Ziconotide is the name given to an analgesic. The drug is used to treat severe chronic pain.
What is ziconotide?
Ziconotide is the name given to an analgesic. The drug is used to treat severe chronic pain. Ziconotide is administered with the help of an intrathecal catheter. The active ingredient ziconotide is a polypeptide used as an analgesic under the trade name Prialt. The drug originally comes from the venom of the sea snail Conus magus. However, medicine uses a synthetic replica of the natural substance. Ziconotide was launched on the market in 2001 for the treatment of rare diseases. Since 2005, the active ingredient has been approved in Europe under the name Prialt. In its initial phase, ziconotide was seen as a possible substitute for morphine. However, since 2010, the drug has been under discussion due to a higher risk of suicide, based on several individual cases.
Pharmacologic action
Ziconotide is not an opioid and does not interact with opiate receptors. Instead, the amino acid peptide’s action is based on acting as an antagonist at N-type calcium channels, which are voltage-gated. These occur in high density in special neuronal cells within the posterior horn of the spinal cord. At these sites, the NCCB channels, as they are also called, regulate the release of neurotransmitters involved in the processing of pain. By binding the calcium channels, ziconotide can slow the influx of calcium toward nociceptive afferent nerves. Due to the blockade of N-type calcium channels, the transmission of pain signals is eventually interrupted. In addition, ziconotide exerts a neuroprotective effect. From a chemical point of view, ziconotide represents the omega-conopeptide MVIIA. This is a small protein molecule composed of 25 amino acids. The active ingredient is not suitable for ingestion in tablet form, as the protein molecule would be broken down by the digestive enzymes in the gastrointestinal tract. Ziconotide would therefore not be able to reach its target site in the spinal cord. For this reason, the active ingredient is administered to the body exclusively by continuous infusion into the spinal canal. The drug is administered as acetate via a mechanical pain pump. A combination of ziconotide and relaxants with a central effect, local anesthetics, and opioids is also possible.
Medical application and use
Although ziconotide belongs to the non-opioid analgesics, it is suitable for the treatment of pronounced chronic pain. However, its administration is limited to people in whom intrathecal anesthesia is required. In this procedure, the analgesic is administered directly into the spinal canal that runs through several vertebrae. In most cases, ziconotide therapy affects patients for whom opioid preparations are insufficient for treatment or who have an intolerance to them. Unlike other non-opioid analgesics, ziconotide is also suitable for the treatment of severe pain. Ziconotide is administered using an intrathecal catheter. It is important to store the drug at temperatures between 2 and 8 degrees Celsius, and it must not be exposed to sub-zero temperatures. In addition, the drug must be protected from light. The dose of ziconotide at the beginning of treatment is 2.4 µg per day. In the further course, the dosage increases to the required level. Thereby, the recommended maximum amount reaches 21.6 µg per day. In most cases, a dose of 9.6 µg is considered sufficient.
Risks and side effects
Taking ziconotide may be associated with several side effects. Feelings of weakness, nausea, vomiting, gait disturbances, blurred vision, and confusion are particularly common. It is also not uncommon to experience adverse side effects such as loss of appetite, sleep problems, mood swings, nervousness, seeing double images, hearing sounds, anxiety, thinking disorders, paranoia, urinary incontinence, urinary retention, muscle pain, water retention in body tissues, chest pain, feelings of coldness, weight loss, difficulty breathing, profuse sweating, itching, low blood pressure, dry mouth, ringing in the ears, fever, and depression.Other possible side effects, which however occur rather rarely, are unconsciousness, walking problems, rashes on the skin, pain in the neck, back pain, increased body temperature, convulsions, acute kidney failure or meningitis. Even a stroke as well as blood poisoning are within the realm of possibility. There is a suspected link between ziconotide use and suicide attempts. Therefore, a thorough examination by the physician should be done prior to treatment. Likewise, consistent monitoring by family members is recommended. If the patient suffers from hypersensitivity to ziconotide, the active substance must not be used. Combination with chemotherapeutic agents should also be avoided. These are anticancer agents and various antibiotics, provided that their administration also takes place via the spinal canal. The use of the drug during pregnancy and lactation is not recommended. Although there are no human studies on the risks during this period, animal studies have shown harmful effects on the offspring. Whether the use of ziconotide in children is advisable is a matter for the treating physician to decide. There have not yet been any studies on this subject. The simultaneous use of ziconotide and certain other drugs can sometimes lead to harmful interactions. For example, active ingredients such as the antihypertensive clonidine, the local anesthetic bupivacaine, the anesthetic propofol, or the muscle relaxant baclofen can cause drowsiness when administered together with ziconotide. If the analgesic is combined with morphine, caution is also advised. Even at low doses of ziconotide, patients often experienced severe side effects such as gait disturbances, confusion and delusions. In addition, patients often suffered from appetite disturbances and vomiting.
