Oxaliplatin AqVida 5 mg/ml

Indications

• Treatment of metastatic colorectal cancer in combination with fluorouracil and folinic acid
• Adjuvant treatment of colon cancer after resection of the primary tumor

Dosage

Children: Refer to the BNF for Children for appropriate dosing in the paediatric population, as specific doses for children are not provided in the BNF for Adults.

Adults: Consult product literature for specific dosing guidelines. The typical adult dose is often around 85 mg/m² administered intravenously every two weeks, but this may vary based on the specific regimen and patient condition.

Mechanism of action

Oxaliplatin exerts its cytotoxic effects by forming DNA cross-links, which inhibit DNA replication and transcription. The drug is converted within the body to reactive platinum species that bind to DNA, leading to the formation of interstrand cross-links and ultimately triggering apoptosis in rapidly dividing cancer cells. This mechanism is particularly effective in targeting cancerous tissues that are highly proliferative.

Pharmacodynamics

The pharmacodynamics of oxaliplatin involve its ability to induce apoptosis in cancer cells through DNA damage. This damage activates several cellular pathways, including the p53 pathway, which is critical for cell cycle regulation and apoptosis. Additionally, oxaliplatin's unique structure allows it to bypass some resistance mechanisms that cancer cells develop against other platinum compounds, making it a valuable option in chemotherapy regimens.

Pharmacokinetics

Oxaliplatin is administered intravenously and has a distribution volume of approximately 16 L/m². Its plasma protein binding is around 95%. The drug undergoes rapid biotransformation in the liver, resulting in several metabolites, with the active form being the platinum-DNA adducts. The elimination half-life is approximately 1-2 hours, and it is primarily excreted via the urine as metabolites and unchanged drug. Dose adjustments may be necessary in patients with hepatic impairment.

Contra-indications

• Peripheral neuropathy with functional impairment

Adverse effects

• Alopecia
• Anaemia
• Appetite decrease
• Arthralgia
• Asthenia
• Chills
• Conjunctivitis
• Constipation
• Cough
• Decreased leukocytes
• Dehydration
• Depression
• Diarrhoea
• Dizziness
• Dyspnoea
• Electrolyte imbalance
• Embolism
• Thrombosis
• Fever
• Flushing
• Gastrointestinal discomfort
• Gastrointestinal disorders
• Haemorrhage
• Headache
• Hiccups
• Hyperglycaemia
• Hyperhidrosis
• Hypersensitivity
• Hypertension
• Increased risk of infection
• Insomnia
• Meningism
• Mucositis
• Nail disorders
• Peripheral neuropathy
• Skin reactions
• Stomatitis
• Taste alteration
• Thrombocytopenia
• Urinary disorders
• Vision disorders
• Vomiting
• Weight changes

Pregnancy

Manufacturer advises to avoid due to toxicity in animal studies.

Breast-feeding

Discontinue breastfeeding.

Storage

Store below 25 degrees Celsius. Protect from light.

Formulations

• Oxaliplatin 50mg/10ml concentrate for solution for infusion vials
• Oxaliplatin 100mg/100ml solution for infusion vials
• Oxaliplatin 200mg/40ml concentrate for solution for infusion vials

Indications

• Pain management
• Vaccination
• Antibiotic therapy
• Hormonal therapies
• Anesthesia
• Nutritional support
• Chemotherapy

Dosage

Children: Refer to specific drug guidelines for paediatric dosing, as it requires careful consideration of weight and age.

Adults: Refer to specific drug guidelines for adult dosing, as it varies widely depending on the medication and clinical condition.

Mechanism of action

The mechanism of action of injected drugs varies widely based on the specific medication being administered. Generally, injected drugs enter the bloodstream directly, allowing them to circulate rapidly throughout the body. For instance, antibiotics may work by inhibiting bacterial cell wall synthesis, while analgesics may modulate pain pathways in the central nervous system. Each drug has unique pathways through which it achieves its therapeutic effects.

Pharmacodynamics

Pharmacodynamics refers to the effects of drugs on the body and their mechanisms of action. For injectable medications, effects can be immediate or delayed, depending on the drug's formulation and route of administration. Factors influencing pharmacodynamics include receptor affinity, drug concentration, and the presence of other substances that may enhance or inhibit the drug's effects. For example, some injectable drugs may require specific receptors to exert their effects, while others may have a broader range of action.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of injected drugs. After administration, drugs are rapidly absorbed into the bloodstream, leading to quick therapeutic effects. The distribution depends on factors such as blood flow, tissue permeability, and protein binding. Drugs are metabolized primarily in the liver and excreted through the kidneys or bile. The pharmacokinetic profile can vary widely based on the drug's chemical nature, dosage, and individual patient factors.

Pregnancy

Safety during pregnancy depends on the specific injection and its active ingredients. It is essential to consult a healthcare professional for guidance.

Breast-feeding

The safety of injections during breastfeeding varies by the specific medication. It is recommended to seek advice from a healthcare provider.

Storage

Store injections as per manufacturer's guidelines, usually in a cool, dry place away from direct sunlight. Some may require refrigeration.

Indications

• Cryotherapy for the destruction of abnormal tissue
• Treatment of warts, moles, and other skin lesions
• Nitrogen narcosis in diving

Dosage

Children: Refer to the BNF for Children for appropriate dosing recommendations in paediatric patients.

Adults: For cryotherapy, the dosage and duration depend on the specific condition being treated and should be determined by the healthcare provider. Refer to specific guidelines for each condition.

Mechanism of action

In cryotherapy, the mechanism of action involves three stages: heat transfer, cell injury, and inflammation. The boiling point of liquid nitrogen is -196°C, which initiates heat transfer, leading to cell injury during the thawing process. The inflammation stage follows, characterized by edema and erythema, resulting from cellular death and contributing to local cell destruction. Additionally, nitrogen can cause direct toxic effects on brain functions, leading to nitrogen narcosis, which impairs cognitive abilities and motor functions due to its impact on nerve conduction.

Pharmacodynamics

Nitrogen's pharmacodynamics relate to its behavior in cryotherapy and asphyxiation. In cryotherapy, it induces tissue destruction through rapid cooling, leading to apoptosis of abnormal cells. In high-pressure environments, nitrogen narcosis affects the central nervous system, producing symptoms similar to alcohol intoxication, ultimately decreasing reasoning, decision-making abilities, and manual dexterity.

Pharmacokinetics

Nitrogen does not undergo metabolism in the traditional sense, as it is an inert gas at physiological conditions. Its pharmacokinetics involve physical principles of gas exchange and partial pressures. In the case of nitrogen narcosis, the effects are influenced by the partial pressure of nitrogen in the bloodstream, which increases with depth during diving. Nitrogen is primarily eliminated from the body through respiration.

Adverse effects

• Narcotic effect at high pressures
• Stupor or euphoria
• Decreased motor function and manual dexterity
• Asphyxiation due to oxygen displacement

Precautions

• Careful monitoring in environments with high nitrogen pressures
• Avoidance of rapid ascents in diving to prevent nitrogen narcosis
• Use in controlled settings to prevent asphyxiation risks

Pregnancy

Nitrogen is generally considered safe in terms of direct effects during pregnancy; however, the safety of exposure in high-pressure environments should be assessed.

Breast-feeding

Nitrogen is not known to affect breastfeeding; however, caution is recommended in environments where nitrogen levels may displace oxygen.

Storage

Store in a cool, dry place away from heat sources; liquid nitrogen should be handled with care due to extreme cold.

Formulations

• Liquid nitrogen
• Nitrogen gas (compressed)

Mechanism of action

In cryotherapy, mechanism of action could be classified into three stages: 1. heat transfer, 2. cell injury and 3. inflammation. Boiling point of liquid nitrogen is -196°C, which is the responsible for creating the initial stage which is heat transfer. The second stage is cell injury which is induced during thawing conditions of the cells. The last step in the cryotherapy is the inflammation stage which is characterized by edema and erythema. Inflammation occurs as a result of cellular death and it helps in local cell destruction. ... Nitrogen also has a direct toxic action of its own, affecting brain functions and inducing a stupor or euphoria. Nitrogen narcosis ("rapture of the deep" or "the martini effect") results from a direct toxic effect of high nitrogen pressure on nerve conduction and produces effects similar to alcohol intoxication. Complex reasoning, decision-making ability, motor function, and manual dexerity decrease. Individuals vary in this response widely, but it typically can be noticed among divers at depths exceeding 100 ft (30 m). For example, certain individuals experience no effect at depths of < or = 130 ft, whereas others feel some effect at around 80 ft. Nonetheless, the narcotic effect increases with increasing depth so that each additional 50 ft incrementally produces the effect of "another martini". A simple asphyxiant, nitrogen's main toxicty arises from its ability to displace O2 and generate an atmosphere that does not support the chemical reactions needed for maintenance of life. The displacement of O2 can be complete or incomplete, leading to varying degrees of hypoxia. Nitrogen is an inert substance and does not exert a direct toxicological effect. Nitrogen acts by the physiological effect of simple asphyxia on the target species within a Controlled Atmosphere Treatment (CAT) bubble. The biocide action of nitrogen is due to its displacement of oxygen from an atmospheric oxygen level of 20.8% to levels < 0.2% v/v in the CAT bubble. The level of oxygen is the critical factor. Victims exposed to atmospheres deficient in oxygen, i.e. < 19%, will begin to display signs and symptoms of oxygen-deficient exposure of air due to an increase in nitrogen.