H1/H2 ANTAGONIST PROPERTIES

-earliest family of H1 antihistamines

-two aryl groups aryl and benzyl

first ethylenediamine (used as protype)

Anticholinergic sedative effects

Used to treat a variety of conditions:

-allergies

-motion sickness

-local anesthetic

-cough suppressant

Introducing the pyridyl ring

MOST EFFECTIVE OTC sedative in the US

-effective for allergies but causes serious sedation

Used to treat:

-allergies (hay fever)

-hives, skin rash itching

-symptoms of common cold

-less sedative effects

-more anticholinergic activity

-longer duration of action (than other ethanolamine)

Useful antiemetics (to treat nausea vomiting, motion sickeness)

-used as antinauseant

-useful for treatment of hives

-commonly used for anxiety at higher doses

-primarily used for antinauseant (due to anticholinergic effects)

-lincreased lipid nature allows better CNS penetration

-acid metabolite of cetirizine

-decreased sedative effects

-second-generation

-widely used as OTC antihistamines for mild seasonal allergies

-have less sedative effects

-have little antiemetic effects

-used as a racemic mixture

-antihistamine almost exclusively S enantiomer

-E-alkene is more potent than Z-alkene

analog of ethanolamine

-planar (8 pi)

-boat conformation

-aromatic rings are not co-planar

moderately potent antihistamine

-Significant antiemetic, anticholinergic, sedative effects

ANTIPSYCHOTIC

-enhances antidopamine acitivity

ANTIDPRESSANT/ANTI-ANXIETY

(tricyclic antidepressant)

-selective serotonin reuptake inhibitor

-cross between a piperazine and phenothiazine

-has antihistamine and anicholinergic properties

-anticholinergic and antiserotonin properties

-most commonly used for itching and hives

-also used to stimulate appetite

-used for nightmares

NO ANTISEROTONIN PROPERTIES

-only used an antihistamine for allergies

-second-generation

-selective for peripheral over central H1 receptors

-similar to Azatadine

-used for allergies and hives

-low anticholinergic activity and side effects

-metabolized by CYP3A4 and 2D6

-second-generation

-Metabolite of loratadine

-basic amine

-high affinity for H1 receptors

-further metabolized into 3'-hydrocydesloratatdine (does not reach CNS)

-second-generation

-less potent than loratadine

-less than 10% metabolized by liver

-mostly excreted unchanged

-developed after terfenadine was pulled from the market due to cardiac arrhythmias

-second-generation

-racemic mixture

-used for treatment of hay fever allergies

-long duration of action

-excreted primarily unchanged

-side effects: dry mouth blurred vision, stomach ache

-second-generation

-active enantiomer of levocetirizine

-analog of tripolidine

-minimal anticholinergic activity

-limited BB penetration

-weak H2 antagonist

-partial H2 agonist

-inhibits gastric acid secretion at high concentrations

-full H2 Antagonist

-used to treat peptic ulcers

-poor bioavailability

-low potency

H2 antagonist

-used to treat peptic ulcers

TOXICITY ISSUES

-many patients got agranulocytosis

H2 antagonist

-inhibits stomach acid production

-used to treat peptic ulcers and heartburn

NO LONGER TOXIC

FIRST H2 ANTAGONIST ON THE MARKET

-short half-life (due to first-pass metabolism)

-significant drug interactions

H2 antagonist

-used for peptic ulcers GERD

-longer lasting

-much weaker binder to CYP450s

-minimized drug-drug interactions

H2 antagonist

-inhibits stomach acid production

-treats peptic ulcer disease & GERD

-as potent as ranitidine

-high bioavailability

-no effect on CYP450

LAST H2 ANTAGONIST BEFORE PROTON PUMP INHIBIOTRS

H2 antagonist

-inhibits stomach acid production; treats peptic ulcer disease GERD

-no effect on CYP450

-30X more active than cimetidine

-poor bioavailibity due to insolubility in acidic stomach (combining with antacids helps)

PPI

-first PPI

-enteric-coated drug (resists stomach acid)

-release and absorption in small intestine in 3-6 hours

-bioavaibility impaired by food; better to take on empty stomach

-completelt metabolized by CYP450s

-R enantiomer is cleared more rapidly

PPI

-S enantiomer of omeprazole

-both enantiomers are approx. equipotent

-benefit: loss of interindividual variability

-improved therapeutic effect higher bioavaibility

PPI

-racemic mixtures of enantiomers

-both enantiomers are approx. equipotent

-extensively metabolized

-now availble as OTC

PPI

-R enantiomer of Lansoprazole

-no evidence it has any clinical benefits over lansoprazole

-OTC prevacid is significantly cheaper

PPI

-racemic mixtures

-used for short term treatment of erosion and ulceration caused by GERD

-metabolized largerly by CYP2C19

PPI

-racemic mixture

-small difference found in plasma concentrations of enatiomers

-metabolized by CYP3A4 ad CYP2C19