PRESENTED BY:

VISHNU.R.NAIR,

FIFTH YEAR PHARM.D,

NATIONAL COLLEGE OF PHARMACY.

“Urticaria refers to a HETEROGENEOUS group of disorders, characterized by ERUPTION of WHEALS, that are transient, itchy, well-demarcated, superficial, erythematous/ pale swellings of the dermis”. . .

According to a study published by Simons FE Most cases of simple acute urticaria can be treated with H1-antihistamines

According to a study published by Lin RY et.al in cases of severe/ persistent urticaria add H2-antihistamines to H1-Antihistamines may be given orally/ i.v

If a patient with CHRONIC URTICARIA, is refractory to non-sedating antihistamines doses, upto 4 times the recommended maximum dose may be effective

If maximum doses of non-sedating antihistamines are not effective focus on other therapies

In patients, with urticaria resistant to the standard dosage of CETIRIZINE/ FEXOFENADINE Double the daily dose.

In a study of 51 patients, treated with CETIRIZINE(at a dose of 10 mg OD) 18 patients showed less response. When those patients were given CETIRIZINE at DOUBLE the DOSE (20 mg OD) They showed significant improvements in severity of wheals, itching and also in QUALITY OF LIFE

Refractory cases of chronic urticaria improves with GLUCOCORTICOIDS

CHRONIC URTICARIA may also benefit from DOXEPIN, which possesses potent antihistaminic properties

CYPROHEPTADINE may be useful to suppress recurrent cold urticaria

According to a study by Wan KS combination of a LT-receptor antagonist and non-sedating antihistamine found to be more effective than antihistamine alone, to treat Chronic Idiopathic Urticaria.

H-1 Antihistamines are mainly used

Efficacy is attributed to the fact, that most symptoms of urticaria are mediated by the action of HISTAMINE(via H-1 receptors)

For acute urticaria focus on <6 weeks duration of therapy

For chronic urticaria prolonged use, for longer duration, is warranted

Antihistamines can be used in 5 ways:

1. USE OF A SINGLE ANTIHISTAMINE:

- Usually, 2nd or 3rd generation antihistamines are preferred over 1st

generation ones

2. USE OF COMBINATION OF ANTIHISTAMINES:

- Refers to combination of FIRST GENERATION & SECOND/ THIRD GENERATION ANTIHISTAMINES

- Example :

a. Cetirizine + chlorpheniramine

b. Loratadine + fexofenadine

3. INCREASING DOSES OF A SINGLE AGENT:

- According to a study published by Zuberbier et al if a patient, with CHRONIC URTICARIA refractory to non-sedating antihistamines doses, upto 4 TIMES RECOMMENDED MAXIMAL DOSES may be effective.

- Example: Higher doses (4 times) of FEXOFENADINE may be used.

4. ADDITION OF H2-ANTIHISTAMINES:

- According to a study by Lin RY, Knight RJ, Lee HS in cases of severe/ persistent urticaria H2 antihistamines may be added to H1 agents.

- Drugs usually given include:

a. Ranitidne

b. Famotidine

5. USAGE OF DUAL RECEPTOR ANTIHISTAMINES:

Examples include:

a. Doxepin

b. Cyproheptadine.

Drugs block histamine response at H1-receptor reduce flare and wheal reactions associated with urticaria alleviate symptoms.

Dosages:

a. Cetirizine : 5-10 mg, PO, per day

b. Levocetirizine : 5 mg, PO, per day

c. Loratadine : 10 mg, PO, per day

d. Desloratadine: 5 mg, PO, per day

e. Ebastine : 10-20 mg, PO, per day

f. Fexofenadine : 30-180 mg, PO, per day

g. Cyproheptadine : 4 mg, PO, TID.

ADRs and Safety issues associated with H1-antihistamines:

WITH RESPECT TO EFFECTS

SEDATION Increased sedation

ANTICHOLINERGIC EFFECTS Dry mouth, glaucoma, urinary retention(in

geriatric males), with Prostatic Hypertrophy

CARDIAC EFFECTS Terfenadine and astemizole may cause TdP

PEDIATRICS & GERIATRICS Paradoxical excitation(with 1st generation

drugs)

PREGNANT WOMEN Avoid in pregnancy(except chlorpheniramine,

loratadine)

LACTATING WOMEN Irritability, drowsiness, in breastfed babies

LIVER & KIDNEY IMPAIRMENT Avoid 1st generation drugs & mizolastine in

liver disease, and cetirizine in renal

impairment.

DOXEPIN Blocks both H1 & H2 receptors found effective in the treatment of allergic reactions, especially urticaria.

ADRs:

a. Anticholinergic effects

b. Sedation

c. Weight gain

d. ECG changes

e. Tachycardia

- DOSE : 10-50 mg, at night.

Include:

A. SYSTEMIC STEROIDS

B. LEUCOTRIENE ANTAGONISTS

C. OTHER DRUGS

Drug shows 3 actions, thereby controlling/ preventing inflammation:

a. Reduce migration of PMNs

b. Reverse capillary permeability

c. Reduce migration of fibroblasts

- Mainly indicated in patients, that are refractory to H1 & H2-antihistamines

- Can be used in :

a. severe, acute, recalcitrant urticaria

b. Severe urticarial vasculitis

c. Treatment of histamine-resistant acute urticaria, or when angioedema is present

- Long-term usage is discouraged, owing to long-term ADRs

- ADRs include:

a. Precipitation/ worsening of DM

b. High risk of infections

c. Osteoporosis

d. Psychosis

e. Glaucoma

f. HTN

- Dose : ORAL PREDNISOLONE (0.5-1 mg/kg/day).

Drug inhibits LT-receptors reduces inflammatory cascade associated with urticaria

Mainly used as ADJUVANTS to conventional therapies

ADRs:

a. Headache (18.4%)

b. Abdominal pain(>2%)

c. Increased LFTs(>2%)

- Drugs used include:

a. MONTELUKAST (10 mg OD)

b. ZAFIRLUKAST (20 mg BD)

Mainly used as ADJUVANTS to antihistamines

NIFEDIPINE(CCB) possesses mast-cell stabilizing characteristics may be helpful for CHRONIC URTICARIA(according to a research article, published by Bressler RB et al)

NIFEDIPINE is started at a dose of 5 mg TID, and the dose may be increased upto 20 mg TID(as per need)

Other treatments also include PUVA and Narrowband UV-B

Mainly used in patients, that do not respond to 1st and 2nd line treatments

Treatment strategies include:

a. PLASMAPHERESIS

b. IVIG INFUSION (0.4 g/kg/day, for 5 days)

c. CYCLOSPORINE A (2.5-4 mg/kg/day, upto 3 months)

d. Methotrexate.

e. Omalizumab

URTICARIAL VASCULITIS is a condition, that is characterized by occurrence of urticarial wheals, that persist beyond 24 hours

Lesions may burn, as well as itch

Usually tender and painful, and resolve with residual staining.

Treatment includes the following:

1. For MILD CASES:

a. Antihistamines f. HCQ.

b. Oral steroids

c. NSAIDS

d. Colchicine

e. Dapsone

2. For severe/ refractory cases:

a. Methotrexate

b. Mycophenolate mofetil

c. Azathioprine

d. Cyclosporine

e. Cyclophosphamide

3. Other treatments include:

a. Pentoxifylline

b. Thalidomide

c. Interferons

d. Plasmapheresis

e. Omalizumab .

1. COLD COMPRESS:

- Cold temperatures helps shrink blood vessels blocks further release of histamine alleviates swelling, inflammation and itching

- Wrap some ice cubes in a cloth place over affected skin(for 10 minutes at a time), thrice/ four times a day

- ALTERNATIVE REMEDY: Take a cold bath/ shower, to calm the skin inflamed by hives

2. BAKING SODA:

- Baking soda has anti-inflammatory properties helps reduce inflammation, as well as itching

- Add half- 1 cup of baking soda to a bathtub, filled with lukewarm water mix well soak in this water for 20-30 minutes

- ALTERNATIVE REMEDY:

Put 2 tbsp. of baking soda in a small bowl add enough water to make a thick paste spread the paste on the affected area leave it on for 10 minutes rinse it off with warm water do this once daily.

3. OATMEAL:

- OATMEAL has anti-irritating, anti-inflammatory, and soothing properties

- Provides relief from itching

- Also helps skin to heal quickly

- Mix a cup of oatmeal with enough water to form a paste apply it on the affected skin for 15-20 minutes wash it off with lukewarm water do it once daily

4. TURMERIC:

- Turmeric has anti-inflammatory and anti-histaminic properties

- Mix 1 tsp. of turmeric powder in a glass of hot milk/ water drink it twice daily.

5. GINGER:

- Ginger has strong anti-inflammatory and anti-histaminic properties reduces inflammation, by:

a. Improving circulation to skin

b. Relieving swelling

c. Reducing itching

- Peel the skin off a piece of fresh ginger root gently apply it on the inflamed skin do it twice/ thrice daily

- ALTERNATIVE REMEDY: Drink ginger tea/ chew 2-3 pieces of fresh ginger pieces a few times daily.

6. ALOE VERA:

- ALOE VERA GEL contains anti-inflammatory and anti-microbial properties helps reduce redness, inflammation and itching(when applied topically)

- Apply aloe vera gel to affected skin leave it on for 10-15 minutes rinse it off with lukewarm water.

7. KEEP A FOOD DIARY:

- Patient is instructed to make a list of foods, that are suspected to be allergenic

- This will help the patient to avoid the trigger/s.

8. Wear loose, smooth-textured, cotton clothing, to avoid further skin irritation

9. Reduce stress, since it can worsen your condition

10. Increase Vitamin C intake in your diet

11. Avoid hot baths/ showers during an outbreak

12. Stay out of direct sunlight as far as possible.

1. Singhal E, Sonthalia S; “Chapter 14: Urticaria and Angioedema”; IADVL’s Concise Textbook of Dermatology; 1st edition; WILEY-BLACKWELL Publications; Page: 175- 82.

2. Simons FE. H1-Antihistamines:more relevant than ever in the treatment of allergic disorders. J Allergy Clin Immunol. 2003 Oct. 112(4 Suppl): S42-52

3. Lin RY, Curry A, Pesola GR, Knight RJ, Lee HS, Bakalchuk L, et al. Improvedoutcomes in patients with acute allergic syndromes who are treated with combined H1 and H2 antagonists. Ann Emerg Med. 2000 Nov. 36(5):462-8

4. Zuberbier T, Asero R, Bindslev-Jensen C, Walter Canonica G, Church MK, Gimenez-Arnau AM, et al. Guidelines for the management of urticaria. Allergy. 2009 Oct. 64(10):1427-43

5. Balaraman B, Bergstrom KG. Beyond antihistamines: Treating chronic urticaria. J Allergy Dermatol. 2009 Nov. 8(11): 1043-8.

6. Okubo Y, Shigoka Y, Yamazaki M, Tsuboi R. Double dose of cetirizine hydrochloride is effective for patients with urticaria resistant: a prospective, randomized, non-blinded, comparative clinical study and assessment of quality of life. J Dermatol Treat. 2013 Apr. 24(2): 153-60.

7. Kai AC, Flohr C, Grattan CE. Improvement in quality of life impairment followed by relapse with 6-monthly periodic administration of omalizumab for severe treatment-refractory chronic urticaria and urticarial vasculitis. Clin ExpDermatol. 2014 Apr 23.

8. Lang DM. Omalizumab is efficacious for management of recalcitrant, antihistamine-resistant chronic urticaria. Drugs Today(Barc). 2015 Jun. 51(6): 367-74.

9. Wan KS. Efficacy of Leukotriene receptor antagonist with an anti-H1 receptor antagonist for treatment of chronic idiopathic urticaria. J Dermatol Treat. 2009.20(4): 194-7.

10. http://www.top10homeremedies.com/home-remedies/home-remedies-hives.html.

THANK YOU !!!!!!