Patizra

Indications

• Neovascular (wet) age-related macular degeneration
• Diabetic macular edema

Dosage

Children: Dosage information for pediatric patients is not established; refer to the BNF for Children for specific guidelines.

Adults: The recommended dose for adults is usually 0.5 mg (0.05 ml) administered as an intravitreal injection, with treatment intervals typically every month or as directed by a specialist based on the patient's response.

Mechanism of action

Ranibizumab binds to and inhibits the activity of VEGF-A, preventing it from interacting with its receptors on the surface of endothelial cells. This action reduces vascular permeability and neovascularization, stabilizing the retinal tissue and improving visual function.

Pharmacodynamics

The pharmacodynamic effects of ranibizumab include the reduction of fluid leakage from retinal vessels and the regression of newly formed blood vessels, which improves the visual acuity in patients with retinal disorders. The effects are generally seen within a few weeks of administration.

Pharmacokinetics

Ranibizumab is administered via intravitreal injection, leading to localized concentrations in the eye. Systemic absorption is minimal due to the large molecular weight of the drug. It has a half-life of approximately 9 days in the vitreous humor. Clearance is primarily via retinal and choroidal mechanisms.

Contra-indications

• Intra-ocular inflammation (active)
• Ocular or periocular infection
• Previous retinal detachment or macular hole with visual impairment due to diabetic macular oedema

Adverse effects

• Endophthalmitis
• Intra-ocular pressure increase
• Retinal detachment
• Vitreous hemorrhage
• Cataract formation

Interactions

• Danaparoid: Unknown (increases risk of bleeding events)
• Phenindione: Unknown (increases risk of bleeding events)
• Thrombin inhibitors: Unknown (increases risk of bleeding events)
• Argatroban: Unknown (increases risk of bleeding events)
• Bivalirudin: Unknown (increases risk of bleeding events)

Precautions

• Monitor intra-ocular pressure and perfusion of the optic nerve head following injection
• Counsel patients or their carers to report symptoms suggestive of endophthalmitis, retinal detachment or intra-ocular inflammation
• Use with caution in patients with a history of ocular or periocular infections

Pregnancy

Avoid unless potential benefit outweighs risk-systemic exposure very low; limited information available.

Breast-feeding

Specialist sources indicate use with caution-no information available. Large molecular weight suggests limited excretion into milk and likely partial destruction in the infant’s gastrointestinal tract.

Storage

Store in a refrigerator (2–8°C). May be stored unopened at room temperature (20–25°C) for up to 24 hours before use; protect from light.

Formulations

• Solution for injection (pre-filled disposable injection)

Indications

• Hypertension
• Benign prostatic hyperplasia
• Urinary retention related to prostate enlargement

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines in the paediatric population.

Adults: Refer to the BNF for specific dosing recommendations based on individual clinical scenarios.

Mechanism of action

Alpha acts by selectively blocking alpha-1 adrenergic receptors, which are responsible for mediating vasoconstriction in blood vessels. By inhibiting these receptors, alpha promotes vasodilation, leading to a decrease in peripheral vascular resistance and subsequently lowering blood pressure. Additionally, this action can help alleviate urinary symptoms associated with an enlarged prostate.

Pharmacodynamics

The pharmacodynamics of alpha involve its competitive antagonism at alpha-1 adrenergic receptors, resulting in decreased vasoconstriction and increased blood flow. This mechanism is beneficial in conditions characterized by high blood pressure and urinary retention due to prostatic enlargement. The onset of action typically occurs within hours, with peak effects observed within a few days of consistent dosing.

Pharmacokinetics

Alpha is absorbed well from the gastrointestinal tract, with peak plasma concentrations achieved within 1-3 hours post-administration. The drug undergoes hepatic metabolism, primarily via cytochrome P450 enzymes, resulting in active and inactive metabolites. The elimination half-life varies, but it generally is around 6-12 hours, allowing for once-daily dosing in many cases. Renal excretion is a significant route for its metabolites, necessitating caution in patients with renal impairment.

Interactions

• maois, irreversible + alpha blockers: Severe (increases effects)
• ribociclib + alpha blockers: Severe (increases exposure)
• cobicistat + alpha blockers: Moderate (increases exposure)
• idelalisib + alpha blockers: Moderate (increases exposure)
• dronedarone + alpha blockers: Unknown (increases exposure)
• antifungals, azoles + alpha blockers: Unknown (increases exposure)
• crizotinib + alpha blockers: Unknown (increases exposure)
• imatinib + alpha blockers: Unknown (increases exposure)
• letermovir + alpha blockers: Unknown (increases exposure)
• clarithromycin + alpha blockers: Unknown (increases exposure)

Indications

• Rheumatoid arthritis
• Allergic diseases
• Peptic ulcers
• Anemia

Dosage

Children: Refer to BNF for Children for specific paediatric dosing recommendations.

Adults: Refer to BNF for specific dosing information based on condition and individual patient factors.

Mechanism of action

The specific actions of supplemental L-histidine are not completely understood, but it is known that L-histidine serves as a precursor for histamine through the process of decarboxylation. Histamine is associated with immunomodulatory and antioxidant effects, which may help in conditions such as rheumatoid arthritis by activating suppressor T cells and reducing reactive oxygen species production in immune cells. Additionally, L-histidine can chelate metals that participate in oxidative reactions, potentially protecting tissues from oxidative damage.

Pharmacodynamics

Histidine is essential for the synthesis of proteins and is found in high concentrations in hemoglobin. Its metabolites, including histamine, play significant roles in immune response regulation and oxidative stress management. A deficiency in histidine can lead to various health issues, including impaired hearing and reduced immune function.

Pharmacokinetics

Histidine is readily absorbed in the intestines and distributed throughout the body. It undergoes metabolic conversion primarily in the liver, where it is transformed into histamine and other metabolites. The elimination of histidine occurs through various metabolic pathways, and it is excreted in urine primarily as metabolites.

Pregnancy

Histidine is generally regarded as safe during pregnancy when consumed in food. However, the safety of high-dose supplementation has not been established.

Breast-feeding

Histidine is considered safe during breastfeeding in dietary amounts. The effects of high-dose supplementation are not well studied.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.

Formulations

• L-histidine capsules
• L-histidine powder

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.

Dosage

Children: Refer to specific drug monographs for dosing information, as monohydrate does not represent a specific active ingredient.

Adults: Refer to specific drug monographs for dosing information, as monohydrate does not represent a specific active ingredient.

Mechanism of action

The mechanism of action of a monohydrate compound is dependent on the active pharmaceutical ingredient it contains. Typically, the monohydrate form improves the dissolution and absorption of the drug, thereby enhancing its bioavailability. This can lead to more effective therapeutic outcomes compared to anhydrous forms.

Pharmacodynamics

Pharmacodynamics of a monohydrate drug will vary based on the specific active ingredient. Generally, the pharmacodynamic profile includes the drug's effects on physiological systems and its mechanism of action at the cellular level. Monohydrate forms may show altered pharmacodynamic properties due to differences in solubility and absorption rates.

Pharmacokinetics

The pharmacokinetics of a monohydrate drug formulation will also depend on the specific drug. Typically, pharmacokinetic parameters such as absorption, distribution, metabolism, and excretion can be influenced by the presence of water molecules in the hydrated form. Monohydrates may exhibit enhanced absorption rates due to increased solubility, which can lead to faster onset of action.

Pregnancy

Safety in pregnancy has not been established. Use only if potential benefits justify the risks.

Breast-feeding

Caution is advised when using during breastfeeding, as effects on the nursing infant are unknown.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Indications

• Emulsifying agent in drug formulations
• Stabilizer for parenteral preparations
• Solubilizer for hydrophobic drug compounds
• Ingredient in topical formulations

Dosage

Children: Refer to specific product guidelines, as dosing varies based on formulation and intended use.

Adults: Refer to specific product guidelines, as dosing varies based on formulation and intended use.

Mechanism of action

Polysorbate functions primarily as an emulsifying agent. It reduces the surface tension between immiscible liquids, allowing them to mix more easily. This property is particularly useful in stabilizing emulsions and suspensions, facilitating the delivery of active pharmaceutical ingredients in various formulations.

Pharmacodynamics

Polysorbate does not exert pharmacological effects in the traditional sense, as it does not bind to specific receptors to elicit a physiological response. Instead, it plays a crucial role in modifying the physical properties of drug formulations, thereby enhancing drug delivery and absorption. Its ability to solubilize drugs enhances their bioavailability, particularly for poorly soluble compounds.

Pharmacokinetics

Polysorbate is generally considered to be non-toxic and is not absorbed to a significant extent when administered orally. It is metabolized by the liver and excreted primarily through the gastrointestinal tract. The pharmacokinetic profile may vary depending on the route of administration and the specific formulation in which it is used.

Adverse effects

• Allergic reactions
• Skin irritation
• Gastrointestinal disturbances

Precautions

• Use cautiously in patients with known allergies to polysorbates or related compounds
• Monitor for allergic reactions in susceptible individuals

Pregnancy

Polysorbate is generally considered safe for use during pregnancy, but consult with a healthcare provider for specific cases.

Breast-feeding

Polysorbate is considered safe during breastfeeding, but consult with a healthcare provider for individual advice.

Storage

Store at room temperature, away from direct sunlight and moisture.

Formulations

• Polysorbate 20
• Polysorbate 80

Indications

• Neurodegenerative diseases
• Diabetes management
• Protective agent in stress conditions
• Potential use in rare metabolic disorders

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations, as pediatric dosing should be determined based on age, weight, and clinical condition.

Adults: Refer to the BNF for specific dosing guidelines as they may vary based on indication and formulation.

Mechanism of action

Trehalose acts by modulating cellular processes, particularly by stabilizing proteins and cellular structures under stress conditions. It enhances autophagy, a cellular degradation and recycling process, which plays a critical role in maintaining cellular homeostasis. The modulation of this pathway can lead to neuroprotective effects, making trehalose a compound of interest in neurodegenerative disease research.

Pharmacodynamics

Trehalose is believed to exert its effects by improving cellular resilience to stress and enhancing the clearance of misfolded proteins. It may also influence glucose metabolism and help maintain osmotic balance, reducing cellular damage in conditions such as diabetes and neurodegenerative diseases. The compound has shown promise in preclinical studies for its ability to improve cognitive function and protect against cellular injury.

Pharmacokinetics

Trehalose is absorbed in the intestine and metabolized primarily by trehalase enzymes. It has a relatively low bioavailability, and its metabolism can vary based on dietary intake and individual enzymatic activity. The pharmacokinetics of trehalose are influenced by its solubility and stability in aqueous environments, with a half-life that may vary depending on the dosage form and route of administration.

Mechanism of action

Since the actions of supplemental L-histidine are unclear, any postulated mechanism is entirely speculative. However, some facts are known about L-histidine and some of its metabolites, such as histamine and trans-urocanic acid, which suggest that supplemental L-histidine may one day be shown to have immunomodulatory and/or antioxidant activities. Low free histidine has been found in the serum of some rheumatoid arthritis patients. Serum concentrations of other amino acids have been found to be normal in these patients. L-histidine is an excellent chelating agent for such metals as copper, iron and zinc. Copper and iron participate in a reaction (Fenton reaction) that generates potent reactive oxygen species that could be destructive to tissues, including joints. L-histidine is the obligate precursor of histamine, which is produced via the decarboxylation of the amino acid. In experimental animals, tissue histamine levels increase as the amount of dietary L-histidine increases. It is likely that this would be the case in humans as well. Histamine is known to possess immunomodulatory and antioxidant activity. Suppressor T cells have H2 receptors, and histamine activates them. Promotion of suppressor T cell activity could be beneficial in rheumatoid arthritis. Further, histamine has been shown to down-regulate the production of reactive oxygen species in phagocytic cells, such as monocytes, by binding to the H2 receptors on these cells. Decreased reactive oxygen species production by phagocytes could play antioxidant, anti-inflammatory and immunomodulatory roles in such diseases as rheumatoid arthritis. This latter mechanism is the rationale for the use of histamine itself in several clinical trials studying histamine for the treatment of certain types of cancer and viral diseases. In these trials, down-regulation by histamine of reactive oxygen species formation appears to inhibit the suppression of natural killer (NK) cells and cytotoxic T lymphocytes, allowing these cells to be more effective in attacking cancer cells and virally infected cells.

Pharmacodynamics

Is found abundantly in hemoglobin; has been used in the treatment of rheumatoid arthritis, allergic diseases, ulcers and anemia. A deficiency can cause poor hearing.