Med Chem 2 Exam 4: antihistamines part 2

Propylamines general structure

N with 2 R groups, alkyl chain with 2 carbons, and two aromatic groups

Pheniramine maleate is used as a

maleate salt

the binding of pheniramine to H4 receptors, and subsequent inverse agonism, may also contribute to

reduced itching by antagonizing inflammation

One of the most widely used of the classical antihistaminic

Used in the treatment of rhinitis, urticaria, allergy, commoncold, asthma and hay fever

Chlorpheniramine maleate

is available as a prescription drug indicated for adjunctive therapy for allergic and anaphylactic reaction

Dexchlorpheniramine

Brompheniramine maleate

treatment and relief of symptoms of allergies, hay fever, and colds

Brompheniramine also has moderate

antimuscarinic actions

Due to its anticholinergic effects, dex/brompheniramine may cause

drowsiness, sedation, dry mouth, dry throat, blurred vision, and increased heart

Indicated for symptomatic relief of seasonal or perennial allergic rhinitis or nonallergic rhinitis; allergic conjunctivitis; and mild, uncomplicated allergic skin manifestations of urticaria and angioedema

Triprolidine

what are symptoms of Triprolidine

drowsiness, weakness, incoordination, difficulty with micturition, respiratory depression, hypotension, agitation, irritability, convulsions, hypertension, palpitation and tachycardia

structure of Triprolidine

double bond and ring system with tertiary amine

Promethazine hydrochloride is a predominant

antagonist of histamine H-1, But also has antagonist activity towards dopamine, α-adrenergic, muscarinic, and NMDA receptors

promethazine can treat

allergies, dermographism, sedation, nausea, vomiting and motion sickness

it is a potent antagonist of both serotonin and histamine H-1 receptors used primarily to treat allergic symptoms

Cyproheptadine

what are some off label uses of Cyproheptadine

appetite stimulation and the treatment of serotonin syndrome

Benzocycloheptathiophene-piperidines

Ketotifen fumarate and Cyproheptadine (three rings)

Ketotifen fumarate shows potent antihistaminic and

mast cell stabilizing properties

what enzyme does Ketotifen fumarate inhibit

phosphodiesterase and inflammatory mediator release

the second generation of H-1 antihistaminic agents was focused on agents with

lower sedation potential and reduced binding affinities of off-target receptors

first Second generation H-1 Antihistaminics examples

Astemizole and Terfenadine (pulled off the market due to serious cardiovascular toxicity)

It shows little to no activity at off-targets and does not cross the blood-brain barrier.

fexofinadine

manage symptoms of allergic rhinitis, wheal formation, urticaria, and other allergic dermatologic conditions

loratadine

active descarboethoxy metabolite of loratadine

desloratadine

desloratadine has long lasting effect and does not cause

drowsiness bc it does not cross the BBB

it is indicated for the prevention of itching associated with allergic conjunctivitis

Alcaftadine

Alcaftadine decreases chemotaxis and

inhibition of eosinophil activation

effective in the treatment of various allergic symptoms, such as sneezing, coughing, nasal congestion, hives, and other symptoms

cetirizine and levocetirzine

Levocetirizine is also indicated to

uncomplicated skin manifestations of chronic idiopathic urticaria

Second generation H-1 Antihistaminic: Phthalazinone

Azelastine

Azelastine is available as an intranasal spray for the treatment of

allergic and vasomotor rhinitis and as an ophthalmic solution for the treatment of allergic conjunctivitis.

FDA approved in June 2021 through a process called a partial prescription to nonprescription switch

Azelastine

what is an important structural feature of Azelastine

middle ring with 2 N and a ketone

Second generation H-1 Antihistaminic: Dibenzoxepine

Olopatadine

Olopatadine is a mast cell

stabilizer that works by attenuating inflammatory and allergic reactions.

used for the symptomatic treatment of ocular itching associated with allergic conjunctivitis

Olopatadine

structurally, olopatadine contains

an acidic group (CA) and a long alkyl chain that connects the tertiary amine

the therapeutic application of histamine H-2 antagonist is related to the treatment of

acidic-peptic disorders such as, heartburn, gastroesophageal reflux disease (GERD), erosive esophagitis, gastric and duodenal ulcers

Selective agonist H2>H1

5-Methyl histamine, add a methyl group to the ring in histamine

N-Guanylhistamine

Partial H2 agonist

2 Nh2 groups with a double bond on one

Full H2 antagonist, low potency and poor bioavailability

Burimamide

long chain, doubled bonded S between 2 Ns

Metiamide

Full H2 antagonist, high potency, improved bioavailability, but toxic (2 S)

First clinically used H-2 receptor antagonist (inverse agonist) inhibiting gastric acid secretion

Cimetidine hydrochloride

Cimetidine hydrochloride binds to H2 receptors located on

basolateral membrane of the gastric parietal cell blocking histamine's effect

the competitive inhibition of cimedtidine results in

reduced gastric acid secretion and a reduction in gastric volume and acidity

what does cimetidine also inhibit resulting in increased estrogen levels

2-hydroxylation of estradiol, which are involved in the metabolic inactivation of estradiol

treats short-term treatment of active duodenal ulcer, treating gastric acid hypersecretion due to Zollinger-Ellison syndrome, systemic mastocytosis

Ranitidine

In 2021 all ______ contained products were withdraw from market

ranitidine

the FDA approved the reformulation of ranitidine

removed the carcinogen compound of NDMA (nitrosodimethylamine)

it is 20 to 50 times more potent at inhibiting gastric acid secretion than cimetidine and 8 times more potent than ranitidine

famotidine

famotidine is an example of

an inverse agonist

used to treat ulcers in the stomach and intestines

Nizatidine

GERD

a condition in which acid backs up from the stomach into the esophagus

The H-3 histaminic receptors are identified in

CNS, stomach, lung and cardiac tissue where they appeared to regulate neurotransmitter release

Histaminergic nerves are located in the hippocampus and project to the brain regions where they regulate

sleep, alertness, feeding behavior and memory

Pitolisant

H-3 Antihistaminic

it is a selective inverse agonist of the histamine H-3 receptor used to treat type 1or 2 narcolepsy

Pitolisant

H-4 receptors are expressed on cells with

inflammatory or immune functions and can mediate histamine-induced chemotaxis, induction of cell shape change, secretion of cytokines, and upregulation of adhesion molecules

TheH-4 receptors also have a role in

pruritus and neuropathic pain

Because of the unique localization and function of H-4 receptors, H-4 receptor antagonists are currently under clinical evaluation for their potential therapeutic exploitation in

inflammatory disorders such as atopic dermatitis, as well as investibular disease

H-1 histamine receptor antagonists (first and second generation) were developed mainly for treatment of

allergic disease

The H-2 receptor antagonists inhibit acid production by

reversibly competing with histamine for binding to H-2 receptors on the basolateral membrane of parietal cells.

The clinical utility of H-2 antagonists is inhibiting

gastric acid secretion in the treatment of GI disorders

H3 receptors treat

nacrolepsy