Nasal Decongestants: Uses, Advantages, Disadvantages

• Nasal decongestants reduce congestion of nasal passages, opening clogged passages and enhancing sinus drainage.
• They are agonists for topical application as dilute solutions (0.05-0.1%), producing local vasoconstriction.
• Nasal decongestants stimulate alpha adrenergic receptors of the respiratory mucosa.
• This stimulation causes vasoconstriction which leads to shrinkage of swollen nasal mucous membrane.
• This stimulation also causes reduction of tissue hyperemia, edema, and nasal congestion.

Advantages

• Drug degradation in the GIT is absent.
• Hepatic first-pass metabolism is absent.
• They have rapid drug absorption and quick onset of action.
• They have large bioavailability
• They are easy to administer and are non-invasive.
• They have lower doses and cause reduced side effects.
• Nasal decongestants allow for self-administration.

Disadvantages

• Rebound congestion
• Aggravated sinusitis
• Short term stinging irritation and tachyphylaxis
• Sinus dryness and permanent damage can occur
• Rhinitis medicament
• Nasal decongestants should not be used for children.
• Use in children can cause loss of consciousness, convulsion and death

Mechanism of Action

• Decongestants stimulate alpha 1 adrenergic receptors.
• This stimulation enhance noradrenaline activity.
• Enhanced noradrenaline activity causes vasoconstriction and constricts nasal vasculature.
• These effects decongest the nasal mucosa and paranasal sinus.
• Vasoconstriction results in reduced inflammation, swelling, and mucus formation in the area.

Classification Of Nasal Decongestants

• Adrenaline releasing agents: Ephedrine, Levo-methamphetamine, Phenyl propanolamine, Pseudoephedrine.
• Alpha-adrenergic receptor agonists: Naphazoline, Oxymetazoline, phenylephrine.
• Corticosteroids: Beclomethasone dipropionate, Prednisolone.

Adrenaline Releasing Agents

• Includes ephedrine, levo-methamphetamine, phenyl propanolamine and pseudoephedrine.

Ephedrine

• Ephedrine is a decongestant and bronchodilator.
• It reduces swelling and constricting blood vessels in the nasal passages.
• It widens the lung airways, allowing easier breathing.
• Ephedrine's mechanism relies on indirect stimulation of the adrenergic receptor system.
• This is achieved by increasing norepinephrine activity at postsynaptic alpha and beta receptors.
• Ephedrine stimulates alpha-adrenergic receptors in blood vessels of nasal mucosa.
• This produces vasoconstriction and nasal decongestion.

Pharmacological actions of Ephedrine

• On the heart, ephedrine acts on beta-adrenergic receptors.
• This action produces a positive ionotropic effect.
• Ephedrine activates pathways in human brain that are responsible for weight loss.
• Ephedirne activates those pathways mediated through beta 2 receptor.
• Ephedrine relaxes gastro-intestinal tract smooth muscles by stimulating alpha 1 and beta 1 receptors.
• Ephedrine exhibits a biphasic response on blood pressure.
• Low doses via IV and s/c routes decrease BP, mediated through beta 2 receptors.
• High doses increase BP.

Pharmacokinetics of Ephedrine

• Ephedrine is absorbed orally, IV, IM AND SC.
• It has a bioavailability of 85%.
• Metabolism occurs in the liver by oxidative deamination.
• Onset of action: IV [seconds], IM [10-20 min], orally [15-60 min].
• Duration of action: IV/IM [60 min], orally [2-4 hrs].
• Elimination half-life: 3-6 hrs.
• Excretion: 22-99% through urine.

Adverse reactions of Ephedrine

• CNS: Insomnia, euphoria, dizziness, headache, confusion, nervousness and excitation with nasal solution.
• CV: Palpitations, hypertension, tachycardia with nasal solution.
• ENT: Dry nose and throat, rebound nasal congestion.
• ENT: Excessive use of Ephedrine can cause mucosal irritation with nasal solution.
• GI: Nausea, vomiting, anorexia.

Contraindications of Ephedrine

• Ephedrine is contraindicated to patients with severe hypertension, cardiac arrhythmias.
• Ephedrine is contraindicated to patients with organic heart disease, coronary artery disease, angina or other cardiac disease.
• Ephedrine is contraindicated in patients with closed-angle glaucoma.

Uses of Ephedrine

• Ephedrine is a central nervous system stimulant used to treat breathing problems (as a bronchodilator).

• It can be used for nasal congestion (as a decongestant).

• It treats low blood pressure problems (orthostatic hypotension).

• Also used for myasthenia gravis

• Levo-methamphetamine is a sympathomimetic vasoconstrictor.

• It is the active ingredient in some over-the-counter nasal decongestants inhalers in the united states.

• It temporarily relieves nasal congestion by constricting blood vessels in the nasal mucosa.

• Levo methamphetamine is the levorotatory (L-enantiomer) form of methamphetamine.

• The elimination half-life of levo methamphetamine is between 13.3 and 15 hours.

• Adverse reactions: Hypertension (elevated blood pressure), tachycardia (rapid heart rate), nausea, stomach cramps, dizziness.

• Adverse reactions: Headache, sweating, muscle tension, and tremors.

• It is used as a sympathomimetic vasoconstrictor.

• Used in nasal decongestant inhalers

• Phenylpropanolamine is a decongestant.

• It works by constricting (shrinking) blood vessels (veins and arteries) in your body.

• Constriction of blood vessels in your sinuses, nose, and chest allows drainage of those areas.

• Drainage decreases congestion.

• Phenylpropanolamine acts directly on alpha- and to a lesser degree, beta-adrenergic receptors, in respiratory tract mucosa.

• Stimulation of alpha-adrenergic receptors produces vasoconstriction and reduces tissue hyperemia

• Alpha stimulation reduces edema, and nasal congestion.

• Alpha stimulation increases nasal airway patency.

• Phenylpropanolamine drug was shown to be rapidly absorbed with a mean tmax of 1.47 ± 0.49 h.

• Phenylpropanolamine drug mean elimination half-life of 4.0 ± 0.5 h.

• Phenylpropanolamine is predominantly excreted via kidney.

• Phenylpropanolamine is excreted with a mean renal clearance of 0.646 ± 0.089 liter/kg/h and 90.2 ± 1.7%, unchanged in the urine.

• Adverse reactions: An allergic reaction (difficulty breathing), swelling of your lips, tongue, or face; or hives.

• Adverse reactions: Seizures, unusual behavior or hallucinations, irregular or fast heartbeat.

• Phenylpropanolamine Uses: Cough and cold medications as a decongestant and OTC weight loss products

• Pseudoephedrine is less potent than ephedrine in producing tachycardia and increased blood pressure.

• Pseudoephedrine is less potent than ephedrine in producing CNS stimulation.

• Pseudoephedrine is a decongestant that relieves a stuffy or blocked nose.

• It thins and loosens mucus in the airways, clearing congestion, and making breathing easier.

• It reduces nasal congestion by narrowing the blood vessels in the nose.

• It indirectly stimulates alpha-adrenergic receptors, causing release of endogenous norepinephrine.

• It directly stimulates beta-adrenergic receptors.

• Pseudoephedrine is active after oral administration and is easily absorbed from the gastrointestinal tract.

• The onset of action occurs after 30 min and after 1-4hours drug reaches its maximum concentration in the blood.

• Duration of action: 4-12hours

• Onset of action: 30 min

• Biological half-life: 3-16hours

• Renal clearance: 0.44-0.46 L/H/kg,

• Adverse reactions include nervousness, restlessness, trouble sleeping, dysuria, tachycardia, palpitations.

• Adverse reactions include headache, nausea and vomiting, trembling, and weakness.

• Uses: It is used to relieve nasal congestion caused by colds and allergies.

• Uses: It is used to relieve sinus congestion and pressure temporarily.

Alpha-Adrenergic Receptor Agonist

• Drugs in this class include: Naphazoline, Oxymetazoline, phenylephrine.

• Naphazoline is a decongestant used to relieve redness, puffiness, and itchy/watering eyes.

• It relieves those eye systems due to colds, allergies, or eye irritations.

• It is a sympathomimetic (alpha receptor agonist) that works in the eye to decrease congestion.

• Naphazoline nasal is a decongestant that shrinks blood vessels in the nasal passages.

• Dilated blood vessels can cause nasal congestion (stuffy nose).

• Naphazoline nasal is for temporary relief of a stuffy nose caused by hay fever, allergies, or the common cold.

• It is a vasoconstrictor that functions by stimulating alpha adrenergic receptors in arterioles.

• Alpha stimulation leads to decreased congestion at the site of administration.

• Naphazoline causes norepinephrine release in sympathetic nerves.

• Adverse reactions: Dizziness, nausea, sweating, drowsiness, weakness, nervousness.

• Adverse effects: Worsening redness/itching/swelling in or around the eyes.

• It can be used a a nasal decongestant

• Oxymetazoline is a decongestant that shrinks blood vessels in the nasal passages.

• Dilated blood vessels cause nasal congestion (stuffy nose).

• Oxymetazoline nasal (for the nose) is for temporary relief of nasal congestion (stuffy nose) caused by allergies or the common cold.

• Oxymetazoline binds to activates a2 adrenergic receptors upon nasal administration.

• Oxymetazoline constricts arterioles in the nose, decreasing nasal congestion.

• The elimination half-life in humans is 5-8hours.

• Metabolism: Kidney (30%), fecal (10%)

• Elimination half-life: 5-6hours

• It can be used for colds, allergies, and hay fever.

• It is also used to relieve sinus congestion and pressure.

• Phenylephrine is a decongestant that shrinks blood vessels in the nasal passages.

• Dilated blood vessels can cause nasal congestion (stuffy nose).

• Phenylephrine nasal is used to treat nasal congestion and sinus pressure caused by allergies, the common cold, or the flu.

• It activates alpha 1-adrenoceptors in the arterioles of the nasal mucosa.

• Phenylephrine is readily and completely absorbed from the gastrointestinal tract after oral administration.

• It is subject to extensive pre systemic metabolism in the gut wall.

• Systemic affect leads to a systemic bioavailability of approximately 40% relative to intravenous dosing.

• Phenylephrine has an effective half life of 5 minutes and an elimination half life of 2.5 hours

• Phenylephrine has an average clearance of 2100mL/min

• Adverse reactions include mild upset stomach, trouble sleeping.

• Other adverse reactions include dizziness, light headedness, headache, nervousness, shaking, or fast heartbeat.

• It is used to relieve nasal discomfort caused by colds and allergies and hay fever.

• It is also used to relieve sinus congestion and pressure

• Xylometazoline is a nasal decongestant spray that constricts nasal blood vessels.

• It increases nasal airflow, enabling patients with a blocked nose to breathe more easily.

• Its mechanism of action is by sympathomimetic directly acting on alpha-adrenergic receptors in arterioles of the nasal mucosa.

• Sympathomimetic causes vasoconstriction, resulting in decreased blood flow.

• Its therapeutic effect is decreased nasal congestion.

Corticosteroids

• Includes: Beclomethasone dipropionate and Prednisolone

Beclomethasone dipropionate

• Beclomethasone dipropionate works by attenuating the inflammatory responses associated with asthma.
• It attenuates the inflammatory responses associated with allergic rhinitis, nasal polyps, and corticosteroid-responsive dermatoses.
• It suppresses inflammatory cell actions (mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils).
• Corticosteroids have anti-inflammatory action by inhibiting leukotrienes and prostaglandins formation.
• Histamine, platelet-activating-factor, kinins, & substance are affected indirectly by the inhibitory effects of the corticosteroids.
• They are rapidly absorbed from pulmonary, nasal, and GI tissue.
• It experiences first-pass metabolism in the liver, and has Protein binding: 87%.
• It is primarily eliminated in feces.
• Used for asthma and chronic obstructive pulmonary disease (COPD) and nasal decongestant

Prednisolone

• Prednisone is a steroid medication used to treat certain types of allergies, inflammatory conditions, and autoimmune disorders and cancers.

• Prednisone decreases inflammation via suppression of polymorphonuclear leukocyte migration.

• It reverses increased capillary permeability.

• It suppresses the immune system activity and volume.

• After oral intake, it exhibits rapid absorption and becomes almost completely (80-100%) available.

• Peak plasma concentrations reach one to two hours after oral administration.

• The distribution of prednisolone is dependent on its protein-binding properties.

• Adverse reactions: Heart burn, trouble sleeping, increased sweating or acne, loss of appetite.

• Adverse Reactions: Nausea and vomiting

• Uses: Arthritis, blood problems, immune system disorders, breathing problem and cancer and severe allergies

• A respiratory stimulant is a drug or chemical agent used to stimulate the respiratory system.

• Respiratory stimulants are also known as analeptics.

• It restores normal respiration when lungs are unable to eliminate sufficient carbon dioxide.

• It restores normal respiration when lungs are unable to take sufficient amount of oxygen molecule.

• Respiratory stimulants include the class of those drug which is used to stimulate the CNS.

• They stimulate the central nervous system of the body hence stimulant is known as CNS stimulator.

• Respiratory stimulants stimulate the chemo receptor and vasomotor center (regulates blood vessel diameter) of the body.

• Analeptics are used for overdose with sedatives or hypnotic untill mechanical ventilation is instituted.

• Analeptics are used for suffocation on drowning and for acute respiratory insufficiency.

• Analeptics are used for post anesthetic respiratory depression.

• Analeptics are used for Apnea in premature infant and failure to ventilate spontaneously after general anesthesia.

• Used for idiopathic hypoventilation.

Drugs used for Respiratory Stimulant

• Doxapram
• Prethcamide
• Nikethamide
• Almitrine
• Caffeine

Doxapram

• Doxapram is Short acting analeptic.
• It acts by promoting excitation of central neurons.
• At low doses it is more selective for the respiratory centre than other analeptics.
• Doxapram acts mainly on the brainstem and spinal cord.
• It increases medullary respiratory and vasomotor centres' activity.
• It stimulates respiration through carotid and aortic body chemoreceptors.
• Continuous IV infusion of Doxapram may abolish episodes of apnea in premature infant not responding to theophylline.
• Doxapram administration, an increased release of catecholamines
• Doxapram produces respiratory stimulation mediated through the peripheral carotid chemoreceptors.
• Doxapram stimulates the carotid body by inhibiting certain potassium channels.
• Route of administration is I.V./I.M.
• It excreted rapidly
• Continuous I.V. Infusion of Doxapram has been found to abolish episodes of apnea.
• It helps the premature infant to start responding to theophylline
• Onset: 20-40 sec
• Duration: 5-12 min (single IV injection)
• Peak Plasma Time: 1-2 min
• Half-life: 3.4 hr (2.4-4.1 hr)
• Adverse effects include Nausea, Coughing, Restlessness, Disorientation, Headache, Fever.
• Uses include Acute respiratory failure, Acute hypercapnia, COPD.
• used to treat drug-induced ventilator depression and apnea in newborn animals and humans.

Prethcamide

• Prethcamide is a respiratory stimulant composed of two related drugs, cropropamide and crotethamide.
• It was developed by Ciba-Geigy.
• It acts by stimulation of peripheral chemoreceptors and central respiratory centers.
• It has pressor effects and may also increase catecholamine release.
• Prethcamide acts by promoting excitation of central neurons. It produces respiratory stimulation by an action on peripheral carotid and aortic body chemoreceptors.
• Increasing the dose prethcamide stimulates respiratory centers in the medulla and other parts of brain.
• The respiratory stimulant action is manifested by an increase in tidal volume with a slight increase in respiratory rate.

Nikethamide

• Nikethamide is a stimulant which mainly affects the respiratory cycle.
• It is known as nicotinic acid diethylamide.
• It is an antidote to barbiturate overdose.
• It increase the stimulation of CNS, especially stimulate medulla oblongata respiratory center.
• It also stimulates carotid body and aortic chemoreceptor and then stimulate respiratory center reflectivity.
• It acts on chemoreceptors in carotid body and reflexly stimulate respiratory center in medulla.
• The action is more powerful when respiration is already depressed.
• Large dose may cause convulsion.
• Single intravenous bolus can maintain 5 to 10minutes.
• Administered by subcutaneous, IM or IV route.
• Adverse reactions: Overdose can cause increase in blood pressure.
• Other adverse reactions include Tachycardia, Cough, Vomiting, Perspiration, Convulsion, Dyspnoea
• Uses: Neonatal asphyxia, CO2 intoxication, Respiratory depression.
• Uses: Central respiratory depression, Energy malnutrition, Tranquilizer overdoses Contraindication: Porphyria, epilepsy or other convulsive disorders
• Also contraindicated due to Cerebral edema , Cerebrovascular accident, head injury, acute severe asthma.
• Contraindicated in ischemic heart disease and hyperthyroidism

Almitrine

• Almitrine is a respiratory stimulant that enhances respiration by acting as an agonist of peripheral chemoreceptors.
• These chemoreceptors are located on the carotid bodies.
• It enhances respiration by acting an agonist of peripheral chemoreceptors located on carotid bodies.
• Almitrine increases arterial oxygen tension while decreasing arterial carbon dioxide tension in patients with chronic obstructive pulmonary disease.
• It may also prove useful in the treatment of nocturnal oxygen desaturation without impairing the quality of sleep.
• Almitrine is primarily metabolized in the liver.
• It's main metabolites are the tetra hydroxyl mono-de allyl, di-de allyl and detriazinyl derivatives.
• It's excreted mostly through the bile.
• Plasma elimination half-life varies from 45 to 50 hours.

Adverse effects of Almitrine

• Headache
• Gastrointestinal disturbances
• Uses: It is used in the treatment of chronic obstructive pulmonary disease

Caffeine

• The respiratory stimulant caffeine is the most frequently used xanthine.
• It is used in theophylline or aminophylline for the treatment of apnea in premature infants.
• When consumed in large amounts it can cause anxiety, irritability and sleeplessness.
• Caffeine is a weak Diuretic and its structure is similar to nicotine.
• Caffeine inhibits an enzyme activity known as phosphodiesterase.
• This leads to an increase in intracellular levels of a signaling molecule known as cyclic adenosine monophosphate (cAMP).
• An increase in medullary cAMP levels enhances carbon dioxide sensitivity.
• Mechanisms for stimulatory activity appear to be the blocking of adenosine receptors and inhibition of phosphodiesterase.
• Caffeine is rapidly and completely absorbed within an hour.
• It's distributed throughout body water and readily crosses cells including brain membranes
• Adverse reactions: Insomnia, Nervousness, Restlessness, Nausea, Increased heart rate
• Uses: Caffeine for mental alertness, headache, migraine, athletic performance, memory, and obesity.