Antihistamine

Question 1

First Generation H1 Antihistamine

Answer 1

• 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)

Question 2

First Generation H1 Antihistamine Agents

Answer 2

Doxylamine
Dephenhydramine
Cyclizine
Meclizine
Chlorpheniramine
Brompheniramine
Hydroxyzine HCL
Hydroxyzine PAMoate
Promethazine
Cyproheptadine

Question 3

Doxylamine & Diphenhydramine

Answer 3

OTC
Used: Insomnia, Allergies
Highly sedating, large doses can cause arrhythmias (QT prolongation)
AVOID use in elders

Question 4

Cyclizine & Meclizine

Answer 4

Cyclizine: OTC
Meclizine: OTC & Rx

Uses: Motion sickness, vertigo
Mildly sedating

Question 5

Chlorpheniramine & Brompheniramine

Answer 5

OTC
Uses: Allergies
moderately sedating, possible paradoxical CNS stimulation
** Often found in combination with “cold” products**
Avoid use in elders

Question 6

Hydroxyzine HCL & Hydroxyzine PAMoate

Answer 6

Rx
HCL: allergies, urticaria
PAMoate: insomnia, anxiety

Mild-moderate sedation

Question 7

Promethazine

Answer 7

Rx
Uses: anti-emetic
Highly sedating, alpha-blockade –> hypotension, dystonic reactions, akathisia

Question 8

Cyproheptadine

Answer 8

Rx

Uses: weight gain, 5-HT blockade

Question 9

First Generation Antihistamines ADE

Answer 9

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

Question 10

First Generation Antihistamine DDI

Answer 10

• Majority metabolized via 2D6 and 3A4 (metoprolol, TCAs, Tramadol, AADs)
• Avoid with: alcohol, other hypnotics &/or benzodiazepines, TCA, Acetylcholinesterase inhibitors, MAO inhibitors

Question 11

Second Generation H1 Antihistamines

Answer 11

• 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)

Question 12

Second Generation H1 Antihistamine Agents

Answer 12

Azelastine
Olopatidine
Fexofenadine
Cetirizine
Levocetirizine
Loratidine
Desloratidine

Question 13

Azelastine & Olopatidine

Answer 13

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

Question 14

Fexofenadine

Answer 14

Oral
OTC
Highest safety profile, not metabolized, excreted in feces

Question 15

Cetirizine

Answer 15

Oral
OTC
Most somnolence
Active metabolite of hydroxyzine

Question 16

Levocetirizine

Answer 16

Oral
OTC
Active metabolite of Cetirizine

Question 17

Loratidine

Answer 17

Oral
OTC
Metabolized via 3A4, 2D6 –> check for 3A4 inhibitors

Question 18

Desloratidine

Answer 18

Oral
Rx
Least likely to cause somnolence
Active metabolite of loratadine

Question 19

Second Generation Antihistamines ADE

Answer 19

• Somnolence (usually at higher doses, highest with cetirizine & levocetirizine)
• Constipation
• Headache
• No significan cardiac effects have been ovserved

Question 20

Fexofenadine DDI

Answer 20

• Not metabolized via CYP450 –> high safety profile
  Avoid grapefruit, orange and apple juice
  Must separate by at least 4 hours

Question 21

Loratidine, desloratidine DDI

Answer 21

• Metabolized via 3A4 and 2D6 – watch for DDIs with erythromycin, ketoconazole, clarithromycin, cimetidine and grapefruit juice

Question 22

Ceterizine, levocetirizine DDI

Answer 22

• Not metabolized via CYP450, but both are PgP
  substrates –> watch for DDI with grapefruit juice
• Avoid other sedative drugs –> additive effects

Question 23

H2 Receptor Antagonists

Answer 23

• 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

Question 24

H2 Receptor antagonist Agents

Answer 24

Ranitidine
Cimetidine
Nizatidine
Famotidine

Question 25

H2 Receptor Agonist ADE

Answer 25

• 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

Question 26

H2 Receptor Agonist DDI

Answer 26

• 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