Review Question - QID 210364

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H1 Blockers 2nd generation Toxicity QID: 210364 (M1.OMB.18.2)

QID 210364 (Type "210364" in App Search)

A 22-year-old woman presents to her primary care physician in April for seasonal allergies. She has suffered from seasonal allergies for the past 2 years and takes diphenhydramine as needed when her symptoms worsen. She has not yet seen a physician for her allergies. She reports that diphenhydramine has been helpful in controlling her symptoms, but she does not like feeling drowsy from the medication. Her past medical history is also notable for well-controlled asthma. She uses an albuterol inhaler on an as-needed basis. She smokes marijuana daily. Her temperature is 99.2°F (37.3°C), blood pressure is 120/70 mmHg, pulse is 76/min, and respirations are 16/min. She has a prominent nasal crease. Her nasal turbinates are boggy and bluish-gray. She has copious thin and watery nasal mucus. The physician suggests replacing diphenhydramine with fexofenadine to improve her drowsiness. What characteristic of fexodenadine allows it to be less sedating than diphenhydramine?

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Alpha-adrenergic antagonism

7/175

Beta-adrenergic antagonism

4/175

Muscarinic antagonism

16%

28/175

Relative lipophobicity

62%

108/175

Serotonergic antagonism

11%

19/175

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The patient in this vignette presents with drowsiness associated with antihistamine treatment for allergic rhinitis. Fexofenadine is a second-generation histamine (H1) blocker that is relatively lipophobic, leading to decreased entry into the central nervous system (CNS) and less sedation.

Histamine blockers are commonly used medications for allergies. First-generation histamine blockers often cause sedation because they are able to cross the blood-brain barrier due to their lipophilicity. They are also known to have action at alpha-adrenergic and/or serotonin receptors. Second-generation histamine blockers are often used to replace first-generation histamine blockers because they are less sedating due to their decreased entry in to the CNS secondary to their relative lipophobicity. Additionally, they are more selective for peripheral histamine receptors and have a lower binding affinity for cholinergic, adrenergic, and serotonergic receptors.

Incorrect Answers:
Answer 1: Alpha-adrenergic antagonism is a characteristic of some first-generation histamine blockers. As a result, these medications may cause hypotension.

Answer 2: Beta-adrenergic antagonism is not a major characteristic of first- or second-generation histamine blockers.

Answer 3: Muscarinic antagonism is a characteristic of some first-generation histamine blockers. For this reason, certain first-generation histamine receptors can be used to treat extrapyramidal symptoms such as acute dystonia. They are also associated with anticholinergic side effects including tachycardia, dry skin, urinary retention, dilated pupils, and ileus.

Answer 5: Serotonergic antagonism is a characteristic of some first-generation histamine blockers such as cyproheptadine. For this reason, cyproheptadine is used to treat serotonin syndrome.

Bullet Summary:
Second-generation antihistamine medications are more lipophobic than first-generation antihistamines, leading to decreased entry into the CNS and therefore decreased sedation.

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