SINAREST PAEDIATRIC NASAL DROPS

Indications

• Nasal congestion due to acute rhinitis
• Facial erythema associated with rosacea
• Local anesthesia in dentistry (in combination with tetracaine)

Dosage

Adults: For nasal congestion, adults typically use 0.05% solution, 2-3 sprays in each nostril every 12 hours as needed, not exceeding two doses in 24 hours.

Mechanism of action

Oxymetazoline binds to α1- and α2-adrenoceptors, which are Gq- and Gi-protein-coupled receptors respectively. Agonism of α1-adrenoceptors causes vascular smooth muscle contraction by increasing intracellular calcium levels through the activation of phospholipase C. Stimulation of α2-adrenoceptors, particularly the α2B subtype, can also lead to vasoconstriction by inhibiting adenyl cyclase. This combined action promotes vasoconstriction in the nasal mucosa, alleviating congestion and improving airflow.

Pharmacodynamics

As an adrenergic α1- and α2-agonist, oxymetazoline causes vasoconstriction of dilated arterioles, reducing blood flow and edema in the nasal passages. It has been shown to relieve nasal congestion and improve airflow in patients with acute coryzal rhinitis for up to 12 hours. Additionally, oxymetazoline demonstrates antioxidant properties, potentially offering protective effects against inflammation-related tissue damage.

Pharmacokinetics

Oxymetazoline is administered intranasally, leading to rapid absorption through the nasal mucosa. Its effects can last for up to 12 hours, providing extended relief from nasal congestion. The drug's pharmacokinetics, including its metabolism and excretion pathways, are not extensively detailed in the available literature.

Contra-indications

• Hypersensitivity to oxymetazoline or any of its components
• Severe hypertension
• Narrow-angle glaucoma

Adverse effects

• Local irritation
• Burning or stinging sensation in the nasal cavity
• Rebound congestion with prolonged use
• Headache
• Hypertension
• Tachycardia

Interactions

• Monoamine oxidase inhibitors (MAOIs) may enhance the hypertensive effects of oxymetazoline
• Other sympathomimetics may increase cardiovascular effects

Precautions

• Use with caution in patients with cardiovascular disease
• Caution in patients with diabetes mellitus
• Avoid use in patients with hyperthyroidism

Pregnancy

Oxymetazoline should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data on human use.

Breast-feeding

It is not known whether oxymetazoline is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Nasal spray
• Ophthalmic solution

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.