BEDA EXECT COUGH SYRUP

Indications

• Nitrogen supplementation in clinical nutrition
• Management of metabolic alkalosis
• Treatment of certain types of kidney disorders

Dosage

Children: Specific pediatric dosing information is not detailed in the BNF. Refer to the BNF for Children for appropriate dosing based on age and condition.

Adults: Dosage varies based on clinical indication and should be guided by specific treatment protocols. Refer to clinical guidelines for detailed dosing information.

Mechanism of action

Ammonium ions participate in various metabolic pathways, including the biosynthesis of amino acids and nucleotides. It serves as a nitrogen source for organisms, facilitating the synthesis of essential biomolecules. The presence of ammonium can influence pH levels and osmotic balance within cells, thereby affecting cellular functions and enzyme activities.

Pharmacodynamics

Ammonium affects cellular metabolism by acting as a nitrogen donor in the synthesis of organic compounds. Its role in the nitrogen cycle and as a substrate in biochemical pathways allows for the maintenance of cellular functions, including energy production and cellular growth. Alterations in ammonium levels can influence various physiological processes, including neurotransmitter synthesis and energy metabolism.

Pharmacokinetics

Ammonium is readily absorbed and distributed in biological systems. It can be produced endogenously through amino acid metabolism or obtained from dietary sources. The excretion of ammonium primarily occurs through the kidneys, where it is converted to urea for elimination. Ammonium levels are regulated by various mechanisms, including the action of renal tubular cells that either secrete or reabsorb ammonium based on the body's needs.

Indications

• Cough associated with respiratory tract infections
• Acid-base disorders
• Edema management

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing guidelines based on age and condition.

Adults: Refer to the BNF for specific adult dosing guidelines as they depend on the indication and clinical context.

Mechanism of action

Ammonium chloride increases acidity by raising hydrogen ion concentrations. It dissociates into ammonium and chloride ions; the ammonium is converted to urea in the liver, releasing hydrogen ions that lower pH. The chloride ions displace bicarbonate in extracellular fluid, leading to acidosis and increased renal excretion of electrolytes and water, resulting in fluid mobilization.

Pharmacodynamics

Ammonium chloride acts as a systemic acidifier, facilitating the excretion of chloride and sodium, while also increasing the acidity of body fluids. The conversion of ammonium to urea in the liver with the release of hydrogen ions contributes to a decrease in blood pH, affecting acid-base balance in the body.

Pharmacokinetics

Ammonium chloride is absorbed from the gastrointestinal tract and metabolized in the liver, where it is converted to urea. The dissociated ions impact renal function, leading to increased excretion of sodium, potassium, and water. The elimination half-life and specific metabolism details are not explicitly defined.

Adverse effects

• Nausea
• Vomiting
• Abdominal pain
• Diarrhea
• Dizziness
• Headache

Interactions

• Antacids may reduce the effectiveness of ammonium chloride
• Potassium-sparing diuretics may increase the risk of hyperkalemia

Precautions

• Use with caution in patients with renal impairment
• Monitor electrolyte levels during prolonged therapy
• Consider potential for acidosis in patients with liver disease

Pregnancy

Ammonium chloride should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Consult a healthcare provider for individualized advice.

Breast-feeding

Ammonium chloride is excreted in breast milk. Use caution and consult a healthcare provider if breastfeeding.

Storage

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

Formulations

• Oral solution
• Powder for oral solution

Indications

• Allergic rhinitis
• Allergic conjunctivitis
• Urticaria

Mechanism of action

Diphenhydramine primarily functions by antagonizing H1 (Histamine 1) receptors located in various tissues, including the respiratory system, gastrointestinal tract, and central nervous system. By acting as an inverse agonist at H1 receptors, it mitigates the effects of histamine, thereby reducing allergic symptoms. As a first-generation antihistamine, it also crosses the blood-brain barrier, leading to sedative effects. Furthermore, diphenhydramine exhibits antimuscarinic activity by competitively antagonizing muscarinic acetylcholine receptors, contributing to its use in treating parkinsonian symptoms.

Pharmacodynamics

Diphenhydramine possesses anti-histaminic, anti-emetic, anti-vertigo, and sedative properties. Its antihistaminic action blocks the effects of histamine by competing for H1 receptor sites, preventing symptoms associated with histamine release. Its anti-emetic effects are due to inhibition at the medullary chemoreceptor trigger zone, while its anti-vertigo action arises from a central antimuscarinic effect on the vestibular apparatus and the vomiting center in the midbrain.

Pharmacokinetics

Diphenhydramine is well-absorbed following oral administration and reaches peak plasma concentrations within 1 to 2 hours. It is metabolized in the liver and has a half-life of approximately 4 to 8 hours, although this can vary based on individual factors. The drug is excreted primarily in the urine, with a significant portion eliminated as metabolites rather than unchanged drug. Due to its lipophilic nature, diphenhydramine readily crosses the blood-brain barrier, contributing to its sedative effects.

Contra-indications

• Severe asthma exacerbation
• Hypersensitivity to diphenhydramine or any of its components
• Newborns or premature infants

Adverse effects

• Drowsiness
• Dizziness
• Dry mouth
• Constipation
• Urinary retention
• Blurred vision
• Confusion

Interactions

• CNS depressants (e.g., alcohol, sedatives, tranquilizers) may enhance sedative effects
• MAO inhibitors can prolong and intensify anticholinergic effects

Precautions

• Use with caution in patients with glaucoma
• Prostatic hypertrophy
• Cardiovascular disease
• Elderly patients may be more sensitive to side effects

Pregnancy

Diphenhydramine should only be used during pregnancy if clearly needed. Consult a healthcare provider for advice.

Breast-feeding

Diphenhydramine is excreted in breast milk. Use caution when administering to nursing mothers.

Storage

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

Formulations

• Tablets
• Capsules
• Liquid formulations
• Topical preparations

Mechanism of action

Ammonium chloride increases acidity by increasing the amount of hydrogen ion concentrations. Ammonium chloride can be used as an expectorant due to its irritative action on the bronchial mucosa. This effect causes the production of respiratory tract fluid which in order facilitates the effective cough. The acid-forming properties of ammonium chloride result from dissociation of the salt to an ammonium cation and a chloride anion. In patients with normal hepatic function, the ammonium cation is converted to urea by the liver and a hydrogen cation is released which reacts with a bicarbonate ion to form water and carbon dioxide. The chloride anion combines with fixed bases in the extracellular fluid, thereby reducing the alkaline reserve of the body. The net result is the displacement of bicarbonate ions by chloride anions. The displacement of bicarbonate by chloride alters the bicarbonate:carbonic acid ratio if the body and acidosis results. The increased chloride concentration in the extracellular fluid produces an increased load to the renal tubules and appreciable amounts of chloride anions escape reabsorption. These anions are excreted along with cations and water. Sodium is the principal cation excreted; however, potassium excretion may also be increased to some degree. By increasing the excretion of both extracellular electrolytes and water, ammonium chloride causes a net loss of extracellular fluid and promotes the mobilization of edema fluid.

Pharmacodynamics

Systemic acidifier. In liver ammonium chloride is converted into urea with the liberation of hydrogen ions ( which lowers the pH) and chloride.

Mechanism of action

Diphenhydramine predominantly works via the antagonism of H1 (Histamine 1) receptors. Such H1 receptors are located on respiratory smooth muscles, vascular endothelial cells, the gastrointestinal tract (GIT), cardiac tissue, immune cells, the uterus, and the central nervous system (CNS) neurons. When the H1 receptor is stimulated in these tissues it produces a variety of actions including increased vascular permeability, promotion of vasodilation causing flushing, decreased atrioventricular (AV) node conduction time, stimulation of sensory nerves of airways producing coughing, smooth muscle contraction of bronchi and the GIT, and eosinophilic chemotaxis that promotes the allergic immune response. Ultimately, diphenhydramine functions as an inverse agonist at H1 receptors, and subsequently reverses effects of histamine on capillaries, reducing allergic reaction symptoms. Moreover, since diphenhydramine is a first-generation antihistamine, it readily crosses the blood-brain barrier and inversely agonizes the H1 CNS receptors, resulting in drowsiness, and suppressing the medullary cough center. Furthermore, H1 receptors are similar to muscarinic receptors. Consequently, diphenhydramine also acts as an antimuscarinic. It does so by behaving as a competitive antagonist of muscarinic acetylcholine receptors, resulting in its use as an antiparkinson medication. Lastly, diphenhydramine has also demonstrated activity as an intracellular sodium channel blocker, resulting in possible local anesthetic properties. Antihistamines used in the treatment of allergy act by competing with histamine for H1-receptor sites on effector cells. They thereby prevent, but do not reverse, responses mediated by histamine alone. Antihistamines antagonize, in varying degrees, most of the pharmacological effects of histamine, including urticaria and pruritus. Also, the anticholinergic actions of most antihistamines provide a drying effect on the nasal mucosa. /Antihistamines/ H1 antagonists inhibit both the vasoconstrictor effects of histamine and, to a degree, the more rapid vasodilator effects mediated by activation of H1 receptors on endothelial cells (synthesis/release of NO and other mediators). /H1 Receptor Antagonists/ H1 antagonists suppress the action of histamine on nerve endings, including the flare component of the triple response and the itching caused by intradermal injection. /H1 Receptor Antagonists/ The first-generation antihistamines are widely prescribed medications that relieve allergic reactions and urticaria by blocking the peripheral histamine H(1) receptor. Overdose of these drugs often results in serious neuronal toxic effects, including seizures, convulsions and worsening of epileptic symptoms. The KCNQ/M K(+) channel plays a crucial role in controlling neuron excitability. Here, we demonstrate that mepyramine and diphenhydramine, two structurally related first-generation antihistamines, can act as potent KCNQ/M channel blockers. Extracellular application of these drugs quickly and reversibly reduced KCNQ2/Q3 currents heterologously expressed in HEK293 cells. The current inhibition was concentration and voltage dependent. The estimated IC(50) (12.5 and 48.1 microM, respectively) is within the range of drug concentrations detected in poisoned patients (30-300 microM). Both drugs shifted the I-V curve of KCNQ2/Q3 channel to more depolarized potentials and altered channel gating properties by prolonging activation and shortening deactivation kinetics. Mepyramine also inhibited the individual homomeric KCNQ1-4 and heteromeric KCNQ3/Q5 currents. Moreover, mepyramine inhibited KCNQ2/Q3 current in an outside-out patch excised from HEK293 cells and the inhibitory effect was neither observed when it was applied intracellularly nor affected by blocking phospholipase C (PLC) activity, indicating an extracellular and direct channel blocking mechanism. Finally, in cultured rat superior cervical ganglion (SCG) neurons, mepyramine reduced the

Pharmacodynamics

Diphenhydramine has anti-histaminic (H1-receptor), anti-emetic, anti-vertigo and sedative and hypnotic properties. The anti-histamine action occurs by blocking the spasmogenic and congestive effects of histamine by competing with histamine for H1 receptor sites on effector cells, preventing but not reversing responses mediated by histamine alone. Such receptor sites may be found in the gut, uterus, large blood vessels, bronchial muscles, and elsewhere. Anti-emetic action is by inhibition at the medullary chemoreceptor trigger zone. Anti-vertigo action is by a central antimuscarinic effect on the vestibular apparatus and the integrative vomiting center and medullary chemoreceptor trigger zone of the midbrain.