Diphenhydramine + Levomenthol

Uses

This preparation is used for the relief of cough and associated congestive symptoms. It is also used to relieve runny nose, sneezing, watery eyes, itchy nose/eyes/throat and other allergic symptoms.

Diphenhydramine + Levomenthol is also used to associated treatment for these conditions: Allergic Rhinitis (AR), Allergic cough, Allergies, Anaphylaxis, Angioedema, Common Cold, Common Cold/Flu, Conjunctival irritation, Cough, Cough Variant Asthma, Cough caused by Common Cold, Eye allergy, Fever, Insect Bites, Insect Stings, Insomnia, Irritative cough, Itching of the nose, Itching of the throat, Motion Sickness, Nasal Congestion, Oral Mucositis, Pain, Parkinsonian Syndromes, Pollen Allergy, Productive cough, Pruritus, Rash, Rhinorrhoea, Sinus Congestion, Sinus headache, Skin Irritation, Sneezing, Sunburn, Symptoms of Acute Bronchitis Accompanied by Coughing, Upper respiratory tract hypersensitivity reaction, site unspecified, Urticaria, Dermatographism, Dry cough, Watery itchy eyes, Airway secretion clearance therapy, ExpectorantAllergies, Arthritis, Back Pain Lower Back, Backache, Chilblains, Common Cold, Contusions, Cough, Cough caused by Common Cold, Dandruff, Flu caused by Influenza, Generalised muscle aches, Hemorrhoids, Intercostal Pain, Itching caused by Dandruff, Itching of the scalp, Joint Pain, Mild pain, Muscle Fatigue, Muscle Strain, Nasal Congestion, Orofacial Pain, Pain caused by Fracture Bone, Productive cough, Psoriasis, Redness of the scalp, Seborrheic Dermatitis, Shoulder Stiffness, Sore Throat, Soreness, Muscle, Sprains, Stiff Shoulder, Stiff neck, Swelling, Upper Respiratory Tract Infection, Hematomas, Muscle, joint pains, Nonspecific pain, Scalp irritation, Sports Massage

How Diphenhydramine + Levomenthol works

Diphenhydramine predominantly works via the antagonism of H1 (Histamine 1) receptors . Such H1 receptors are located on respiratory smooth muscles, vascular endothelial cells, the gastrointestinal tract (GIT), cardiac tissue, immune cells, the uterus, and the central nervous system (CNS) neurons . When the H1 receptor is stimulated in these tissues it produces a variety of actions including increased vascular permeability, promotion of vasodilation causing flushing, decreased atrioventricular (AV) node conduction time, stimulation of sensory nerves of airways producing coughing, smooth muscle contraction of bronchi and the GIT, and eosinophilic chemotaxis that promotes the allergic immune response .

Ultimately, diphenhydramine functions as an inverse agonist at H1 receptors, and subsequently reverses effects of histamine on capillaries, reducing allergic reaction symptoms . Moreover, since diphenhydramine is a first-generation antihistamine, it readily crosses the blood-brain barrier and inversely agonizes the H1 CNS receptors, resulting in drowsiness, and suppressing the medullary cough center .

Furthermore, H1 receptors are similar to muscarinic receptors . Consequently, diphenhydramine also acts as an antimuscarinic . It does so by behaving as a competitive antagonist of muscarinic acetylcholine receptors, resulting in its use as an antiparkinson medication .

Lastly, diphenhydramine has also demonstrated activity as an intracellular sodium channel blocker, resulting in possible local anesthetic properties .

Menthol primarily activates the cold-sensitive TRPM8 receptors in the skin. Menthol, after topical application, causes a feeling of coolness due to stimulation of 'cold' receptors by inhibiting Ca++ currents of neuronal membranes. It may also yield analgesic properties via kappa-opioid receptor agonism.

Dosage

Diphenhydramine + Levomenthol dosage

Adults and Children over 12 years: The recommended dose is 10 ml of syrup 4 times a day. Maximum daily dose is 40 ml syrup.

Side Effects

Diphenhydramine may cause drowsiness, dizziness, gastrointestinal disturbance, dry mouth/nose/throat, difficulty in urination or blurred vision

Toxicity

Overdose is expected to result in effects similar to the adverse effects that are ordinarily associated with the use of diphenhydramine, including drowsiness, hyperpyrexia, and anticholinergic effects, among others . Additional symptoms during overdose may include mydriasis, fever, flushing, agitation, tremor, dystonic reactions, hallucinations and ECG changes . Large overdose may cause rhabdomyolysis, convulsions, delirium, toxic psychosis, arrhythmias, coma and cardiovascular collapse . Moreover, with higher doses, and particularly in children, symptoms of CNS excitation including hallucinations and convulsions may appear; with massive doses, coma or cardiovascular collapse may follow .

Although diphenhydramine has been in widespread use for many years without ill consequence, it is known to cross the placenta and has been detected in breast milk . This medication should therefore only be used when the potential benefit of treatment to the mother exceeds any possible hazards to the developing fetus or suckling infant .

Pharmacokinetic studies indicate no major differences in the distribution or elimination of diphenhydramine compared to younger adults . Nevertheless, diphenhydramine should be used with caution in the elderly, who are more likely to experience adverse effects . Avoid use in elderly patients with confusion .

The results of a review on the use of diphenhydramine in renal failure suggest that in moderate to severe renal failure, the dose interval should be extended by a period dependent on Glomerular filtration rate (GFR) .

After intravenous administration of 0.8 mg/kg diphenhydramine, a prolonged half-life was noted in patients with chronic liver disease which correlated with the severity of the disease . However, the mean plasma clearance and apparent volume of distribution were not significantly affected .

LD₅₀=500 mg/kg (orally in rats). Considerable overdosage can lead to myocardial infarction (heart attack), serious ventricular dysrhythmias, coma and death.

Menthol, DL: ORAL (LD50): Acute: 2900 mg/kg [Rat], 3100 mg/kg [Mouse]. DERMAL (LD50): Acute: 5001 mg/kg Rabbit.

Precaution

This preparation may cause drowsiness. Caution should be exercised in patients with moderate to severe renal or hepatic dysfunction or urinary retention when using this preparation. Diphenhydramine should not be taken by individuals with narrow-angle glaucoma or symptomatic prostatic hypertrophy.

Interaction

Diphenhydramine may potentiate the effects of alcohol, codeine, CNS depressants, the effects of anticholinergics (ex- some psychotropic drugs and atropine) and other antihistamines. MAO inhibitors potentiate and intensify the anticholinergic effects of antihistamines.

Volume of Distribution

Diphenhydramine is widely distributed throughout the body, including the CNS . Following a 50 mg oral dose of diphenhydramine, the volume of distribution is in the range of 3.3 - 6.8 l/kg .

Elimination Route

Diphenhydramine is quickly absorbed after oral administration with maximum activity occurring in approximately one hour . The oral bioavailability of diphenhydramine has been documented in the range of 40% to 60%, and peak plasma concentration occurs about 2 to 3 hours after administration .

Half Life

The elimination half-life ranges from 2.4-9.3 hours in healthy adults . The terminal elimination half-life is prolonged in liver cirrhosis .

Clearance

Values for plasma clearance of a 50 mg oral dose of diphenhydramine has been documented as lying in the range of 600-1300 ml/min .

Elimination Route

The metabolites of diphenhydramine are conjugated with glycine and glutamine and excreted in urine . Only about 1% of a single dose is excreted unchanged in urine . The medication is ultimately eliminated by the kidneys slowly, mainly as inactive metabolites .

Pregnancy & Breastfeeding use

Diphenhydramine has been in widespread use for many years without ill consequence. However, it is known to cross the placenta and has been detected in breast milk. Therefore, it is only used when the potential benefit of treatment to the mother exceeds any possible hazards to the developing fetus or suckling infant.

Contraindication

Diphenhydramine + Levomenthol is contraindicated in individuals with known hypersensitivity to the product or any of its constituents and in individuals with chronic or persistent cough, such as occurs with asthma, or where cough is accompanied by excessive secretions, unless directed by the physician. It should not be administered to patients currently receiving monoamine oxidase inhibitors (MAOIs) or those patients who have received treatment with MAOIs within the last two weeks.

Acute Overdose

The signs and symptoms of overdose may include drowsiness, hyperpyrexia and anticholinergic effects. With higher doses, CNS excitation including hallucinations and coma or cardiovascular collapse may appear. Treatment of overdose should be symptomatic and supportive, rapid gastric emptying (with Syrup of Ipecac-induced emesis or gastric lavage and activated charcoal) may be useful. Seizures may be controlled with Diazepam or Thiopental Sodium and Physostigmine IV may be efficacious to antagonise severe antichlolinergic symptoms.

Storage Condition

Should be stored in cool and dry place.

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