antihistamines/flu

• Histamine

  A locally acting compound with prominent and varied effects
• Effects of histamine

  • In the vascular system: dilates small blood vessels and increases capillary permeability
  • In the bronchi: produces constriction of smooth muscle
  • In the stomach: stimulates secretion of acid
  • In the central nervous system: acts as a neurotransmitter
• Clinical use of histamine is limited to diagnostic procedures
• Allergic disorders and peptic ulcer disease

  Pathologic states involving histamine
• Histamine is present in practically all tissues, with especially high levels in the skin, lungs, and the gastrointestinal (GI) tract. The histamine content of plasma is low.
• Mast cells and basophils

  Cells that synthesize and store histamine in the periphery
• Neurons in the posterior hypothalamus

  Cells that produce histamine in the central nervous system
• Allergic release of histamine


  1. Production of IgE antibodies

  2. Attachment of antibodies to mast cells and basophils

  3. Exposure to allergen

  4. Histamine release
• Allergic reactions can also be triggered by certain drugs, radiocontrast media, plasma expanders, and cell injury without prior sensitization
• H1 stimulation

  • Causes vasodilation of the skin, face, and upper body
  • Can cause hypotension from extensive vasodilation
  • Increases capillary permeability, causing edema
  • Can induce bronchial constriction, but is not the cause of bronchoconstriction in asthma
  • Plays a role in sleep, cognition, and memory
  • Causes itching, pain, and secretion of mucous
• H2 receptors

  Activation leads to secretion of gastric acid
• Allergic reactions are mediated by histamine and other compounds like prostaglandins, leukotrienes, and tryptase. The intensity of the reaction depends on which mediator is involved.
• Mild allergic conditions like hay fever, acute urticaria, and mild transfusion reactions are generally responsive to antihistamine therapy.
• H1 antagonists

  First-generation: highly sedating

  Second-generation: do not tend to cause sedation
• Therapeutic effects of H1 antagonists

  • Prevent dilation of arterioles and venules in skin, reducing flushing

  Prevent increased capillary permeability, reducing edema

  Reduce itching and pain by blocking histamine at sensory nerves

  Suppress mucus secretion by blocking H1 receptors in mucous membranes
• CNS effects of H1 antagonists

  At therapeutic doses: CNS depression (slowed reaction time, diminished alertness, drowsiness)

  Overdose: CNS stimulation, seizures
• Therapeutic uses of H1 antagonists

  • Mild allergies

  Urticaria associated with mild transfusion reactions

  Allergic conjunctivitis

  Motion sickness (dimenhydrinate)

  Insomnia (diphenhydramine)
• Adverse effects of H1 antagonists

  • Sedation (less with second and third generation)

  Dizziness, incoordination, confusional states, fatigue (especially in older patients)

  Anticholinergic effects (second generation least)
• Alcohol and other CNS depressants

  Can intensify the depressant effects of H1 antagonists
• The safety of antihistamines in pregnancy is unknown, with reports of fetal malformation but no proven direct involvement. They should be used only when clearly necessary and the benefits outweigh the potential risks.
• Antihistamines can be excreted in breast milk and should be avoided by breastfeeding women, except for small occasional doses which are unlikely to cause harm.
• Categories of first-generation antihistamines

  • Ethanolamines (e.g. diphenhydramine)

  Phenothiazines (e.g. promethazine)

  Alkylamines (e.g. chlorpheniramine)

  Others
• Differences between first-generation antihistamine categories

  • Ethanolamines and phenothiazines cause more CNS depression

  Alkylamines cause less CNS depression
• First-generation antihistamines have significant anticholinergic properties, causing side effects like dry mouth and urinary hesitancy.
• Second-generation antihistamines

  • Cause much less sedation than first-generation

  Have low affinity for CNS H1 receptors

  Have low synergism with alcohol and other CNS depressants

  Largely devoid of anticholinergic effects
• Fexofenadine (Allegra)

  A second-generation antihistamine with good efficacy and safety profile
• Certain fruit juices can reduce fexofenadine absorption, so patients should avoid them around dosing times.
• Allergic rhinitis

  An inflammatory disorder of the upper airway causing symptoms like sneezing, rhinorrhea, pruritus, and nasal congestion
• Forms of allergic rhinitis

  • Seasonal (hay fever)

  Perennial (nonseasonal) - indoor allergens, dust mites, pet dander
• Drug classes used to treat allergic rhinitis

  • Glucocorticoids (intranasal)

  Antihistamines (oral and intranasal)

  Sympathomimetics (oral and intranasal)
• Intranasal glucocorticoids

  • Most effective drugs for prevention and treatment of allergic rhinitis

  Antiinflammatory actions prevent/suppress major symptoms in 90% of patients

  Adverse effects include drying of nasal mucosa, burning/itching, sore throat, epistaxis, headache, and rare systemic effects like adrenal suppression and slowed growth in children
• Oral antihistamines

  First-line drugs for mild to moderate allergic rhinitis, more effective when taken prophylactically
• Intranasal antihistamines (azelastine, olopatadine)


  Can cause somnolence, nosebleeds, headaches, and unpleasant taste
• Intranasal cromolyn

  Extremely safe but only moderately effective for allergic rhinitis, best for prophylaxis
• Sympathomimetics

  • Reduce nasal congestion by vasoconstriction, but do not affect other rhinitis symptoms

  Topical agents act faster and are more effective than oral, but have higher risk of rebound congestion with prolonged use
• Phenylephrine is one of the most widely used nasal decongestants, administered topically and orally.
• Sympathomimetics

  Only relieve congestion in patients with allergic rhinitis, do not reduce rhinorrhea, sneezing, or itching
• Sympathomimetics

  • Can reduce congestion associated with sinusitis and colds
• Adverse effects of sympathomimetics

  • Rebound congestion when used more than a few days
  • Central nervous stimulation including restlessness, irritability, anxiety, and insomnia
  • Generalized vasoconstriction which is most likely with oral drugs
  • Pseudoephedrine is associated with abuse
• All drugs containing pseudoephedrine must be placed behind the counter and patient must have ID and sign a log