Ziconotide Tablet

There are many problems with long-term use of opioid drugs in non cancer chronic suffering patients. On the one hand, there is insufficient evidence for the long-term efficacy of opioid drugs. For acute musculoskeletal suffering, compared to placebo, opioid drugs only have a weak analgesic effect in the first few days, with a suffering score reduction of less than 10% (on a scale of 0-100). The effect disappears after one week and may even slightly worsen the suffering after 12 weeks;

For chronic non cancer suffering, although there is a weak analgesic effect in the short to medium term (<6 months), the effect on improving physical function and quality of life is minimal, similar to the placebo effect. The long-term efficacy beyond 6 months is completely unknown. On the other hand, the risks associated with opioid drugs are clear and dose-dependent, ranging from common adverse reactions such as constipation and drowsiness to serious hazards such as hyperalgesia, respiratory depression, overdose, and even opioid use disorders. When opioid drugs are combined with benzodiazepines or gabapentin drugs, the risks are further compounded.

Ziconotide tablet is a non opioid analgesic drug that is a neuron specific N-type calcium channel blocker with unique advantages. It exerts analgesic effects by selectively blocking the N-type voltage-gated calcium channel (CaV2.2) in the spinal dorsal horn, inhibiting the release of suffering neurotransmitters, and blocking the transmission of suffering signals to the brain. Unlike opioid drugs, it is non addictive, does not develop tolerance after long-term use, and has high safety when discontinued.

Monitoring and evaluation: In the process of replacing opioid therapy, it is necessary to closely monitor the patient's suffering level, occurrence of adverse reactions, and neuroendocrine function. Measure suffering intensity using Visual Analog Scale (VAS), with a score of 0-10 (0: painless, 10: most painful);

Use the Neuropathic Pain Questionnaire -10 items (DN4) to assess neuropathic symptoms, with DN4>4/10 considered as the presence of neuropathic suffering; The quality of life of patients was evaluated using the Eastern Cancer Collaboration Group (ECOG) Patient Quality of Life Scale, with a score of 0-5 (0=normal activity, 5: death); Evaluate patients' overall impression of treatment using the Patient Global Impression Improvement (PGI-I) scale, with a score of 1-7 (1: much better, 7: much worse). At the same time, record any adverse reactions that may be related to medication during each follow-up visit, such as blurred consciousness, decreased consciousness, hallucinations, dizziness, muscle suffering, etc. For related adverse reactions, if the symptoms are mild, reduce the dose by 0.5 μ g/day. If the symptoms persist and the dose is reduced, discontinue use and monitor creatine kinase (CK) levels routinely.

Neuropathic suffering is suffering caused by damage or disease to the somatosensory system, and can be divided into central and peripheral neuropathic suffering based on the initial affected area. Central neuropathic suffering often develops from diseases that affect the brain, brainstem, or spinal cord, such as suffering after central stroke, multiple sclerosis, spinal cord injury, etc; Peripheral neuropathic suffering is more common in lesions or diseases of the peripheral sensory nervous system pathways, such as trigeminal neuralgia, postherpetic neuralgia, and radiculopathy.

Neuropathic suffering is clinically manifested as spontaneous suffering (burning, stabbing, tingling sensation), which may be accompanied by induced suffering, especially when lightly touched or cold. The suffering is usually persistent and recurrent. Its pathogenesis is complex, including changes in ion channels, central and peripheral sensitization, neuroinflammatory reactions, and an imbalance between central excitatory and inhibitory signaling. Due to the limited efficacy and high incidence of adverse reactions of existing first-line treatment drugs such as antidepressants and anticonvulsants, precise intervention drugs are needed to improve treatment outcomes.

Ziconotide tablet can accurately intervene in neuropathic suffering, mainly based on its specific mechanism of blocking N-type calcium channels. After nerve injury, the α 2- δ subunits on the calcium ion channels in the posterior horn of the spinal cord (mainly the presynaptic membrane) are highly expressed, resulting in abnormal opening of calcium ion channels and increased influx of calcium ions, leading to increased release of excitatory neurotransmitters and over excitation of neurons, leading to hyperalgesia and suffering hypersensitivity.

By binding with high affinity to N-type calcium channels in neuronal tissue, the depolarization induced influx of calcium ions is prevented, thereby blocking the release of neurotransmitters, reducing synaptic transmission, inhibiting the excitability of spinal dorsal horn neurons, and blocking the transmission of suffering signals from the source, achieving precise analgesia. For example, animal experiments have shown that intrathecal injection can reduce the levels of IL-1 β and IL-23 in the central nervous system (CNS) of experimental autoimmune encephalomyelitis (EAE) mouse models, as well as the production of IL-17 in the spleen, thereby alleviating neuropathic suffering symptoms.

Significant suffering relief effect: Multiple clinical trials have shown good efficacy in treating neuropathic suffering. In key trials lasting 5-6 or 21 days, titrated doses of ω-conotoxin mviia were found to be more effective than placebo in treating chronic malignant or non malignant suffering. For example, in the clinical practice of the 5 patients mentioned above, for suffering patients with accompanying neuropathic components, the use of ω-conotoxin mviia significantly improved neuropathic symptoms, with the most significant improvements in neuropathic symptoms including tingling sensation (4 patients), decreased tactile sensation (3 patients), and brush induced suffering (3 patients).

Long term efficacy stability: Preliminary results from long-term open label trials show that the analgesic effect of ω-conotoxin mviia can be maintained for up to 12 months. This indicates that it can not only provide short-term relief for neuropathic suffering, but also maintain stable therapeutic effects for a longer period of time, providing sustained suffering control for patients with neuropathic suffering.
Adverse reactions: Most of the adverse events related to it are neurological in nature, with a severity ranging from mild to moderate, and will improve over time. There are no sequelae after discontinuation of the medication. Although dizziness, ataxia, nausea, urinary retention and other adverse reactions may occur, through reasonable dose adjustment and monitoring management, the occurrence of adverse reactions can be effectively controlled and the treatment tolerance of patients can be improved.