Intrathecal Ziconotide

9th June 2007 at 22:11 BST by Dr C.A.Jenner MB BS, FRCA. Permalink.

This article discusses the usage of Intrathecal Ziconotide in detail.

Intrathecal Ziconotide

Introduction

Ziconotide is a therapeutic option for treatment of severe chronic pain in patients who have gone through all other forms of treatment, including intrathecal morphine.

Formerly known as SNX-111, ziconotide is a new class of non-opioid analgesic that selectively blocks the neuron-specific (N-type) calcium channels that inhibit neurotransmitter release and basically affect the primary pain afferents.

A programmable implanted variable-rate microfusion device or an external microfusion device and catheter are generally utilised for the Intrathecal Ziconotide therapy.

History and Research

The Intrathecal Ziconotide therapy was originally designed to provide relief to patients of chronic pain for whom the intrathecal opioid therapy did not provide enough relief.

In the year 2004, the Food and Drugs Administration (FDA) approved Ziconotide (Prialt), a peptide with analgesic and neuroprotective effect, as a treatment for patients who suffer from severe chronic pain. It was established as an alternative remedy for patients who require intrathecal therapy that is not relieved by morphine and other potent pain drugs.

Research indicates that in cases of cancer and AIDS patients, 10-30% of pain is refractory to strong opioids, calling for intraspinal administration for pain management. Clinical trials have shown that ziconotide is helpful in managing severe chronic pain, including nociceptive and neuropathic pain of malignant aetiology.

Working Principle

When administered spinally, ziconotide produces analgesia by blocking transmitter release from primary nociceptive afferents and prevents the propagation of pain signals to the brain.

It is the synthetic equivalent of omega-MVIIA, a component of the venom of the marine snail, Conus magus. The mechanism of action underlying ziconotide's therapeutic profile comes from its potent and selective blockade of a neuron-specific N-type voltage-sensitive calcium channels (N-VSCCs).

Direct blockade of N-VSCCs inhibits the activity of a subset of neurons, including pain-sensing primary nociceptors. This mechanism of action distinguishes ziconotide from all other analgesics, mainly including opioid analgesics.

Intrathecal Ziconotide has an advantage over intrathecal morphine due to the fact that there is no development of tolerance even after prolonged use. In addition, systemic toxicity is considerably reduced by administration of smaller doses intrathecally and by selective delivery to the site of action in the nervous system.

However, neurological adverse effects also occur due to delay in clearance of ziconotide from the neural tissues. Nevertheless, research has proven that ziconotide has a favourable chance of advantages over several currently available intrathecal therapies for pain.

Safety Measures

The FDA has listed a specific set of safety measures and special considerations for Intrathecal Ziconotide to be used. Here we list the main amongst them.

1. It should be noted that Intrathecal Ziconotide has a narrow therapeutic margin. It produces dose-related adverse events that are primarily cerebellar, cognitive and neuropsychiatric in nature.

2. Though Intrathecal Ziconotide is a safer and effective therapy for severe chronic pain refractory to other agents, it is advisable to maintain a slow titration of the drug to a low maximum dose is required.

3. At the slower infusion rates, the most common adverse events possible include dizziness, nausea, asthenia, somnolence, diarrhoea, confusion, ataxia, headache, vomiting and abnormal gait. Urinary retention is also a possible adverse effect during Intrathecal Ziconotide treatment.

4. Patients with a previous history of psychosis are generally advised against the use of Intrathecal Ziconotide, as the ingredients might act counteract adversely in such cases.

5. Patients whose medical history has relevance with concomitant IT chemotherapy are advised to take proper medical consultation before starting on a prescription of Intrathecal Ziconotide.

6. Any possibility of hypersensitivity to ziconotide or the formulation components should be ruled out.

7. Regular follow-up visits are very important in the Intrathecal Ziconotide therapy. Anyone not having enough monitoring services at home or unable to go for regular checkups should be careful about choosing the Intrathecal Ziconotide therapy.

8. Experts suggest discontinuation if no improvement is felt in either pain or functional ability during the first 3 weeks of the Intrathecal Ziconotide therapy.

Other potential ziconotide-related side effects include:

• Depression
• Cognitive impairment
• Hallucinations
• Depressed levels of consciousness
• Elevation of kinase levels
• Increased risk of meningitis

Conclusion

Intrathecal Ziconotide is a safer therapeutic option for treatment of severe chronic pain in patients who have used up all other agents including intrathecal morphine. It is also recommended for those for whom the potential benefits outweigh the risks of serious nueropsychiatric adverse effects.

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