Antihistamine Flashcards
First Generation H1 Antihistamine
- Used: treatment allergic symptoms, motion sickness (n/v), and Insomnia
- Available OTC and Rx
- Poor Receptor selectivity (often interact with other receptors of other amines)
Antimuscarinic, anti-alpha adrenergic, and antiserotonin effect - HIGHLY Lipophilic (crosses BBB to interfere with histaminergic transmission) leads to many ADEs limiting use
- Onset: 2-3 hrs
Dosed multiple times a day (not long lasting)
First Generation H1 Antihistamine Agents
Doxylamine Dephenhydramine Cyclizine Meclizine Chlorpheniramine Brompheniramine Hydroxyzine HCL Hydroxyzine PAMoate Promethazine Cyproheptadine
Doxylamine & Diphenhydramine
OTC
Used: Insomnia, Allergies
Highly sedating, large doses can cause arrhythmias (QT prolongation)
AVOID use in elders
Cyclizine & Meclizine
Cyclizine: OTC
Meclizine: OTC & Rx
Uses: Motion sickness, vertigo
Mildly sedating
Chlorpheniramine & Brompheniramine
OTC
Uses: Allergies
moderately sedating, possible paradoxical CNS stimulation
** Often found in combination with “cold” products**
Avoid use in elders
Hydroxyzine HCL & Hydroxyzine PAMoate
Rx
HCL: allergies, urticaria
PAMoate: insomnia, anxiety
Mild-moderate sedation
Promethazine
Rx
Uses: anti-emetic
Highly sedating, alpha-blockade –> hypotension, dystonic reactions, akathisia
Cyproheptadine
Rx
Uses: weight gain, 5-HT blockade
First Generation Antihistamines ADE
Cholinergic - Increase dry mouth - Increase urinary retention - Increase sinus tachycardia Alpha-Adrenergic - Increase hypotension - Increase dizziness - Increase reflex tachycardia Serotonin - Increase Appetite Histamine H1 - Decrease neurotransmission in the CNS - Increase sedation - Decrease cognitive and psychomotor performance - Increase appetite
First Generation Antihistamine DDI
- Majority metabolized via 2D6 and 3A4 (metoprolol, TCAs, Tramadol, AADs)
- Avoid with: alcohol, other hypnotics &/or benzodiazepines, TCA, Acetylcholinesterase inhibitors, MAO inhibitors
Second Generation H1 Antihistamines
- Used to treat allergic symptoms
- Highly selective for H1 receptor with no anticholinergic effects
- Minimally or non-sedating (limited penetration to BBB) preferred in elders
- Rapid onset of action (~1hr)
- Longer duration of action (once to twice daily dosing)
Second Generation H1 Antihistamine Agents
Azelastine Olopatidine Fexofenadine Cetirizine Levocetirizine Loratidine Desloratidine
Azelastine & Olopatidine
Nasal Spray
Rx
Local application to nose –> associated with less systemic side effects
Local irritation can occur (nasal irritation, nosebleeds, bitter taste or smell, etc.)
Avoid use if any preexisting damage to the nasal passage
Fexofenadine
Oral
OTC
Highest safety profile, not metabolized, excreted in feces
Cetirizine
Oral
OTC
Most somnolence
Active metabolite of hydroxyzine
Levocetirizine
Oral
OTC
Active metabolite of Cetirizine
Loratidine
Oral
OTC
Metabolized via 3A4, 2D6 –> check for 3A4 inhibitors
Desloratidine
Oral
Rx
Least likely to cause somnolence
Active metabolite of loratadine
Second Generation Antihistamines ADE
- Somnolence (usually at higher doses, highest with cetirizine & levocetirizine)
- Constipation
- Headache
- No significan cardiac effects have been ovserved
Fexofenadine DDI
- Not metabolized via CYP450 –> high safety profile
Avoid grapefruit, orange and apple juice
Must separate by at least 4 hours
Loratidine, desloratidine DDI
- Metabolized via 3A4 and 2D6 – watch for DDIs with erythromycin, ketoconazole, clarithromycin, cimetidine and grapefruit juice
Ceterizine, levocetirizine DDI
- Not metabolized via CYP450, but both are PgP
substrates –> watch for DDI with grapefruit juice - Avoid other sedative drugs –> additive effects
H2 Receptor Antagonists
- Reversibly decrease fasting and food stimulated acid secretion by inhibiting histamine on the histamine2 receptor of the parietal cell
- indicated for the treatment of mild-moderate, infrequent, episodic heartburn (good for on-demand, meal provoked symptoms)
Onset: 30-45 min
Duration: 4-10 hr - Take before eating
- All equally efficacious
- All are available both OTC and prescription
- Well absorbed; absorption may be delayed by administration of antacid by not by food
H2 Receptor antagonist Agents
Ranitidine
Cimetidine
Nizatidine
Famotidine
H2 Receptor Agonist ADE
- Well tolerated
- Headache, Dizziness, fatigue, confucion (increased in elderly/renal impairment)
- Dose related gynocomastia occurs with cimetidine
- Tolerance has been reported with prolonged daily use of H2RA (take as needed)
Self-treatment should be limited to no more than two times a day for no more than 2 weeks
H2 Receptor Agonist DDI
- Drugs that depend on acid for proper absorption (ketoconazole, intraconazole, protease inhibitors, calcium carbonate, iron salts
- Cimetidine inhibits CYP450 enzymes (3A4, 2D6, 1A2, 2C9)
Cyclosporine, theophylline, warfarin, phenytoin, amiodarone, antidepressants
