H1 Receptor Antagonists

The primary storage sites of histamine are ______ in tissues and ______ in blood.

mast cells, basophils

Histamine release occurs after antigen binding to ______ antibodies on mast cells.

IgE

Histamine plays a central role in ______ hypersensitivity and ______ responses.

immediate, allergic

Actions of histamine on ______ smooth muscle and ______ account for many allergy symptoms.

bronchial, blood vessels

Non-immune causes of histamine release include ______, ______, and ______.

morphine, antibiotics, venoms

Histamine in the gastric mucosa stimulates secretion of ______.

gastric acid

In neurons, histamine functions as a ______ involved in wakefulness and appetite.

neurotransmitter

The wheal and flare response is due to histamine release from the ______.

epidermis

______ are the major site of histamine storage in the blood.

basophils

______ are rich in tissues prone to injury and serve as a major storage site for histamine in tissues.

mast cells

Histamine is abundant in ______ of the airways, mouth, feet, and bifurcation points in blood vessels.

mucous membrane

H1 receptor activation on vascular endothelium leads to ______ production and smooth muscle relaxation —→ vasodilation

nitric oxide

Histamine increases capillary ______, causing edema and wheal formation.

permeability

Bronchial smooth muscle contraction by histamine is mediated through increased intracellular ______.

calcium

The “triple response” consists of ______, ______, and ______.

red spot, flare, wheal

The red spot results from histamine-induced ______.

vasodilation

The flare is due to axon reflex-mediated ______.

vasodilation

The wheal results from increased ______ permeability.

capillary

H1RAs can treat type I reactions such as ______ and ______.

allergic rhinitis, urticaria

H1RAs are less effective in treating ______ because they do not block histamine-induced bronchoconstriction.

asthma

H1 receptor antagonists act as ______ or ______ at the H1 receptor.

competitive antagonists, inverse agonists

On vascular smooth muscle, H1RAs blunt histamine-induced ______.

vasodilation

On capillaries, H1RAs decrease ______ and thus reduce edema.

permeability

On nerves, H1RAs suppress histamine-induced ______ and ______.

itching, flare response

First-generation H1RAs readily cross the ______ and cause sedation.

blood-brain barrier

Second-generation H1RAs are often called ______ because they cause little sedation.

nonsedating

First-generation H1RAs also block ______ receptors, producing anticholinergic side effects.

muscarinic

Second-generation H1RAs also stabilize ______, reducing mediator release.

mast cells

______ generation H1RAs are better for motion sickness due to their CNS effects.

First

First-generation H1RAs peak in ______ hours and last ______ hours.

1-3, 4-6

Second-generation H1RAs have ______ half-lives.

longer

Children metabolize H1RAs more ______, while adults and those with liver disease metabolize them more ______.

rapidly, slower

First-generation H1RAs interact with alcohol, opioids, and sedatives due to additive ______ effects.

CNS

A common CNS adverse effect of 1st-generation H1RAs is ______.

sedation

In children, H1RAs may cause paradoxical ______.

excitation

Peripheral antimuscarinic effects of H1RAs include dry ______, blurred ______, constipation, and urinary ______.

mouth, vision, retention

Overdose of first-generation H1RAs can cause ______, especially in infants.

convulsions

For motion sickness, the most effective H1RAs are ______, ______, and ______.

dimenhydrinate, cyclizine, meclizine, promethazine

______ is used for sedation due to its strong CNS depressant effect.

diphenhydramine

H1RAs have limited value in treating the ______ and ______ because other therapies are more effective.

common cold, contact dermatitis

In anaphylaxis, H1RAs play a supportive role, but the primary treatment is ______.

epinephrine

For motion sickness, H1 receptor antagonists should be administered about ______ before anticipated motion.

1 hour

Treatment with H1 receptor antagonists after the onset of ______ and ______ is rarely beneficial.

nausea, vomiting

In overdose, first-generation H1 antagonists may rarely cause ______.

tachydysrhythmias

Topical use of first-generation H1 antagonists may trigger ______ reactions, so a topical ______ is preferred instead.

allergic, corticosteroid

CYP inhibitors such as ______ and ______ can increase H1 receptor antagonist levels.

erythromycin, ketoconazole

CYP inducers such as ______ can decrease H1 receptor antagonist levels.

benzodiazepines

______ and ______ are H1 receptor antagonists with <40% metabolism.

cetirizine, acrivastine

______, ______, and ______ are H1 receptor antagonists with <10% metabolism.

fexofenadine, levocetirizine, epinastine

Common second generation antihistamines include ______, ______, ______ and ______.

loratadine, cetirizine, fexofenadine, desloratadine

Another major category of antihistamines are those targeting the ______ receptor.

H2

Histamine is primarily stored in vesicles of the ______ cells.

mast

Mast cells are located in tissues prone to ______.

injury

Common side effects of 1st-generation H1RAs include ______, ______, and ______.

sedation, dizziness, anticholinergic effects

Blocking H1 receptors reduces histamine effects on vascular smooth muscle (↓ ______), capillary permeability (↓ ______), and nerve stimulation (↓ ______).

vasodilation, edema, itching

H1RAs should not be used alone to treat ______ in asthma.

bronchoconstriction

______ generation H1RAs are better for motion sickness because they cross the ______.

first, blood-brain barrier

______ generation H1RAs have a higher rate of CNS effects due to their ability to cross the BBB.

first

First-generation H1RAs have more drug interactions because they undergo extensive ______ metabolism.

hepatic (CYP450)

Agents with the highest rate of drowsiness, anticholinergic effects, and impairment belong to the ______ generation of H1RAs.

first