Citation

Smith HS, Deer TR. Ther. Clin. Risk Manag. 2009; 5(1): 521-534.

Copyright

(Copyright © 2009, Dove Press)

DOI

unavailable

PMID

unavailable

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-eating marine 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 throughout the 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 other drugs 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 adverse effects. 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. © 2009 Smith and Deer, publisher and licensee Dove Medical Press Ltd.

Language: en

Keywords

Safety; human; cognition; suicide; abdominal pain; subdural hematoma; suicidal ideation; depression; psychosis; chronic pain; suicide attempt; Pain; disease severity; drug overdose; pain; review; fatigue; vomiting; anticonvulsive agent; antidepressant agent; anxiolytic agent; neuroleptic agent; drug metabolism; syncope; xerostomia; hallucination; headache; somnolence; paranoia; morphine; anxiety disorder; urine retention; drowsiness; orthostatic hypotension; clonidine; delusion; nonhuman; hostility; dehydration; confusion; drug safety; food and drug administration; drug blood level; drug dependence; sepsis; seizure; drug efficacy; drug tolerability; nausea; drug withdrawal; hypotension; sweating; alertness; delirium; fever; drug distribution; catatonia; disorientation; lung disease; mania; quadriplegia; side effect; thinking; withdrawal syndrome; amnesia; infection; asthenia; pruritus; creatine kinase; muscle weakness; drug half life; sedative agent; ataxia; drug elimination; nystagmus; respiration depression; drug clearance; nervousness; pneumonia; proteinase; baclofen; diplopia; dizziness; drug hypersensitivity; vestibular disorder; amblyopia; memory disorder; urinary tract infection; stupor; aphasia; speech disorder; chill; drug dose increase; drug dose titration; creatine kinase blood level; gait disorder; omega conotoxin MVIIA; Ziconotide; recommended drug dose; drug transformation; drug conjugation; distribution volume; calcium channel N type; drug degradation; exopeptidase; Intrathecal analgesics; Patient acceptability; peptidase; spinal cord