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What is Loratadine and explain in detail?
Loratadine, sold under the brand name Claritin among others, is a medication used to treat allergies. This includes allergic rhinitis (hay fever) and hives. It is also available in combination with pseudoephedrine, a decongestant, known as loratadine/pseudoephedrine. It is taken orally.Common side effects include sleepiness, dry mouth, and headache. Serious side effects are rare and include allergic reactions, seizures, and liver problems. Use during pregnancy appears to be safe but has not been well studied. It is not recommended in children less than two years old. It is in the second-generation antihistamine family of medication.Loratadine was patented in 1980 and came to market in 1988. It is on the World Health Organizations List of Essential Medicines. Loratadine is available as a generic medication. In the United States, it is available over the counter. In 2019, it was the 66th most commonly prescribed medication in the United States, with more than 11 million prescriptions.

Medical uses
Loratadine is indicated for the symptomatic relief of allergy such as hay fever (allergic rhinitis), urticaria (hives), chronic idiopathic urticaria, and other skin allergies. For allergic rhinitis, loratadine is indicated for both nasal and eye symptoms - sneezing, runny nose, and itchy or burning eyes.Similarly to cetirizine, loratadine attenuates the itching associated with Kimuras disease.

Forms
The drug is available in many different forms, including tablets, oral suspension, and syrup, and in combination with pseudoephedrine. Also available are quick-dissolving tablets.

Contraindications
Patients with severe hepatic (liver) disorders may need to start with a lower dose. No dose adaptation is necessary for elderly or renally (kidney) impaired patients.Loratadine is usually compatible with breastfeeding (classified category L-2 - probably compatible, by the American Academy of Pediatrics). In the U.S., it is classified as category B in pregnancy, meaning  animal reproduction studies have failed to demonstrate a risk to the fetus, but no adequate and well-controlled studies in pregnant women have been conducted.

Adverse effects
As a "non-sedating" antihistamine, loratadine causes less (but still significant, in some cases) sedation and psychomotor retardation than the older antihistamines, because it penetrates the blood/brain barrier less.Other side effects include headache and antimuscarinic effects, such as urinary retention, dry mouth, blurred vision, and gastrointestinal problems.

Interactions
Substances that act as inhibitors of the CYP3A4 enzyme such as ketoconazole, erythromycin, cimetidine, and furanocoumarin derivatives (found in grapefruit) lead to increased plasma levels of loratadine — that is, more of the drug was present in the bloodstream than typical for a dose. This had clinically significant effects in controlled trials of 10 mg loratadine treatment Antihistamines should be discontinued 48 hours prior to skin allergy tests, since these drugs may prevent or diminish otherwise-positive reactions to dermal activity indicators.

Pharmacology
Pharmacodynamics
Loratadine is a tricyclic antihistamine, which acts as a selective inverse agonist of peripheral histamine H1 receptors. The potency of second generation histamine antagonists is (from strongest to weakest) desloratadine (Ki 0.4 nM) > levocetirizine (Ki 3 nM) > cetirizine (Ki 6 nM) > fexofenadine (Ki 10 nM) > terfenadine > loratadine.  However, the onset of action varies significantly and clinical efficacy is not always directly related to only the H1 receptor potency, as concentration of free drug at the receptor must also be considered. Loratadine also shows anti-inflammatory properties independent of H1 receptors. The effect is exhibited through suppression of the NF-κB pathway, and by regulating the release of cytokines and chemokines, thereby regulating the recruitment of inflammatory cells.

Pharmacokinetics
Loratadine is given orally, is well absorbed from the gastrointestinal tract, and has rapid first-pass hepatic metabolism; it is metabolized by isoenzymes of the cytochrome P450 system, including CYP3A4, CYP2D6, and, to a lesser extent, several others. Loratadine is almost totally (97–99%) bound to plasma proteins. Its metabolite desloratadine, which is largely responsible for the antihistaminergic effects, binds to plasma proteins by 73–76%.Loratadines peak effect occurs after 1–2 hours, and its biological half life is on average eight hours (range 3 to 20 hours) with desloratadines half-life being 27 hours (range 9 to 92 hours), accounting for its long-lasting effect. About 40% is excreted as conjugated metabolites into the urine, and a similar amount is excreted into the feces. Traces of unmetabolised loratadine can be found in the urine.In structure, it is closely related to tricyclic antidepressants, such as imipramine, and is distantly related to the atypical antipsychotic quetiapine.

History
Schering-Plough developed loratadine as part of a quest for a potential blockbuster drug: a nonsedating antihistamine. By the time Schering submitted the drug to the U.S. Food and Drug Administration (FDA) for approval, the agency had already approved a competitors nonsedating antihistamine, terfenadine (trade name Seldane), and, therefore, put loratadine on a lower priority.  However, terfenadine had to be removed from the U.S. market by the manufacturer in late 1997 after reports of serious ventricular arrhythmias among those taking the drug.Loratadine was approved by the FDA in 1993. The drug continued to be available only by prescription in the U.S. until it went off patent in 2002. It was then subsequently approved for over-the-counter sales. Once it became an unpatented over-the-counter drug, the price dropped significantly.Schering also developed desloratadine (Clarinex/Aerius), which is an active metabolite of loratadine.

Society and culture
Over the counter
In 1998, in an unprecedented action in the United States, an American insurance company, Anthem Inc., petitioned the federal Food and Drug Administration to allow loratadine and two other antihistamines to be made available over the counter (OTC) while they were still protected by patents; the administration granted the request, which was not binding on manufacturers. In the United States, Schering-Plough made loratadine available over the counter in 2002. In 2015, loratadine was available over the counter in many countries.

Brands
In 2017, loratadine was available under many brand names and in many forms worldwide, including several combination drug formulations with pseudoephedrine, paracetamol, betamethasone, ambroxol, salbutamol, phenylephrine, and dexamethasone.

Marketing
The marketing of the Claritin brand is important in the history of direct-to-consumer advertising of drugs.The first television commercial for a prescription drug was broadcast in the United States in 1983, by Boots. It caused controversy