Antihistamines

Question 0

Histamine distribution

Answer 0

Present in practically all tissues, especially high in skin, lungs, and GI tract, low content in plasma

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

Question 2

Histamine

Synthesis/storage and release

Answer 2

Synthesis/storage: mast cells and basophils, produced by neurons; release: allergic, nonallergic

Question 3

Histamine receptors: H1

Answer 3

• Vasodilation: skin of the face and upper body, extensive: can cause hypotension
• Increased capillary permeability: edema
• Bronchoconstriction: does not cause asthma attack
• CNS effects: Role in cognition, memory, and sleep-waking cycles
• Other: itching, pain, secretion of mucus

Question 4

H2 receptors

Answer 4

Secretion of gastric acid, act directly on parietal cells to promote acid release, dominant role in acid release

Question 5

Histamine antagonists/antihistamines

Answer 5

Act primarily on H1 and H2 receptors; used primarily for two pathologic states: allergic disorders, peptic ulcer disease

Question 6

Allergic responses

Answer 6

Mediated by histamine and other compounds: prostaglandins, leukotrienes, tryptase

Question 7

Mild allergic responses

Answer 7

Caused largely by histamine acting at H1 receptors
-Rhinitis, itching, localized edema, hay fever, mild transfusion reaction, acute urticaria; usually responsive to antihistamine therapy

Question 8

Severe allergic responses

Answer 8

Anaphylaxis; anaphylactic shock: bronchoconstriction, hypotension, edema of the glottis
-Histamine plays a minor role, leukotrienes are the principal mediators, antihistamines are of little use in treatment, epinephrine is the drug of choice

Question 9

Antihistamine: H1 antagonists

Answer 9

Produce selective blockade of H1 receptors, used for treatment of mild allergic disorders

Question 10

Antihistamine: H2 antagonists

Answer 10

Produce selective blockade of H2 receptors, used for treatment of gastric and duodenal ulcers, not used for treatment of allergies

Question 11

H1 Antagonists

Answer 11

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

Question 12

H1 Antagonists: Pharmacologic effects

Answer 12

Peripheral effects: reduce localized flushing, reduce itching and pain
Effects on CNS:
-Therapeutic dose: CNS depression; second generation negligible CNS depression
Overdose: CNS stimulation, convulsions, very young children especially sensitive to CNS stimulation

Question 13

H1 Antagonists: Therapeutic uses

Answer 13

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

Question 14

H1 Antagonists: Adverse effects

Answer 14

Sedation (less with second and third generation); nonsedative CNS effects: dizziness, fatigue, coordination problems, confusion;
GI effects: nausea, vomiting, loss of appetite, constipation;
Anticholinergic effects: weak atropine-like effects
-Severe respiratory depression, severe local tissue injury, cardiac dysrhythmias (rare)

Question 15

H1 Antagonists: Drug interactions

Answer 15

CNS depressants; use of pregnancy and lactation

-Acute toxicity: large margin of safety, widespread availability of drugs, CNS and anticholinergic reactions

Question 16

High risk patients

Answer 16

Antihistamines contraindicated during: 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