SINAREST PD

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

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.