Antihistamines

Introduction

All medications designated as antihistamines are strong antagonists or inverse agonist at the peripheral and central histamine receptors.

Blockade or the inverse agonism of the peripheral H-1 receptor alleviates allergy symtpoms.
Blockade or inverse agonism of the central H-1 receptor increases sedation.
Second-generation antihistamines do not cross the blood-brain barrier, and thus are less sedating.

Benadryl is a first-generation antihistamine; in addition to blocking H-1 receptors, it is a potent anti-cholinergic drug (blocks muscarinic receptors) and therefore can be used to mitigate extrapyramidal effects of antipsychotics, and has a role in treatment of Parkinson's disease. As noted above, it crosses the blood-brain barrier, and thus quite sedating
- Its use is generally avoided in the elderly due to significant sedation (risk of falls) and potential for anti-cholinergic toxicity (dry mouth, tachycardia, urinary retention, and delirium)
Benadryl is frequently used in inpatient child psychiatry as a PRN medication (PO or IM) for its sedating properties.
Benadryl is generally safe in pregnancy (Category B), but is excreted in breast milk.
It can prolong QTc interval in large doses or in combination with other QTc-prolonging medications.
It is possible to be allergic to Benadryl. Benadryl can also worsen restless leg syndrome

Vistaril is another first generation antihistamine commonly used in psychiatry. It is just as sedating as Benadryl, but has weaker anti-cholinergic effects. It should not be used for treating EPS or dystonic reactions of anti-psychotics.
Just like Benadryl, it is widely used in child psychaitry for sleep and as PRN in behavioral emergencies. Unfortunately it is not available in intramuscular (IM) form.

Benadryl was discovered and FDA-approved in 1940s; in 1960s it was discovered that it inhibits serotonin reuptake (inhibits the serotonin transporter, 5-HTT). This eventually led to discovery of Prozac, the first SSRI.
- This also means that Benadryl can contribute to a serotonin toxicity, particularly when combined with other serotonergic drugs.
Vystaril acts on 5-HT2a receptor which justifies its clinical use in generalized anxiety disorder.
Most antihistamines undergo hepatic metabolism; one of Vistaril's metabolites is ceterizine, a 2nd generation antihistamine. Ceterizine is excreted in urine.