DACOF DRY COUGH SYRUP

Indications

• Cough associated with the common cold
• Cough due to bronchitis
• Cough caused by upper respiratory tract infections

Dosage

Children: Refer to established medical guidelines or product labeling for specific dosing recommendations.

Adults: Refer to established medical guidelines or product labeling for specific dosing recommendations.

Mechanism of action

Dextromethorphan primarily acts as a non-competitive antagonist at the NMDA receptor and inhibits the reuptake of serotonin, which contributes to its cough-suppressing effects. It also has sigma-1 receptor agonist properties, which may play a role in its analgesic and anti-cough effects.

Pharmacodynamics

Dextromethorphan reduces the frequency and intensity of coughing. It does this by acting on the medullary cough center in the central nervous system, decreasing the sensitivity to cough stimuli. Its effects can typically be observed within 15 to 30 minutes after oral administration, lasting for several hours.

Pharmacokinetics

Dextromethorphan is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 2 to 3 hours post-administration. It undergoes extensive hepatic metabolism primarily via the cytochrome P450 system, particularly CYP2D6, resulting in various metabolites. The elimination half-life of dextromethorphan is approximately 2 to 4 hours, and it is excreted in urine, predominantly as metabolites.

Adverse effects

• Dizziness
• Nausea
• Drowsiness
• Constipation
• Stomach upset
• Allergic reactions

Interactions

• MAO inhibitors
• Alcohol
• CNS depressants
• Serotonergic drugs

Precautions

• Use with caution in patients with a history of substance abuse
• May cause respiratory depression in high doses
• Not recommended for use in children under 2 years of age
• Monitor for symptoms of serotonin syndrome when used with other serotonergic agents

Pregnancy

Dextromethorphan is classified as category C. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Dextromethorphan is excreted in breast milk. Caution is advised when administered to nursing mothers.

Storage

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

Formulations

• Oral syrup
• Tablets
• Extended-release capsules
• Lozenges

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

Indications

• Motion sickness
• Nausea and vomiting
• Preoperative sedation
• Reduction of salivary secretions
• Irritable bowel syndrome

Dosage

Children: Refer to BNF for Children for appropriate dosing based on age and weight.

Adults: Refer to specific guidelines or BNF for appropriate dosing as it may vary based on indication and patient condition.

Mechanism of action

Hybromide acts by blocking the action of acetylcholine on muscarinic receptors in the parasympathetic nervous system. This inhibition leads to decreased gastrointestinal motility, reduced secretions in various glands, and relaxation of smooth muscles. The drug's effects are mediated through the inhibition of the parasympathetic nervous system, resulting in decreased activity of the gastrointestinal tract and other smooth muscle tissues.

Pharmacodynamics

The pharmacodynamics of hybromide involve its capacity to inhibit the effects of acetylcholine at muscarinic receptors, which leads to a decrease in secretory and motor functions in the gastrointestinal tract. This results in reduced salivation, bronchial secretions, and gastrointestinal motility, making it useful for treating conditions related to overactivity of these systems. The onset of action is typically rapid, with effects lasting several hours depending on the dose and route of administration.

Pharmacokinetics

Hybromide is well absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It is widely distributed throughout the body, crossing the blood-brain barrier, which contributes to its central nervous system effects. The drug undergoes hepatic metabolism, primarily by CYP450 enzymes, and is excreted mainly in urine as metabolites. The elimination half-life is approximately 3 to 4 hours.

Pregnancy

The safety of hybromide during pregnancy has not been established. It is advisable to use caution and consult with a healthcare provider.

Breast-feeding

It is not known whether hybromide is excreted in human 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.

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.