1. Hydroxyzine
SCI/2011/02/058

2. Itch
Itch is a common skin sensation
Lancet 2003; 361: 690–94

3. Itch
Clin Exp Allergy. 2011 Jun 6

4. Itch
Clin Exp Allergy. 2011 Jun 6

5. Pruritoceptive itch
• Itch originating in the skin, due to
– Inflammation,
– Dryness, or other skin damage
• Transmitted by C nerve fibers
• One of the most debilitating symptoms in
allergic and atopic diseases
• Example: itch due to
– Scabies, urticaria, and reactions to insect bite.
Lancet 2003; 361: 690–94; Allergy 2010;65(7):805-21

6. Neurophysiology of itch
Lancet 2003; 361: 690–94

7. Neuroanatomical and
Neurophysiologcial pathways

8. Dermatological Causes of Pruritus
Psychosomatic Medicine 2007;69:970–8

9. Role of histamine in pathology of itch
• Histamine directly stimulates histamine
type 1 (H1)‐receptors on itch‐specific C ‐
fibres
• An intradermal injection of histamine
causes:
– An itch which begins after 30–45 s, peaks
after about 2 min, then slowly declines over
10–15min

10. Role of SSAO enzyme in pruritus
J Pharmacol Exp Ther (2005) 315(2), 553-562

11. Pathology of histamine induced pruritus
Histamine
Toxic
Chemicals
SSAO
Fund Clin Pharmacol 2007; 21: 467-479

12. Nocturnal Itch
Acta Derm Venereol 2007; 87: 295–98

13. Nocturnal itch
Acta Derm Venereol 2007; 87: 295–98

14. Nocturnal Itch: Causes
•
•
•
•
Psoriasis
Atopic Dermatitis
Chronic Idiopathic Urticaria
Cutaneous Diseases
– Lichen Simplex Chronicus
– Scabies
• Patients With Systemic Diseases Including
– Chronic Renal Failure
– Hematopoietic Disorders
Up to 65% of patients with inflammatory skin conditions including atopic dermatitis
and chronic idiopathic urticaria have reported increased itching at night.
Acta Derm Venereol 2007; 87: 295–98

15. Nocturnal itch: possible mechanisms
• Decreased epidermal barrier function
• Increased skin temperature
• Normal circadian rhythms
– Corticosteroids
– Autonomic nervous system
• Disruption of circadian rhythms
– Opioids
– Cytokines
– Prostaglandin
• Lack of external stimuli and distraction
Acta Derm Venereol 2007; 87: 295–98

16. Nocturnal itch: Consequences
• Disruption of sleep patterns
• Reduction in the amount and quality of sleep
• Deleterious effect on human performance,
contributing to
– Irritability,
– Daytime somnolence,
– Impaired functioning and psychological problems
• Pruritus also contributes to depression,
agitation, changes in eating habits, and difficulty
concentrating
Acta Derm Venereol 2007; 87: 295–98

17. Itch & Anxiety

18. Aim of treatment
Acta Derm Venereol 2007; 87: 295–98

19. And break the vicious cycle

20. Treatment options
• Emollients and moisturizers
• Topical corticosteroids
• Antihistamines
• Topical calcineurin inhibitors
• Mirtazapine
Acta Derm Venereol 2007; 87: 295–98

21. Hydroxyzine
Efficacious in relieving pruritus in
various forms of eczema and
dermatitis

22. Guidelines in Management of Chronic
Pruritus

23. General measures

24. Step wise management

25. Hydroxyzine
• Derivative of piperazine not related to
phenothiazines
• Main mechanism of action is an antagonism of
histamine (H1) receptors
Current ther Res 1977;22:N1 section 2; Molecular pharmacology 1992;3:78-84

26. Mechanism of action of hydroxyzine to
reduce pruritus
• Hydroxyzine was found to be a potent
competitive inhibitor of SSAO
• By occupying the active site, hydroxyzine
prevents the binding of histamine to SSAO
– This prevents release of toxic chemicals thereby
preventing pruritus
Hydroxyzine
Histamine
SSAO
eural Transm Suppl. 2006;(71):105-12.

27. Hydroxyzine: Indications

28. Psychosomatic Medicine 2007;69:970–8

29. Anxiety-Allergy relationship
• Psychological comorbidity is a known aspect of
allergic disease
• Chronic pruritus is one of the major complaints
in these patients
– Patients experience anxiety and decreased quality of
life
• The pruritus is histamine induced
• 2 therapeutic choices
– Antihistamines
– Drugs used to treat psychological disorders
Br J of Dermatology 2006; 154(6):1128-36

30. MOA of hydroxyzine as an Anxiolytic
Acta Psychiatr Scand 1998; suppl 393:102-108

31. Benefits with hydroxyzine
• 2 in 1 action
– Acts as an H1 receptor antagonist
• Tackles pruritus
– Acts as an anxiolytic

32. To conclude….
• Efficacious in relieving pruritus in various
forms of urticaria, eczema and dermatitis 1
– Most potent antihistamine in alleviating IgEmediated pruritus2
– Suppresses the wheal-and-flare response for
greater than 24 hours2
– Antihistaminic effect begins approximately
after 1 hour with oral formulation1
– Clinically significant anxiolytic effect3
1. Hydroxyzine Prescribing Information Version 1.0-2009 2. Micromedex Health Care Series, accessed on 12/03/2009, 3.
Encephale. 1994;20(6):785-91.

33. Abbreviated Prescribing Information
•
•
•
•
Composition:
Each film-coated tablet contains 10 mg of hydroxyzine dihydrochloride.
Each film-coated tablet contains 25 mg of hydroxyzine dihydrochloride.
Each ml of syrup contains 5 mg of hydroxyzine dihydrochloride.
Each ml of solution for injection contains 25 mg of hydroxyzine dihydrochloride, and an ampoule containing 2 ml of
solution for injection contains 50 mg of hydroxyzine dihydrochloride.
Each ml of oral drops contains 6mg of hydroxyzine dihydrochloride USP.
Therapeutic indications
hydroxyzine is indicated in:
the symptomatic treatment of anxiety in adults;
the symptomatic treatment of pruritus;
the premedication before surgery.
Posology and method of administration
hydroxyzine solution for injection is intended to be administered by the intramuscular route.
Adults
For symptomatic treatment of anxiety: 50 mg/day in 3 separate administrations of 12.5-12.5-25 mg; in more severe cases
doses of up to 300 mg/day can be used.
For symptomatic treatment of pruritus: Starting dose of 25 mg before resting, to be followed if necessary with doses up to
25 mg 3 to 4 times daily.
For premedication before surgery: 50 to 200 mg/day in 1or 2 administrations: single administration 1 hour before surgery,
which may be preceded by 1 administration the night before anaesthesia.
Children (from 12 months)
– For symptomatic treatment of pruritus: from 12 months to 6 years old: 1 mg/kg/day up to 2.5 mg/kg/day in divided
doses, over 6 years old 1 mg/kg/day up to 2 mg/kg/day in divided doses.
– For premedication before surgery: Single administration of 1 mg/kg 1 hour before surgery, which may be preceded by
1 mg/kg the night before anaesthesia.
Contra-indications
History of hypersensitivity to any of the constituents of hydroxyzine, to cetirizine, to other piperazine derivatives, to
aminophylline, or to ethylenediamine.
Patients suffering from porphyria.
Pregnancy and breast-feeding
Fructose intolerance, glucose-galactose mal-absorption or sucrase-isomaltase
Galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

34. Abbreviated Prescribing Information
•
•
Special warnings and precautions for use
– Concomitant use of hydroxyzine with alcohol.
– hydroxyzine should be administered cautiously in patients with increased potential for convulsions & cardiac
arrhythmia, in patients suffering from glaucoma, bladder outflow obstruction, decreased gastro-intestinal motility,
myasthenia gravis, or dementia.
– Dosage adjustments may be required if used simultaneously with other CNS depressant drugs or with drugs having
anticholinergic properties.
– Patients should be cautioned against driving a car or operating machinery, as hydroxyzine may impair the ability to
react and to concentrate.
– In the elderly, it is advised to start with half the recommended dose due to a prolonged action.
– hydroxyzine dosage should be reduced in patients with hepatic dysfunction and with moderate or severe renal
impairment.
– Before intramuscular administration of hydroxyzine solution for injection, careful check that the needle did not enter
any vessel must be performed.
– hydroxyzine 2 mg/ml syrup contains 0.1 vol % of alcohol, this has to be taken into account in alcoholics, in pregnant
or lactating women, children, and high-risk groups such as patients with liver disease, or epilepsy.
– hydroxyzine antagonizes the effects of betahistine, and of anticholinesterase drugs.
– Simultaneous administration of hydroxyzine with monoamine oxidase inhibitors should be avoided.
Side-effects
The following undesirable effects have been reported:
– Very common: somnolence
– Common: dry mouth, fatigue, headache, sedation, agitation, confusion,
– Uncommon: nausea, malaise, pyrexia, dizziness, insomnia, tremor
– Rare: tachycardia, accommodation disorder, vision blurred, constipation, vomiting, hypersensitivity, liver function test
abnormal, convulsions, dyskinesia, disorientation, hallucination, urinary retention, pruritus, rash erythematous, rash
maculo-papular, urticaria, dermatitis, hypotension
– Very rare: anaphylactic shock, bronchospasm, angioneurotic oedema, sweating increased, fixed drug eruption
Please refer to full prescribing information before usage

35. ?