Chronic pruritus - linkages between skin & psyche, current treatment options - hydoxyzine &...

Hydroxyzine

SCI/2011/02/058

Itch

Itch is a common skin sensation

Lancet 2003; 361: 690–94

Itch

Clin Exp Allergy. 2011 Jun 6

Itch

Clin Exp Allergy. 2011 Jun 6

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

Neurophysiology of itch

Lancet 2003; 361: 690–94

Neuroanatomical and Neurophysiologcial pathways

Dermatological Causes of Pruritus

Psychosomatic Medicine 2007;69:970–8

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 10–15 min

Role of SSAO enzyme in pruritus

J Pharmacol Exp Ther (2005) 315(2), 553-562

Pathology of histamine induced pruritus

Fund Clin Pharmacol 2007; 21: 467-479

SSAO

Histamine

Toxic Chemicals

Nocturnal Itch

Acta Derm Venereol 2007; 87: 295–98

Nocturnal itch

Acta Derm Venereol 2007; 87: 295–98

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

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

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

Itch & Anxiety

Aim of treatment

Acta Derm Venereol 2007; 87: 295–98

And break the vicious cycle

Treatment options

• Emollients and moisturizers

• Topical corticosteroids

• Antihistamines

• Topical calcineurin inhibitors

• Mirtazapine

Acta Derm Venereol 2007; 87: 295–98

Hydroxyzine

Efficacious in relieving pruritus in various forms of eczema and

dermatitis

Guidelines in Management of Chronic Pruritus

General measures

Step wise management

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

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

J Neural Transm Suppl. 2006;(71):105-12.

Hydroxyzine

SSAO

Histamine

Hydroxyzine: Indications

Psychosomatic Medicine 2007;69:970–8

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

MOA of hydroxyzine as an Anxiolytic

Acta Psychiatr Scand 1998; suppl 393:102-108

Benefits with hydroxyzine

• 2 in 1 action– Acts as an H1 receptor antagonist

• Tackles pruritus

– Acts as an anxiolytic

To conclude….

• Efficacious in relieving pruritus in various forms of urticaria, eczema and dermatitis1

– Most potent antihistamine in alleviating IgE-mediated 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.

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. AdultsFor 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-feedingFructose intolerance, glucose-galactose mal-absorption or sucrase-isomaltase Galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

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-effectsThe 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

?