CP-OXYLINE FORTE

Indications

• Allergic rhinitis (hay fever)
• Urticaria (hives)
• Allergic conjunctivitis
• Common cold symptoms

Dosage

Children: For children aged 6-12 years, the dose is typically 2 mg every 4 to 6 hours, not exceeding 12 mg per day. For children under

Adults: The usual adult dose for chlorpheniramine is 4 mg every 4 to 6 hours, not to exceed 24 mg per day.

Mechanism of action

Chlorpheniramine binds to the histamine H1 receptor, preventing endogenous histamine from exerting its effects. This leads to temporary relief from symptoms such as sneezing, pruritus, and increased vascular permeability associated with allergic reactions. The drug competes with histamine for H1-receptor sites on effector cells, thus antagonizing most of the pharmacological effects of histamine, including its actions on smooth muscle and vascular permeability.

Pharmacodynamics

In allergic reactions, allergens trigger the degranulation of mast cells and basophils, leading to the release of histamine. Chlorpheniramine, as an H1 antagonist, competes for receptor binding, effectively blocking histamine-induced effects, such as itching, vasodilation, and bronchoconstriction. This results in relief from symptoms like sneezing, watery eyes, and nasal discharge.

Pharmacokinetics

Chlorpheniramine is well absorbed from the gastrointestinal tract. It undergoes hepatic metabolism and its effects can last for several hours. The onset of action is typically observed within 1 to 2 hours following oral administration, with peak effects occurring around 2 to 6 hours. The drug is eliminated primarily through urine, with a half-life ranging from 12 to 15 hours, though this can vary based on individual factors.

Contra-indications

• Hypersensitivity to chlorpheniramine or any component of the formulation
• Acute asthma attacks
• Severe hypertension
• Narrow-angle glaucoma
• Prostatic hypertrophy

Adverse effects

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

Interactions

• Alcohol
• CNS depressants
• MAO inhibitors
• Anticholinergic agents
• Beta-blockers

Precautions

• Use with caution in patients with cardiovascular disease
• Caution in patients with liver or kidney impairment
• Avoid in elderly patients due to increased risk of sedation and anticholinergic effects
• May impair the ability to drive or operate machinery

Pregnancy

Chlorpheniramine should be used in pregnancy only if clearly needed. Consult medical professionals for guidance.

Breast-feeding

Chlorpheniramine 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
• Syrup
• Oral suspension

Indications

• Nasal congestion due to rhinitis
• Rosacea (facial erythema)
• Blepharoptosis
• Local anesthesia in dentistry (in combination with tetracaine)

Dosage

Adults: Refer to the BNF for specific dosing

Mechanism of action

Oxymetazoline binds to α1- and α2-adrenoceptors, which are Gq- and Gi-protein-coupled receptors respectively. Agonism of α1-adrenoceptors promotes vascular smooth muscle contraction by increasing intracellular calcium levels, while agonism of α2-adrenoceptors can elicit vasoconstriction through the inhibition of adenyl cyclase. This leads to decreased blood flow in the nasal mucosa, reducing congestion, and it may elevate the upper eyelid by stimulating α-adrenergic receptors on the Müller muscle.

Pharmacodynamics

Oxymetazoline is an adrenergic α1- and α2-agonist with direct sympathomimetic activity. It causes vasoconstriction of dilated arterioles, effectively reducing blood flow and improving nasal airflow in patients with acute coryzal rhinitis. It has shown higher affinity for α1A-adrenoceptors but greater potency at α2B-adrenoceptors. Additionally, oxymetazoline exhibits antioxidant properties, inhibiting lipid peroxidation and scavenging hydroxyl radicals, which may provide protective effects against tissue damage during inflammation.

Pharmacokinetics

Oxymetazoline is typically used as a nasal spray, which allows for rapid absorption through the nasal mucosa, leading to quick onset of action. The duration of action can last up to 12 hours post-administration. Specific pharmacokinetic parameters such as half-life and volume of distribution are not detailed in the provided resources.

Contra-indications

• Hypersensitivity to oxymetazoline or any component of the formulation
• Use in patients receiving monoamine oxidase inhibitors (MAOIs)

Adverse effects

• Local irritation or burning sensation in the nasal passages
• Dryness of the nasal mucosa
• Rebound congestion (rhinitis medicamentosa) with prolonged use
• Headache
• Dizziness
• Increased blood pressure
• Palpitations

Interactions

• MAOIs may enhance the hypertensive effects of oxymetazoline
• Concurrent use with other sympathomimetics may increase the risk of cardiovascular side effects

Precautions

• Caution in patients with cardiovascular disorders, hypertension, or hyperthyroidism
• Should not be used for longer than 3 consecutive days to prevent rebound congestion
• Use with caution in pregnant or breastfeeding women

Pregnancy

Safety in pregnancy has not been established; use only if clearly needed and prescribed by a healthcare provider.

Breast-feeding

Oxymetazoline is excreted in breast milk; caution is advised when used by nursing mothers.

Storage

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

Formulations

• Nasal spray
• Ophthalmic solution

Pregnancy

Consult a healthcare provider before use, as safety during pregnancy is not established.

Breast-feeding

Consult a healthcare provider before use, as safety during breastfeeding is not established.

Storage

Store at room temperature, away from moisture and heat.

Mechanism of action

Chlorpheniramine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine. 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 most responses of smooth muscle to histamine. Antagonism of the constrictor action of histamine on respiratory smooth muscle is easily shown in vivo and in vitro. /Histamine Antagonists: H1 Antagonists/ H1 antagonists strongly block the action of histamine that results in increased permeability and formation of edema and wheal. /Histamine Antagonists: H1 Antagonists/ Within the vascular tree, the H1 antagonists inhibit both the vasoconstrictor effects of histamine and, to a degree, the more rapid vasodilator effects that are mediated by H1 receptors on endothelial cells. Residual vasodilatation reflects the involvement of H2 receptors on smooth muscle and can be suppressed only by the concurrent administration of an H2 antagonist. Effects of the histamine antagonists on histamine induced changes in systemic blood pressure parallel these vascular effects. /Histamine Antagonists: H1 Antagonists/ Many of the H1 antagonists tend to inhibit responses to acetylcholine that are mediated by muscarinic receptors. These atropine like actions are sufficiently prominent in some of the drugs to be manifest during clinical usage ... . /Histamine Antagonists: H1 Antagonists/

Pharmacodynamics

In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H₁-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Chlorpheniramine, is a histamine H1 antagonist (or more correctly, an inverse histamine agonist) of the alkylamine class. It competes with histamine for the normal H₁-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies.

Mechanism of action

Oxymetazoline binds to α₁- and α₂-adrenoceptors, which are Gq- and Gi-protein-coupled receptors respectively. α₁-adrenoceptors agonism promotes vascular smooth muscle contraction by increasing intracellular calcium levels through activating phospholipase C, while α₂-adrenoceptors agonism, specifically the α_2B-adrenoceptors, can also elicit vasoconstriction through the inhibition of adenyl cyclase. Rosacea is a condition characterized by transient and persistent facial erythema. By stimulating α_1A-adrenoceptors and causing vasoconstriction, oxymetazoline is believed to diminish the symptoms of erythema. In blepharoptosis, it is hypothesized that oxymetazoline works by stimulating α-adrenergic receptors on the Müller muscle that elevates the upper eyelid, causing muscle contraction. Oxymetazoline is used in combination with tetracaine for local anesthesia in dentistry. Such combination use adds beneficial effects: the vasoconstrictor counteracts the local anesthetic agent's vasodilatory action, thereby constricting dilated arterioles and reducing blood flow to the application area. Oxymetazoline relieves nasal congestion by vasoconstricting the respiratory microvasculature, in both resistance and capacitance blood vessels on the human nasal mucosa, leading to decreased nasal mucosal blood flow, edema, and airflow resistance. The mechanism of action of oxymetazoline has not been conclusively determined. Most pharmacologists believe that the drug directly stimulates a-adrenergic receptors of the sympathetic nervous system and exerts little or no effect on beta-adrenergic receptors. Intranasal application of oxymetazoline results in constriction of dilated arterioles and reduction in nasal blood flow and congestion. In addition, obstructed eustachian ostia may be opened. Nasal ventilation and aeration are improved temporarily; however, rebound vasodilation and congestion usually occur to some degree. Following topical application of oxymetazoline hydrochloride ophthalmic solution, conjunctival congestion is temporarily relieved, but overuse of the drug may produce rebound hyperemia.

Pharmacodynamics

Oxymetazoline is an adrenergic α₁- and α₂-agonist and a direct-acting sympathomimetic drug. By stimulating adrenergic receptors, oxymetazoline causes vasoconstriction of dilated arterioles and reduces blood flow. In a radioligand competition study, oxymetazoline displayed higher affinity at α_1A-adrenoceptors compared to α_2B-adrenoceptors, but with higher potency at α_2B-adrenoceptors. When sprayed intranasally, oxymetazoline relieved relief nasal congestion and improved nasal airflow in patients with acute coryzal rhinitis for up to 12 hours following a single dose. An early _in vitro_ study demonstrated oxymetazoline to exert anti-oxidant actions, where it inhibited microsomal lipid peroxidation and mediated hydroxyl radical scavenging activity. This suggests that oxymetazoline has a beneficial effect against oxidants, which play a role in tissue damage in inflammation.