SEDILIX DM LINCTUS

Indications

• Cough
• Pseudobulbar affect

Dosage

Children: Refer to the BNF for Children for specific dosing information tailored to paediatric patients.

Adults: Refer to the BNF for specific dosing guidelines based on the formulation and clinical context.

Mechanism of action

Dextromethorphan acts as a low-affinity uncompetitive antagonist of NMDA receptors and as an agonist at sigma-1 receptors. It also antagonizes α3/β4 nicotinic receptors. The clinical effects are thought to arise from NMDA receptor blockade and serotonin (5-HT) uptake inhibition, which may lead to increased serotonin receptor stimulation. However, the precise mechanisms by which these actions translate into therapeutic effects remain incompletely understood.

Pharmacodynamics

Dextromethorphan is considered an opioid-like molecule with a moderate therapeutic window, indicating that while it is effective at standard doses, higher doses can lead to intoxication. It has a moderate duration of action, making it suitable for use in cough management. Due to its potential for abuse and risk of intoxication, patients are advised to use it cautiously.

Pharmacokinetics

Dextromethorphan is metabolized primarily in the liver through the cytochrome P450 enzyme system, leading to the formation of its active metabolite, dextrorphan. The pharmacokinetics may be influenced by individual variations in metabolic pathways, which can affect the drug's efficacy and safety profile.

Contra-indications

• Hypersensitivity to dextromethorphan or any of its components
• Concurrent use with monoamine oxidase inhibitors (MAOIs)
• Severe respiratory insufficiency or asthma
• Persistent cough due to smoking, emphysema, or chronic bronchitis

Adverse effects

• Dizziness
• Nausea
• Vomiting
• Drowsiness
• Confusion
• Constipation
• Abdominal discomfort
• Euphoria or dysphoria
• Serotonin syndrome (when used with serotonergic drugs)

Interactions

• May interact with MAOIs, leading to serious side effects
• Potential interactions with other CNS depressants, leading to increased sedation
• May enhance the effects of alcohol
• Can interact with medications that affect serotonin levels, increasing the risk of serotonin syndrome

Precautions

• Use with caution in patients with a history of substance abuse
• Monitor use in patients with hepatic impairment
• Caution advised in patients with a history of seizures
• Should not be used in children under 2 years unless directed by a physician

Pregnancy

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

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
• Capsules
• Lozenges

Indications

• Nasal congestion due to colds
• Allergic rhinitis
• Sinusitis
• Eustachian tube dysfunction

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing recommendations, which depend on the child's age and weight.

Adults: Refer to the specific product labeling for dosing recommendations, as doses can vary based on the formulation and indication.

Mechanism of action

Pseudoephedrine acts as an agonist at alpha-adrenergic receptors, leading to vasoconstriction of the blood vessels in the nasal passages. This mechanism reduces blood flow to the affected areas, resulting in decreased swelling and congestion. Additionally, pseudoephedrine has mild beta-adrenergic activity, which may contribute to bronchodilation.

Pharmacodynamics

The pharmacodynamic effects of pseudoephedrine include the alleviation of nasal congestion through vasoconstriction and reduction of mucosal edema. Its effects may also include increased heart rate and blood pressure due to its sympathomimetic properties. The onset of action typically occurs within 30 minutes to 1 hour after oral administration, with a duration of action lasting up to 4 to 6 hours.

Pharmacokinetics

Pseudoephedrine is well absorbed from the gastrointestinal tract following oral administration. It has a bioavailability of approximately 100%. The drug is metabolized in the liver, primarily through N-demethylation, and is excreted mainly in the urine. The half-life of pseudoephedrine is approximately 6 hours, and its clearance may be affected by urine pH, with more alkaline urine leading to increased elimination.

Contra-indications

• Hypersensitivity to pseudoephedrine or any of its components
• Severe hypertension
• Severe coronary artery disease
• Concurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuation

Adverse effects

• Insomnia
• Nervousness
• Dizziness
• Increased blood pressure
• Tachycardia
• Dry mouth
• Nausea
• Headache

Interactions

• MAOIs may increase the risk of hypertensive crisis
• Other sympathomimetics may enhance cardiovascular effects
• Antihypertensive agents may have reduced effectiveness
• Stimulants may increase the risk of cardiovascular side effects

Precautions

• Use with caution in patients with hypertension, diabetes, thyroid disease, or prostatic hypertrophy
• Monitor blood pressure regularly during treatment
• Avoid use in patients with a history of substance abuse

Pregnancy

Use during pregnancy only if clearly needed. Pseudoephedrine crosses the placenta and may affect the fetus.

Breast-feeding

Pseudoephedrine is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Tablets
• Extended-release tablets
• Liquid formulations
• Combination products with antihistamines or analgesics

Indications

• Allergic rhinitis
• Motion sickness
• Nausea and vomiting
• Sedation
• Insomnia

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Promethazine exerts its effects by blocking H1 histamine receptors in the central nervous system and peripheral tissues. This blockade inhibits the action of histamine, which is responsible for allergy symptoms such as itching, sneezing, and runny nose. Additionally, promethazine has anticholinergic properties, which contribute to its effectiveness in reducing motion sickness and nausea.

Pharmacodynamics

The pharmacodynamic effects of hydrobromide promethazine include sedation, antiemetic effects, and relief from allergic symptoms. Its sedative effects are due to central nervous system depression, which can lead to drowsiness and reduced anxiety. The anticholinergic effects help to reduce secretions and gastrointestinal motility, further aiding in the management of nausea and vomiting.

Pharmacokinetics

Promethazine is well absorbed after oral administration, with peak plasma concentrations typically reached within 2 to 4 hours. It is extensively metabolized in the liver, primarily via cytochrome P450 enzymes, and has a half-life ranging from 10 to 19 hours. The drug is excreted mainly in the urine, primarily as metabolites. Due to its lipophilic nature, it can cross the blood-brain barrier, contributing to its sedative effects.

Contra-indications

• Hypersensitivity to promethazine or any component of the formulation
• Severe respiratory depression
• Comatose states
• Concurrent use of monoamine oxidase inhibitors (MAOIs)

Adverse effects

• Drowsiness
• Dizziness
• Dry mouth
• Blurred vision
• Constipation
• Urinary retention
• Extrapyramidal symptoms
• Anaphylactic reactions

Interactions

• Increased sedation with alcohol or central nervous system depressants
• Anticholinergic effects may be potentiated by other anticholinergic agents
• May reduce the effectiveness of certain antihypertensive medications
• Caution with other medications that prolong QT interval

Precautions

• Use with caution in patients with asthma, particularly in those with a history of respiratory issues
• May cause severe tissue injury if administered intravenously
• Caution in elderly patients due to increased sensitivity to central nervous system effects
• Monitor for potential exacerbation of seizures in those with seizure disorders

Pregnancy

Promethazine is classified as a category C drug. Animal studies have shown adverse effects on the fetus, but there are no adequate and well-controlled studies in pregnant women. Use only if clearly needed.

Breast-feeding

Promethazine is excreted in breast milk. Caution is advised when administering to breastfeeding women due to potential sedation effects on the infant.

Storage

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

Formulations

• Tablets
• Syrup
• Injection

Mechanism of action

Dextromethorphan is a low-affinity uncompetitive NMDA antagonist and sigma-1 receptor agonist. It is also an antagonist of α3/β4 nicotinic receptors. However, the mechanism by which dextromethorphan's receptor agonism and antagonism translate to a clinical effect is not well understood. Dextromethorphan (DXM) is the dextro isomer of levomethorphan, a semisynthetic morphine derivative. Although structurally similar to other /CNS depressants/, DXM does not act as a mu receptor opioid (eg, morphine, heroin). DXM and its metabolite, dextrorphan, act as potent blockers of the N-methyl-d-aspartate (NMDA) receptor. Amantadine and dextromethorphan suppress levodopa (L-DOPA)-induced dyskinesia (LID) in patients with Parkinson's disease (PD) and abnormal involuntary movements (AIMs) in the unilateral 6-hydroxydopamine (6-OHDA) rat model. These effects have been attributed to N-methyl-d-aspartate (NMDA) antagonism. However, amantadine and dextromethorphan are also thought to block serotonin (5-HT) uptake and cause 5-HT overflow, leading to stimulation of 5-HT(1A) receptors, which has been shown to reduce LID. We undertook a study in 6-OHDA rats to determine whether the anti-dyskinetic effects of these two compounds are mediated by NMDA antagonism and/or 5-HT(1A) agonism. In addition, we assessed the sensorimotor effects of these drugs using the Vibrissae-Stimulated Forelimb Placement and Cylinder tests. Our data show that the AIM-suppressing effect of amantadine was not affected by the 5-HT(1A) antagonist WAY-100635, but was partially reversed by the NMDA agonist d-cycloserine. Conversely, the AIM-suppressing effect of dextromethorphan was prevented by WAY-100635 but not by d-cycloserine. Neither amantadine nor dextromethorphan affected the therapeutic effects of L-DOPA in sensorimotor tests. We conclude that the anti-dyskinetic effect of amantadine is partially dependent on NMDA antagonism, while dextromethorphan suppresses AIMs via indirect 5-HT(1A) agonism. Combined with previous work from our group, our results support the investigation of 5-HT(1A) agonists as pharmacotherapies for LID in PD patients. Dextromethorphan (DM) is a dextrorotatory morphinan and an over-the-counter non-opioid cough suppressant. We have previously shown that DM protects against LPS-induced dopaminergic neurodegeneration through inhibition of microglia activation. Here, we investigated protective effects of DM against endotoxin shock induced by lipopolysaccharide/d-galactosamine (LPS/GalN) in mice and the mechanism underlying its protective effect. Mice were given multiple injections of DM (12.5 mg/kg, s.c.) 30 min before and 2, 4 hr after an injection of LPS/GalN (20 ug/700 mg/kg). DM administration decreased LPS/GalN-induced mortality and hepatotoxicity, as evidenced by increased survival rate, decreased serum alanine aminotransferase activity and improved pathology. Furthermore, DM was also effective when it was given 30 min after LPS/GalN injection. The protection was likely associated with reduced serum and liver tumor necrosis factor alpha (TNF-alpha) levels. DM also attenuated production of superoxide and intracellular reactive oxygen species in Kupffer cells and neutrophils. Real-time RT-PCR analysis revealed that DM administration suppressed the expression of a variety of inflammation-related genes such as macrophage inflammatory protein-2, CXC chemokine, thrombospondin-1, intercellular adhesion molecular-1 and interleukin-6. DM also decreased the expression of genes related to cell-death pathways, such as the DNA damage protein genes GADD45 and GADD153. In summary, DM is effective in protecting mice against LPS/GalN-induced hepatotoxicity, and the mechanism is likely through a faster TNF-alpha clearance, and decrease of superoxide production and inflammation and cell-death related components. This study not only extends neuroprotective effect of DM, but also suggests that DM may be a novel compound for the therapeutic intervention for sepsis. /The

Pharmacodynamics

Dextromethorphan is an opioid-like molecule indicated in combination with other medication in the treatment of coughs and pseudobulbar affect. It has a moderate therapeutic window, as intoxication can occur at higher doses. Dextromethorphan has a moderate duration of action. Patients should be counselled regarding the risk of intoxication.