1. Pharmacological Treatment of Cough, Cold, & Flu

2. Common Cold Facts On average, people have 3-12 colds per year
The common cold and related conditions annually result in:
250 million restricted activity days
30 million lost work or school days
one of the most expensive illnesses in the U.S.
More prevalent in children

3. Common Cold Etiology Viruses rhinoviruses (40-50% of cases)
influenza viruses
parainfluenza viruses
respiratory syncytial viruses
coronaviruses
adenoviruses
coxsackieviruses
enteric cytopathic human orphan (ECHO) viruses

4. Transmission of the Common Cold
Direct virus spread
touching infected object (inoculum of virus)
self-inoculation (touching own mucous membranes- eyes or nose, etc.)
commonly transmitted by children
Indirect droplet spread
sneezing and coughing
secondary method of transmission

5. Clinical Presentation: Common Cold
Sore or scratchy throat
Sneezing
Rhinorrhea (clear or purulent)
Nasal congestion
Fever may occur in children
Adults may experience malaise
Non-productive cough that may become productive as the cold progresses

6. Common Cold Median duration of symptoms Seasonal variation 7-13 days
peak occurrence:
September (back to school surge)
October
early spring

7. Clinical Presentation: Influenza
Headache, sore throat, cough, runny nose, and sneezing
Non-productive cough
Disabling impact
Sudden fever, sweating, and chills
Malaise and mylagia
may last up to 2 weeks
Backache
Sensitivity to light

8. Common Cold and Influenza

9. Common Cold Prevention and Treatment
patient education
hand washing
Treatment goal:
relieve symptoms
minimize adverse effects
improve patient quality of life

10. Natural Products

11. Zinc Mechanism of action is unknown.
Hypothesized to inhibit viral shedding but unproven.
In the mid 1970s, it was reported that zinc ions inhibit rhinovirus replication in vitro.
Clinical studies are limited and controversial.
Lozenges generally have 23 mg Zn and should be taken q2h while awake!
Adverse effects are not uncommon but are not life-threatening.
Adverse Effect
Incidence(%)
Nausea
20.4
Mouth Irritation
24.5
Bad Taste
79.6
Dry mouth
10.2

12. Vitamin C Anecdotal evidence only!
Correlational data suggest vitamin C may participate in immune function
Enhance WBC function and activity
Increases interferon levels
Improves antibody levels and responses
Increases secretion of thymic hormones

13. Vitamin C
A meta-analysis has found that Vitamin C, at a minimum dose of 200 mg, did not improve cold symptoms. Seven trials (3300 episodes of respiratory infection) found vitamin C, initiated after the onset of cold symptoms, was not different than placebo in decreasing cold duration. Four separate trials (involving a total of 2750 respiratory infections) found that vitamin C was not superior to placebo in decreasing cold severity. However, this same meta-analysis did find some effectiveness for vitamin C in preventing colds.

14. Echinacea
Chemical analysis has revealed numerous constituents with pharmacological activity.
Appears to be most effective in patients with compromised immune systems.
Echinacea is the most frequently used botanical in the United States. Several rigorously designed studies and meta-analysis have failed to demonstrate a beneficial effect of echinacea as treatment for the common cold

15. Expectorants and Cough Suppressants
“Cough Medicine”
Expectorants and Cough Suppressants

16. Decongestants Mechanism of action: Effect as decongestant:
Activate  adrenergic receptors.
Effect as decongestant:
directly stimulate alpha-adrenergic receptors of respiratory mucosa causing vasoconstriction
shrinks swollen mucosa and improves ventilation
Other effects (adverse effects)
Vasoconstriction
CNS stimulation
As covered in previous lectures, the nasal tissue is erectile tissue and is highly innervated by the sympathetic and parasympathetic nervous sytems. Sympathetic stimulation of the tissue results in vasoconstriction, decreased blood flow, and corresponding decreases in tissue size and airway widening. Parasympathetic stimulation results in vasodilation, increased blood flow, tissue engorgement, and subsequent airway constriction. Mast cells which contain histamine and other immunological mediators line the upper airways and are involved in the immunological response to foreign antigens and in the regulation of nasal patency.
Decongestants provide sympathetic stimulation and therefore, results in vasoconstriction of the vessels in the nose, decreased blood flow to the area, and a corresponding decrease in tissue size and thus an airway widening. They also directly stimulate beta cells on the airways resulting in bronchodilation and improved air flow. However, this also results in cardiac stimulation and increased heart rate, contractility, and blood pressure. This can be problematic in patients with cardiac disease.
Can result in angina, HTN, and worsening of CV disease

17. Topical Decongestants
Available in nasal drops or sprays
Local action
minimizes systemic absorption
Available OTC
Side Effects:
rhinitis medicamentosa (rebound vasodilation)
burning, stinging, sneezing, nasal dryness
Limit use to 2-3 days
Topical nasal decongestants are available in nasal drops and sprays. The topical application minimizes systemic absorption. Side effects include rhinitis medicamentosa which is rebound vasodilation (once the agents are discontinued) associated with prolonged use of topical agents. This can be very serious. Due to the risk of rhinitis medicamentosa, the use of topical decongestant products should be limited to 3-5 days. Other side effects include burning, stinging, sneezing, and nasal dryness.

18. NaCl (Saline) Drops (0.65%) , Baxters MOA: Dosage Forms: Dosage:
soothes irritated nasal tissues
moisturizes nasal mucosa
Dosage Forms:
commercial: sprays, drops
homemade solution: 1 tsp. salt / 7 oz. warm water
Dosage:
2-6 drops per nostril QID PRN nasal dryness or discomfort
Normal saline irrigation can soothe irritated nasal tissues and moisturize the nasal mucosa. Commercial saline nasal sprays are available, such as Afrin Saline Mist, Ayr Nasal Mist, and Ocean Nasal Spray. Two sprays in each nostril four times a day or as needed for nasal dryness is the typical dosage. For children under the age of six, the nasal drops may be easier to administer and the dosage is 2-6 drops per nostril QID PRN nasal dryness or discomfort. A homemade solution can be made using 1 teaspoon salt to every 7 ounces of warm water. A bulb syringe can be used to administer this solution to the nose.

19. Topical Decongestants
Again, note that phenylephrine has the shortest duration of action and oxymetazoline and xylometazoline have the longest.

20. Phenylephrine Nasal drop: 0.25%, 0.5% Adults: 2-3 drops q4h
6-12 y: 2-3 drops (0.25%) q4h
6m-6y: 1drop (0.25%) q4h

21. Naphazoline Nasal drop: 0.05% Adults : 2drops q3h
Children : not recommended
Lactation : not recommended
Caution in pregnancy, hyperthyroidism, diabetes, cardiac disease

22. Systemic Decongestants
Include
Pseudoephedrine
duration is 4-6 hours
Phenylpropanolamine (PPA)
phenylephrine
Effects on blood pressure, heart rate
PPA>Ephedrine>Pseudoephedrine

23. Systemic Decongestants
Compared to topical decongestants:
longer onset of action (no immediate relief)
longer duration of effect
no rebound vasodilation
no local irritation
Risks:
increases heart rate, contractility
can significantly increase BP
can worsen angina
Systemic decongestants are often used for congestion symptoms. They have a delayed onset of action, but they also have a longer duration of effect with no risk of rebound vasodilation and local irritation. However, these agents do have an increased side effects profile, including an increased heart rate and contractility, increased BP, and worsened angina.

24. Pseudoephedrine Tab. 30 mg / syrup: 30mg/5ml
Adults : 30-60mg q6-8 h max=240mg
Suggested oral doses for children are: 2 to 5 years, 15 mg three or four times daily; 6 to 12 years, 30 mg three or four times daily.

25. Pseudoephedrine
In the past, pseudoephedrine was frequently purchased and then used as an ingredient in the illegal manufacture of amphetamine drugs. Consequently, FDA has restricted the sale of cold medications containing pseudoephedrine to behind-the-counter. The FDA has also limited the amount of pseudoephedrine that an individual can purchase each month, and required stores to retain records for at least two years about who purchases this drug.

26. Drug interaction
Pseudoephedrine may cause a hypertensive crisis in patients receiving an MAOI

27. Decongestants
Phenylephrine is less effective than pseudoephedrine for treatment of rhinitis symptoms. Most studies suggest that 10 mg of phenylephrine (the dose commonly used in most cold products) is not more effective than placebo. Despite this lack of efficacy, phenylephrine remains a common component in many over-the-counter cold preparations.
Phenylpropanolamine, formerly a common ingredient in OTC cold remedies, has been associated with a small but significant risk of hemorrhagic stroke in women. As a result, the FDA in 2005 mandated that it be removed from all preparations sold in the US.

28. Adult cold Tablets
Acetaminophen 325, Phenylephrine 5 mg, Chlorpheniramine 2mg
2tabs every 4-6h (max. 12 tabs)

29. Systemic Decongestants
Overview of Side Effects:
>10%
CV: tachycardia, palpitations, arrhythmias
CNS: nervousness, transient stimulation, insomnia, excitability, dizziness, drowsiness
neuromuscular: tremor
1-10%
CNS: HA
GI: xerostomia, nausea
other: weakness, diaphoresis
<1%
respiratory: SOB, dyspnea
As a class, the side effects of these agents include tachycardia, palpitations, arrhythmias, nervousness, transient stimulation, insomnia, excitability, dizziness, tremor, and possibly drowsiness (unpredictable).
When used in combination products, these effects often offset the sedative side effects of the antihistamines.

30. Topical Nasal Decongestants (cont'd)
Adrenergics
Naphazoline
phenylephrine (Neo-Synephrine)
Intranasal steroids
beclomethasone dipropionate (Beconase, Vancenase)
flunisolide (Nasalide)
fluticasone (Flonase)

31. Nasal Decongestants: Drug Effects
Shrink engorged nasal mucous membranes
Relieve nasal stuffiness

32. Nasal Decongestants: Indications
Relief of nasal congestion associated with:
Acute or chronic rhinitis
Common cold
Sinusitis
Hay fever
Other allergies

33. Nasal Decongestants: Indications (cont'd)
May also be used to reduce swelling of the nasal passage and facilitate visualization of the nasal/pharyngeal membranes before surgery or diagnostic procedures

34. Nasal Decongestants: Side Effects
Adrenergics Steroids
Nervousness Local mucosal dryness
Insomnia and irritation
Palpitations
Tremors
(systemic effects due to adrenergic stimulation of the heart, blood vessels, and CNS)

35. Antitussives

36. Cough Physiology Cough reflex To remove secretions or foreign objects
Induces coughing and expectoration
Initiated by irritation of sensory receptors in the respiratory tract
To remove secretions or foreign objects

37. Two Basic Types of Cough
Productive cough
Congested, removes excessive secretions
Nonproductive cough
Dry cough

38. Coughing Most of the time, coughing is beneficial
Removes excessive secretions
Removes potentially harmful foreign substances
In some situations, coughing can be harmful, such as after hernia repair surgery

39. Antitussives: Definition
Drugs used to stop or reduce coughing
Opioid and nonopioid (narcotic and nonnarcotic)
Used only for nonproductive coughs!

40. Other drugs
Bronchodilators
Antihistamines
Local anesthetics

41. Antitussives: Mechanism of Action
Opioids
Suppress the cough reflex by acting on the cough center in the medulla
Examples:
Codeine
Hydrocodone
Dextromethorphan
Clobutinol

42. Codeine Use High abuse potential Consider drug interactions
narcotic analgesic
anti-tussive-direct central action in the medulla
High abuse potential
Schedule V
Consider drug interactions
CNS depressant

43. Codeine Adverse Effects: >10%: 1-10: Drowsiness, Constipation
CNS: dizziness, confusion, euphoria, malaise, headache, restlessness, CNS stimulation
Respiratory: SOB, dyspnea (use with caution in patients with respiratory disorders)
Skin: rash, urticaria
GI: xerostomia, anorexia, N/V
GU: decreased urination, ureteral spasm

44. Dextromethorphan HBr Tab 15 mg Drop 4mg/ ml Syrup 15 mg/5ml
For dry cough

45. Dextromethorphan
Dextromethorphan is an antitussive agent and, unlike the isomeric levorphanol, it has no analgesic or addictive properties.
The drug acts centrally and elevates the threshold for coughing. It is about equal to codeine in depressing the cough reflex. In therapeutic dosage dextromethorphan does not inhibit ciliary activity.
Dextromethorphan is rapidly absorbed from the gastrointestinal tract and exerts its effect in 15 to 30 minutes. The duration of action after oral administration is approximately three to six hours.

46. Dextromethorphan
Dextromethorphan may produce central excitement and mental confusion. Very high doses may produce respiratory depression. One case of toxic psychosis (hyperactivity, marked visual and auditory hallucinations) after ingestion of a single dose of 20 tablets (300 mg) of dextromethorphan has been reported.

47. Dextromethorphan (cautions)
Hepatic disease
Asthmatic
With MAOI (hallucination, delirium, hyperpyrexia)

48. Clobutinol HCl
Drop 60mg/ml
Injection 20mg/2ml
Tablets 40 mg

49. Clobutinol HCl (dosage)
Adults
30-40 drops or 1-2 tab tid
Children
1drop/kg tid
Contraindication
Epilepsy , pregnancy

50. Antitussives: Mechanism of Action (cont'd)
Nonopioids
Suppress the cough reflex by preventing the cough reflex from being stimulated
Examples:
benzonatate (Tessalon Perles)

51. Antitussives: Indications
Used to stop the cough reflex when the cough is nonproductive and/or harmful

52. Antitussives: Side Effects
Benzonatate
Dizziness, headache, sedation, nausea, and others
Dextromethorphan
Dizziness, drowsiness, nausea
Opioids
Sedation, nausea, vomiting, lightheadedness, constipation

53. Expectorants

54. Expectorants: Definition
Drugs that aid in the expectoration (removal) of mucus
Reduce the viscosity of secretions
Disintegrate and thin secretions

55. Expectorants: Mechanisms of Action
Direct stimulation
Reflex stimulation
Final result: thinner mucus that is easier to remove

56. Expectorants: Mechanism of Action (cont'd)
Reflex stimulation
Agent causes irritation of the GI tract
Loosening and thinning of respiratory tract secretions occur in response to this irritation
Example: guaifenesin

57. Expectorants: Mechanism of Action (cont'd)
Direct stimulation
The secretory glands are stimulated directly to increase their production of respiratory tract fluids
Examples: iodine-containing products such as iodinated glycerol and potassium iodide

58. Mucolytics
Bromhexine
NAC

59. Bromhexine Elexir: 4mg/5ml Inj. : 4mg/2ml Tab : 8mg
Dose: Adult 1-2 tabs (10-20 cc elexir) tid
5-10 years : 4mg qid
< 5 years : 4mg bid

60. Bromhexine Mechanism of action:
Bromhexine is an oral mucolytic agent with a low level of associated toxicity. Bromhexine acts on the mucus at the formative stages in the glands, within the mucus-secreting cells. Bromhexine disrupts the structure of acid mucopolysaccharide fibres in mucoid sputum and produces a less viscous mucus, which is easier to expectorate.
Contraindications
Bromhexine is contraindicated for use in patients with known hypersensitivity or idiosyncratic reaction to bromhexine hydrochloride (or any of the other ingredients in the product).

61. Bromhexine Precautions
Since mucolytics may disrupt the gastric mucosal barrier, bromhexine should be used with caution in patients with a history of gastric ulceration.

62. Bromhexine Use in pregnancy
Category A: Bromhexine has been taken by a large number of pregnant women and women of child bearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed.
Lactation
It is not known whether bromhexine is excreted in breast milk or whether it has a harmful effect on the breastfeeding infant. Therefore it is not recommended for breastfeeding mothers unless the potential benefits to the patient are weighed against the possible risk to the infant.
Adverse reactions
Gastrointestinal side effects may occur occasionally with bromhexine and a transient rise in serum aminotransferase values has been reported. Other reported adverse effects include headache, vertigo (dizziness), sweating and allergic reactions.

63. NAC
Inj : 200mg/ml
Tab : 200mg
Eff. Tab.: 600mg

64. NAC
Mucomyst is used for: Treatment of abnormal, sticky, or thick mucus secretions in various lung problems (eg, chronic emphysema, bronchitis, asthmatic bronchitis, pneumonia, during anesthesia, following surgery or various lung tests).

65. Guaifenesin
Helps loosen phlegm (mucus) and thin bronchial secretions to rid the bronchial passageways of bothersome mucus, drain bronchial tubes and make coughs more productive. Helps loosen phlegm and thin bronchial secretions in patients with stable chronic bronchitis.

66. Guaifenesin Syrup (100mg/5ml)
syrup - Adults and children 12 years of age and older: Two to four teaspoonfuls (200 mg to 400 mg) every four hours, not to exceed 2400 mg (24 teaspoonfuls) in 24 hours.
Children 6 years to under 12 years of age: One to two teaspoonfuls (100 mg to 200 mg) every four hours, not to exceed 1200 mg (12 teaspoonfuls) in 24 hours.
Children 2 years to under 6 years of age: ½ to 1 teaspoonful (50 mg to 100 mg) every four hours, not to exceed 600 mg (6 teaspoonfuls) in 24 hours.
Children 6 mo. to under 2 years of age: A common dosage is 1/4 to ½ teaspoonful (25 mg to 50 mg) every four hours, not to exceed 300 mg (3 teaspoonfuls) in 24 hours.

67. Expectorant syrup Each 5 ml contains: Guaifenesin 100 mg
Chlorpheniramine 2mg
Phenylpropanolamine 5mg

68. Expectorant codeine syrup
Each 5 ml contains:
Guaifenesin 100 mg
Chlorpheniramine 2mg
Phenylpropanolamine 12.5mg
Codeine phosphate 10 mg

69. Expectorants: Common Side Effects
guaifenesin
Nausea, vomiting, gastric irritation
iodinated glycerol
GI irritation, rash, enlarged thyroid gland
potassium iodide
Iodism, nausea, vomiting, taste perversion

70. Antihistamines

71. Histamine and the Immune Response

72. Histamine release IgE – Mediated Some drugs (morphine,…)
Nerve stimulation

73. receptors History in 1972 H1 and H2, In 1980s H3 H1 (PLC, NO)
H2 (activation of AC) H3 H4

74. Histamine Immediate pharmacologic effects: pruritus (H1)
 vascular permeability/vasodilatation (H1)
smooth muscle contraction (H1)
gastric acid secretion (H2)

75. Allergic Diseases: Allergic rhinitis (hay fever)
Atopic dermatitis (eczema)
Urticaria
Asthma
Anaphylaxis

76. Allergic Rhinitis: Paroxysms of sneezing
Itchy eyes, nose, pharynx, palate
Watery (nonpurulent) rhinorrhea
Nasal congestion
Seasonal or perennial symptoms
Associated atopy
Family history

78. Representative 1st generation Antihistamines
Ethylenediamines: triplennamine, pyriliamine, antazoline
Ethanolamines: carbinoxamine, diphenhydramine, doxylamine, dimenhydrinate
Alkylamines: chlorpheniramine, brompheniramine, triprolidine
Piperazines: cyclizine, meclizine, hydroxyzine
Piperadines: cyproheptadine
Phenothiazines: promethazine

79. Drug sedation anticholinergic marked +++ moderate + slight _
dimenhydrinate
marked
+++
diphenhydramine
promethazine
hydroxyzine
cyproheptadine
moderate +
chlorpheniramine
slight
Loratadine _

80. selection anticholinergic effects are not good for Constipation
Glucoma
Prostat hypertrophy
GERD
Alzeimer
Erectile dysfunction

81. Pharmacological activity
Sedation
Anticholinergic
Antiparkinson
Alpha- blocker
Local anesth.
antiserotonin

82. Indications Allergy Pruritis Antianxiety Cough
Motion sickness (Dim. Cyc. Mec. Pro.)
Parkinson (diph.)
Insomnia (Diph.)
Vomiting (Pro. Diph.)
Anorexia (cancer chem., cystic fibrosis)

83. Second Generation Antihistamines
Terfenadine
Astemizole
Fexofenadine (60mg bid)
Loratadine
Desloratadine (5mg once)
Cetirizine
Ebastine (10-20 mg)
Azelastine (2sprays per nostril)

84. Drug
Duration of action (hr)
chlorpheniramine 6
promethaine
4-6
Terfenadine
12-24
Astemizole
Fexofenadine
Loratadine 24
Desloratadine
Cetirizine
Ebastine
Azelastine

85. Second Generation Antihistamines
Less sedation
Less anticholinergic
Ter and Ast cause arrhythmia
Attention to drug interaction

86. Second Generation Antihistamines
Cetirizine (Zyrtec): 10 mg daily
Age 6-adult; contraindication: hypersensitivity to cetirizine or hydroxyzine
Hydroxyzine metabolite; Renal excretion
Loratadine (Claritin): 5-10 mg daily
Age 6-adult; contraindication: hypersensitivity
Fexofenadine (Allegra): 60 mg b.i.d
Terfenadine metabolite
Age 12-adult; contraindication: hypersensitivity

87. Terfenadine
RARE CASES OF DEATH, CARDIAC ARREST, TORSADES DE POINTES, AND OTHER VENTRICULAR ARRHYTHMIAS.

88. Terfenadine
TERFENADINE IS CONTRAINDICATED IN PATIENTS TAKING KETOCONAZOLE, ITRACONAZOLE, OR ERYTHROMYCIN, CLARITHROMYCIN, OR TROLEANDOMYCIN, AND IN PATIENTS WITH SIGNIFICANT HEPATIC DYSFUNCTION.
DO NOT EXCEED RECOMMENDED DOSE.
IN SOME CASES, SEVERE ARRHYTHMIAS HAVE BEEN PRECEDED BY EPISODES OF SYNCOPE, SYNCOPE IN PATIENTS RECEIVING TERFENADINE SHOULD LEAD TO DISCONTINUATION OF TREATMENT AND FULL EVALUATION OF POTENTIAL ARRHYTHMIAS.

89. Cardiotoxicity risks
There is an increased risk of cardiac toxic effects from the use of any H1-antihistamine that prolongs the QT interval in women and in patients with preexisting organic heart disease (e.g., ischemia or cardiomyopathy), cardiac arrhythmias (congenital or acquired, including bradycardia), or electrolyte imbalance (i.e., hypokalemia, hypocalcemia, and hypomagnesemia). Also at an increased risk are persons who take grapefruit juice.

90. Loratadine
Adults and children 6 years of age and over: The recommended dose is one 10 mg tablet or 2 teaspoonfuls (10 mg) of syrup once daily.
Children 2 to 5 years of age: The recommended dose of Syrup is 5 mg (1 teaspoonful) once daily. In adults and children 6 years of age and over with liver failure or renal insufficiency (GFR < 30 mL/min), the starting dose should be 10 mg (one tablet or two teaspoonfuls) every other day. In children 2 to 5 years of age with liver failure or renal insufficiency, the starting dose should be 5 mg (one teaspoonful) every other day.

91. DRUG INTERACTIONS
Loratadine (10 mg once daily) has been coadministered with therapeutic doses of erythromycin, cimetidine, and ketoconazole in controlled clinical pharmacology studies in adult volunteers. Although increased plasma concentrations (AUC 0-24 hrs) of loratadine and/or descarboethoxyloratadine were observed There were no significant effects on QTc intervals, and no reports of sedation or syncope.

92. Second Generation Antihistamines
Desloratadine (Clarinex): 5 mg daily
High potency (Kd = 7 nM) and long T1/2 (27 hours)
Age 6-adult; contraindication: hypersensitivity

93. Cetirizine
Active metabolite of hydroxyzin
Less sedative than 1st gen. Antihistamines
Slightly more sedative than fexofenadine and loratadine

94. cetirizine
Adults and Children 12 Years and Older: The initial dose of cetirizine is 5 or 10 mg per day with or without food.
Children 6 to 11 Years: The recommended initial dose of cetirizine in children aged 6 to 11 years is 5 or 10 mg once daily depending on symptom severity.
Children 2 to 5 Years: mg (½ teaspoon) once daily. The dosage in this age group can be increased to a maximum dose of 5 mg per day given as 1 teaspoon (5 mg) once daily, or as ½ teaspoon (2.5 mg) given every 12 hours.
Children 6 months to <2 years: mg (1/2 teaspoon) once daily.

95. cetirizine
Dose Adjustment for Renal and Hepatic Impairment: In patients 12 years of age and older a dose of 5 mg once daily is recommended. Similarly, pediatric patients aged 6 to 11 years with impaired renal or hepatic function should use the lower recommended dose. below the age of 6 years with impaired renal or hepatic function, its use in this impaired patient population is not recommended.
Dose Adjustment for Geriatric Patients: In patients 77 years of age and older, a dose of 5 mg once daily is recommended.

96. DRUG INTERACTIONS
Drug-Drug Interactions: No clinically significant drug interactions have been found with theophylline at a low dose, azithromycin, pseudoephedrine, ketoconazole, or erythromycin.

97. Side effect
The most common adverse reaction in patients aged 12 years and older that occurred more frequently on cetirizine than placebo was somnolence. The incidence of somnolence associated with cetirizine was dose related, 6% in placebo, 11% at 5 mg and 14% at 10 mg. Discontinuations due to somnolence for cetirizine were uncommon (1.0% on cetirizine vs. 0.6% on placebo). Fatigue and dry mouth also appeared to be treatment-related adverse reactions.

98. Fexofenadine Is not cardiotoxic Is non-sedative
Is widely used in combination with pseudoephedrine

99. Doxepine (sinequan) Is tolerated better in depressed patients
Is used for treating intractable pruritus
In non-depressed even 25 mg causes confusion and disorientation

100. FDA category 1st gen. Chlorpheniramine (B) Diphenhydramine (B )
Hydroxyzin (C )
Ketotifen (C )
2nd gen.
Fexofenadine (C )
Loratadine (B)
Desloratadine (C )
Cetirizine (B )

101. Antihistamines in pregnancy
Loratadine and cetrizine are the best and diphenhydramine is an alternative.

102. Antihistamines and hepatic failure
Diphenhydramine, doxepine , hydroxyzin, cetirizine, levocetirizine, loratadine, desloratadine and ebastine need dose adjustment.

103. Antihistamines and renal failure
Cetirizine, levocetirizine, desloratadine, fexofenadine and ebastine need dose adjustment.

104. Elderly 2nd generation is prefered due to Less sedation
Less anticholinergic
Less alpha-blockade

105. Mast cell stabilizers
Cromolyn Na (cap. for inhal., opht. drop, nasal spray)
Nedocromil
Ketotifen
corticostroids

106. KETOTIFEN Zaditen, ketof Antihistamine and mast cell stabilizer
In most countries is used topically

107. Nasal Topical Antihistamines
Azelastine (Astelin): 2 sprays/side b.i.d.
Ages 12-Adult
Adverse reactions: bitter taste (19% vs 0.6%)