MIRCERA 75 MCG

Indications

• Asthma
• Chronic Obstructive Pulmonary Disease (COPD)
• Hypertension
• Heart Failure
• Cardiac Arrhythmias

Dosage

Children: Refer to the BNF for Children for appropriate dosing

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated and the formulation of the drug used.

Mechanism of action

Beta-adrenergic agonists stimulate beta-adrenergic receptors, leading to increased intracellular cAMP levels, which causes relaxation of bronchial smooth muscle and dilation of the airways. This mechanism is particularly important in the treatment of asthma and COPD, where airway constriction is a major issue. Beta-blockers, on the other hand, inhibit the effects of catecholamines on beta receptors, resulting in decreased heart rate and myocardial contractility, which is beneficial in managing hypertension and certain types of cardiac arrhythmias.

Pharmacodynamics

The pharmacodynamics of beta drugs vary depending on whether they are agonists or antagonists. Agonists lead to a dose-dependent bronchodilation and increased heart rate, while antagonists decrease heart rate and myocardial oxygen demand. The effects of these drugs can be influenced by patient-specific factors such as receptor sensitivity, presence of comorbid conditions, and concurrent medications.

Pharmacokinetics

The pharmacokinetics of beta drugs can differ substantially. Agonists are typically rapidly absorbed and distributed, with onset of action occurring within minutes. They may have short half-lives, necessitating multiple doses throughout the day. Beta-blockers, in contrast, may have longer half-lives and can be administered once or twice daily. Metabolism usually occurs in the liver, and renal excretion is common for both classes, affecting their dosing in patients with renal impairment.

Interactions

• betablockers, selective + aminophylline: Severe (increases risk of bronchospasm)
• dacomitinib + betablockers, selective: Severe (increases exposure)
• mexiletine + betablockers, selective: Severe (increases risk of cardiovascular adverse effects)
• betablockers, selective + theophylline: Severe (increases risk of bronchospasm)
• beta 2 agonists + linezolid: Severe (increases risk of elevated blood pressure)
• mao-b inhibitors + beta: Severe (increases risk of severe hypertension)
• verapamil + betablockers, non-selective: Severe (increases risk of cardiovascular adverse effects)
• cobicistat + beta: Severe (increases exposure)
• dacomitinib + betablockers, non-selective: Severe (increases exposure)
• idelalisib + beta: Severe (increases exposure)

Indications

• Anemia of chronic kidney disease
• Anemia associated with cancer chemotherapy
• Anemia in patients undergoing major surgery
• Anemia in patients with HIV receiving zidovudine

Dosage

Children: Refer to the BNF for Children for specific pediatric dosing information.

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated.

Mechanism of action

Epoetin binds to the erythropoietin receptor on erythroid progenitor cells in the bone marrow, promoting their differentiation and proliferation. This action stimulates erythropoiesis, leading to increased production of RBCs. Additionally, it enhances the survival of erythroid progenitor cells and promotes the release of reticulocytes into the bloodstream, ultimately leading to an increase in hemoglobin levels.

Pharmacodynamics

Epoetin exhibits dose-dependent effects on erythropoiesis. Its activity results in increased hemoglobin concentration and hematocrit levels. The onset of action is generally observed within a few days, with peak effects typically seen within 1 to 2 weeks of administration. Long-term use may lead to increased RBC mass and improved oxygen delivery to tissues.

Pharmacokinetics

Epoetin is administered via subcutaneous or intravenous routes. It has a half-life of approximately 4 to 13 hours, depending on the formulation and route of administration. The drug is primarily eliminated through the kidneys, with a significant portion undergoing metabolic degradation. The pharmacokinetics may be influenced by factors such as renal function and patient-specific characteristics.

Contra-indications

• Uncontrolled hypertension
• Pure red cell aplasia
• Hypersensitivity to epoetin or any of its components

Adverse effects

• Hypertension
• Headache
• Fatigue
• Nausea
• Diarrhea
• Injection site reactions
• Thrombotic events (e.g., stroke, myocardial infarction)

Interactions

• Antihypertensive agents may require dose adjustments due to the potential for increased blood pressure
• Iron supplements may be used concurrently; ensure adequate iron stores for optimal erythropoiesis

Precautions

• Monitor hemoglobin levels regularly to avoid excessive increases
• Use with caution in patients with a history of cardiovascular disease
• Assess iron status before and during treatment

Pregnancy

Epoetin may be used during pregnancy if the benefits outweigh the risks, as it is classified as category C.

Breast-feeding

Epoetin is excreted in breast milk; caution is advised when administered to nursing mothers.

Storage

Store in the refrigerator (2°C to 8°C), do not freeze. Keep protected from light.

Formulations

• Epoetin alfa injectable solution
• Epoetin beta injectable solution

Dosage

Children: Refer to the BNF for Children for appropriate dosing information in paediatric cases, especially in instances of overdose.

Adults: Refer to the BNF for specific dosing information based on clinical circumstances, particularly in cases of overdose.

Mechanism of action

Ethylene glycol is metabolized by alcohol dehydrogenase to glycoaldehyde, which is subsequently converted to glycolic, glyoxylic, and oxalic acids. These metabolites contribute to anion gap metabolic acidosis and are responsible for tissue injury through the formation of insoluble calcium oxalate crystals.

Pharmacodynamics

The toxicity of ethylene glycol arises from its metabolites, particularly glycolic and oxalic acids. These compounds induce metabolic acidosis, lead to renal failure through calcium oxalate crystal deposition in the kidneys, and can cause neurological impairment. The anion gap increases due to the accumulation of these acids, leading to complications such as cardiovascular instability and potential multi-organ failure.

Pharmacokinetics

Ethylene glycol is rapidly absorbed after oral ingestion. It undergoes first-pass metabolism primarily in the liver, where it is converted into its toxic metabolites. The elimination half-life of ethylene glycol varies but is generally prolonged in cases of renal impairment. Renal excretion of metabolites contributes to the duration of toxicity, necessitating prompt medical intervention in cases of overdose.

Adverse effects

• Metabolic acidosis
• Renal failure
• CNS depression
• Hypocalcemia
• Cardiovascular collapse
• Pulmonary edema

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of metabolic acidosis
• Evaluate electrolyte levels, particularly calcium

Pregnancy

There is limited data on the safety of ethylene glycol in pregnancy. It should only be used if clearly needed.

Breast-feeding

It is unknown if ethylene glycol is excreted in human milk. Caution is advised.

Storage

Store in a tightly closed container at room temperature, away from heat and moisture.

Formulations

• Liquid

Indications

• Pain relief in emergency settings
• Procedural sedation
• Anesthesia for minor surgical procedures

Dosage

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

Adults: Refer to the BNF for specific dosage recommendations based on the clinical context and patient factors.

Mechanism of action

Methoxyflurane acts primarily as a central nervous system depressant, enhancing the inhibitory effects of gamma-aminobutyric acid (GABA) at GABA-A receptors. This mechanism contributes to its anesthetic properties by reducing neuronal excitability and promoting sedation. Additionally, methoxyflurane may affect other neurotransmitter systems, including glutamate, but the primary action is through GABA modulation.

Pharmacodynamics

Methoxyflurane provides analgesic and sedative effects through inhalation, rapidly inducing loss of consciousness and analgesia. The drug's potency is influenced by its relatively low MAC (minimum alveolar concentration), which indicates the concentration required to prevent movement in response to surgical stimuli in 50% of patients. The analgesic effect is often noted within minutes of administration, making it suitable for acute pain management.

Pharmacokinetics

Methoxyflurane is characterized by high lipophilicity, leading to rapid absorption into the bloodstream via the lungs. It is quickly distributed throughout body tissues, with a rapid onset of action. The metabolism of methoxyflurane occurs primarily in the liver, and renal excretion is a significant pathway for elimination. Due to its nephrotoxic potential, particularly when used in conjunction with other nephrotoxic agents such as rifampicin, careful consideration of renal function is necessary when prescribing methoxyflurane.

Interactions

• rifampicin+methoxyflurane: Severe (increases risk of nephrotoxicity)

Pregnancy

There is limited data on the use of methoxyflurane in pregnancy. Caution is advised.

Breast-feeding

It is not known whether methoxyflurane is excreted in human milk. Caution is advised.

Storage

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

Indications

• Constipation
• Bowel preparation prior to colonoscopy
• Preparation for intestinal surgery

Dosage

Children: Refer to specific guidelines or product information for paediatric dosing.

Adults: Refer to specific guidelines or product information for adult dosing.

Mechanism of action

Polyethylene glycol works by osmotically drawing water into the lumen of the gastrointestinal tract. This increase in water content leads to increased stool volume and promotes peristalsis, aiding in the evacuation of the bowel. It is not absorbed systemically, which minimizes potential side effects.

Pharmacodynamics

Polyethylene glycol acts as an osmotic laxative, increasing the water content of the intestines, which helps to soften the stool and stimulate bowel movements. The action typically occurs within 24 to 72 hours after ingestion. It is considered effective for treating occasional constipation and is also used in bowel preparation before surgeries or diagnostic procedures.

Pharmacokinetics

Polyethylene glycol is not absorbed through the gastrointestinal tract, and thus does not undergo significant metabolism. Its primary action is local within the gut. The elimination of PEG occurs through fecal excretion, and its effects can last as long as the osmotic pressure remains in the intestinal lumen.

Adverse effects

• Abdominal cramps
• Nausea
• Diarrhea
• Bloating
• Dehydration

Precautions

• Use with caution in patients with a history of gastrointestinal obstruction
• Ensure adequate hydration during use to prevent dehydration
• Assess for electrolyte imbalances, particularly in patients with renal impairment

Pregnancy

Polyethylene glycol is generally considered safe during pregnancy. However, it should be used under medical supervision.

Breast-feeding

Polyethylene glycol is excreted into breast milk in small amounts and is considered safe for use during breastfeeding.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Powder for oral solution
• Liquid formulation

Mechanism of action

Ethylene glycol is metabolized by alcohol dehydrogenase to glycoaldehyde, which is then metabolized to glycolic, glyoxylic, and oxalic acids. These acids, along with excess lactic acid are responsible for the anion gap metabolic acidosis. Oxalic acid readily precipitates with calcium to form insoluble calcium oxalate crystals. Tissue injury is caused by widespread deposition of oxalate crystals and the toxic effects of glycolic and glyoxylic acids.