February 1, 2023

Group 1.8’s Integrated Project for Concepts in Pharmaceutical Sciences and Clinical Practice 1 on the drug Cetirizine Hydrochloride, commonly known as Zyrtec.

Hello is there anything you could help you with today oh yes i was going to find static as my friend suggested it to treat my allergy can you please go through this with me because i’m a bit nervous to use it yes of course what symptoms are you experiencing my three years old son and i have been experiencing symptoms for a week we are constantly smoothing with

Runny nose and watery but itchy eyes do you currently take any other medications and have you been taking any other antihistamines before oh no i haven’t i’m not taking any other medication at the moment do you have a history of medical illness yeah i have been diagnosed with a minor renal problem recently all right now there are a few zyrtec formulations that

Have been developed let me go through them with you now we have oral tablets oral drops and liquids and a nasal spray i would recommend the oral tablets for you just because they provide a 24 hour relief oral tablets do tend to be the preferred mode of dosing as it is simple and convenient i wouldn’t recommend the nasal spray and it may be harder for you to use

Due to your runny nose i would recommend the liquid formulation of 2.5 ml dosage for your son as he is only three years old with regard to taking this drug there is no severe complication with other medication just make sure that you do not drink alcohol while taking the medication as it can exacerbate drowsiness now this is not a drowsy medication however you may

Experience drowsiness if you are sensitive to it and because you have a minor renal impairment i do recommend you take half the tablet with or without food rather than the full tablet because cetirizine can remain in the body for a long period of time which can cause a risk of toxicity to your kidneys and further deteriorate your renal impairment if you experience

Any complication while taking it feel free to come back to us for another consultation now would you like to learn more about satirizing oh yeah sure the active ingredient of zyrtec is cetirizine hydrochloride it is a second generation antihistamine and it is a synthetic drug specifically it is a metabolite of hydroxine now hydroxyzine was considered a first

Generation antihistamine that came from the pipperzine derivatives which is an organic compound naturally occurring or it can be synthesized by reacting alcoholic ammonia with one two dichloroethane now cetirizine was developed because first generation antihistamines like hydroxyzine induced various side effects including sedation worsened cognitive functions vision

Disorders and tachycardia in comparison to fewer side effects with second generations the indication for use for cetirizine is mainly for allergic rhinitis but also conjunctivitis asthma hives and anaphylaxis allergic rhinitis is a common disease referred to as hay fever it could flare up at any season of the year with the main trigger being exposure to pollen dust

Particles mold spores or animal hairs hence why it is considered a type 1 hypersensitivity reaction when an irritant enters the nose dendritic cells will recognize it as an invader collect it and present it to cells nearby once the t cell gets activated it will produce cytokines that will activate and ensure other immune cells are involved in allergic rhinitis the

Imbalanced number of t cells will stimulate these cells that produce ige antibodies which are released into the bloodstream further binding to mast cells mass cells carry lots and lots of histamine and over time constant exposure will cause degradation and histamine therefore mast cells primed with ige antibodies will release histamine in turn causing your blood

Capillaries to dilate successfully flooding your facial tissues with fluid hence why you’re experiencing surplus fluid in your facial tissues itchy and red swollen eyes and nasal congestion now interestingly cetirizine is a competitive and highly selective antagonist used in order to downgrade the level of histamine accumulating in your body it is fast acting

And has specific properties that enable it to target the peripheral histamine h1 receptor which is a rhodopsin-like g-protein-coupled receptor these receptors that an inhibited biceptirizine can be detected predominantly on immune cells respiratory smooth muscle cells and vascular endothelial cells cetirizine advantageously does not cross the blood-brain barrier

Hence it minimizes the likelihood of severe sedation side effects in addition based on satirizing’s antagonistic properties on the h1 receptor it could reduce the volume of fluid leaving your blood capillaries reduce vascular absorbency and they can inhibit bronchospasm induced by histamine if you could remember from the beginning i mentioned that ceterisine is a

Synthetic drug but how is it synthesized exactly firstly a chloride and the pipperzine react with the presence of sodium carbonate to give a piprezin carboxylate this then formed compound undergoes acid hydrolysis to produce another fibrizine derivative this then reacts with the presence of both an acetate and a carbonate to give an ethoxy acetate the obtained

Ester is finally converted to cetirizine using potassium hydroxide now let us look at the relationship between cetirizine structure and activity how does s2 medication act the way it does and how does it influence its pharmacodynamic and kinetic properties ceterising contains five functional groups vital for its activity the difference between the hydroxyzine

And its metabolite cetirizine is the addition of the carboxyl acid group the replacement of the hydroxyl group to the carboxyl group makes the component less lipophilic and because the ph is greater than the pka of the carboxyl group of 2.9 it is mainly ionized in plasma so absorption across the blood vein barrier is limited under physiological ph the amine is

Protonated to form a positive charge and the negative oh on the carboxyl group is deprotonated to form a negative charge when positive and negative charges exist a zwitter ion is formed which increases water solubility of the drug and decreases blood-brain barrier permeability the carboxyl and the amine groups provide more selectivity for the h1 receptors and

Without these groups unwanted side effects are more likely to occur the hydrophilic ether has electrons on the oxygen atom that can enable hydrogen bonding with water and the tertiary amine is also a hydrophilic part of the heterocyclic ring and the terminal nitrogen atom must be polar or ionized to enable ionic bonding with the target receptor enzyme the aromatic

Hydrocarbon interacts with the hydrophobic pocket and enhances binding greatly and increases absorption if the hydrophobic halogen chloride atom on the peri-aromatic ring was removed or substituted with something else the stability of cetirizine would decrease substantially these are the reasons why cetirizine is well tolerated and has minimal sedation now how

Exactly did drug researchers confirm that cetirizine actually can effectively target the h1 receptors to produce medication that is effective in preventing allergies the target is first validated using conformational mutational analysis which is in silico data to visualize the bonding between cetirizine and h1 receptor specifically lysine 200 amino acid which

Is on the fifth trans membrane and acts as an anchor point for antagonistic bonding this visualization shows the carboxyl group which is attached to the nitrogen by the long ether of the cetirizine attaching itself by a strong ionic hydrogen bonding to the fifth transmembrane this interaction is key to the slow dissociation rate of cetirizine and denotes its

Long-acting property as mentioned in the oral tablet formulation site-directed mutagenesis is then used to verify the in-silico data guinea pig h1 receptors were extracted and mutated with the lysine 200 amino acid was mutated into alanine and the finite to limit the suspected antagonist binding on the receptor cetirizine was used as the antagonist and showed

That there was an eight-fold loss of affinity for the cetirizine with the receptor this shows modulation of the target lysine 200 on the h1 receptor which could induce a potential therapeutic effect recently there have been a hypothesis regarding antihistamines particularly h1 and 2 receptor blockers ability to improve covet 19 in patient outcome this may be due

To the possibility of them reducing the histamine-mediated pulmonary cytokine storm in cova-19 a 2020 cohort study of 110 patients conducted in the states examined patients who had severe to critical pulmonary symptoms that were given a dual histamine receptor blockade of cetirizine and phantodyne twice a day for 48 hours an interesting outcome was derived where

A reduction of intubation was seen and a beneficial reduction in inpatient mortality and symptom progression in comparison to other reports on covid 19 inpatients it was important to note that hydrochloroquine which is a treatment mainly used for covert 19 was correlated with worse outcomes this study illustrated an exciting use of cetirizine beyond the treatment

Of allergic rhinitis however this does not suggest long-term benefits or outcomes more studies need to be conducted to examine this combinational antihistamine treatment benefit

Transcribed from video
Zytec (Cetirizine Hydrochloride) By Magdalina Saad