HIstamine antagonists

what type of reaction turns histidine → histamine

a) Hydrolysis

b) Decarboxylation

c) Oxidation

d) Reduction

b) Decarboxylation

what type of drugs or chemicals can cause histamine release?

• morphine

• IV contrast dyes

role of H1 receptors

• allergy, inflammation, CNS arousal

role of H2 receptors

• gastric acid secretion

• cardiac function

what type of receptor is H1

• Gq/11 protein coupled

what type of receptor is H2

• Gs coupled

H1 receptor antagonists MOA

• inverse agonists at H1 receptors

H1 receptor antagonist physiological effects

• decreased vasodilation

• capillary permeability

• itching

• bronchoconstriction

ADR of first generation H1 antagonists

• sedation

• anticholinergic side effects

  • BEERS CRITERIA

which of the following 1st gen H1 antagonists also has serotonin antagonism?

a) diphenhydramine

b) brompheniramine

c) cyproheptadine

d0 meclizine

c) cyproheptadine

which 1st gen H1 antagonist can cause qt prolongation?

a) chlorpheniramine

b) hydroxyzine

c) meclizine

d) doxylamine

b) hydroxyzine

which 1st gen H1 antagonists cause the strongest sedation?

• diphenhydramine

• hydroxyzine

• doxylamine

which 1st gen H1 antagonist can cause weight gain?

a) cyproheptadine

b) hydroxyzine

c) dimenhydrinate

d) meclizine

a) cyproheptadine

diphenhydramine indication

• acute allergic criticals

brompheniramine indication

• used in combo cold products

hydroxyzine indication

• pruritus

• anxiety

meclizine indication

• vertigo

doxylamine indication

• used in Diclegis combo

which 1st gen H1 antagonist is contraindicated in early pregnancy

• hydroxyzine

does first gen or second gen h1 antagonists have better CNS penetration

• 1st gen = better CNS penetration

benefits of second generation h1 antagonists

• less sedating

• no anticholinergic side effects

• longer duration of action

which second gen h1 antagonist is the most sedating?

• cetirizine (Zytrec)

which second gen h1 antagonists is the non-sedating classic?
a) levocetirizine

b) fexofenadine

c) olopatadine

d) loratadine

d) loratadine

if a patient is taking fexofenadine, they should avoid…

• fruit juice

  • decreases absorption of the drug

azelastine formulation

• intranasal

olopatadine formulation

• intranasal

• ophthalmic

ketotifen formulation

• ophthalmic

what is ketotifen’s dual mechanism?

• H1 + mast cell stabilization

Which second-generation H1 antagonists should be avoided in patients with renal impairment?

• cetirizine

• levocetirizine

Which second-generation H1 antagonists should be avoided in patients with hepatic impairment?

• loratadine

• desloratadine

1st generation + alcohol or benzodiazepines can cause…

• intense sedation

all antihistamines + CYP3A4 inhibitors can cause….

• very high antihistamine levels → arrhythmias

which antihistamine was shown NOT to cause torsades de pointes when combined with CYP3A4 inhibitors

• fexofenadine

H2 antagonist MOA

• blockage od H2 receptors in parietal cells → decreases gastric acid secretion

H2 antagonists vs PPIs

• H2 antagonists = less potent but faster onset

H2RAs develop ________ within 3-7 days

• tachyphylaxis

which H2 antagonist has the most DDI (inhibits many CYP450s)

a) cimetidine

b) famotidine

c) nizatidine

c) ranitidine

a) cimetidine

what is a major ADE of cimetidine

• gynecomastia

which H2 antagonist was removed from US market (NDMA contamination)

a) cimetidine

b) famotidine

c) nizatidine

c) ranitidine

c) ranitidine

which H2 antagonist is the most commonly used in US

a) cimetidine

b) famotidine

c) nizatidine

c) ranitidine

b) famotidine

indications of H2RA

• peptic ulcer disease

• GERD

• zollinger-ellison syndrome

• prevention of stress ulcers

• adjunct in anaphylaxis

which H2RA is used in the prevention of stress ulcers in ICU patients?

• famotidine IV

which of H2RA should be cautioned in renal/hepatic impairment

a) cimetidine

b) famotidine

c) nizatidine

c) ranitidine

a) cimetidine

which of H2RA should be dose adjusted in severe renal impairment

a) cimetidine

b) famotidine

c) nizatidine

c) ranitidine

b) famotidine

which of H2RA should be contraindicated in renal impairment

a) cimetidine

b) famotidine

c) nizatidine

c) ranitidine

c) nizatidine

what are the H3 receptors

• presynaptic auto receptors + heteroreceptors

  • CNS + PNS

Pitolisant MOA + indication

• H3 inverse agonist

  • approved for narcolepsy

Pitolisant ADE

• qt prolongatoon

• insomnia

• nausea

• HA

what does H4 receptor activation cause?

• chemotaxis of mast cells + eosinophils → sites of inflamation

• Th-2 skewing of immune responses

• peripheral itch (pruritus)

T/F: the peripheral itch caused by H4 receptors is the same as H1-mediated itches

• false

  • distinct from H1 mediated itch

Th-2 skewing of immune responses is relevant to …

• allergy and asthma

H4 receptor antagonists are promising for…

• inflammatory diseases

  • asthma

  • atopic dermatitis

T/F: some H1 antagonists may have secondary affinity for H4 receptors, contributing to anti-inflammatory effects

• true

what type of receptors are the H3 + H4 receptor

• Gi/o coupled

Transporter responsible for limiting CNS penetration of second generation antihistamines

• p-glycoprotein

Common counseling point for fexofenadine regarding absorption

• fruit juice

Receptor subtype responsible for gastric acid secretion

• H2

Drug class causing CNS depression interaction with antihistamines

• benzodiazepines

Histamine receptor involved in wakefulness and cognition

• H3

Most commonly used H2 blocker in the U.S

• famotidine

Ophthalmic antihistamine also acting as mast cell stabilizer

• olopatadine

Drug for narcolepsy (H3 inverse agonist)

• pitolisant

Key ion required for histamine release

• calcium

Pharmacological term utilized to describe the receptor activity of H1 antihistamines

• inverse agonists

H2 blocker with many CYP450 interactions

• cimetidine

OTC ophthalmic antihistamine with dual mechanism

• ketotifen

Intranasal H1 antihistamine with rapid onset

• azelastine

Non-sedating second-generation antihistamine

• loratadine

Least sedating antihistamine

• fexofenadine

Withdrawn H2 blocker due to NDMA contamination

• ranitidine

Histamine receptor involved in immune chemotaxis

• H4