Cetrizet D Mechanism of Action

Pharmacology: Pharmacodynamics: Cetirizine is a potent antihistamine with a low potential for drowsiness at pharmacologically active doses and with additional anti-allergic properties. It is selective H₁-antagonist with negligible effects on other receptors and so is virtually free from anti-cholinergic and anti-serotonin effects. At pharmacologically active doses, it induces neither sedation nor behaviour changes. This may be explained by the fact that cetirizine does not cross the blood-brain barrier.
It was shown in human pharmacology studies that cetirizine inhibits certain effects produced by exogenous histamine. This activity appears rapidly. Cetirizine also inhibits the effects produced by endogenous histamine released in vivo by any agent. It also inhibits the cutaneous reaction induced by VIP (Vasoactive Intestinal Polypeptide) and substance P, neuropeptides, which are believed to take part in the allergic reaction.
Cetirizine inhibits the histamine-mediated 'early' phase of the allergic reaction and also reduces the migration of inflammatory cells and the release of mediators associated with the 'late' allergic response.
Cetirizine markedly reduces bronchial hyper-reactivity to histamine in the asthmatic patient. It also reduces the allergic reaction induced by specific allergens. These effects are obtained without any central effects being demonstrated either by psychometric tests or by quantified EEG.
Pseudoephedrine has direct and indirect sympathomimetic activity and is an orally effective upper respiratory tract decongestant. Pseudoephedrine is substantially less potent than ephedrine in producing both tachycardia and elevation in systolic blood pressure and considerably less potent in causing stimulation of the central nervous system.
Pharmacokinetics: Cetirizine: After oral administration, cetirizine is rapidly and almost completely absorbed. Under fasting conditions, C_max is about 1 hour. The extent of absorption is not reduced by food; however, the rate of absorption is reduced and the peak levels are expected about 3 hrs after dosing. Cetirizine does not undergo any appreciable first-pass metabolism. After repeated oral administration, the daily urinary excretion of unchanged cetirizine is approximately 65% of the dose. The absorption and the elimination of cetirizine are independent of the dose. Inter- and intra-subject variations are low. The plasma half-life of cetirizine is approximately 9 hours. This value is increased in patients with reduced renal function. Cetirizine is strongly bound to plasma proteins.
Pseudoephedrine: Pseudoephedrine is rapidly and completely absorbed after oral administration. Pseudoephedrine, given as a sustained-release formulation, provides maximum plasma levels 8 hrs after administration. About ¼-½ of the administered dose of pseudoephedrine is transformed by the liver into inactive metabolite through N-demethylation. This metabolite and the remaining non-metabolized pseudoephedrine are excreted via the kidneys.
The rate of urinary excretion is increased when the urine is acidic, and reduced in case of alkalinization of urine. The absorption of pseudoephedrine is not affected by fatty meals. After repeated oral administration (every 12 hrs), the steady state is obtained within 6 days and the effective half-life is estimated to 15 hrs.
There was no evidence for a relevant pharmacokinetic interaction between cetirizine and pseudoephedrine.