Total body Total body clearanceclearance

16.5 L/hr16.5 L/hr 9.7 L/hr9.7 L/hr Not reportedNot reported 15.8 L/hr15.8 L/hr

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.

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

It is the disease of not listening, the malady of not marking, that I am troubled withal - Shakespeare

sborgharkar16165

It would be prudent to start treatment of patients who are elderly or have evidence of renal impairment with half the dose of flupirtine recommended for younger patients with normal renal function

Flupirtine DosageFlupirtine Dosage33

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 thereBy the Big Printer in the sky

Flupirtine Dosage in Special Flupirtine Dosage in Special PopulationsPopulations

34

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

Flupirtine ContraindicationsFlupirtine Contraindications35

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

Flupirtine PrecautionsFlupirtine Precautions36

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

Flupirtine Drug InteractionsFlupirtine Drug Interactions37

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

Flupirtine Adverse EffectsFlupirtine Adverse Effects38

Rare↑ in liver enzymes, hepatitis

Knowledge without action is useless;Action without knowledge is foolish

Analgesic Activity: Human StudiesAnalgesic Activity: Human Studies39

1Hummel T, et al. Dose-related analgesic effects of flupirtine. Br Journal of Clin Pharmacol. 32; 69-76; 19912Kobal G, et al. Effects of flupirtine on pain-related evoked potential and spontaneous EEG. Agents and Actions. 23: 117-19; 19883Bromm B. Assessment of analgesia by evoked cerebral potential measurements in humans. Postgrad Med J. 63: 9-13; 19874Gatto R. et al. Study on the analgesic effect of flupirtine in dentistry. Quadeni di Odontostomatologia. 3: 71-82: 1986

AuthorAuthor DoseDose TestTest ResultsResults

Hummel Hummel (1991)(1991)11

50-100 50-100 mgmg

COCO22 application to application to nasal mucosanasal mucosa

Linear dose-related reduction Linear dose-related reduction in pain intensityin pain intensity

Kobal (1988)Kobal (1988)22 200 mg200 mg COCO2 2 application to application to nasal mucosanasal mucosa

Pain threshold ↑ within 30-60 Pain threshold ↑ within 30-60 min with max effect 1.5-2 hr min with max effect 1.5-2 hr postdosepostdose

Bromm Bromm (1987)(1987)33

IV 80 IV 80 mgmg

Evoked cerebral Evoked cerebral potentials in potentials in response to phasic response to phasic pain stimulipain stimuli

Equivalent analgesia with Equivalent analgesia with flupirtine and pentazocineflupirtine and pentazocine

Gatto (1886)Gatto (1886)44 Thermal stimulation Thermal stimulation of tooth pulpof tooth pulp

Flupirtine superior to placebo Flupirtine superior to placebo producing ↑ pain threshold producing ↑ pain threshold within 15 min and lasting up within 15 min and lasting up to 45 minto 45 min

Post-op pain in general Sx settingPost-op pain in general Sx setting40

Borgognone A, et al. A new non-opioid analgesic (flupirtine) in the treatment of postoperative pain. Therapeutika 1986; 86: 1-9

Analgesic efficacy of flupirtine versus placebo in 28 patients undergoing general surgical proceduresPain 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

perc

ent

Reduction in pain intensityReduction in pain intensity

Post-op pain in orthopedic settingPost-op pain in orthopedic setting41

Galasko CSB, et al. Current Medical Research and Opinion, 1985, vol 9: 594-601

Analgesic 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 d1Patients (n) in each severity grade on d1 Patients (n) in each severity grade on d4 Patients (n) in each severity grade on d4



FLU 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 (%)



Higher proportion of patients reported being satisfied with flupirtine than with pentazocin

Patients satisfied with analgesia (%)Patients satisfied with analgesia (%)



Teachers are reservoirs from which, through the process of education, the students draw the water of life

Post-op pain in orthopedic Sx settingPost-op pain in orthopedic Sx setting45

Mastronardi P, et al. J Int Med Res, 1988; 16: 338-348

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 = 20Assessments 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)Overall Clinical Assessment (values = number of patients)

TherapyTherapy ExcellentExcellent Good Good ModerateModerate UselessUseless

Flupirtine (n = Flupirtine (n = 20)20)

44 22 88 66

Diclofenac (n = Diclofenac (n = 20)20)

11 44 44 1111

It is not your position that makes you happy or unhappyIt is your disposition



Analgesic effect of first administration of FLU or DIC (mean VAS scores)

A good teacher is a perpetual learner



Analgesic effect of third administration of FLU or DIC (mean VAS scores)

* * * * * * *

* Statistically significant between groups

Learn to adapt, adjust and accommodate Learn to give, not to take and learn to serve not to rule

sborgharkar16165

Independent of the dosage, flupirtine showed a greater overall analgesic activity than diclofenac sodium irrespective of its speed of effect100 mg flupirtine reduces pain in terms of speed and duration, to be significantly improved compared with 50 mg DIC



Hate screeches, fear squeals; conceits trumpetsbut love since lullabies

Post-op pain in gynecological Sx settingPost-op pain in gynecological Sx setting49

Moore RA ,et al. Br J Anaesth. 1983; 55: 429-432

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 = 25Assessments made twice daily x 3 days post-op

Pain intensity and relief scoresPain intensity and relief scores Total analgesic and antiemetics interventionsTotal analgesic and antiemetics interventions

sborgharkar16165

Inadequate analgesia with test drug was treated with additional 30-60 mg dihydrocodeine or papavertum intramuscular if necessary. This graph shows that the requirement for additional analgesia is similar to both groups

Post-op pain in gynecological Sx settingPost-op pain in gynecological Sx setting50

Moore RA ,et al. Br J Anaesth. 1983; 55: 429-432

Reputation is made in a moment; character is built in a life time

Clinical experience with flupirtine in USClinical experience with flupirtine in US51

McMahon FG, et al. Postgrad Med Journal , 1987; 63: 81-85

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 mgFLU 100-300 mg (max 600 mg/d)

Total Pain Relief (TOPAR) scoresTotal Pain Relief (TOPAR) scores

Clinical experience with flupirtine in USClinical experience with flupirtine in US52

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 completion

53

Phase IV study in 869 patients

Max dose 600 mg/dDuration: 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-related19 AEs rated as drug-related 10 AEs rated possibly not drug-related10 AEs rated possibly not drug-related

1.3% CNS related1.1% GI related1.3% CNS related1.1% GI related

no drug dependencyno toleranceno withdrawal symptoms

no drug dependencyno toleranceno withdrawal symptoms

25 of 29 AEs resolved by study end25 of 29 AEs resolved by study end

It is the providence of the knowledge to speak and it is the privilege of the wisdom to listen - Hodly’s

Efficacy of flupirtine in osteoporosis Efficacy of flupirtine in osteoporosis painpain

55

Ringe, et al. Arzneim Forschung, 2003

Opinion is ultimately determined by the feelings and not by the intellect

56

Low Back Pain: Comparison with Low Back Pain: Comparison with TramadolTramadol

209 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 RatesPain Relief Rates

Li C, et al. Current Medical Research and Opinion 2008, 24(12): 3523-3530

57


Mean LBP Intensity ScoresMean LBP Intensity Scores

59% 56%p < 0.001

p = 0.02

ADR events and ADR related dropouts (%)ADR events and ADR related dropouts (%)


A great many people think they are thinking when they are merely re arranging their prejudices

W. James


58


The Truth is fear and immorality are two of the greatest inhibitors of Performance to progress

Efficacy in Musculo-Skeletal DisordersEfficacy in Musculo-Skeletal Disorders59

G.Mueller-Schwefe. Progress of Medicine 121 Jg.- Original No.1/2003, Pg.11-18

7,806 pts with musclo-skeletal disorders (cervical/lumbar spine pain, myofascial pain, tension headache, muscle spasm associated with arthritis) evaluatedFlupirtine 100 mg (2-3 doses/d) max dose 600 mg/dAssessment on pain scale: 0 = no pain to 4 = very severe pain

A true commitment is a heart felt promise to yourself from which you will not back down - D. Mcnally



% patients with response (improvement by at least 1 step) at end of 1 wk

% patients with response (improvement by at least 1 step) at end of 1 wk

% patients with continuous pain at beginning and end of 4 wks Rx

% patients with continuous pain at beginning and end of 4 wks Rx

Serious, sincere, systematic studies, surely secure supreme success



% patients with response (improvement by at least 1 step): reduction of muscle spasm

% patients with response (improvement by at least 1 step): reduction of muscle spasm

% patients with response (improvement by at least 1 step): restriction of daily activities

% patients with response (improvement by at least 1 step): restriction of daily activities

God is a comedian performing before an audience that is afraid to laugh

Clinical experience in migraineClinical experience in migraine62

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

47 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

50

40

30

20

10

0

1 2 3 4 5

% pts

PAR

FLU

1 2 3 4 5

20

10

0

% pts

PAR

FLU

% patients unable to work % patients confined to bed



70

60

50

40

30

20

10

0

1 2 3 4 5

PAR

FLU

Score

Time (d)

Mean VAS scores of pain severity during migraine attack



Man is made by his beliefs; as he beliefs, so he is

65

10 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

66

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

67

71 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)

No Pre-Rx Successful Pre-Rx Not successful Pre-Rx All patients

Pain Intensity Differences after 4 wksPain Intensity Differences after 4 wks

In any field, find the strangest thing and explore it

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54 % 36 %

% pts with pain alleviation after 4 wks% pts with pain alleviation after 4 wks

There are sixty trillion cells in the human body


“Men of Genius Admired: Men of Wealth envied women of power feared but only women of character are trusted”

A- Friedman

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SummarySummary 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 tolerated1,2,3,4

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

1Scheef W. Analgesic efficacy and safety of oral flupirtine in the treatment of cancer pain. J Postgrad Med 1987;63(suppl 3):67–702Galasko CS, et al. Trial of oral flupirtine maleate in the treatment of pain after orthopaedic surgery. Curr Med Res Opin1985;9(9):594–6013Heusinger JH. Efficacy and tolerance of flupirtine and pentazocine in 2 multicentre trials. J Postgrad Med 1987;63(suppl 3):71–94Riethmuller-Winzen H. Flupirtine in the treatment of post-operative pain. Postgrad Med J 1987; 63(suppl 3):61–55Scheef W, Wolf-Gruber D. [Flupirtine in patients with cancer pain]. Arzneimittelforschung 1985; 35(1):75–7

Dedicated to my family for Dedicated to my family for making everything worthwhile making everything worthwhile

READ not to contradict or confute

Nor to Believe and Take for Granted

but TO WEIGH AND CONSIDER

THANK YOUMy sincere thanks to SUN-SOLARISMy sincere thanks to SUN-SOLARIS

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

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