MORSKI PUŽEVI VRSTE CONUS MAGUS LOVERIBU U AKVARIJUMU
MORSKI PUŽ NAPADA RIBU OTROVNOM IGLOM KOJA SE NALAZI NA KRAJU DUGE CEVI; EKSPERIMENT U AKVARIJUM
CEV SA OTROVNOM IGLOM (HARPUNOM)
OTROVNI PUŽEVI TROPSKIH MORA - IZVOR NOVOG ANALGETIÈKOG PREPARATA, PEPTIDA CONOTOXIN-a
IZGLED OTROVNE IGLE (HARPUNA)
OTROVNI PUŽEVI TROPSKIH MORA - IZVOR NOVOG ANALGETIÈKOG PREPARATA, PEPTIDA CONOTOXIN-a
SHEMATSKI PRIKAZ ANATOMIJE PUŽA
KESICA SA OTROVNIMIGLAMA
SIFON
CEV SA OTROVNOMIGLOM NA KRAJU
USNA DUPLJAKESICA SA OTROVOM
OTROVNA IGLA
OTROVNA IGLA - SKENIRAJUÆAELEKTRONSKA MIKROGRAFIJA
STOPALO
USNA DUPLJA
LJUŠTURA
OÈI NA PIPCIMA
SIFON
OTROVNI PUŽEVI TROPSKIH MORA - IZVOR NOVOG ANALGETIÈKOG PREPARATA, PEPTIDA CONOTOXIN-a
PRIKAZ ANATOMIJE PUŽA - DETALJI
PRIKAZ ANATOMIJE PUŽA - DETALJI
OTROVNI PUŽEVI TROPSKIH MORA - IZVOR NOVOG ANALGETIÈKOG PREPARATA, PEPTIDA CONOTOXIN-aOTROVNI PUŽEVI TROPSKIH MORA - IZVOR NOVOG ANALGETIÈKOG PREPARATA, PEPTIDA CONOTOXIN-a
SIFON
CEV SA OTROVNOMIGLOM NA KRAJU
IZLAZI KROZUSNU DUPLJU
OÈI NA PIPCIMASTOPALO
LJUŠTURA
USNA DUPLJA
PRIKAZ ANATOMIJE PUŽA - DETALJI
OTROVNI PUŽEVI TROPSKIH MORA - IZVOR NOVOG ANALGETIÈKOG PREPARATA, PEPTIDA CONOTOXIN-a
OTVORENAUSNA DUPLJA
SIFON
STOPALO
LJUŠTURA
OÈI NA PIPCIMA
PUŽ GUTA RIBU KOJU JE PRETHODNO PARALIZOVAO OTROVNIM UBODOM
OTROVNI PUŽEVI TROPSKIH MORA - IZVOR NOVOG ANALGETIÈKOG PREPARATA, PEPTIDA CONOTOXIN-a
OTVORENAUSNA DUPLJA
OÈI NA PIPCIMA
SIFON
OTROVNI PUŽEVI TROPSKIH MORA - IZVOR NOVOG ANALGETIÈKOG PREPARATA, PEPTIDA CONOTOXIN-a
PUŽ GUTA RIBU KOJU JE PRETHODNO PARALIZOVAO OTROVNIM UBODOM - DRUGI PRIMER
OTVORENAUSNA DUPLJA
SIFON
OÈI NA PIPCIMA
LJUŠTURA
Therapeutics and Clinical Risk Management 2009:5 521–534
SAFETY AND EFFICACY OF INTRATHECAL ZICONOTIDE IN THE MANAGEMENT OF SEVERE CHRONIC PAIN
Howard S Smith Timothy R Deer
R E V I EW
Abstract: Ziconotide is a conopeptide intrathecal (IT) analgesic which is approved by the US Food and Drug Administration (FDA) for the management of severe chronic pain. It is a synthetic equivalent of a naturally occurring conopeptide found in the venom of the fish-eatingmarine cone snail and provides analgesia via binding to N-type voltage-sensitive calcium channels in the spinal cord. As ziconotide is a peptide, it is expected to be completely degraded by endopeptidases and exopeptidases (Phase I hydrolytic enzymes) widely located throughoutthe body, and not by other Phase I biotransformation processes (including the cytochrome P450 system) or by Phase II conjugation reactions. Thus, IT administration, low plasma ziconotide concentrations, and metabolism by ubiquitous peptidases make metabolic interactions of otherdrugs with ziconotide unlikely. Side effects of ziconotide which tend to occur more commonly at higher doses may include: nausea, vomiting, confusion, postural hypotension, abnormal gait, urinary retention, nystagmus/amblyopia, drowsiness/somnolence (reduced level of consciousness),dizziness or lightheadedness, weakness, visual problems (eg, double vision), elevation of serum creatine kinase, or vestibular side effects. Initially, when ziconotide was first administered to human subjects, titration schedules were overly aggressive and led to an abundance of adverseeffects. Subsequently, clinicians have gained appreciation for ziconotide’s relatively narrow therapeutic window. With appropriate usage multiple studies have shown ziconotide to be a safe and effective intrathecal analgesic alone or in combination with other intrathecal analgesics.Keywords: pain, ziconotide, intrathecal analgesics, safety, patient acceptability
Introduction
The US Food and Drug Administration (FDA) approved ziconotide (Prialt®; Elan Pharmaceuticals, Inc.) on December 28, 2004 for the management of severe chronic pain in patients whom intrathecal (IT) therapy is warranted, and who are intolerant of or refractory to other treatments, such as systemic analgesics, adjunctive therapies, or IT morphine. Ziconotide is approved for use only in the Medtronic SynchroMed® EL, SynchroMed® II Infusion System, and the CADD-Micro® ambulatory infusion pump.
Prialt®contains ziconotide acetate, with L-methionine (0.05 mg/mL) and sodium chloride as excipients at pH 4.0 to 5.0. Ziconotide is a synthetic equivalent of a naturally occurring conopeptide found in the venom of the fish-eating marine cone snail, Conus magnus. This peptide, formerly known as SNX-111 or ù-conotoxin MVIIA, is a component of the venom used to immobilize the snail’s prey. Ziconotide is a 25 aminoacid, polybasic peptide containing 6 cysteine residues linked by 3 disulfide bridges with a molecular weight of 2639 Da and a molecular formula of C102H172N36O32S7 .1
FARMAKOLOŠKO TESTIRANJE w-CONOTOXIN-a (ZICONOTIDE, PRIALT) U LJUDI.
SCREEN SHOT VEB STRANICE
KOJA OPISUJE ODREÐIVANJE STRUKTURE -CONOTOXIN-a, PRIMENOM NMR SPEKTROSKOPIJE. ODGOVARAJUÆI 3D FAJL
( U pdb FORMATU), DEFINIŠE STRUKTURU w-CONOTOXIN-a I SLOBODNO JE DOSTUPAN. UÈITAVANJEM FAJLA U POGODAN
3D ÈITAÈ (npr. ACCELRYS DISCOVERY STUDIO VISUALIZER 2.5, ILI NEKI DRUGI), STRUKTURA SE MOŽE SE DETALJNO
ANALIZIRATI (PRIMER NA SLEDEÆOJ STRANI).
PROTEIN DATA BANK SAJTA. STRANICA SE ODNOSI NA PUBLIKACIJU (J. Biol. Chem...),
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KADA SE FAJL UÈITA U ACCELRYS DISCOVERY STUDIO VISUALIZER 2.5, STRUKTURA SE MOŽE SE DETALJNO
ANALIZIRATI. SLIKA PRIKAZUJE SCREEN SHOT EKRANA, ODN. STRUKTURU . w-CONOTOXIN-a
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VISOKOJ REZOLUCIJI.
PRIBLIŽNI IZGLED MOLEKULA
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ATOMI VODONIKA NISU PRIKAZANI.
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