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multiple sclerosis

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by

Camilla Carfagna

on 6 October 2014

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Transcript of multiple sclerosis

MULTIPLE SCLEROSIS
Camilla Carfagna


Farmacoterapia II
PATHOPHYSIOLOGY
CENTRAL NERVOUS SYSTEM
WHITE MATTER
GREY MATTER
OPTIC NERVE
BRAIN STEM
BASAL GANGLIA
SPINAL CORD
IMMUNE-MEDIATED DISEASE
DEMYELINATION
INFLAMMATION
AXONAL DAMAGE
BBB RUPTURE
2.3
1
HORMONES AS RISK FACTORS ?
GENETIC FACTORS
NOT HEREDITARY
2-5%
20-30%
HLA SYSTEM
MHC
VIRAL INFECTION
HUMAN HERPES VIRUS 6
EPSTEIN-BARR VIRUS
80 %
90%
HYGIENE HYPOTHESIS
PREVALENCE HYPOTHESIS
CHRONIC CEREBROSPINAL VENOUS INSUFFICIENCY
2008
PAOLO ZAOMBONI
IRON DEPOSITION
INTERNAL JUGULAR/AZIGOUS VEIN ANGIOPLASTY?
< 15
VITAMINE D
2010 2.5 MILLION PEOPLE
18.000 DEATHS

20 - 40
SECONDARY COMPLICATIONS
SUICIDE
UNRELATED CAUSES
30-YEAR LIFE EXPECTANCY
5-0 YEARS LOWER THAN NORMAL
MEDICAL HISTORY
RECENT OR PAST SYMPTOMS
UHTHOFF'S PHENOMENON
GENERAL HEALTH
FAMILIAR HISTORY
RECENT TRAVELS
LIFESTYLE
TRAUMAS
ALLERGIES
McDONALD CRITERIA
NEUROLOGIC EXAM
MAGNETIC RESONANCE IMAGING
NON INVASIVE
SAFE AND ACCURATE
PRESENCE OF DARK/LIGHT SPOTS
LUMBAR PUNCTURE
INVASIVE
PRESENCE OF OLIGOCLONAL BANDS
EVOKED POTENTIALS TEST
NON INVASIVE
RECORD ABNORMAL ELECTRICAL IMPULSES
DIFFERENTIAL DIAGNOSIS
INFLAMMATORY DISEASES
LUPUS
SJOGRE'S DISEASE
SCLERODERMIA
CNS VASCULITIS
SYPHILIS
HIV
CELIAC DISEASE
CNS LYMPHOMA
DIAGNOSIS
FINAL
MULTIPLE SCLEROSIS
RELAPSES
CORTICOSTEROIDS
PREDNISONE oral
METHYLPREDNISOLONE i.v.
DEXAMETHASONE i.v.
SIDE EFFECTS
PLASMAPHERESIS
APRIL 2013
APPROVED BY
D
ISEASE
M
ODIFYING
D
RUGS/
T
REATMENTS
INTERFERON BETA-1B
INTERFERON BETA-1A
GLICOPROTEINS
INCREASE OF ANTI INFLAMMATORY CYTOKINES
DECREASE OF PRO INFLAMMATORY CYTOKINES
APOPTOSIS OF ACTIVATED T-CELL AND REDUCED BBB ADHESION
BETA : 0,25 mg s.c. every other day
POSOLOGY
ALFA : 30 mcg i.m. once a week
increasing doses
SIDE EFFECTS
INJECTION SITE NECROSIS 4%
FLU-LIKE SYNDROME
OTC NSAIDs
DEPRESSION/SUICIDAL THOUGHTS
MISCARRIAGE
LIVER DAMAGE
ALLERGIC REACTION
NEUTROPENIA/LEUKOPENIA
30%
NON RESPONSIVE
GLATIRAMER
ACETATE
IMMUNOMODULATOR
LING TERM SHIFT FROM THE PRO INFLAMMATORY RESPONSE
TO THE ANTI INFLAMMATORY RESPONSE
STUDIES
REGARD (IFN BETA-1A)
BEYOMD (INF BETA-1B)
no differences
Cochrane review 2005
only reduces the frequency of relapses
POSOLOGY
20 mg s.c. once daily
SIDE EFFECTS
INJECTION SITE REACTION 30%
FLU-LIKE SYNDROME 10%
CHEST PAIN
MISCARRIAGE
LIPOATROPHY
FINGOLIMOD
IMMUNOMODULATOR
SEQUESTERS LYMPHOCYTES IN LYMPHONODES
STIMULATES THE REPAIR PROCESS OF GLIAL CELLS
STUDIES
FREEDOM (PLACEBO)
0.18-0.40
TRANSFORMS (IFN BETA-1A)
0.16-0.33
POSOLOGY
0.5 mg ORAL
SIDE EFFECTS
POTENTIALLY FATAL INFECTIONS
BRADYCARDIA
MACULAR EDEMA
TERIFLUNOMIDE
IMMUNOMODULATOR
INHIBITS ACTIVATED T CELLS
STUDIES
TENERE (IFN BETA-1A)
more relapses
POSOLOGY
7-14 mg daily ORAL
SIDE EFFECTS
RISK OF SECONDARY INFECTIONS
MISCARRIAGE
LIVER DAMAGE
MANY DRUGS INTERACTIONS
RRMS
PRMS
SPMS
DIMETHYL
FUMARATE
IMMUNOMODULATOR
INHIBITS PRO INFLAMMATORY CYTOKINES
PROMOTES ANTI INFLAMMATORY ACTIVITY
ANTIOXIDANT
POSOLOGY
120-240 mg twice daily ORAL
SIDE EFFECTS
GI ADRs
FLUSHING
LYMPHOPENIA non reversible
LIVER DAMAGE
REDUCTION OF RELAPSES
AND DISABILITY
HIGH COSTS (5.000$ per month)
LIFETIME THERAPY
NO CURE
NATALIZUMAB
MONOCLONAL Ab
ANTAGONIST OF THE CELL ADHESION MOLECULE RECEPTOR
POSOLOGY
300 mg every 28 days i.v. infusion
SIDE EFFECTS
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
(JC VIRUS)
ONLY US AVAILABLE
MITOXANTRONE
ANTINEOPLASTIC
TOPOISOMERASE II INHIBITOR
POSOLOGY
12 mg/m i.v. infusion every 3 months
2
SIDE EFFECTS
ANTINEOPLASTIC SIDE EFFECTS
NON REVERSABLE CARIOMIOPATHY
PPMS
TRIALS
IFN BETA
MITOXANTRONE
GLATIRAMER ACETATE
AZATHIOPRINE
METHOTREXATE
CYCLOPHOSPHAMIDE
SYMPTOMS
MANAGMENT
DIET AND SUPPLEMENTS
VITAMINS D A C E B6 B12
SELENIUM, CALCIUM, ZINC
WATER
FIBERS
PUFA
HERBAL MEDICINE
VALERIAN
HYPERICUM
GINKGO BILOBA
PHARMACOLOGIC INTERVENTIONS
CORTICOSTEROIDS
ANTICONVULSANTS
ANTIDEPRESSANTS
BENZODIAZEPINES
ALTERNATIVE MEDICINE
ACUPUNTURE
TAI CHI
HOMEOPATHY
MIND-BODY MEDICINE
MANIPULATIVE SYSTEMS
REHABILITATION THERAPY
PHYSICAL THERAPY
OCCUPATIONAL THERAPY
LANGUAGE THERAPY
COUNSELING
DEALING WITH EMOTIONAL IMPACT
EVERYDAY LIFE
PHATOPTSIOLOGY OF THE DISEASE
PEG-IFN BETA-1A
MONOCLONAL Ab
MORE ORAL DRUGS
POLITHERPY
STEM CELLS
GENOME SEQUENCING
years
Full transcript