BRONCHALIX

Indications

• Reversal of hypotension from spinal or epidural anesthesia
• Reversible airways obstruction (e.g., asthma, bronchospasm)
• Nasal congestion

Dosage

Children: For children aged 1 month to 11 years, the dose is 1 mg/kg/hour by intravenous infusion, adjusted according to plasma-theophylline concentration. For children aged 12 to 17 years, administer 500–700 micrograms/kg/hour by intravenous infusion, also adjusted according to plasma-theophylline concentration.

Adults: For reversal of hypotension, administer 3–7.5 mg by slow intravenous injection every 3–4 minutes, adjusting according to response, with a maximum of 9 mg per dose. For airways obstruction, 30–60 mg may be given orally three times a day.

Mechanism of action

Ephedrine acts by stimulating adrenergic receptors, leading to bronchodilation and vasoconstriction. It increases the release of norepinephrine from sympathetic nerve endings, enhancing its action on alpha and beta-adrenergic receptors, which results in increased peripheral resistance and cardiac output.

Pharmacodynamics

Ephedrine exhibits both alpha- and beta-adrenergic activity. Its alpha-adrenergic effects lead to vasoconstriction, while beta-adrenergic stimulation results in bronchodilation. The drug also has a mild central nervous system stimulant effect, which can contribute to side effects such as anxiety and insomnia.

Pharmacokinetics

Ephedrine is well-absorbed from the gastrointestinal tract and is distributed widely throughout the body. It has a relatively long half-life due to its resistance to metabolism. The drug is primarily excreted unchanged in the urine. Its pharmacokinetic profile can be influenced by factors such as renal function and the presence of other medications that may affect its clearance.

Contra-indications

• Hypersensitivity to ephedrine or any of its components
• Severe hypertension
• Tachyarrhythmias
• Severe coronary artery disease
• Hyperthyroidism
• Prostatic hypertrophy

Adverse effects

• Anxiety
• Headache
• Insomnia
• Nausea
• Tremor
• Dry mouth
• Dizziness
• Cardiac arrhythmias
• Hypertension
• Urinary retention
• Myocardial infarction
• Psychotic disorders
• Pulmonary edema

Interactions

• Other sympathomimetics
• Xanthines (e.g., theophylline)
• Monoamine oxidase inhibitors
• Antihypertensive agents
• Antidepressants
• Corticosteroids

Precautions

• Use with caution in patients with diabetes mellitus
• Caution in elderly patients
• Hypertension
• Ischaemic heart disease
• Glaucoma (risk of angle-closure)
• Chronic obstructive pulmonary disease

Pregnancy

Manufacturer advises avoidance due to potential risks, including increased fetal heart rate.

Breast-feeding

Present in breast milk; manufacturer advises avoidance due to reported irritability and disturbed sleep in infants.

Storage

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

Formulations

• Oral suspension
• Oral solution
• Tablets (15 mg, 30 mg)
• Solution for injection (30 mg per 10 ml)

Indications

• Choline deficiency
• Support in liver function
• Neurological health, including cognitive function
• Fat metabolism disorders

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Choline is a major component of phosphatidylcholine, which is essential for maintaining cell membrane integrity, facilitating information flow, and intracellular communication. It is involved in the synthesis of acetylcholine, a key neurotransmitter in the central nervous system. Choline deficiency can lead to apoptosis by affecting cell membrane composition and increasing ceramide levels, which activates apoptotic pathways. Additionally, choline is a precursor to betaine, which helps regulate homocysteine levels, thus reducing cardiovascular risks.

Pharmacodynamics

Choline is crucial for proper nerve conduction in the central nervous system as it is a precursor for acetylcholine. It supports liver function, gallbladder regulation, and lipid metabolism. Adequate choline levels are associated with the prevention of excessive fat accumulation in the liver and may mitigate conditions such as Parkinsonism and tardive dyskinesia. Deficiencies can lead to serious health problems, including liver dysfunction and stunted growth.

Pharmacokinetics

Choline is absorbed in the intestines and distributed throughout the body, where it is utilized in various metabolic pathways. The liver plays a central role in choline metabolism, converting it into phosphatidylcholine and other metabolites. The half-life and excretion pathways of choline are not well defined but are influenced by dietary intake, physiological state, and individual metabolism.

Interactions

• corticosteroids+cholinesalicylate: Unknown (decreases concentration)

Pregnancy

Choline is generally considered safe during pregnancy, as it is essential for fetal development, particularly for brain development and function. However, it is important to adhere to recommended dietary allowances.

Breast-feeding

Choline is important during breastfeeding as it supports infant brain development. Adequate intake is recommended for nursing mothers.

Storage

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

Indications

• Bronchial asthma
• Hypotension
• Nasal congestion
• Cardiac arrest

Dosage

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

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

Mechanism of action

Ephedrine acts by activating alpha-adrenergic and beta-adrenergic receptors. Directly, it stimulates these receptors, leading to vasoconstriction (alpha-1), increased cardiac chronotropy and inotropy (beta-1), and bronchodilation (beta-2). Indirectly, it inhibits norepinephrine reuptake and promotes the release of norepinephrine from nerve cells, resulting in prolonged sympathetic stimulation.

Pharmacodynamics

Ephedrine elevates blood pressure through increased heart rate and cardiac output, while also variably raising peripheral resistance. It induces bronchodilation through beta-adrenergic receptor activation in the lungs. Additionally, it enhances urine outflow resistance by stimulating alpha-adrenergic receptors in bladder smooth muscle. The therapeutic dose range is broad, with potential dosages from 5mg to 50mg, and caution is advised regarding the risk of hypertension and tachyphylaxis.

Pharmacokinetics

Ephedrine is rapidly absorbed and reaches peak plasma concentrations within 1 to 2 hours following oral administration. It is metabolized in the liver and excreted primarily via the kidneys. The duration of action is variable, but it generally lasts for 2 to 4 hours. Its pharmacokinetic profile can be influenced by individual patient characteristics, including renal function.

Adverse effects

• Tachycardia
• Hypertension
• Palpitations
• Nervousness
• Dizziness
• Nausea
• Vomiting

Interactions

• mianserin+ephedrine: Unknown (decreases effects)
• volatile halogenated anaesthetics+ephedrine: Unknown (additive effect)

Precautions

• Use with caution in patients with cardiovascular disorders
• Monitor blood pressure and heart rate during treatment
• Consider potential for tachyphylaxis with prolonged use

Pregnancy

Use only if clearly needed, as safety in pregnancy has not been established.

Breast-feeding

Caution is advised; ephedrine may pass into breast milk.

Storage

Store in a cool, dry place, away from direct sunlight.

Formulations

• Oral tablets
• Injectable solution

Indications

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Bronchospasm associated with asthma or COPD
• Acute bronchospasm

Dosage

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

Adults: Refer to the BNF for specific dosing information, as it varies based on the formulation and clinical scenario.

Mechanism of action

Theophyllinate acts as a non-selective phosphodiesterase inhibitor, leading to increased levels of cyclic AMP (cAMP) in cells. This results in the relaxation of bronchial smooth muscle, inhibition of inflammatory mediator release, and overall bronchodilation. Additionally, theophyllinate has adenosine receptor antagonistic properties, which further contribute to its bronchodilatory effects.

Pharmacodynamics

Theophyllinate exhibits dose-dependent bronchodilation, with therapeutic effects typically observed at plasma concentrations ranging from 10 to 20 mcg/mL. It also has diuretic effects due to increased renal blood flow and glomerular filtration rate. The drug may enhance the contractility of the diaphragm and improve respiratory muscle function due to its stimulatory effects on the central nervous system.

Pharmacokinetics

Theophyllinate is well-absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1 to 2 hours after oral administration. It has a half-life of approximately 8 hours in adults, but this can vary significantly based on factors such as age, smoking status, and the presence of liver disease. Theophyllinate is extensively metabolized in the liver, primarily via cytochrome P450 enzymes, and its metabolites are excreted via the kidneys. The drug's clearance can be altered by various factors, necessitating careful monitoring of serum levels.

Contra-indications

• Hypersensitivity to theophylline or any of its components
• Acute myocardial infarction
• Severe hepatic impairment
• Severe arrhythmias

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Headache
• Insomnia
• Palpitations
• Tachycardia
• Tremors
• Seizures

Interactions

• CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine) may increase theophylline levels
• CYP1A2 inducers (e.g., rifampicin, carbamazepine) may decrease theophylline levels
• Beta-adrenergic agonists may enhance the effects of theophylline
• Smoking may decrease theophylline clearance

Precautions

• Use with caution in patients with liver disease
• Monitor for signs of toxicity, especially in elderly patients or those with comorbidities
• Regular monitoring of theophylline serum levels may be necessary
• Use with caution in patients with cardiovascular disorders

Pregnancy

Theophylline should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It crosses the placenta.

Breast-feeding

Theophylline is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Oral tablets
• Oral solution
• Injectable solution
• Extended-release formulations

Mechanism of action

Choline is a major part of the polar head group of phosphatidylcholine. Phosphatidylcholine's role in the maintenance of cell membrane integrity is vital to all of the basic biological processes: information flow, intracellular communication and bioenergetics. Inadequate choline intake would negatively affect all these processes. Choline is also a major part of another membrane phospholipid, sphingomyelin, also important for the maintenance of cell structure and function. It is noteworthy and not surprising that choline deficiency in cell culture causes apoptosis or programmed cell death. This appears to be due to abnormalities in cell membrane phosphatidylcholine content and an increase in ceramide, a precursor, as well as a metabolite, of sphingomyelin. Ceramide accumulation, which is caused by choline deficiency, appears to activate Caspase, a type of enzyme that mediates apoptosis. Betaine or trimethylglycine is derived from choline via an oxidation reaction. Betaine is one of the factors that maintains low levels of homocysteine by resynthesizing L-methionine from homocysteine. Elevated homocysteine levels are a significant risk factor for atherosclerosis, as well as other cardiovascular and neurological disorders. Acetylcholine is one of the major neurotransmitters and requires choline for its synthesis. Adequate acetylcholine levels in the brain are believed to be protective against certain types of dementia, including Alzheimer's disease.

Pharmacodynamics

This compound is needed for good nerve conduction throughout the CNS (central nervous system) as it is a precursor to acetylcholine (ACh). Choline is also needed for gallbladder regulation, liver function and lecithin (a key lipid) formation. Choline also aids in fat and cholesterol metabolism and prevents excessive fat build up in the liver. Choline has been used to mitigate the effects of Parkinsonism and tardive dyskinesia. Choline deficiencies may result in excessive build-up of fat in the liver, high blood pressure, gastric ulcers, kidney and liver dysfunction and stunted growth.

Mechanism of action

Ephedrine is a direct and indirect sympathomimetic amine. As a direct effect, ephedrine activates alpha-adrenergic and beta-adrenergic receptors. As an indirect effect, it inhibits norepinephrine reuptake and increases the release of norepinephrine from vesicles in nerve cells. These actions combined lead to larger quantities of norepinephrine present in the synapse for more extended periods of time, increasing stimulation of the sympathetic nervous system. Ephedrine acts as an agonist of alpha-1, beta-1 and beta-2-adrenergic receptors. The stimulation of alpha-1-adrenergic receptors causes the constriction of veins and a rise in blood pressure, the stimulation of beta-1-adrenergic receptors increases cardiac chronotropy and inotropy, and the stimulation of beta-2-adrenergic receptors causes vasodilation and bronchodilation. Ephedrine alkaloids are members of a large family of sympathomimetic compounds that include dobutamine and amphetamine. Members of this family increase blood pressure and heart rate by binding to alpha- and beta-adrenergic receptors present in many parts of the body, including the heart and blood vessels. These compounds are called sympathomimetics because they mimic the effects of epinephrine and norepinephrine, which occur naturally in the human body. In addition to their direct pharmacological effects, many of these compounds also stimulate the release of norepinephrine from nerve endings. The release of norepinephrine further increases the sympathomimetic effects of these compounds, at least transiently. Ephedrine does not contain a catechol moiety, and it is effective after oral administration. The drug stimulates heart rate and cardiac output and variably increases peripheral resistance; as a result, ephedrine usually increases blood pressure. Stimulation of the alpha-adrenergic receptors of smooth muscle cells in the bladder base may increase the resistance to the outflow of urine. Activation of beta-adrenergic receptors in the lungs promotes bronchodilation. Ephedrine stimulates both alpha- and beta-adrenergic receptors. It is believed that beta-adrenergic effects result from stimulation of the production of cyclic adenosine 3',5'-monophosphate (AMP) by activation of the enzyme adenyl cyclase, whereas a-adrenergic effects result from inhibition of adenyl cyclase activity. In contrast to epinephrine, ephedrine also has an indirect effect by releasing norepinephrine from its storage sites. With prolonged use or if doses are given frequently, ephedrine may deplete norepinephrine stores in sympathetic nerve endings and tachyphylaxis may develop to the cardiac and pressor effects. Tachyphylaxis to the bronchial effects of the drug may also occur, but it is not the result of norepinephrine depletion.

Pharmacodynamics

Ephedrine increases blood pressure by stimulating heart rate and cardiac output and variably increasing peripheral resistance. It causes bronchodilation due to the activation of beta-adrenergic receptors in the lungs. By stimulating alpha-adrenergic receptors in bladder smooth muscle cells, ephedrine also increases the resistance to the outflow of urine. The therapeutic window of ephedrine is wide, as patients can be given doses of 5mg up to 50mg. Patients should be counselled regarding the pressor effects of sympathomimetic amines and the risk of tachyphylaxis. Also, the use of ephedrine for hypotension prophylaxis is associated with a higher risk of hypertension, compared to when ephedrine is used to treat hypotension.