ACEFYL COUGH SYRUP

Indications

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Bronchospasm

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Acefylline acts as a phosphodiesterase inhibitor, leading to an increase in intracellular cyclic AMP (cAMP). This increase in cAMP results in bronchodilation by relaxing smooth muscle cells in the airways. Additionally, it has anti-inflammatory effects that contribute to its therapeutic efficacy in respiratory disorders.

Pharmacodynamics

The pharmacodynamic profile of acefylline includes its ability to enhance mucociliary clearance, reduce airway resistance, and improve respiratory function. Its anti-inflammatory properties help decrease airway hyperreactivity, making it beneficial in both acute and chronic respiratory conditions.

Pharmacokinetics

Acefylline is absorbed from the gastrointestinal tract and has a volume of distribution that allows it to effectively reach respiratory tissues. Its metabolism primarily occurs in the liver, and it is excreted through the kidneys. The half-life of acefylline can vary based on individual patient factors such as age, liver function, and concurrent medications.

Adverse effects

• Nausea
• Vomiting
• Headache
• Dizziness
• Palpitations
• Insomnia

Precautions

• Use with caution in patients with a history of cardiovascular disease
• Monitor for signs of gastrointestinal disturbance

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Use with caution. It is not known if acefylline is excreted in human milk.

Storage

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

Formulations

• Tablets
• Injectable 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

Indications

• Ascariasis
• Partial intestinal obstruction due to Ascaris lumbricoides

Dosage

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

Adults: Refer to BNF for specific dosing information.

Mechanism of action

Piperazine functions as a GABA receptor agonist, selectively binding to muscle membrane GABA receptors in nematodes. This binding induces hyperpolarization of nerve endings, leading to flaccid paralysis of the worms. By blocking the response of worm muscle to acetylcholine, piperazine alters cell membrane permeability to ions, resulting in hyperpolarization and suppression of spontaneous spike potentials, thereby facilitating the expulsion of the worm through normal intestinal peristalsis.

Pharmacodynamics

Piperazine is effective as an anthelminthic, particularly for treating infections from Ascaris lumbricoides. It induces reversible muscle paralysis in nematode parasites by hyperpolarizing their cell membranes. The primary clinical use is in addressing complications such as partial intestinal obstruction caused by these worms, a condition more frequently encountered in children.

Pharmacokinetics

The pharmacokinetics of piperazine, including absorption, distribution, metabolism, and excretion, have not been well-characterized in the available literature. However, it is generally understood that piperazine is absorbed from the gastrointestinal tract and is metabolized in the liver. Further detailed studies may be required to elucidate its complete pharmacokinetic profile.

Adverse effects

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

Precautions

• Use with caution in patients with renal impairment
• Consider potential interactions with other central nervous system depressants

Pregnancy

Limited data are available on the safety of piperazine during pregnancy. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Piperazine is excreted in breast milk; use with caution and consider the need for monitoring the infant.

Storage

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

Formulations

• Piperazine citrate
• Piperazine hydrate

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.

Mechanism of action

Piperazine is a GABA receptor agonist. Piperzine binds directly and selectively to muscle membrane GABA receptors, presumably causing hyperpolarization of nerve endings, resulting in flaccid paralysis of the worm. While the worm is paralyzed, it is dislodged from the intestinal lumen and expelled live from the body by normal intestinal peristalsis. Piperazine blocks the response of the /target species/ worm muscle (best studied in Ascaris), causing flaccid paralysis of the worm. While the worm is paralyzed, it is dislodged from the intestinal lumen and expelled live from the body by normal intestinal peristalsis. The predominant effect of piperazine on /the target species/ Ascaris is to cause a flaccid paralysis that results in expulsion of the worm by peristalsis. ... Piperazine blocks the response of Ascaris muscle to acetylcholine, apparently by altering the permeability of the cell membrane to ions that are responsible for the maintenance of the resting potential. The drug causes hyperpolarization and suppression of spontaneous spike potentials with accompanying paralysis. Piperazine citrate causes reversible muscle paralysis in intestinal nematodes, presumably by causing hyperpolarization of nerve endings /in this target species/. /Piperazine citrate/ Piperazine and its salts, as a gamma-aminobutyric acid (GABA)-like substance, induce a reversible flaccid paralysis in the /target/ nematode parasites. This is provoked by a hyperpolarization of the cell membrane followed by suppression of spontaneous spike potentials. THe paralyzed nematodes are expelled from the gut lumen by normal peristaltic actions. In mammals, motorcortical GABAa inhibition is important for initiation of smooth flexion and/or extension movements of the extremities affecting motor and postural control. When injected into the hand motor cortical area of three infant macaque monkeys, the GABA agonist muscimol disrupted forelimb movement showing a posture of dropped wrist and fingers as if the radial nerve were paralysed. Interestingly, the three investigated animals exhibited large inter-individual differences in sensitivity to the action of the same dose of muscimol, being low in one, moderate in the second and substantial in the third. Injection into the medial segment of globus pallidus elicited choreiform movements and injections into substantia nigra pars reticulata provoked severe axial posture anomalies with rotational behaviour as well as contralateral hypotonia. Although the symptoms induced by piperazine in sensitive species exhibits some of these features, it is possible that its effects in mammals also involve other modes of action as well, in as much as a nicotinic action on rat sympathetic ganglia in vitro was reported in one series of experiments.

Pharmacodynamics

Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines.