Histamines (no structures)

What class is Brompheniramine (dimetapp)?

alkylamine

what class is cyroheptadine (periactin)?

piperidine

what class is diphenhydramine (benadryl)?

ethanolamie

What class is promethazine (phenergan)?

phenothiazine

What class is hydrozyzine (atarax)?

piperazine

What class is pyrilamine?

ethenediamine

What generation is the H1 receptor antagonist brompheniramine (dimetapp)?

first generation

What generation is the H1 receptor antagonist cyproheptadine (periactin)?

first generation

What generation is the H1 receptor antagonist diphenhydramine (benadryl)?

first generation

What generation is the H1 receptor antagonist promethazine (phenergan)?

first generation

What generation is the H1 receptor antagonist hydroxyzine (atarax)?

first generation

What generation is the H1 receptor antagonist pyrilamine?

first generation

What generation of antihistamines induces the most sedation?

first generation by blocking H1/H2 CNS receptors by blocking histaminergic neuronal projections from the tumeromamillary nucleus (TMN) to the basal forebrain and thalamus to reduce wakefullness…hydroxyzine (atarax) is an extremely sedating first generation antihistamine and is more commonly used as an angeolytic and sedation medication

What generation of antihistamines indues the most anti-cholinergic effect and why?

First generation due to a lack of receptor selectivity, these drugs are also more lipid soluble which increases their CNS access. Increased CNS access is most likely where the anti-motion sickness/ anti-emetic effect is derived from. Due to anti-cholinergic activity, most first generation drugs have typical anticholinergic effects including decreased urination and dry mouth.

What are the strong anti-motion sickness and anti-emetic first generation antihistamines?

promethazine (phenergan) [phenothiazine]…most potent and main use is anti-emetic and diphenhydramine (benadryl) [ethanolamine]

What additional side effect may be experienced from pyrilamine [ethylendiamine]?

Local anesthetic properties due to the blockage of voltage gated sodium channels (lack of selectivity) which can lead to numbness.

What additional side effects may be experienced with promethazine (phenergan) [phenothiazine]?

Local anesthetic, due to blockage of voltage gated sodium channels leading to numbness, headaches to due anti-seretonin activity, hypotension due to binding to alpha adrenergic receptors antagonistically, and dystonia/ akathisia due to extrapyramidal activity which results in dopamine antagonism (D2 antagonist)

What additional side effects may be experienced with cyproheptadine (peroactin) [piperadine]?…also azatadine (no longer widely used, 1st generation antihistamine, precursor to loratadine/desloratadine)

Headaches due to anti-serotonin activity

What differentiates second generation antihistamines from first generation antihistamines?

Second generation antihistamines have decreased lipid solubility, this decreases their CNS access… Although they are able to get into the brain, they are often quickly effluxed out by p-glycoprotein (PGP) resulting in low CNS accumulation/concentrations. Due to lower CNS activity second generation antihistamines have little to no sedation. no anti-muscarinic activity, no anti-emetic activity, and no anti-motion sickness activity.

What generation of antihistamines is loratadine (claratin)?

second generation

What generation of antihistamines is desloratadine (clarinex)?

second generation

What generation of antihistamines is fexofenadine (allegra)?

second generation

What generation of antihistamines is cetirizine (zyrtec)?

second generation

What generation of antihistamines is levocetirizine (xyzal)

second generation

Where is loratadine (claritin) and desloratadine (clarinex) derived from?

These drugs are derived from the 1st generation anti-histamine azatidine by the removal of a methyl and addition of a Cl to make the structures less sedative/ less anti-muscarinic

What is the difference between loratadine (claratin) and desloratadine (clarinex)?

loratadine (claratin) has a carbamate group and desloratadine (clarinex) has a H in place of the carbamates connection to N.

What is the difference between cetirizine (zyrtec) and levocetirizine (xyzal)

Cetirizine (zyrtec) is a racemic mixture and levocetirizine (xyzal) is a purified levorotatory enantiomer that is more active than cetirizine.

What generation of anti-histamines is terfenidine (seldane)?

first generation

Why is terfenidine (seldane) no longer in use?

Terfenidine (a prodrug) is the first 2nd generation antihistamine and it is no longer in use because it blocked the HERG potassium channel in hearts which had the potential to trigger arrhythmia in some patients due to the isobutyl group. It was found that the purified active metabolite (fexofenadine) was more effective and produced no HERG side effects. The active metabolite is generated in the liver by CYP metabolism (carboxylation) during the first pass. Fexofenadine (allegra) was produced by carboxylaitng the isobutyl group. The carboxylation of the isobutyl creates a metabolite that has no CNS access and no HERG blocking.

What is the active metabolite of hydroxyzine (atarax)?

Hydroxyine (atarax) is a first generation antihistamine with extremely sedating properties. In the body hydroxyzine is converted to cetirizine (zyrtec) in the liver by first pass metabolism (carboxylation). The carboxylation to the active metabolite cetirizine reduces sedating properties by blocking CNS access/accumulation.

What other actions may cetirizine (zyrtec) have?

Cetirizine may block LTC4, neutrophil migration, eosinophil migration, and is potentially an H4 block (there is some activity /support for this but it is not the primary action)

What is the topical antihistamine olopatadine (patanol) used for?

It is used as an eyedrop or nasal spray for treatment of seasonal allergic rhinitis and conjunctivitis. If taken orally or as a nasal spray it has the potential to cause drowsiness.

What is the topical antihistamine azelastine (astelin) used for?

It is used as an eye drop or nasal spray for treatment of seasonal allergic rhinitis and conjunctivitis. If taken orally or as a nasal spray it has the potential to cause drowsiness. This medication is approved for systemic use is europe.

what is the topical antihistamine ketotifen (zaditor) used for?

It is used as an eye drop for treatment of seasonal allergic rhinitis and conjunctivitis. If taken orally or as a nasal spray it has the potential to cause drowsiness. This medication is approved for systemic use is europe.

What are the therapeutic uses of H2 receptor antagonist?

reduce gastric acid secretion, treat peptic ulcers, and GERD

What are the severe side effects associated with H2 antagonist?

CNS dysfunction, anti-androgen (gynecomastia, galactorrhea), impotence, blood dyscarsias, and hepatotoxicity

What type of antagonist is famotidine?

H2 receptor antagonist

What type of antagonist is cimetidine?

H2 receptor antagonist

what type of antagonist is nizatidine?

H2 receptor antagonist

What type of anatagonist is ranitidine?

H2 receptor antagonist

H1 antagonist mimic what part of the histamine?

ethyl amine group mimic, no imidazole mimic

H2 antagonist mimic what part of the histamine?

imidazole group mimic, no ethyl amine group mimic

What other class of drugs may also be used in the treatment of allergic rhinitis?

Glucocorticoids (especially nasal sprays) may also be used along side H1 antagonists (in conjunction) to inhibit inflammatory reactions within the nasal epithelium and combat seasonal allergies. These drugs inhibit late phase allergic response, by interacting on the T cell dependent pathway to reduce the release of chemoattractants/inflammatory cell production such as TH2, mast cells, and goblet cells which lead to allergic inflammation and congestion (Histamines work on the early phase pathway and ONLY inhibit histamine). These drugs have a slow onset so the max benefit may take several days to develop before it is seen. If these drugs are used too long (prolonged use) they have the potential to suppress the HPA axis (block the cortisol negative feedback loop).

What class of drug is fluticasone (flonase)?

It is an intranasal glucocorticoid, available RX or OTC. Flonase has low systemic absorption from intranasal dose, which minimizes potential side effects.

What class of drug is budesonide (rhinocort)?

It is an intranasal glucocorticoid, available RX or OTC. With budesonide ~1/3 the dose is absorbed in <1 hr meaning it has low systemic absorption from intranasal dose, which minimizes potential side effects.

Why would it be beneficial to use an H1 antagonist and H2 antagonist together?

The use of an H1 and H2 antagonist together insures complete “reversal” of histamine response as H1 receptors are located in the bronchial smooth muscle and vascular endothelium and H2 receptors are located in the cardiac smooth muscle (vascular system and SA node) and in the stomach.

Why would it be beneficial to use an H1 antagonist and an glucocorticoid?

H1 antagonist only impact histamine, to produce a more complete anti-inflammatory/ anti- allergic rhinitis effect a glucocorticoid can be used to reduce T cell mediated inflammatory responses.

How is histamine inactivated in the body?

Histamine is inactivated by metabolism by N-methylation on an imidazole nitrogen by N-methyl transferase, oxidation by diamine oxidase, or imidazolacetic acid 5’- phosphoribosyl transferase (conjugation reaction)

How is histamine converted to N-methylhistamine?

By N-methyl transferase (most immediate metabolic histamine reaction)

How is histamine converted to imidazole acetic acid?

By diamine oxidase

How is N-methylhistamine converted to N-methylimidazole acetic acid?

By diamine oxidase

How is imidazole acetic acid converted to imidazole acetic acid riboside?

by imidazoleacetic acid 5’-phosphoribosyl transferase

What are the inactive forms of histamine?

N-methylhistamine

N-methylimidazole acetic acid

imidazole acetic acid

Imidazole acetic acid riboside