Antihistamines Flashcards
What medical conditions are antihistamines used for?
Allergic Rhinitis Eczema Urticaria Hives GERD/PUD Insomnia Motion Sickness
What is histamine?
Vasoactive amine derived from the amino acid histadine
Where is histamine stored/found?
MAST Cells and BASOPHILS = allergic reactions
CNS = Neurotransmitter
Gut = regulates gastric acid production
Where are H1 receptors located?
Bronchial Smooth muscle
CNS
Endothelium
Cardiac muscle
What is the action of H1 receptors?
Sleep wake Cycle Learning Memory Stimulates nerve endings Bronchoconstriction Vasodilation of blood vessels Contraction of smooth muscle
Where are H2 receptors located?
Parietal cells of stomach
Cardiac muscle
CNS
What is the action of H2 receptors?
gastric acid production
Where are H3 receptors located?
CNS
Peripheral tissue
What is the action of H3 receptors?
Modulation of neurotransmitter release (ACh, DA, GABA, NE, 5-HT)
Where are H4 receptors located?
Basophils Bone marrow Small intestine Colon Spleen Thymus
What is the action of H4 receptors?
Facilitates mast cell chemotaxis
What two histamine receptors have drug therapy?
H1
H2
What are the cardiovascular effects of histamine?
Mast cells present in normal cardiac tissue and greatly present in diseased hearts
Enhances influx of Ca2+ into cardiac myocytes causing:
Increased contractility
Tachycardia
Hypotension secondary to vasodilation
What causes histamine to be released from mast cells on occasion?
mast cell injury like morphine use
What is the role of histamine in immune modulation?
Vasodilation causing capillaries to become permeable allowing for WBC to move into site of “threat”
What symptoms occur from histamine release in immune modulation?
Facial Flushing and Edema
Hives (urticaria) = separation of endothelial cells
Induces fluid secretion causing runny nose, water eyes
What is gastric acid secretion mediates by in parietal cells?
Binding of:
Histamine
Gastrin
Acetylcholine
This causes increase in cAMP and Ca2+ influx allowing HCl to be secreted
What does histamine do in the CNS?
It is considered a neurotransmitter
Modulates: ACh release = learning and cognition Emotional memory acquisition Alertness = sleep-wake cycle Serotonin = mood Food intake = suppression of appetite Emesis center = nausea/vomiting
What does an antihistamine do to H1 receptors?
Bronchodilation
Constipation
Anti-itch, reduce pain
Reduced inflammatory/allergic response
What does an antihistamine do to H2 receptors?
Suppression of gastric acid production
What are the histamine antagonists?
Epinephrine
Cromolyn sodium
Antihistamines = H1 and H2 blockers
What is epinephrine?
works quickly
smooth muscle relaxation
Stimulates alpha and beta receptors
What is Cromolyn Sodium?
works over several weeks
Stabilizes mast cells to prevent degranulation
What do H1 blockers treat?
Allergies
Insomnia
Motion sickness
What do H2 blockers treat?
GERD/PUD
What are first generation H1 antihistamines?
Have poor receptor selectivity and often interact with other receptors of other amines having antimuscarinic, anti-alpha adrenergic, and antiserotonin effects
Highly lipophillic and will cross the BBB with histaminergic transmission causing many ADRs
What first generation H1 antihistamines have severe anticholinergic effects?
Doxylamine
Diphenhydramine
Promethazine
Which first generation H1 antihistamines have mild anticholinergic effects?
Cyclizine
Meclizine
Hydroxyzine HCl
Cyproheptadine
What is Doxylamine and Diphenhydramine?
Use: Insomnia, allergies
ADRs: highly sedating, large doses can cause arrhythmias (QT prolongation)
AVOID USE IN ELDERS
OTC
What is Cyclizine?
OTC
Use: motion sickness, vertigo
Mildly sedating
What is Meclizine?
OTC, Rx
Use: motion sickness, vertigo
Mildly sedating
What is Chlorpheniramine and Brompheniramine?
OTC
Use: allergies
Moderately sedating, possible paradoxical CNS stimulation
Often found in combo with “cold” products
AVOID USE IN ELDERLY
What is Hydroxyzine HCl?
Use: allergies, urticaria
Mild-moderate sedation
What is Hydroxizine PAMoate?
Use: insomnia, anxiety
Mild-moderate sedation
What is Promethazine?
Use: anti-emetic
Highly sedating, alpha-blockade causing hypotension, dystonic reactions, akathisia
What is Cyproheptadine?
Use: weight gain
5-HT blockade
What are the ADRs of first generation H1 antihistamines?
Cholinergic: dry mouth, urinary retention, sinus tachy
Alpha-adrenergic: hypotension, dizziness, reflex tachy
Serotonin: increased appetite
Histamine 1: increased sedation, decreased cognitive and psychomotor performance, increased appetite
What are the DDIs of first generation H1 antihistamines?
Majority are metabolized via 2D6 and 3A4
Metoprolol
TCAs
Tramadol
AADs
Avoid with alcohol, other hypnotics and/or benzos, tricyclic antidepressants, acetylcholinterase inhibitors, and MAO inhibitors
What are second generation H1 antihistamines use to treat?
Allergic symptoms
What are second generation H1 antihistamines?
Highly selective for H1 receptors with NO anticholinergic effects
Minimally or non-sedating due to limited penetration of BBB = preferred in elders
Rapid onset of action
Longer duration of action = once to twice daily dosing
What is Azelastine and Olopatidine?
Nasal Spray
Rx only
Local application to nose is associated with less sytemic side effects
Local irritation can occur like nosebleeds and bitter taste or smell
Avoid use if any preexisting damage to the nasal passage
What is Fexofenadine?
Oral, OTC Highest safety profile Not metabolized Excreted in feces DDIs: avoid grapefruit, orange, and apple juice = separate by 4 hours Not metabolized via CYP450
What is Cetirizine?
Oral, OTC
Most somnolence
Active metabolite of hydroxyzine
Not metabolized by CYP450 but is P glycoprotein substrate
DDIs: grapefruit juice and sedative drugs
What is Levocetirizine?
Oral, OTC
Active metabolite of cetirizine
Not metabolized by CYP450 but is P glycoprotein substrate
DDIs: grapefruit juice and sedative drugs
What is loratidine?
Oral, OTC
Metabolized via 3A4, 2D6
Check for 3A4 inhibitors
DDIs: Erythromycin, Ketoconazole, Clarithromycin, Cimetidine, and grapefruite juice
What is Desloratidine?
Oral, Rx
Less likely to cause somnolence
Active metabolite of loratidine
DDIs: Erythromycin, Ketoconazole, Clarithromycin, Cimetidine, and grapefruite juice
What are the ADRs of second generation H1 antihistamines?
Somnolence at higher doses
Constipation
Headache
No significant cardiac effects
Which two second generation H1 antihistamines have the highest risk of somnolence?
Cetirizine
Levocetirizine
What is the MOA of H2 receptor antagonists?
Reversibly decrease fasting and food stimulated acid secretion by inhibiting histamine on the histamine 2 receptor of the parietal cell
What is H2 receptor antagonists used to treat?
Mild-moderate, infrequent, episodic heartburn
Good for on-demand, meal provoked symptoms
What are the characteristics of H2 receptor antagonists?
All available are equally efficacious
All are available both OTC and prescription = OTC is usually 1/2 of the Rx
Well absorbed; absorption may be delayed by administration of anatacid but not by food
What are the available H2 receptor antagonist?
Ranitidine
Cimetidine
Nizatidine
Famotidine
What are the ADRs of H2 receptor antagonists?
Well tolerated
CNS effects usually; often increased in the elderly
Headache
Dizziness
Fatigue
Confusion
Dose related gynecomastia occurs with Cimetidine
Tolerance has been reported with prolonged daily use
What is the limit for self-treatment with H2 receptor antagonists?
limit to no more than two times a day for no more than 2 weeks
What are the DDIs of H2 receptor antagonists?
Ketoconazole Itraconazole Protease Inhibitors (atazanavir) Calcium Carbonate Iron Salts
What is the ADRs and DDI’s of Cimetidine?
ADR: Dose related gynecomastia
DDI: Cyclosporine, theophylline, warfarin, phenytoin, amiodarone, antidepressants
