Ethanolamines

Diphenhydramine (Benadryl)

First generation H₁ blocker

Sedative, non prescription sleep aid

(two aromatic and two methyl groups)

Ethylenediamines

Tripelennamine (PBZ)

First gen H₁ blocker

Mildly sedative

Alkylamines

Chlorpheniramine (Chlor-Trimeton)

First gen H₁ blocker

-common ingredient in OTC cold remedies

-less sedative

-can inhibit reuptake of serotonin (antidepressant)

Phenothiazines

Promethazine (Phenergan)

First Gen H₁ blocker

Treatment: commonly used antiemetic with prominent sedative action

Adverse Effects: contraindicated for children under 2 years of age (respiratory depression)

Piperazines

Hydroxyzine (Atarax)

First gen H₁ blocker

Treatment: widely used for chronic urticaria and dermatological allergies, sedation common

Adverse Effects: contraindicated in early pregnancy

Piperazines

Cyclizine (Marezine)

Meclizine (Antivert)

First gen H₁ blocker

Treatment: antiemetic

Piperidines

Cyproheptadine (Periactin)

Phenindamine (Nolahist)

Mechanism: antihistamine, antiserotonin

Adverse Effects: drowsiness and significant anticholinergic effects

H₁ Antihistamines

Side Effects

1. CNS Toxicity. interference with NT effect of histamine through H1. Usual dose causes drowsiness, fatigue, dizziness, impairment of congnitive function and memory agitation, hallucinations. OD causes restlessness, anxiety, and convulsions (infants)

2. Cardiac Toxicity. blockade of muscarinic and alpha-adrenergic receptor; blockade of cardiac ion current. Dose related sinus tachycardia, reflex tachycardia and SV arrythmias. Dose related prolongation of QT interval and ventricular arrhythmias (diphenhydramine, hydroxyzine, etc.)

3. Other. blockade of muscarinic, alpha adrenergic, and serotonin receptors. Pupillary dilation (mydriasis), dry eye, dry mouth, urinary retention, hesitancy. Contraindicated in patients with glaucoma or prostatic hypertrophy

Piperidines

Fexofenadine (Allegra)

Second gen H₁ blockers

Lower risk of arrhythmia

excreted largely unchanged in the feces

up to 360mg daily dose with no side effects

second gen H1 blocker piperadine

Metabolized by P450 system

Metabolism prolonged by ketoconazole

up to 10mg daily dose without side effects

second gen H1 blocker piperazine

carboxylated hydroxyzine

excreted largely unchanged in urine

doses of 10 mg or higher causes sedation in adults

H2 blocker

Mechanism: least potent (6hrs)

Side effects: neural effects (confusion, slurred speech, delirium, hallucination, and coma) in patients with impaired renal function. Anti-androgen (gynecomastia, impotence, enhanced prolactin secretion). Interference with P450 drug metabolism pathways. Diarrhea, dizziness, rash

H2 blocker

Mechanism: binds less to P450, long lasting (8 hrs), highly effective gastric secretion blocker

H2 blocker

Mechanism: does not interfere with hepatic drug metabolism pathway, most potent (12hrs), OTC

H2 blocker

Mechanism: does not interfere with hepatic metabolism, little first pass metabolism with almost 100% bioavailability, highly potent (8hrs)