Lehne Chapter 70

Question 1

Histamine

Answer 1

Endogenous compound​

Found in specialized cells​

Important role in:​

Allergic reaction​

Regulation of gastric acid secretion​

Histamine use limited to diagnostic procedures
Distribution​

Present in practically all tissues​

Especially high in skin, lungs, and gastrointestinal (GI) tract​

Low content in plasma
Synthesis/storage​

Mast cells and basophils​

Produced by neurons​

Release​

Allergic: Allergic release of histamine requires prior exposure to the allergen; an allergic reaction cannot occur during initial allergen exposure.​

Nonallergic: Several agents (certain drugs, radiocontrast media, plasma expanders) can act directly on mast cells to trigger histamine release. With these agents, no prior sensitization is needed. Cell injury can also cause direct release.

Question 2

H1 Receptors

Answer 2

Vasodilation​

Skin of the face and upper body​

Extensive vasodilation can cause hypotension​

Increased capillary permeability​

Edema​

Bronchoconstriction​

Not the cause of asthma attack​

CNS effects​

Role in cognition, memory, and sleep-waking cycles​

Other​

Itching, pain, secretion of mucus

Question 3

H2 Receptors

Answer 3

Secretion of gastric acid​

Act directly on parietal cells to promote acid release​

Dominant role in acid release

Question 4

Role of Histamine in ​

Allergic Response

Answer 4

Mild allergy​

Rhinitis, itching, localized edema are caused largely by histamine, acting at H1 receptors​

Severe anaphylactic reaction​

Anaphylactic shock: Bronchoconstriction, hypotension, and edema of the glottis​

Histamine plays a minor role​

Leukotrienes: Principal mediators​

Antihistamines are little help as treatment​

Epinephrine is the drug of choice

Question 5

H1 antagonists

Answer 5

Produce selective blockade of H1 receptors​

Used for treatment of mild allergic disorders
H1 antagonists are divided into two major groups:​

First-generation H1 antagonists (highly sedating)​

Second-generation H1 antagonists​

Mechanism of action​

Block the actions of histamine at H1 receptors​

Do not block H2 receptors​

Some bind to muscarinic receptors
Pharmacologic effects​

Peripheral effects​

Reduce localized flushing​

Reduce itching and pain​

Effects on the CNS​

Therapeutic dose: CNS depression​

Second-generation negligible CNS depression​

Overdose​

CNS stimulation​

Convulsions​

Very young children especially sensitive to CNS stimulation
Therapeutic uses​

Mild allergy​

Severe allergy ​

Adjunct only; benefits may be limited​

Motion sickness​

Promethazine, dimenhydrinate​

Insomnia​

Common cold​

May decrease rhinorrhea through anticholinergic properties, not H1 blockade
Adverse effects​

Sedation​

Less with second and third generation​

Nonsedative CNS effects​

Dizziness, fatigue, coordination problems, confusion​

GI effects​

Can cause nausea, vomiting, loss of appetite, constipation (give with food)​

Anticholinergic effects​

Weak atropine-like effects
Severe respiratory depression​

Severe local tissue injury
Drug interactions​

CNS depressants​

Use during pregnancy and lactation​

Acute toxicity​

Large margin of safety​

Widespread availability of drugs​

CNS and anticholinergic reactions: Dilated pupils, flushed face, hyperpyrexia, tachycardia, dry mouth, urinary retention ​

Children: CNS excitation​

Extreme cases: Coma, cardiovascular collapse, death
Treatment​

No specific antidote to antihistamine poisoning​

Treatment directed at drug removal and managing symptoms​

Activated charcoal​

Cathartic​

Convulsions: IV benzodiazepines (lorazepam, midazolam)​

Hyperthermia: Ice packs or sponge baths

Question 6

H2 antagonists

Answer 6

Produce selective blockade of H2 receptors​

Used for treatment of gastric and duodenal ulcers​

Not used for treatment of allergies

Question 7

High-Risk Patients

Answer 7

Antihistamines contraindicated in: ​

Third trimester of pregnancy​

Nursing mothers​

Newborn infants​

Use antihistamines with caution in:​

Young children​

Older adults​

Patients whose conditions may be aggravated by muscarinic blockade

Question 8

H1 Antagonists: Second Generation

Answer 8

Second generation​

Produce much less sedation than first-generation agents​

Cross the blood-brain barrier poorly​

Have a low affinity for H1 receptors of the CNS​

Largely devoid of anticholinergic actions​

​Second-generation H1 antagonists available over the counter (OTC)​

Cetirizine​

Fenofexadine​

Loratadine

Question 9

Fexofenadine [Allegra, Allegra Allergy, Allegra ODT]

Answer 9

Uses: Oral therapy of seasonal allergic rhinitis and for chronic idiopathic urticaria​

Of second-generation antihistamines, offers best combination of efficacy and safety​

Use with caution in patients with renal impairment​

Do not take with fruit juice

Question 10

Cetirizine [Zyrtec]

Answer 10

Uses: Allergic rhinitis and chronic idiopathic urticaria​

Food delays absorption​

More sedating than other second-generation antihistamines but less sedating than first-generation drugs

Question 11

Levocetirizine [Xyzal]

Answer 11

Uses: Allergic rhinitis and chronic idiopathic urticaria​

More sedating than other second-generation antihistamines but less sedating than first-generation agents​

Most common side effects: Drowsiness, fatigue, muscle weakness, dry mouth​

Avoid alcohol and other CNS depressants

Question 12

Loratadine [Claritin]

Answer 12

Use: Seasonal allergic rhinitis​

Generally well tolerated​

Food delays absorption​

Use with caution in patients with significant hepatic and renal impairment

Question 13

Desloratadine [Clarinex]

Answer 13

Uses: Seasonal allergic rhinitis, perennial allergic rhinitis, and chronic idiopathic urticaria