Hydroxyzine
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Hydroxyzine
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| Systematic (IUPAC) name | |
| Hydroxyzine: 2-[2-[4-[(4-chlorophenyl)- phenyl-methyl] piperazin-1-yl] ethoxy]ethanol (Hydroxyzine) |
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| Identifiers | |
| CAS number | |
| ATC code | N05 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C21H27ClN2O2 |
| Mol. mass | 374.904 g/mol |
| SMILES | search in , |
| Synonyms | Hydroxyzine pamoate: Vistaril Hydroxyzine hydrochloride: |
| Pharmacokinetic data | |
| Bioavailability | High in-vivo |
| Protein binding | 93% |
| Metabolism | Liver |
| Half life | 20 to 25 hours |
| Excretion | Urine, Feces |
| Therapeutic considerations | |
| Pregnancy cat. | |
| Legal status |
℞ Prescription only |
| Routes | Oral, intramuscular injection |
Hydroxyzine (IPA: [haɪ ˈdrɔks ɪ ˌzin]) is a piperazine derivative that is an H1 receptor antagonist. It is used primarily as an antihistamine for the treatment of itches and irritations, an antiemetic for the reduction of nausea, as a weak analgesic and as an anxiolytic for the treatment of anxiety.[1] The drug is available in two formulations, the hydroxyzine pamoate and the hydroxyzine hydrochloride salts.
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[edit] Prescription and use
Hydroxyzine is prescribed when the onset of an organic disease state manifests through anxiety, as general anxiety disorder, or in other more serious cases as psychoneurosis, and is therefore prescribed as a means of regulating normal function. Hydroxyzine can also be used for the treatment of allergic conditions, such as chronic urticaria, atopic or contact dermatoses, and histamine-mediated pruritus.[1] These have also been confirmed in both recent and past studies to have no adverse effects on the liver, blood, nervous system or urinary tract.[2]
In terms of Vistaril, its usage in premedication as a sedative has no effects on belladonna alkaloids, such as atropine, but may, following general anesthesia, potentiate meperidine and barbiturates, and use in pre-anesthetic adjunctive therapy should be modified depending upon the state of the individual.[2] Hydroxyzine is also safe to use alongside other medications or cardiac agents derived from the digitalis plant, as it does not yield any side-effects, due to its effects on the sympathetic, rather than the central nervous system.[2]
In other cases, the usage of hydroxyzine is as a form of non-barbiturate tranquilizer[3] used in the treatment of neurological disorders, such as psychoneurosis and other forms of anxiety or tension states.[3] It has been suggested through pharmacological trials that the usage of hydroxyzine on dogs reduced the incidence and duration of ventricular arrythmias,[4] and that it is able to block the spasmogenic actions associated with other substances such as serotonin, reserpine, histamine, acetylcholine and the effect of pituitary extract on the duodenum.[3] Similarly, in experiments conducted on the ileum of small rabbits, hydroxyzine was found to inhibit hypermotility caused by the presence of barium chloride.[3]
Hydroxyzine is not thought to be an effective treatment if used for a period of over 4 months, and it is therefore a prerequisite of any medical professional prescribing such drugs, to re-assess the usefulness for the individual patient. Reasoning for this decision stems from the fact that hydroxyzine is mainly used as an antihistamine and has a somewhat short shelf-life in its common form. Rather than its use as an anxiety-reducing agent, hydroxyzine should be reconsidered if the patient has more intense anxiety or other psychoneurosis; then other compounds specifically designed for such conditions should be considered.[5]
[edit] Treatment of learned helplessness
Aside from its prescription as an antihistamine, hydroxyzine has also shown slight possibilities for use in other species, such as dogs, from results and effects observed in rats with "learned helplessness" induced through the use of random inescapable shocks (max 0.8 mA) administered in 1 minute intervals for a period of 15 seconds for an hour.[6] After the condition was induced, rats were then given a conditioned stimulus of a light, and shocked if unable to move to safety from the area producing the current within 3 seconds.[7] Those unable to move were determined as having a conditioned stimulus of expecting shocks from the initial random condition.[6][7]
In the initial treatment to this condition, rats were given hydroxyzine as a curative treatment for the shocks received and as a treatment for the prevention of learned helplessness by injection beforehand; results indicating that beforehand, hydroxyzine decreased the overall amount of escape failures by a similar amount to those observed in diazepam, which achieved similar results, however, with side effects of amnesia.[8][7] Despite the fact that hydroxyzine clearly increased the ability of the rats to avoid stimuli, it had almost no effect on the rats ability to respond to the shocks nor remove "stress" after exposure to shocks.[8]
[edit] Clinical description
[edit] Metabolisation and pharmacokinetics
Hydroxyzine can be administered orally as hydroxyzine hydrochloride or hydroxyzine embonate, or via intramuscular injection as hydroxyzine hydrochloride. When given orally, hydroxyzine is rapidly absorbed from the gastro-intestinal tract. The effect of hydroxyzine is notable in 30 minutes.
Pharmacokinetically, hydroxyzine is rapidly diffused in the body and absorbed in oral and intramuscular administration, and is metabolised in the liver; the main metabolite (45%) through oxidation of the alcohol moiety to a carboxylic acid, is cetirizine and overall effects are observed within one hour of administration. It has a half-life observed on average for around 7-10 hours in adults, 6-7 hours in children, and 18-21 hours in the elderly, or those with renal insufficiency, with higher concentrations found in the skin than in the plasma. Cetirizine, although less sedating, is non-dialyzable and possesses similar anti-histaminergic properties. In a 10mg dose, 70% of the drug is excreted unchanged in the urine within 72 hours and 10% excreted within feces.
Administration in geriatrics differs from the administration of hydroxyzine (pamoate or Vistaril) in younger patients; according to the FDA, there have not been significant studies made (2004), which include population groups over 65, and therefore have not provided a distinction between elderly aged patients and other younger groups:[9] any hydroxyzine administered should be done with doses at the small end of the dosing range, and be carried out with the knowledge that any existing concomitant disease, or decrease in the function, or lessened excretion, such as the case may be with hepatic, renal or cardiac states.[9]
Similarly, the use of sedating drugs alongside hydroxyzine can cause over-sedation and confusion if administered in large amounts—any form of treatment alongside sedatives should be done under supervision of the patient.[9][3]
[edit] Contraindications
The administration of hydroxyzine in large amounts by ingestion or intramuscular administration during the onset of pregnancy can cause fetal abnormalities—when administered to pregnant rats, mice and rabbits, hydroxyzine caused abnormalities with doses significantly above that of the human therapeutic range.[5] In terms of humans, a significant dose has not yet been established in studies, and by default, the FDA has introduced contraindication guidelines in regard to hydroxyzine.[5] Similarly, those at risk from, or showing previous signs of hypersensitivity are also contraindicated.[5]
Other contraindications include the administration of hydroxyzine alongside depressants and other compounds which affect the central nervous system, such as narcotics, non-narcotic analgesics and barbiturates, as well as alcohol,[5] and if absolutely necessary, should only administered concomitantly in small doses[5] as any pre-existing grogginess from these substances may be enhanced. If administered in small doses with other substances, such as mentioned, then patients should refrain from using dangerous machinery, motor vehicles or any other practice requiring absolute concentration, in accordance with safety law.[5]
Studies have also been conducted which show that long-term prescription of hydroxyzine can lead to tardive dyskinesia after years of use, but has also been reported after periods of 7½ months showed effects related to dyskinesia,[10] such as continual head rolling, lip licking and other forms of athetoid movement. In certain cases, elderly patients' previous interactions with phenothiazine derivatives or pre-existing neuroleptic treatment may have had some contribution towards dyskinesia at the administration of hydroxyzine due to hypersensitivity caused due to the prolonged treatment,[10] and therefore some contraindication is given to the short-term administration of hydroxyzine to those with previous phenothiazine use.[10]
[edit] Adverse reactions
- For a full list of side effects, consult the full technical specification of hydroxyzine.
Several reactions have been noted in manufacturer guidelines for two forms of hydroxyzine: Atarax and Vistaril. In Atarax, symptoms are similar to those of Vistaril -- deep sleep, incoordination and dizziness have been reported, as in children and adults, as well as others such as hypotension, tinnitus and headaches.[11] Gastro-intestinal effects have also been observed in both Visatril and Atarax, as well as less serious effects such as dryness of the mouth, constipation caused by antimuscarinic properties of hydroxyzine.[11]
Central nervous system problems such as hallucinations or confusion have been observed in rare cases, attributed mostly to overdosage.[11][9] Such properties have been attributed to hydroxyzine in several cases, particularly in patients treated for neuropsychological disorders, as well as in cases where overdoses have been observed. While there are reports of the "hallucinogenic" or "hypnotic" properties of hydroxyzine, several clinical data trials have not reported such side effects from the sole consumption of hydroxyzine, but rather, have described its overall calming effect described through the stimulation of areas within the formatio reticularis. The description of hallucinogenic or hypnotic properties have been described as being an additional effect from overall central nervous system suppression by other CNS agents, such as Lithium or Alcohol.[12]
The effect of hydroxyzine has also been tested on the ability of humans in the registration and storage of memory, and was used in comparison with relatively safe drugs, such as hydroxyzine, to illustrate the effects of benzodiazepines, which are thought to have adverse effects on the capacity of memory storage. Hydroxyzine was found to have no adverse effects on memory in relation to lorazepam, which caused several deficiencies in the capacity of memory storage.[13]
In comparison to lorazepam, patients involved a study on memory who had taken hydroxyzine experienced sedative effects similar to drowsiness, but recalled that they felt capable, attentive and able to continue with a memory test under these conditions.[14] Conversely, those under the effects of lorazepam felt unable to continue due to the fact they felt out of control with its effects; 8 out of 10 patients describing tendencies of problems with balance and control of simple motor functions.[14]
Severe somnolence with or without vivid dreams or nightmares may occur in users with antihistamine sensitivities or other CNS depressants available in their systems. Hydroxyzine exhibits very potent anxiolytic and sedative properties in many psychiatric patients. Other studies have suggested that hydroxyzine acts as an acute hypnotic, reducing sleep onset latency and reciprocal increases in sleep duration -- also showing that some drowsiness did occur, but in female patients who also had greater hypnotic response. It did not, however, show any significant or noticeable effect of drowsiness, other than in female patients' subjective responses.[15]
In contrast to drugs in the benzodiazepine class, (i.e. alprazolam, diazepam) which carry a potential for abuse and dependence, hydroxyzine is very unlikely to cause any dependence due to its relative strength compared to other substances.
[edit] References
[edit] Notes
- ^ a b RxList, et al. (2004)
- ^ a b c United States Food & Drug Administration, (2004), p1
- ^ a b c d e Dolan, C. M., (1958)
- ^ Hutcheon, D. E., Scriabine, A., et al. (1956)
- ^ a b c d e f g United States Food & Drug Administration, (2004), p2
- ^ a b Porsolt, R. D.; P. Martin, A. Lenegre, S. Frornage, and C.E. Giurgea (1989), p229
- ^ a b c Porsolt, R. D.; P. Martin, A. Lenegre, S. Frornage, and C.E. Giurgea (1989), p228
- ^ a b Porsolt, R. D.; P. Martin, A. Lenegre, S. Frornage, and C.E. Giurgea (1989), p230
- ^ a b c d United States Food & Drug Administration, (2004), p3
- ^ a b c Clark, B. G., Araki, M., et al. (1976)
- ^ a b c UCB South-Africa, et al., (2004)
- ^ Anderson, P. O., Knoben, J. E., et al. (2002), p794-796
- ^ Brabander, A. DE, Debert, W., (1990), p1
- ^ a b Brabander, A. DE, Debert, W., (1990), p3
- ^ Alford, C.; N. Rombautt, J. Jones, S. Foley, C. Idzikowskit and I. Hindmarch (1992).
[edit] Print sources
- Hutcheon, D. E.; D.L. Morris, A. Scriabine (December 1956). "Cardiovascular action of hydroxyzine (Atarax)". J Pharmacol Exp Ther. 118 (4): 451-460. PMID 13385806. Retrieved on 2007-03-09.
- Dolan, C. M. (June 1958). "Management of emotional disturbances -- Use of Hydroxyzine (Atarax®) in General Practice". Calif Med. 88 (6): 443–444. PMID 13536863. Retrieved on 2007-03-09.
- Pfizer Labs, Division of Pfizer Inc, NY, NY 10017 (2004), Vistaril ® (hydroxyzine pamoate) Capsules and Oral Suspension, United States Food and Drug Administration [link accessed 2007-03-09]
- Anderson, Philip O.; James E. Knoben, William G. Troutman (2002). Handbook of Clinical Drug Data. McGraw-Hill Medical. ISBN 0071363629.
- de Brabander, A.; W. Deberdt (1990). "Effect of Hydroxyzine on Attention and Memory". Human Psychopharmacology 5 (4): 357-362. DOI:10.1002/hup.470050408. Retrieved on 2007-03-09.
- Clark, B. G.; M. Araki, H. W. Brown (1982). "Hydroxyzine-Associated Tardive Dyskinesia". Ann Neurol. 11 (4): 435. PMID 7103423. Retrieved on 2007-03-09.
- Porsolt, R. D.; P. Martin, A. Lenegre, S. Frornage, and C.E. Giurgea (1989). "Prevention of “Learned Helplessness” in the Rat by Hydroxyzine". Drug Dev. Res. 17 (3): 227-236. DOI:10.1002/ddr.430170306. Retrieved on 2007-03-10.
- Alford, C.; N. Rombautt, J. Jones, S. Foley, C. Idzikowskit and I. Hindmarch (1992). "Acute Effects of Hydroxyzine on Nocturnal Sleep and Sleep Tendency the Following Day: a C-EEG Study". Human Psychopharmacology 7 (1): 25-35. DOI:10.1002/hup.470070104. Retrieved on 2007-03-10.
[edit] Internet-based
- RxList , et al. (2004). Atarax Indications, Dosage, Storage, Stability. RxList - The internet drug index. Retrieved on 2007-03-09.
- Medscape (2004). Vistaril Oral: Monograph - Hydroxyzine Hydrochloride, Hydroxyzine Pamoate. medscape.com. Retrieved on 2007-03-09.
[edit] Drug information pamphlets
- UCB South-Africa, et al., (2004). ATERAX® 25 mg TABLETS; ATERAX® 100 mg TABLETS; ATERAX® SYRUP (Manufacturing guidance package insert) Pharmacare Ltd, (a division of Aspen Pharmacare Ltd)
