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Ziconotide--a novel neuron-specific calcium channel blocker for the intrathecal treatment of severe chronic pain--a short review.
Int J Clin Pharmacol Ther. 2006 Oct; 44(10):478-83.IJ

Abstract

Worldwide a large number of patients suffer from severe chronic pain even after treatment with opioids following the 3-step analgesic ladder developed by the WHO. Intraspinal agents, including morphine, have been tried as a fourth step. However, approximately 20% of cases remain refractory. Ziconotide, an intrathecal analgesic with orphan drug status, is a novel alternative for the management of chronic intractable pain. Ziconotide is a synthetic peptide based on the toxin of the fish-hunting marine snail, Conus magus. It is the first therapeutic agent in a new pharmacological class of "topically" active analgesics that selectively target neuron-specific (N-type), voltage-gated calcium channels. Ziconotide produces potent analgesia by interruption of Ca-dependent primary afferent transmission of pain signals in the spinal cord. Ziconotide was significantly more effective than placebo in the treatment of chronic malignant (p < 0.001) and non-malignant pain (p < 0.001). In several clinical studies morphine dosages could be substituted by ziconotide. The drug has a lag-time for the onset and offset of analgesia and adverse effects. Initial doses should therefore be low (2.4 microg/day) and titrated slowly (increasing up to a maximum of 21.6 microg/day in increases of 2.4 microg/day no more than twice weekly). The gradual increase in dose helps to reduce the incidence and severity of adverse events which affect primarily the central nervous system (e.g. dizziness, nausea, confusion). Ziconotide maintains its analgesic efficacy over months and does not cause tolerance, dependence or respiratory depression. Following intrathecal infusion ziconotide is distributed within the cerebral spinal fluid (CSF) where its clearance (0.38 ml/min) corresponds to the rate of turnover of the CSF. Negligible amounts of ziconotide are present in the systemic circulation where it is rapidly degraded by proteolysis. In conclusion, ziconotide is a new and valuable alternative analgesic for the acute and long-term treatment of severe pain, especially in patients refractory to opioids.

Authors+Show Affiliations

Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany. ulrich.klotz@ikp-stuttgart.de

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

17063978

Citation

Klotz, U. "Ziconotide--a Novel Neuron-specific Calcium Channel Blocker for the Intrathecal Treatment of Severe Chronic Pain--a Short Review." International Journal of Clinical Pharmacology and Therapeutics, vol. 44, no. 10, 2006, pp. 478-83.
Klotz U. Ziconotide--a novel neuron-specific calcium channel blocker for the intrathecal treatment of severe chronic pain--a short review. Int J Clin Pharmacol Ther. 2006;44(10):478-83.
Klotz, U. (2006). Ziconotide--a novel neuron-specific calcium channel blocker for the intrathecal treatment of severe chronic pain--a short review. International Journal of Clinical Pharmacology and Therapeutics, 44(10), 478-83.
Klotz U. Ziconotide--a Novel Neuron-specific Calcium Channel Blocker for the Intrathecal Treatment of Severe Chronic Pain--a Short Review. Int J Clin Pharmacol Ther. 2006;44(10):478-83. PubMed PMID: 17063978.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ziconotide--a novel neuron-specific calcium channel blocker for the intrathecal treatment of severe chronic pain--a short review. A1 - Klotz,U, PY - 2006/10/27/pubmed PY - 2007/1/25/medline PY - 2006/10/27/entrez SP - 478 EP - 83 JF - International journal of clinical pharmacology and therapeutics JO - Int J Clin Pharmacol Ther VL - 44 IS - 10 N2 - Worldwide a large number of patients suffer from severe chronic pain even after treatment with opioids following the 3-step analgesic ladder developed by the WHO. Intraspinal agents, including morphine, have been tried as a fourth step. However, approximately 20% of cases remain refractory. Ziconotide, an intrathecal analgesic with orphan drug status, is a novel alternative for the management of chronic intractable pain. Ziconotide is a synthetic peptide based on the toxin of the fish-hunting marine snail, Conus magus. It is the first therapeutic agent in a new pharmacological class of "topically" active analgesics that selectively target neuron-specific (N-type), voltage-gated calcium channels. Ziconotide produces potent analgesia by interruption of Ca-dependent primary afferent transmission of pain signals in the spinal cord. Ziconotide was significantly more effective than placebo in the treatment of chronic malignant (p < 0.001) and non-malignant pain (p < 0.001). In several clinical studies morphine dosages could be substituted by ziconotide. The drug has a lag-time for the onset and offset of analgesia and adverse effects. Initial doses should therefore be low (2.4 microg/day) and titrated slowly (increasing up to a maximum of 21.6 microg/day in increases of 2.4 microg/day no more than twice weekly). The gradual increase in dose helps to reduce the incidence and severity of adverse events which affect primarily the central nervous system (e.g. dizziness, nausea, confusion). Ziconotide maintains its analgesic efficacy over months and does not cause tolerance, dependence or respiratory depression. Following intrathecal infusion ziconotide is distributed within the cerebral spinal fluid (CSF) where its clearance (0.38 ml/min) corresponds to the rate of turnover of the CSF. Negligible amounts of ziconotide are present in the systemic circulation where it is rapidly degraded by proteolysis. In conclusion, ziconotide is a new and valuable alternative analgesic for the acute and long-term treatment of severe pain, especially in patients refractory to opioids. SN - 0946-1965 UR - https://www.unboundmedicine.com/medline/citation/17063978/Ziconotide__a_novel_neuron_specific_calcium_channel_blocker_for_the_intrathecal_treatment_of_severe_chronic_pain__a_short_review_ L2 - https://medlineplus.gov/pain.html DB - PRIME DP - Unbound Medicine ER -