Cetirizine dihydrochloride

Description

Cetirizine hydrochloride, a second generation antihistaminic drug, is one of the carboxylated metabolites of hydroxyzine that can typically bind to histamine H1 receptor. It is effective against diseases such as allergic rhinitis, urticaria, conjunctivitis. and hay fever.

Chemical properties

Cetirizine Hydrochloride occurs as a white crystalline powder or crystalline solid. It is very soluble in water, and slightly soluble in ethanol (99.5). It dissolves in 0.1 mol/L hydrochloric acid TS. A solution of Cetirizine Hydrochloride (1 in 10) shows no optical rotation.

The Uses of Cetirizine dihydrochloride

Cetirizine hydrochloride is a Histamine H1 receptor inverse agonist. A major metabolite of Hydroxyzine. Pharmacological activity resides primarily in the (R)-isomer. It is Cetirizine is an antihistamine medicine that is effective in the treatment of allergic rhinitis, chronic urticaria, and pollen-induced asthma. Unlike many traditional antihistamines, it does not cause drowsiness or anticholinergic side effects.

Indications

Cetirizine HCl (Zyrtec) is the carboxylic acid metabolite of hydroxyzine. It is a selective, peripheral H1 receptor antagonist. It is a long-lasting antihistamine. It does not appear to have the same adverse cardiac effects as the other nonsedating H1 antihistamines; however, additional data are required. Indicated for allergic rhinitis and chronic urticaria.

Definition

ChEBI: Cetirizine hydrochloride is a diarylmethane.

Manufacturing Process

Preparation of 2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]- ethoxy]acetic acid (cetirizine).
To a mixture of 50 g 2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]- ethanol and 225 ml of tert-butanol at 45°C under a nitrogen was added 21 g tert-BuOK. The temperature was raised to 75-80°C and the mixture was kept at this temperature. After 45 min was added 11 g sodium chloracetate; after 1.5 hour was added 5.2 g tert-BuOK; after 2 hours was added 5.64 g sodium chloracetate; after 2.5 hours was added 1.9 g tert-BuOK; after 3 hours was added 1.9 g sodium chloracetate; after 3.5 hours was added 0.8 g tert-BuOK; and after 4 hours was added 1.13 g sodium chloracetate. Then about 150 ml tert-butanol was distilled of, 190 ml of water was added and the distillation of tert-butanol was continued until the temperature of the vapour reaches 100°C. To the reaction mixture was added 60 ml of water and 8 ml concentrated hydrochloric acid to pH 8. Unreacted 2-[4-[(4-chlorophenyl) phenylmethyl]-1-piperazinyl]-ethanol was extracted with diethyl ether. The aqueous phase was acidified to pH 5 by addition of hydrochloric acid and extracted with dichloromethane (200 ml x 3). The extract was dried over MgSO4, filtered and concentrated in a rotary evaporator. An obtained oil was allowed to crystallize by addition of 150 ml of 2-butanone, yields of 2-[4-[(4- chlorophenyl)phenylmethyl]-1-piperazinyl]-ethoxy]acetic acid 55.5%, M.P. 146-148°C.
32.7 g 2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]-ethoxy]acetic acid was suspended in a mixture of 125 ml of water and 13.8 ml 37% aqueous hydrochloric acid. The mixture was concentrated in a rotary evaporator. An obtained oil was allowed to crystallize by addition of 245 ml of 2-butanone, yields of Cetirizine hydrochloride 88%, M.P. 228.22°C.

brand name

Zyrtec (Pfizer).

Therapeutic Function

Antihistaminic; Antiallergic

Biochem/physiol Actions

Cetirizine hydrochloride is an orally active and selective H1-receptor antagonist. Antihistaminic; Piperazines. Non-sedating type histamine H1-receptor antagonist; major metabolite of hydroxyzine. Pharmacological activity resides primarily in the (R)-isomer.

Side Effects

There are many side effects of Cetirizine hydrochloride which can be classified into five levels including common side effects (10%), more common side effects (1%), rare side effects (0.1%), very rare side effects (0.01%) and other side effects.
Common side effects include: drowsiness, dizziness, headache, pharyngitis, rhinitis (children), diarrhoea (children), nausea, dry mouth, fatigue. More common side effects include: restlessness, paresthesia (tingling or numbness in the hands and feet), diarrhoea, stomach pain, pruritus (itching), rash, asthenia (unusual weakness), weakness.
Rare side effects include: hypersensitivity, aggression, confusion, depression, hallucinations, insomnia, convulsions, tachycardia (fast heartbeat), abnormal liver function, hives, oedema (swelling), weight gain. Very rare side effects: Thrombocytopenia (low platelet count), anaphylaxis, convulsions (uncontrolled body movements), gustatory disturbances (disturbances in taste or loss of taste), dyskinesia (dyskinesia (uncontrolled movements), dystonia (uncontrolled muscle spasms), syncope (fainting), ophthalmoplegia (uncontrolled circular movements of the eyes), angioedema (severe). allergic reaction that causes swelling of the face or throat), dysuria (pain when urinating), incontinence (bedwetting).
Other side effects include: increased appetite, suicidal thoughts, nightmares, amnesia, memory problems, dizziness (spinning sensation), inflammation of the liver, urinary retention (difficulty in urinating), pain in the joints, rash with pus-containing blisters, and severe itching after stopping the drug (pruritus).

Drug interactions

Potentially hazardous interactions with other drugs
Antivirals: concentration possibly increased by ritonavir.

Metabolism

Cetirizine does not undergo extensive first pass metabolism.
About two thirds of the dose is excreted unchanged in urine.