PHOLTEX LINCTUS

Indications

• Allergic rhinitis
• Allergic conjunctivitis
• Urticaria

Dosage

Children: Refer to the BNF for Children for specific dosage guidance.

Adults: Refer to the BNF for specific dosage guidance.

Mechanism of action

Phenyltoloxamine interferes with the agonist activity of histamine at the H1 receptor, which helps in the attenuation of inflammatory processes. It operates through the phospholipase C and phosphatidylinositol (PIP2) signaling pathways, leading to a reduction in the activity of the NF-kB immune response transcription factor. This mechanism decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Additionally, it enhances mast cell stability by lowering calcium ion concentration, which reduces further histamine release. Furthermore, phenyltoloxamine's ability to cross the blood-brain barrier results in sedation and various CNS effects.

Pharmacodynamics

As a first-generation H1 antihistamine, phenyltoloxamine has significant central nervous system effects due to its ability to cross the blood-brain barrier. This results in common adverse effects such as drowsiness, sedation, and fatigue. These sedative effects may contribute to its potential adjunctive analgesic and antitussive actions in specific clinical scenarios, particularly when distress from pain or cough is prevalent.

Pharmacokinetics

The pharmacokinetics of phenyltoloxamine, like many first-generation antihistamines, are characterized by rapid absorption and significant distribution throughout the body, including the central nervous system. The metabolism and elimination pathways are not well-defined in the provided sources, but first-generation antihistamines are generally metabolized in the liver and excreted primarily via the kidneys.

Adverse effects

• Drowsiness
• Sedation
• Somnolence
• Fatigue
• Nervousness
• Insomnia

Pregnancy

Safety in pregnancy has not been established. Use only if clearly needed and after assessing potential benefits and risks.

Breast-feeding

It is not known if phenyltoloxamine is excreted in human milk. Caution is advised when administered to breastfeeding women.

Storage

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

Formulations

• Tablets
• Syrup

Indications

• Dry cough
• Cough caused by respiratory infections

Dosage

Children: For children aged 6-11 years, the recommended dose is 2-5 mg taken 3-4 times a day. For children aged 12-17 years, the dosage is 5-10 mg taken 3-4 times a day. Pholcodine should be avoided in children under 6 years.

Adults: For adults, the typical dosage is 5-10 mg taken 3-4 times a day.

Mechanism of action

Pholcodine exerts its effects directly on the cough center in the medulla oblongata, acting on peripheral reflexogenic receptors to suppress the cough reflex. This mechanism allows pholcodine to alleviate coughing without significantly impacting respiratory function.

Pharmacodynamics

Therapeutic doses of pholcodine do not typically cause respiratory depression, CNS excitation, or other side effects commonly associated with narcotics. It selectively targets the cough center while preserving respiratory activity, thus reducing the risk of addiction and psychological dependence. However, it is noted to have a stronger respiratory depression effect compared to codeine and can induce hypotension similar to codeine. Additional pharmacological effects include histamine release induction, anti-histaminic activity, anti-acetylcholinic action, anti-convulsant properties, and mild tranquilizing effects.

Pharmacokinetics

Pholcodine is absorbed well when taken orally and is metabolized in the liver. Its pharmacokinetic profile indicates it is distributed widely throughout the body. The elimination half-life and specific metabolic pathways are not detailed in the provided sources, but it is important to consider hepatic and renal function when prescribing.

Contra-indications

• Known hypersensitivity to pholcodine or any of its components
• Severe hepatic impairment
• Severe renal impairment
• Children under 6 years of age

Adverse effects

• Drowsiness
• Nausea
• Constipation
• Dry mouth
• Dizziness
• Hypotension

Interactions

• Caution with other cough and cold preparations that may contain similar active ingredients
• May interact with central nervous system depressants, enhancing sedative effects
• Caution is advised when combined with antihistamines

Precautions

• Use with caution in patients with respiratory conditions
• Care should be taken to administer the correct dose, especially in children
• Avoid use in patients with a history of substance abuse

Pregnancy

Pholcodine should only be used in pregnancy if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Pholcodine is excreted in breast milk; caution is advised when administering to breastfeeding mothers.

Storage

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

Formulations

• Pholcodine 5 mg/5 mL linctus
• Pholcodine 10 mg/5 mL linctus strong
• Pholcodine 2 mg/mL oral solution
• Pholcodine sugar-free linctus

Mechanism of action

As a first-generation H1 antihistamine, phenyltoloxamine interferes with the agonist activity of histamine at the H1 receptor and are ostensibly used to attenuate inflammatory processes as a means to treat conditions like allergic rhinitis, allergic conjunctivitis, and urticaria. Reduction of the activity of the NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) immune response transcription factor via the phospholipase C and phosphatidylinositol (PIP2) signaling pathways also serves to decrease antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Moreover, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. Additionally, first-generation antihistamines like phenyltoloxamine readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects, like nervousness and insomnia. By comparison, second-generation antihistamines are more selective for H1 receptors in the peripheral nervous system and do not cross the blood-brain barrier, resulting in fewer adverse drug effects overall. Furthermore, although some studies propose that phenyltoloxamine may possess some intrinsic antispasmodic and distinct local anesthetic properties, the specific mechanisms of action for these effects have not been formalized. Also, even though the combination of phenyltoloxamine's ability to cross the blood-brain barrier and cause various tranquilizing effects may explain to some extent how it may be able to potentiate analgesic effects, there are also studies that observed no potentiating effects associated with phenyltoloxamine use either.

Pharmacodynamics

As a member of the first generation H1 antihistamines, it is known that phenyltoloxamine - like virtually all first generation H1 antihistamines - has a propensity for crossing the blood-brain barrier and acting on H1 histamine receptors there to interfere with neurotransmission. The most common results of this kind of first generation H1 antihistamine CNS neurotransmission interference are adverse effects like drowsiness, sedation, somnolence, and fatigue. Given these effects, under specific circumstances like a patient experiencing a pain or a cough that may be preoccupying all of their waking energy and attention, it is perhaps possible that the sedative and tranquilizing characteristics of phenyltoloxamine may be the factors that contribute to its apparent adjunctive analgesic and antitussive actions.

Mechanism of action

The mechanism of action of pholcodine is directly performed in the medulla oblongata. In this site, it exerts analgesic properties on the peripheric reflexogenic receptors. This site is commonly known as the "cough center."

Pharmacodynamics

The therapeutic doses of pholcodine have been shown not to cause depression of respiration, CNS excitation or other side effects associated with narcotics. It is thought that the impact of pholcodine is selective on the cough center without affecting the respiratory center. Pholcodine is not euphorigenic, and thus, psychological dependence is unlikely. Clinical trials have not shown any evidence of addiction after prolonged administration of pholcodine. It is well reported that pholcodine presents a more considerable respiratory depression effect than codeine and it causes hypotension in the same degree than codeine. Some other noted impacts of pholcodine in preclinical trials are: 1) the induction of histamine release, 2) anti-histaminic effect, 3) anti-acetylcholinic action, 4) anti-convulsant action and 5) mild tranquilizing action.