Structural Biochemistry/Loratadine

Loratadine

(C22H23CIN2O2) is generally known as Claritin, an over the counter drug. It often comes in a white to off-white powder form. It is not soluble in water, but very soluble in acetone, alcohol, and chloroform. It is called ethyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene) -1-piperidinecarboxylate, with a molecular weight of 382.89g.

In tablet form, it contains ingredients other than loratadine and antihistamines, which are inactive ingredients such as corn starch, lactose, and magnesium stearate. In Syrup form, it also contains loratadine and antihistamine, but also includes other inactive ingredients such as citric acid, edetate disodium, artificial flavor, glycerin, propylene glycol, sodium ben-zoztem and water. It's pH is around 2.5 -3.1.

Loratadine is used to relive allergy symptoms caused by dust, pollen, and other substances. Loratadine is in the drug class called antihistamines and blocks the histamines on H1 receptors from working and causing allergic symptoms in the body. Common allergy symptoms include but are not limited to sneezing, itching, and runny nose. Loratadine is a second-generation histamine H1 receptor antagonist because it does not have a sedative side effective. Loratadine comes in 4 different forms: liquid, oral suspension, immediate or extended release tablet, and orally disintegrating tablet. Loratadine can also be combined with pseudophedrine. When taken orally, loratadine is absorbed through the gastrointestinal tract and metabolized by cytochrom P450 before binding to plasma membrane proteins.

Although loratadine is considered a ‘non-sedating’ antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness when used concurrently with other CNS depressants such as barbiturates, benzodiazepines, opiate agonists, antipsychotics, tricyclic antidepressants, ethanol, other H1-blockers, and anxiolytics, sedatives, and hypnotics.

Loratadine Pharmacokinetics

CYP3A4

In vitro studies, loratadine is metabolized to descarboethoxyloratadine mainly by CYP3A4, and some by cytochrome CYP2D6. CYP3A4 inhibitor, loratadine is metabolized to descarboethoxyloratadine mainly by CYP2D6. Ketoconazole, erythromycin(both CYP3A4 inhibitors), or cimetidine (CYP2D6 and CYP3A4 inhibitor) increases plasma concentration of loratadine. The half life of loratadine is about ~8.4 hours and its metabolite is ~28 hours. Elimination occurs through the fecal and renal routes.

Loratadine is also a substrate for P-glycoprotein transport.

Cimetidine, erythromycin, nefazodone and ketoconazole have been shown to interfere with the metabolism of loratadine. the inhibition of P-450 CYP3A4 isozyme lead to increasing serum concentrations of loratadine and its metabolite. Increased level of loratadine serum concentrations do not result in significant differences in adverse reactions compare to control patients. However, it is important to be caution of using loratadine with other drug combination in the concurrent risk for arrhythmogenic events. Although the drug interaction have not been confirmed between loratadine and cytochrome P-450, it is need to be are of potent CYP3A4 due to the serious nature of interactions between these drugs and certain other H1-antagonists.

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Side effects

Some people have allergic reactions when this drug is ingested. Some serious side effects include:

• fast and uneven heart rate
• jaundice (yellow skin or eyes)
• seizures
• feelings of passing out

People can be mildly allergic and present following symptoms that are not as severe:

• headache
• nausea
• nervousness
• drowsiness
• stomach pain, diarrhea
• dry mouth
• sore throat

It is recommended for people to contact the doctor immediately if they present any of the serious symptoms.

Reference

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001010/ http://en.wikipedia.org/wiki/Loratadine http://www.rxlist.com/claritin-drug.htm http://www.rxlist.com/claritin-drug.htm