Vinca alkaloids
Alkaloid
Alkaloids are a class of naturally occurring organic compounds that mostly contain basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar structure may also be termed alkaloids. In additi…
Tubulin
Tubulin (tubul- + -in) in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoskeleton. Microtubules function i…
What are vinca alkaloids used for?
The vinca alkaloids thus prevent microtubule polymerization, as opposed to the mechanism of action of taxanes. Vinca alkaloids are now produced synthetically and used as drugs in cancer therapy and as immunosuppressive drugs. These compounds include vinblastine, vincristine, vindesine, and vinorelbine.
What are the FDA labeling updates for vinca alkaloids (Vinca sulfate)?
[1/15/21] The U.S. Food and Drug Administration is alerting health care professionals to labeling updates for the preparation of vinca alkaloids, a group of chemotherapy agents that includes vincristine sulfate injection, vinblastine sulfate (for) injection, and vinorelbine tartrate injection.
What are the alkaloids in Madagascar periwinkle?
The two alkaloids vinblastine and vincristine are minor constituents of the Madagascar periwinkle (Vinca rosea) (see Figure 4.2). The periwinkle is the common name for herbs of the dogbane family, which make up the genus Vinca of the family Apocynaceae. The lesser periwinkle, a native of many parts of Europe, grows in
Do vinca alkaloids have cross-resistance to chemotherapy?
The vinca alkaloids have been generally included in combination chemotherapy regimens for medicinal therapies. They do not have cross-resistance with drugs that alkylate deoxyribonucleic acid (DNA) and have a different mechanism of action.[3]
What are vinca alkaloids used for?
A type of drug that blocks cell growth by stopping mitosis (cell division). Vinca alkaloids interfere with microtubules (cellular structures that help move chromosomes during mitosis). They are used to treat cancer.
What medicine comes from periwinkle?
Vincristine and vinblastine derived from periwinkle are recognized pharmacological agents in chemotherapy and are used to treat Hodgkin disease, lymphocytic leukemia, and other cancers.
What is a commonly used vinca alkaloid to treat cancer?
Vindesine is a Vinca alkaloid obtained from vinblastine that is being used to treat a variety of cancers, the most common of which being acute lymphocytic leukemia (Additional file 1).
How do vinca alkaloids act as chemotherapy drugs?
Vinca alkaloids are used in chemotherapy for cancer. They are a class of cell cycle–specific cytotoxic drugs that work by inhibiting the ability of cancer cells to divide: Acting upon tubulin, they prevent it from forming into microtubules, a necessary component for cellular division.
What type of drug is vinblastine?
Vinblastine is in a class of medications called vinca alkaloids. It works by slowing or stopping the growth of cancer cells in your body.
Which among the following are the pharmacological action of vinca?
The mechanism of action of vinca alkaloids is to arrest dividing cells in metaphase by binding tubulin and preventing its polymerization into microtubules. This is also the proposed mechanism of causing neuropathy by inhibiting anterograde and retrograde axonal transport, thereby causing axonal degeneration.
What drug contains vincristine?
Vincristine, also known as leurocristine and marketed under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer.
What does periwinkle do to the body?
When taken by mouth: Periwinkle is UNSAFE. It can cause side effects such as nausea, vomiting, and other stomach and intestinal symptoms. It can also cause nerve, kidney, and liver damage. Large amounts can cause very low blood pressure.
What cancers is vincristine used for?
Vincristine is used in combination with other chemotherapy drugs to treat certain types of leukemia (cancer of the white blood cells), including acute myeloid leukemia (AML, ANLL) and acute lymphoblastic leukemia (ALL), Hodgkin's lymphoma (Hodgkin's disease), and non-Hodgkin's lymphoma (types of cancer that begin in a ...
What does vincristine do to cancer cells?
Vincristine works by stopping the cancer cells from separating into two new cells. So it blocks the growth of the cancer. How you have vincristine You have vincristine into your bloodstream (intravenously). You can have it through a thin, short tube (a cannula) put into a vein in your arm each time you have treatment.
Does vincristine cause hair loss?
Other side effects may occur that usually do not need medical attention. This medicine often causes a temporary loss of hair. After treatment with vincristine has ended, or sometimes even during treatment, normal hair growth should return.
What are the 6 classes of chemotherapy drugs?
Some of the well known classes of cancer chemotherapy agents include alkylating agents, plant alkaloids, antimetabolites, anthracyclines, topoisomerase inhibitors and corticosteroids.
What is the most commonly used chemotherapy drug?
Alkylating agents were among the first anti-cancer drugs and are the most commonly used agents in chemotherapy today. Alkylating agents act directly on DNA, causing cross-linking of DNA strands, abnormal base pairing, or DNA strand breaks, thus preventing the cell from dividing.
What are the three types of chemotherapy?
Below are the main types of chemotherapy: Alkylating agents. Antimetabolites. Anti-tumor antibiotics.
What is another name for vincristine?
Vincristine Sulfate is another name for Oncovin. Originally known as Leurocristine, Oncovin has also been referred to as LCR and VCR. In some cases, health care professionals may use the trade names Oncovin and Vincasar Pfs or other names Leurocristine, LCR or VCR when referring to the generic drug name Vincristine.
What is the brand name for vinblastine?
Vinbastine is the generic name for the trade name drug Alkaban-AQ® or Velban®. In some cases, health care professionals may use the trade names Alkaban-AQ and Velban® or other names; such as VLB, Vinblastine Sulfate, or Vincaleukoblastine when referring to the generic drug name vinblastine.
What is the difference between vincristine and vinblastine?
Vinblastine (1) has two monomer alkaloid parts: catharanthine (3) and vindoline (4). The difference between vinblastine (1) and vincristine (2) is that the former has a methyl while the latter has a formyl group on the indole nitrogen of the vindoline skeleton (Figure 1).
What Is vinca drug?
Vinca alkaloids are a subset of drugs obtained from the Madagascar periwinkle plant. They are naturally extracted from the pink periwinkle plant, Catharanthus roseus G. Don and have a hypoglycemic as well as cytotoxic effects.
Is Taxol a vinca alkaloid?
Taxol belongs to a class of chemotherapy drugs called plant alkaloids. Plant alkaloids are made from plants. The vinca alkaloids are made from the periwinkle plant (catharanthus rosea). The taxanes are made from the bark of the Pacific Yew tree (taxus).
What are antimetabolite drugs?
Antimetabolites are called a “cytotoxic” type of drug because they kill cells. They work by mimicking the molecules that a cell needs to grow. Cells are tricked into taking in the drugs and then using the antimetabolites instead of their normal building blocks of genetic material: RNA and DNA.
Which part of periwinkle is poisonous?
Symptoms: All parts of the plant are toxic but symptoms are unlikely from small ingestions. Symptoms may include fever, nausea, vomiting, nerve damage, headache and hallucinations.
How do diabetics use Madagascar periwinkle?
Take 1 tsp of the dried leaf powder by infusing it with water or fresh fruit juice on an empty stomach every morning to keep diabetes under control. Chew 3-4 leaves of the Sadabahar plant throughout the day to prevent sudden blood sugar spikes. Boil freshly plucked Sadabahar flowers in water.
Is periwinkle edible?
All parts of the Periwinkle are poisonous. These plants contain a wide range of naturally-occurring toxic alkaloids which cause poisoning when ingested.
Is periwinkle good for skin?
Some people apply Madagascar periwinkle directly to the skin to stop bleeding; relieve insect bites, wasp stings, and eye irritation; and treat infections and swelling (inflammation).
What are vinca alkaloids?
Vinca alkaloids are a subset of drugs obtained from the Madagascar periwinkle plant. They are naturally extracted from the pink periwinkle plant, Catharanthus roseus G. Don and have a hypoglycemic as well as cytotoxic effects. They have been used to treat diabetes, high blood pressure and have been used as disinfectants. The vinca alkaloids are also important for being cancer fighters. There are four major vinca alkaloids in clinical use: Vinblastine (VBL), vinorelbine (VRL), vincristine (VCR) and vindesine (VDS). VCR, VBL and VRL have been approved for use in the United States. Vinflunine is also a new synthetic vinca alkaloid, which has been approved in Europe for the treatment of second-line transitional cell carcinoma of the urothelium is being developed for other malignancies. Vinca alkaloids are the second-most-used class of cancer drugs and will stay among the original cancer therapies. Different researches and studies for new vinca alkaloid applications will be carried out in this regard.
Where are vinca alkaloids found?
Vinca alkaloids are obtained from the Madagascar periwinkle plant. They are naturally occurring or semi synthetic nitrogenous bases extracted from the pink periwinkle plant Catharanthus roseusG. Don[3] [Figure 1]. Vinca alkaloids were found out in the 1950's by Canadian scientists, Robert Noble and Charles Beer for the first time. Medicinal applications of this plant lead to the monitoring of these compounds for their hypoglycemic activity, which is of little importance compared to their cytotoxic effects.[4] They have been used to treat diabetes, high blood pressure and the drugs have even been used as disinfectants. Nevertheless, the vinca alkaloids are so important for being cancer fighters. There are four major vinca alkaloids in clinical use: Vinblastine (VBL), vinorelbine (VRL), vincristine and vindesine (VDS), but only VCR, VBL and VRL are approved for use in the United States.[3] From 2008, there is also a new synthetic vinca alkaloid, vinflunine that is currently approved in Europe for medicinal treatment.[5,6]
What are the mechanisms of vinca alkaloid cytotoxicity?
The main mechanisms of vince alakaloid cytotoxicity is due to their interactions with tubulin and disruption of microtubule function , particularly of microtubules comprising the mitotic spindle apparatus, directly causing metaphase arrest.[7] However, they can do many other biochemical activities that may or may not be related to their effects on microtubules. Many of the effects that do not include microtubule interruption happen only after treatment of cells with clinically irrelevant doses of the vinca alkaloids. Nevertheless, the vinca alkaloids and other antimicrotubule agents also have an effect on both non-malignant and malignant cells in the non-mitotic cell cycle, because microtubules are involved in many non-mitotic functions.[3]
Where do vinca alkaloids connect to tubulin?
The vinca alkaloids connect to binding sites on tubulin that they are separate from those of the taxanes, colchicine, podophyllotoxin and guanosine-5’-triphosphate.[8] Binding occurs rapidly and can reverse too. Existing evidence maintains the existence of two vinca alkaloid binding sites per mole of tubulin dimer.[9] We can see near to 16-17 high-affinity binding sites in each microtubule that located at the ends of per microtubule. Binding of the vinca alkaloids to these sites interrupts microtubule congregation, but one of the most important effect of low drug concentrations can be decreasing the rates of both growth and shortening at the assembly end of the microtubule that can cause produces a “kinetic cap” and suppresses function.[10] The disturbing effects of the vinca alkaloids on microtubule dynamics, particularly at the ends of the mitotic spindle, which cause metaphase arrest, occur at drug concentrations below those that decrease microtubule mass.[11]
Is VCR a neurotoxic drug?
All vinca alkaloids make a characteristic peripheral neurotoxicity, but VCR has most potential in this case. The neurotoxicity is mostly distinguished by a peripheral, symmetric varied sensory-motor and autonomic polyneuropathy.[7] The primary pathologic effect is related to axonal degeneration and decreasing of axonal transport, most likely caused by a drug-induced perturbation of microtubule function. The uptake of VCR into the brain is low and central nervous system effects, such as confusion, mental status changes, depression, hallucinations, agitation, insomnia, seizures, coma, syndrome inappropriate secretion of antidiuretic hormone and visual disturbances are infrequent. Laryngeal paralysis has also been informed. The only known effective interference for vinca alkaloid neurotoxicity is discontinuing treatment or decrease of the dose or frequency of drug administration. Although a number of antidotes, including thiamine, vitamin B12, folinic acid, pyridoxine and neuroactive agents, have been applied, these treatments have not been obviously shown to be effective. The symptoms of neurotoxicity are similar for all vinca alkaloids; severe neurotoxicity is observed less frequently with VBL and VRL as compared with VCR. Neutropenia is the main dose-limiting toxicity of VBL, VDS and VRL. Thrombocytopenia and anemia usually have been seen less. In addition, VCR is related with hematologic toxicity rarely, severe myelosuppression has been monitored in situations resulting in profoundly increased drug exposure and hepatic deficiency.[3]
Does Vinca alkaloids cross resistance?
The vinca alkaloids have been generally included in combination chemotherapy regimens for medicinal therapies. They do not have cross-resistance with drugs that alkylate deoxyribonucleic acid (DNA) and have a different mechanism of action.[3] VBL has been used as an integral part of medicinal treatment regimens for testicular carcinoma and both Hodgkin and non-Hodgkin lymphomas.[15] It is also used in breast cancer and germ cell tumors. Side-effects of VBL consist of toxicity to white blood cells, nausea, vomiting, constipation, dyspnea, chest or tumor pain, wheezing and fever. It is also rarely associated with antidiuretic hormone secretion.[3]
Can you take chemo with VCR?
These drugs should not be used by a patient who is pregnant, has planning for pregnancy or has breast-feeding as it may cause birth defects. Patients should not receive any vaccinations while taking this medication. VCR may cause weakness of immunity system and can lead to an illness.[20] Patients should notify their clinician about any prescription drugs taken concurrently with the chemotherapy and any other medical conditions, such as, chickenpox, herpes zoster infection, gout, kidney stones, infections, liver disease, nerve or muscle disease.[20] Over all, drug concentration and duration of treatment are important for determining of both drug accumulation and cytotoxicity, but the importance of available information show that using of drug above a critical threshold concentration is the most important determinant.[21]
How do vinca alkaloids affect the cell cycle?
The vinca alkaloids are classed as cell-cycle-specific because they block mitosis by causing cell-cycle arrest at metaphase . Their cytotoxic effects result from binding of the alkaloids to the microtubules. Microtubules are long tubular structures of about 25 nm in diameter that form the major component of the mitotic spindle apparatus responsible for the movement of chromosomes during cell division. These structures were first characterized in the cytoplasm over 25 years ago and comprise two main proteins, the a and p tubulins (Mr c 55 000), which form the microtubule scaffolding upon which many of the dynamic internal processes in living cells, including cell division, depend. Binding of the vinca alkaloids to the tubulins interferes with microtubule assembly, causing damage to the mitotic spindle apparatus and preventing chromosomes from traveling out to form daughter cell nuclei. This is similar to the action of colchicine but is different from the action of paclitaxel, which interferes with cell division by preventing the spindles from being broken down. There is some evidence that the vinca alkaloids may also block DNA and RNA synthesis with a degree of selectivity towards tumor cells. Overall, the basis for the tumor cell selectivity of these agents is not fully understood although it is assumed that, because of their mechanism of action, rapidly dividing cancer cells are more vulnerable than the nondividing cells of healthy tissues.
Which plant produces anticancer agents?
FIGURE 4.2 The periwinkle (Vinca rosea), which produces the anticancer agents vinblastine and vincristine.
What is the name of the plant that has periwinkle?
The two alkaloids vinblastine and vincristine are minor constituents of the Madagascar periwinkle (Vinca rosea) (see Figure 4.2). The periwinkle is the common name for herbs of the dogbane family, which make up the genus Vinca of the family Apocynaceae. The lesser periwinkle, a native of many parts of Europe, grows in
Does vinca cause neurotoxicity?
Although all members of the family cause some neurological side effects, which normally manifest initially as autonomic or peripheral neuropathy, vincristine is the most affected and neurotoxicity is the dose-limiting toxicity for this agent. Conversely, vincristine causes the least myelosuppression of the four alkaloids, which is interesting from a structure activity relationship (SAR) standpoint given the similarity of chemical structures. The neurological effects may include loss of deep tendon reflexes, peripheral paresthesia, abdominal pain, constipation, and motor weakness, with the latter being taken as an indication that treatment should be discontinued. In general, most patients make a slow but complete recovery from these nervous system problems. The neurological toxicities are much less pronounced in the case of vinblastine, vindesine, and vinorelbine, which all have myelosuppression as their dose-limiting toxicity. Reversible alopecia commonly results from treatment with all members of the vinca family. Finally, it is important that administration techniques are carefully managed; all of the compounds are capable of causing severe local irritation at the injection site, so extravasation must be avoided.
What is vinca alkaloids?
Food and Drug Administration is alerting health care professionals to labeling updates for the preparation of vinca alkaloids, a group of chemotherapy agents that includes vincristine sulfate injection, vinblastine sulfate (for) injection, and vinorelbine tartrate injection. To reduce the potential for unintended intrathecal (spinal) administration, which causes death or severe neurological injury, FDA is working with drug application holders to remove instructions for preparation of these drugs by syringe and to recommend preparation in intravenous infusion bags only.
When will the FDA change the labeling of vinblastine sulfate?
The changes should be completed during 2021.
What is FDA working with?
To reduce the potential for unintended intrathecal (spinal) administration, which causes death or severe neurological injury, FDA is working with drug application holders to remove instructions for preparation of these drugs by syringe and to recommend preparation in intravenous infusion bags only. about medication errors related ...
Can you dispense vinca alkaloids in a syringe?
suggests that dispensing vinca alkaloids prepared in intravenous bags reduces the risk of medication errors due to erro neous intrathecal administration , FDA is taking action to remove instructions for preparing vinca alkaloids in a syringe from the prescribing information for vinca alkaloids.
Is Vinca alkaloids safe for intravenous administration?
In response, FDA has twice strength ened safety warnings in labeling for vinca alkaloids to warn against intrathecal administration and emphasize the products are for intravenous administration only. As published data. suggests that dispensing vinca alkaloids prepared in intravenous bags reduces the risk of medication errors due to erroneous ...
Does the FDA report Vinca alkaloid?
FDA encourages health care professionals and patients to report adverse events or quality problems experienced with the use of vinca alkaloid products to FDA’s MedWatch Adverse Event Reporting program:
