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...),

w

1TTK.PDB

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

FAJL 1TTK.pdb, RENDEROVAN U

VISOKOJ REZOLUCIJI.

PRIBLIŽNI IZGLED MOLEKULA

ZICONOTIDE-A U RASTVORU.

ATOMI VODONIKA NISU PRIKAZANI.

1.

2. 3.

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NERVNIH ZAVRŠETAKA U KIÈMENOJ MOŽDINI I BLOKIRA PRENOS BOLNOG IMPULSA DO MOZGA. DO BLOKADE DOLAZI

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4.

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