Anticholinergic Medications:
What’s the Best Allergy Medication? Comparing Allegra, Benadryl, Claritin, and Zyrtec
This page compares many classes of medications including first and second generation antihistamines, nasal steroids, and decongestants.
Info page on NIH site, discusses mode of action, names and indications of each drug.
Anticholinergics "(anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous system by selectively blocking the binding of ACh to its receptor in nerve cells. The nerve fibers of the parasympathetic system are responsible for the involuntary movement of smooth muscles present in the gastrointestinal tract, urinary tract, lungs, sweat glands, and many other parts of the body."
Dementia 'linked' to common over-the-counter drugs
All medicines can have side-effects and anticholinergic-type drugs that
block a neurotransmitter called acetylcholine are no exception.
Cumulative Use of Strong Anticholinergic Medications and Incident Dementia
"Higher cumulative anticholinergic medication use is associated with an
increased risk for dementia. Efforts to increase awareness among health
professionals and older adults about this potential medication-related
risk are important to minimize anticholinergic use over time."
Oral anticholinergic drugs versus placebo or no treatment for managing overactive bladder syndrome in adults
"The use of anticholinergic drugs by people with overactive bladder
syndrome results in important but modest improvements in symptoms
compared with placebo treatment."
Antihistamines:
There are 4 types of histamine receptors on cells, named H1 through H4, each one is involved in different types of reactions and autoimmune conditions. H1 receptors are associated with most of the "normal" allergy symptoms such as sneezing, itching, runny nose, watery eyes, and anaphylaxis. Nearly all meds that are thought of as antihistamines block the H1 receptor, including OTC and prescription allergy meds. H2 receptors are located in the stomach, where they are involved in the release of stomach acid, so some medications to treat GERD and heartburn (such as Pepcid and Tagamet) are H2 blockers. H2 blockers are also located in heart tissue and some
The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation: The Hunt for New Therapeutic Targets
"Histamine and its receptors (H1R–H4R) play a crucial and significant
role in the development of various allergic diseases. Mast cells are
multifunctional bone marrow-derived tissue-dwelling cells that are the
major producer of histamine in the body. H1R are expressed in many
cells, including mast cells, and are involved in Type 1 hypersensitivity
reactions. H2R are involved in Th1 lymphocyte cytokine production. H3R
are mainly involved in blood–brain barrier function. H4R are highly
expressed on mast cells where their stimulation exacerbates histamine
and cytokine generation. Both H1R and H4R have important roles in the
progression and modulation of histamine-mediated allergic diseases.
Antihistamines that target H1R alone are not entirely effective in the
treatment of acute pruritus, atopic dermatitis, allergic asthma, and
other allergic diseases. However, antagonists that target H4R have shown
promising effects in preclinical and clinical studies in the treatment
of several allergic diseases."
Comparative pharmacology of H1 antihistamines: clinical relevance
Epinephrine (Adrenaline) is both a hormone and neurotransmitter (catecholamine) that is used in the form of EpiPens and other autoinjectors to treat the acute allergic reaction of anaphylaxis. It opens airways in the respiratory system.
H1 BLOCKERS:
Allegra (fexofenadine)
Benadryl (Diphenhydramine)
How I almost killed my mom with a simple anti-itch pill
Clinicaland patient characteristics associated with severe outcome in diphenhydramine toxicity
Diphenhydramine: It is time to say a final goodbye?
The gist of the article is that diphenhydramine, and other first-generation antihistamines, have a risk profile that is higher than the more recently developed second- and third-generation antihistamines (such as cetirizine or loratidine), but are not more effective. The primary risks associated with diphenhydramine are due to the fact that it's effects are not limited to blocking the H1 receptor and as a result they have anticholinergic effects and cause sedation and drowsiness in many people. These effects can last well beyond the night into the next day, and can result in traffic accidents and other problems.
Brompheniramine- serotonergic (led to discovery of SSRIs)
Cetirizine (Zyrtec)
and Levocetirizine (Xyzal)
FDA requires warning about rare but severe itching after stopping long-term use of oral allergy medicines cetirizine or levocetirizine (Zyrtec, Xyzal, and other trade names)
Chlorphenamine- serotonergic. A large study on people 65 years old or older linked the development of Alzheimer's disease and other forms of dementia to the use of chlorphenamine and other first-generation antihistamines, due to their anticholinergic properties.
Claritin
Pharmacology and clinical efficacy of desloratadine as an anti-allergic and anti-inflammatory drug
"Desloratadine is a biologically active metabolite of the
second-generation antihistamine loratadine. Desloratadine is a highly
selective peripheral H1 receptor antagonist that is
significantly more potent than loratadine. Results of in vitro and in
vivo studies have suggested that desloratadine has anti-allergic effects
that are unrelated to its ability to antagonise the effects of
histamine. Desloratadine inhibits the expression of cell adhesion
molecules, inhibits the generation and release of inflammatory mediators
and cytokines, attenuates eosinophil chemotaxis, adhesion and
superoxide generation. Studies in animals indicate that desloratadine
does not cross the blood-brain barrier and therefore does not cause
sedation and does not impair cognition or psychomotor performance.
Desloratadine has an excellent overall safety profile. It has no effect
on QRS and QTc intervals and does not cause arrhythmias.
Desloratadine is not associated with any significant changes in
gastrointestinal function. In clinical studies, oral desloratadine is
rapidly absorbed and bioavailability is not affected by ingestion with
food or grapefruit juice. The half-life of desloratadine in humans is 27
h; the linear kinetic profile is unaltered by race or gender.
Desloratadine is not a substrate for P-glycoprotein or organic anion
transport polypeptide and the drug does not appear to be metabolised to a
significant extent by the cytochrome P450 CYP3A4 pathway. It therefore
may be safely administered with ketoconazole, erythromycin, fluoxetine,
or azithromycin. Clinically, desloratadine effectively controls both
nasal and non-nasal symptoms of seasonal allergic rhinitis (SAR),
including nasal congestion. Desloratadine also provides significant
relief of SAR symptoms in patients with co-existing asthma and is
effective in the treatment of chronic idiopathic urticaria.
Desloratadine improves quality of life and is well-tolerated."
Chlortrimaton
Cyproheptadine (Periactin) is an antihistamine that is used mostly to treat hay fever and itching, but can also be used to treat
serotonin toxicity and is used to increase appetite in some people. It has many other off-label uses including prevention of migraine headaches, treatment of PTSD, akathisia, and insomnia.
Doxepin is a tricyclic antidepressant used to treat anxiety and depression, and it "also displays antagonistic properties in the central nervous system by blocking the following receptors: histamine (H1), alpha-1 adrenergic, and muscarinic. It also inhibits sodium and potassium channels in cardiomyocytes. Doxepin has H1 and H2 histamine receptor blocking actions, which explains the antipruritic effect of doxepin."
Seldane Removed From U.S. Market Over Safety Concerns
"In January of 1997, the FDA
recommended that the terfenadine-containing drugs be removed from the
market and that physicians
consider alternative medications for their patients. The reason for
concern is the existence of
potentially severe drug interactions with SELDANE. The interactions
result in abnormalities of the
electrical impulse that stimulates the heart to contract and pump
blood, and the interactions could
be life threatening."
Desloratadine and loratadine stand out among common H1-antihistamines for association with improved breast cancer survival
"We investigated use of the six major H1-antihistamines
(cetirizine, clemastine, desloratadine, ebastine, fexofenadine and
loratadine) and breast cancer-specific and overall mortality in a
nation-wide register-based study of all 61,627 Swedish women diagnosed
with breast cancer 2006–2013... We found a consistently improved survival of desloratadine users (HR = 0.67; 95% CI 0.55–0.81, p < .001), as well as of loratadine users (HR = 0.80; 95% CI 0.67–0.95, p = .012), relative to nonusers... Based on their safety and current use within the patient population,
together with our observations, we suggest the initiation of trials of
desloratadine and loratadine as treatment of breast cancer as well as
studies of the mechanism behind their possible effect. Further studies
on any effects of other H1-antihistamines may also be merited, as well as of H1-antihistamine use and survival in other malignancies."
H2 receptors are found on parietal cells located in the stomach lining, and are mainly responsible for regulating the levels of gastric acid.
Famotidine (Pepcid)
H2 Receptor Antagonists - Clinical Use and Side Effects (video by Dr Been)
Inhibitory effects of benzodiazepines on the adenosine A2B receptor mediated secretion of interleukin-8 in human mast cells
"We demonstrated that each of the two BZDs studied inhibited the proliferation of MMC- and CTMC-like elements in a dose-dependent fashion (10 to 100 μM). Furthermore, the BZDs inhibited the IgE-mediated release of β-hexosaminidase, TNF-α and nitrites from MMC- or CTMC-like cells. Altogether, these data provide new insights into the pharmacological regulation of MC activation and may lead to the discovery of new and potent antiallergic compounds."
Ventolin (Albuterol/salbutamol)
Xopenex (levalbuterol hydrochloride)
Benralizumab (Fasenra) for Severe Eosinophilic Asthma
Dupilumab Associated With Reduction of Food-Specific IgEs at 12, 24 Months
Omalizumab Therapy for Mast Cell-Mediator Symptoms in Patients with ISM, CM, MMAS, and MCAS
"A complete response was achieved for 1 patient (1.8%), a major response for 30 patients (54.5%), and a partial response for 12 patients (21.8%), resulting in an overall best response rate of 78.2% (43 of 55 patients). The response was persistent at least 3 months in 33 of 43 responding patients (76.7%). At the last follow-up, the final overall response rate was 58.2% (32 of 55 patients). Median time to first response was 2 months and median time to best response was 6 months. Omalizumab was dramatically effective on all superficial and general vasomotor symptoms and on most gastrointestinal or urinary symptoms, and partially effective on most neuropsychiatric symptoms. Safety profile was acceptable, except for one severe adverse event (edema of the larynx and dyspnea after the first injection of omalizumab). Side effects were reported in 16 patients (29%), mainly of low to mild intensity, yet causing interruption of treatment in 5 patients (9%)."
MAST CELL STABILIZERS:
Cromolyn Sodium (Gastrocrom)
Ketotifen (Alaway, Zaditor)
Dupixent (Dipulimab) is an interleukin-4 receptor alpha antagonist and interleukins are another type of mediator released from mast cells
EOSINOPHILIC MEDS
Singulair (Monteleukast)
Budesonide (a steroid med used for asthma) that patients drink. The form Eohilia is budesonide in an oral suspension specifically for use in EoE.
Gleevec (Imatinib)
