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The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 36

43. What is a rebound reaction?

Rebound is a term that gets used a lot in the mast cell community, often incorrectly. Rebound reactions occur when medication taken to suppress symptoms wears off. This phenomenon is easiest to see with the older H1 antihistamines like diphenhydramine (Benadryl). Benadryl is broken down pretty quickly by the body so it wears off in about 4-6 hours. In some situations, it can break down even faster.

When you take diphenhydramine, as soon as it’s in your body, the diphenhydramine looks for the molecules on the outsides of cells called histamine receptors. In order for histamine to affect your body, they have to find one of these histamine receptors and sit on it. If it can’t do that, the histamine is not able to cause symptoms or perform its normal function. The antihistamine finds those receptors and sits on top of it so that the histamine can’t fit in. This translates into fewer symptoms because the histamine is blocked.

How effective antihistamines are at finding those receptors and sitting on them differs from drug to drug. Some do this really quickly but others take a few hours to find the receptors. Some drugs can get knocked off the histamine receptors they sat on. Drugs like this are less effective antihistamines.

Diphenhydramine finds the histamine receptors very quickly and sticks to them very strongly. This is why it is such an effective antihistamine. Because it is such a strong antihistamine, when your body breaks it down, your symptoms can come back quickly and forcefully. This is called rebound. Your symptoms reappear because there’s no longer enough medication in your body to keep the histamine from working. (Please note that rebound reactions can also happen with other medications for other diseases in ways that do not affect histamine. I’m just being general here for the mast cell disease audience.)

Rebound reactions can be tricky to get out of because the natural response to take medication again to control the symptoms. However, when you do this, you may just be setting yourself up for another rebound reaction when this dose wears off. This is one of the reasons why many doctors prefer that their mast cell patients not take Benadryl frequently. When you are stuck in a rebound loop, it can cause a lot of inflammation and that can trigger your mast cells even more.

There are a few strategies to help decrease the likelihood of rebound reactions. One is to stagger medication dosing. If a couple of your medications can cause rebound, don’t take them at the same time if you can avoid it. Take one an hour or two after the other. Some patients find benefit in layering antihistamines. By taking multiple antihistamines, you can cover lots of histamine receptors. Sometimes, it covers enough that when your diphenhydramine wears off, your body doesn’t notice as much. This could lessen a rebound reaction or even prevent one in some circumstances. You could also take another strong medication to help control your mast cells in another way, like a steroid.

Following a major reaction or anaphylaxis, many providers opt to use a taper for diphenhydramine and steroids. This can help with rebound reactions. A patient doing this might take diphenhydramine every 4 hours for one day, then every 6 hours for two more days, then every 12 hours for two more days. By not stopping cold turkey, you can allow your body to adapt. Steroid tapers do the same thing. You want to give your body a chance to compensate for not having the medication around.

Not all medications cause rebound reactions. The second generation H1 antihistamines like cetirizine or loratadine do not normally cause rebound reactions.

One important point is that many people use the term “rebounding” when they actually mean a different thing called biphasic anaphylaxis. Rebounding specifically means the reappearance of symptoms because the medication controlling them has worn off. Biphasic anaphylaxis is when you have anaphylaxis again after having a first anaphylactic event, regardless of treatment. In this scenario, a person has anaphylaxis and takes medications to treat the anaphylaxis effectively. Sometime later on, the body has a second anaphylaxis event without being exposed again to a trigger. This is not tied to any specific treatment and is different than rebounding.

For more detailed reading, please visit these posts:

How to get out of a reaction cycle

Anaphylaxis and mast cell reactions

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 19

I answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

28. Why are so many mast cell patients anemic?
• Anemia occurs when a person has too few red blood cells or not enough hemoglobin. Red blood cells are essentially envelopes that serve specifically to hold hemoglobin. Hemoglobin is a molecule made with iron that picks up oxygen. When you have either too few red blood cells or they don’t have enough hemoglobin, not enough oxygen gets to all the parts of the body that need it.
Patients with chronic illness of many kinds often have anemia. This is called anemia of chronic inflammation or anemia of inflammatory response.
• This type of anemia occurs because of the overactivity of a hormone called hepcidin. This hormone tells cells in the GI tract to hold onto any iron they find. This means they do not pass the iron along to the blood so it can make hemoglobin. Since the body isn’t making enough hemoglobin, the body doesn’t get enough oxygen.
• Mast cell patients often have anemia of chronic inflammation so they may be anemic regardless of how much iron they have in their diet. However, increased supplementation sometimes helps.
• There are several forms of iron that can be taken by mouth. IV iron is also an option. Some people have luck cooking in cast iron pans or using the “Lucky Iron Fish” to get even more iron into their diet in hopes that they can take up a little bit more.
Having enough iron available also decreases mast cell activation. Mast cells make smaller amounts of inflammatory molecules when the body has sufficient iron.
• Mast cell patients may also selectively malabsorb iron in their GI tracts. This means that even if they are absorbing enough of other nutrients, they may not absorb enough iron properly due to inflammation. This sometimes improves with antihistamines.
• Mast cell patients usually take histamine H2 blockers. This decreases the strength of stomach acid which can affect absorption of nutrients like iron. Taking PPIs can do the same thing.
• Malabsorption of other nutrients, like copper, can contribute to anemia.
• Insufficient amounts of B12 or folate can cause also contribute to anemia.

For more detailed reading, please visit these posts:
Anemia of chronic inflammation
MCAS: Anemia and deficiencies
Effect of anemia on mast cells

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 9

I have answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

15. How is mast cell disease treated?
• There are a number of medications to treat mast cell disease. Mast cells release so many chemicals, some in a large quantity. We are not able to totally stop mast cells from releasing the chemicals so we need to use many medications to block their effects on the body.
The baseline regimen for mast cell patients include antihistamines and mast cell stabilizers. Specifically, patients are usually prescribed two antihistamines that work two different ways. These are called H1 antihistamines and H2 antihistamines. The H in these meds stand for histamine. There are many antihistamine options. Antihistamines stop the histamine from working in the body. Even still, many patients experience histamine driven symptoms
Mast cell stabilizers work by making mast cells less likely to release chemicals. There are fewer options for mast cell stabilizers. Cromolyn is a very common mast cell stabilizer. Ketotifen is both a mast cell stabilizer and an antihistamine. Ketotifen that you can take as a pill is not approved in the US because there was not a market for it so it was never submitted to the FDA. However, patients can get ketotifen in pill form through compounding pharmacies in the US.
• Other types of medication commonly used for mast cell disease that block the effect of mast cell chemicals include leukotriene inhibitors and PAF blockers.
Some medications can stop mast cells from making specific chemicals. These include COX inhibitors, lipoxygenase inhibitors, and corticosteroids like prednisone.
Many patients are deficient in some vitamins or minerals because they don’t absorb them well in the GI tract. Vitamin D and iron are commonly low. Patients often take supplements to replace these deficiencies.
• Chemo drugs are sometimes used to treat severe mast cell disease. These drugs can kill mast cells and/or decrease the amount of chemicals released.
• IV fluids are reported by patients to help with symptoms such as fatigue and swelling.
• There are many other medications that can be used to treat other symptoms.

16. Do I have to take medication if I feel okay?
Mast cell patients are usually recommended to take baseline medications like antihistamines and mast cell stabilizers even if they feel okay. This is for two main reasons: mast cells can damage your body even if you don’t feel it; and if you do not take baseline medications, you will have less protection from a severe reaction and anaphylaxis.
• Many patients have other medications prescribed to be taken as needed. These medications are given when symptoms are bad and do not necessarily have to be taken daily.
• Please speak with your provider to clarify what meds are taken as needed and what meds are taken every day.
For more detailed reading, please visit these posts:

The Provider Primer Series: Management of mast cell mediator symptoms and release

The Provider Primer Series: Mast cell activation syndrome (MCAS)

The Provider Primer Series: Cutaneous Mastocytosis/ Mastocytosis in the Skin

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (ISM, SSM, ASM)

The Provider Primer Series: Diagnosis and natural history of systemic mastocytosis (SM-AHD, MCL, MCS)

Cardiovascular manifestations of mast cell disease (Part 2 of 5)

Abnormalities of heart rate and rhythm can occur due to action of several mast cell mediators. Histamine binds at histamine receptors numbered in the order of identification: H1, H2, H3 and H4. Histamine binding at H1 receptors on cardiomyocytes (heart muscle cells) slows the heart rate, while histamine binding at H2 receptors increasing heart rate and the force of heart contraction.

As I mentioned in the previous post, histamine binding at the H3 receptor decreases the release of norepinephrine. Another mast cell product, renin, modulates angiotensin II, which can increase norepinephrine release.  Increased levels of norepinephrine triggers increases in heart rate and force of contraction.  This means that whether or not mast cell activation causes tachycardia depends largely on how much renin and histamine are released. Much less histamine is necessary to trigger the H3 inhibition of norepinephrine release relative to the amount needed to affect heart rate through H1 and H2 receptors.

Prostaglandin D2, a mast cell mediator, can also cause tachycardia.  Of note, prostaglandin D2 is not stored in mast cell granules.  It is made following mast cell activation and is considered part of the “late phase allergy response”, which can occur several hours after exposure to a trigger.

Tachycardia is a common symptom for mast cell patients.  The recommendation in a recent review article is to treat when the heart rate is perpetually over 100-120 bpm, or when it is extremely distressing to the patient. There are a number of options for treatment. As it can be caused directly by mast cell behavior, mast cell medications such as antihistamines (H1 and H2) should be adjusted for maximum effect. Renin inhibitors, such as aliskiren (Tekturna in the US), can be used to treat supraventricular tachycardia (SVT) in mast cell patients, as can angiotensin receptor blockers like losartan, valsartan and others. Patients on renin inhibitors or angiotensin receptor blockers can also decrease blood pressure.

Calcium channel blockers, like verapamil, are also an option.  The medication ivabradine treats tachycardia in patients who have a regular heart rhythm and does not affect blood pressure.  Ivabradine is not used to treat atrial fibrillation. β-blockers are contraindicated in mast cell patients because it interferes with the action of epinephrine, making patients more likely to have reactions and epinephrine less likely to treat effectively.


Kolck UW, et al. Cardiovascular symptoms in patients with systemic mast cell activation disease. Translation Research 2016; x:1-10.

Gonzalez-de-Olano D, et al. Mast cell-related disorders presenting with Kounis Syndrome. International Journal of Cardiology 2012: 161(1): 56-58.

Kennedy S, et al. Mast cells and vascular diseases. Pharmacology & Therapeutics 2013; 138: 53-65.

Antihistamine Table: Generics and US brand names


First generation  
Benztropine Cogentin
Brompheniramine Dimetapp, Bromfed
Carbinoxamine Palgic
Chlorpheniramine Chlor-Trimetron
Clemastine Tavist
Cyproheptadine Periactin
Dexbrompheniramine Drixoral
Diphenhydramine Benadryl
Doxylamine Unisom, Nyquil
Hydroxyzine Atarax, Vistaril
Meclizine Antivert, Bonine, Dramamine
Orphenadrine Norflex
Prometheazine Phenergan
Second and third generation
Acrivastine Semprex-D
Cetirizine Zyrtec
Clemastine Tavist
Desloratadine Clarinex
Fexofenadine Allegra
Ketotifen N/A
Levocetirizine Xyzal
Loratadine Claritin
Tricyclic antidepressants
Amitriptyline Elavil
Clomipramine Anafranil
Desipramine Norpramin
Doxepin Silenor
Imipramine Tofranil
Nortriptyline Pamelor
Protriptyline Vivactil
Atypical antipsychotics
Aripiprazole Abilify
Asenapine Saphris
Clozapine Clozaril
Iloperidone Fanapt
Olanzapine Zyprexa
Paliperidone Invega
Quetiapine Seroquel
Risperdone Risperdal
Ziprasidone Geodon
Typical antipsychotics
Chlorpromazine Thorazine
Fluphenazine Prolixin
Perphenazine Trilafon
Prochlorperazine Compazine
Thioridazine Mellaril
Thiothixene Navane
Tetracyclic antidepressants
Amoxapine N/A
Loxapine Loxitane
Maprotiline Ludiomil
Mirtazapine Remeron

Histamine depletion in exercise

A long known and often repeated finding is that regular exercise can be protective against asthma. This finding was published in 1966 by a group that found the airways of asthmatics grew progressively less reactive following intervals of exercise. This finding was confirmed by several studies that followed. At the time, the reason why exercise protected against reactive airways was unclear, but an early hypothesis was that mediators were depleted after the initial round of exercise and that time was required to restore them.

In the 1980’s, there was a wave of research around the role of histamine in airway reactivity of asthmatics. There were a few competing theories at this point for why asthmatics became less reactive following exercise: depletion of mediators, mainly histamine from mast cells; that bronchial smooth muscle became less responsive to stimulation by histamine via the H1 receptor; and that release of catecholamines (such as epinephrine) by exercise suppresses bronchoconstriction. A number of studies made relevant findings.

Histamine is known to be released in the lungs due to exercise. It is also known to become depleted and quickly metabolized. When exposed to histamine, asthmatics recover quickly from the ensuing bronchoconstriction. Some asthmatic patients show an increase in plasma histamine during exercise.

Plasma epinephrine does not rise in asthma patients as a result of exercise, or at the very least is metabolized almost immediately, and thus is unlikely to be protective. Bronchial smooth muscle was not found to become less responsive to histamine. This was demonstrated in a study that compared repeated inhalation of histamine (such as might be induced by exercise) with actual repeated exercise. This study found that repeated exercise diminished airway reactivity, while repeated inhalation of histamine did not.

Another report indicated that inhalation of cromolyn before exercise can prevent or mitigate exercise induced asthma in most patients. Administration of H1 inverse agonists was found to offer similar protection.

A more recent study (2012) looked at the role of histamine in fatigue from exercise. Histamine is now known to be involved in regulation of oxygen/carbon dioxide exchange, which is important in exercise. In mice that were persistently exercised, the level of histidine decarboxylase was increased. HDC is the enzyme that makes and immediately releases histamine in response to an immediate need. This is different from degranulation, in which histamine is made ahead of time and stored inside the cell until needed.

This study found that treating the mice with an H1 antihistamine, H2 antihistamine, or HDC inhibitor decreased endurance in the mice. Mice deficient in HDC or H1 receptors also had less endurance. This means that histamine is partly responsible for inducing tolerance to exercise and that blocking action of histamine causes fatigue to set in more quickly.

Treatment with fexofenadine, an H1 antihistamine, decreased levels of nitric oxide and glycogen in the muscles of exercised mice. Taken together, these findings mean that histamine protects against fatigue from exercise; that this effect is achieved via H1 receptors and production of nitric oxide; and that at least some of this histamine is provided by immediate production and release of histamine via HDC. This means that your body does not simply release its histamine stores in response to exercise; it makes it on the fly so as not to exhaust its supply.



Hahn, Allan G., et al. Histamine reactivity during refractory period after exercise induced asthma. Thorax 1984; 39: 919-923.

Niijima-Yaoita, Fukie, et al. Roles of histamine in exercise-induced fatigue: favouring endurance and protecting against exhaustion. Biol Pharm Bull 2012; 35; 91-97.

Schoeffel, Robin E., et al. Multiple exercise and histamine challenge in asthmatic patients. Thorax, 1980, 35, 164-170.

Graham P, Kahlson G, Rosengren E. Histamine formation in physical exercise, anoxia and under the influence of adrenaline and related substances. J. Physiol., 172, 174—188 (1964).

McNeill RS, Nairn JR, Millar JS, Ingram CG.Exercise-induced asthma. Q J Med 1966; 35: 55-67.


Mast cell medications: Antihistamines by receptor activity

The following medications listed are available in oral or intravenous formulation. Not all medications are available in the US or Europe. Topical and inhaled medications are not included in these lists.

H1 antihistamines interfere with the action of histamine at the H1 receptor. This can help with many symptoms, including flushing, itching, hives, burning skin, nasal congestion, sneezing, constriction of airway, shortness of breath, GI cramping, diarrhea, gas, abdominal pain, tachycardia, blood pressure variability or dizziness. What symptoms are best alleviated varies with the medication; they do not all address all symptoms equally.

First generation Second and third generation Atypical antipsychotics
Alimemazine Acrivastine Aripiprazole
Azatadine Astemizole Asenapine
Benztropine Azelastine Clozapine
Bepotastine Bepotastine Iloperidone
Brompheniramine Bilastine Olanzapine
Buclizine Cetirizine Paliperidone
Captodiame Clemastine Quetiapine
Carbinoxamine Clemizole Risperdone
Chlorcyclizine Clobenztropine Ziprasidone
Chloropyramine Desloratadine Zotepine
Chlorpheniramine Ebastine
Chlorphenoxamine Emedastine
Cinnarizine Epinastine Typical antipsychotics
Clemastine Fexofenadine Chlorpromazine
Cyclizine Ketotifen Flupenthixol
Cyproheptadine Latrepirdine Fluphenazine
Dexbrompheniramine Levocabastine Perphenazine
Dexchlorpheniramine Levocetirizine Prochlorperazine
Dimenhydrinate Loratadine Thioridazine
Diphenhydramine Mebhydrolin Thiothixene
Diphenylpyraline Mizolastine
Doxylamine Rupatadine
Embramine Setastine Tetracyclic antidepressants
Etodroxizine Talastine Amoxapine
Ethylbenztropine Terfenadine Loxapine
Etymemazine Maprotiline
Flunarizine Mianserin
Histapyrrodine Tricyclic antidepressants Mirtazapine
Homochlorcyclizine Amitriptyline Oxaprotiline
Hydroxyethylpromethazine Butriptyline
Hydroxyzine Clomipramine
Isopromethazine Desipramine
Meclizine Dosulepin
Mequitazine Doxepin
Methdilazine Imipramine
Moxastine Iprindole
Orphenadrine Lofepramine
Oxatomide Nortriptyline
Oxomemazine Proptriptyline
Phenindamine Trimipramine


H2 antihistamines interfere with the action of histamine at the H2 receptor. This helps mostly with symptoms affecting the GI tract, such as abdominal pain, nausea, and diarrhea. To a lesser extent, H2 antihistamines can decrease vasodilation.

H2 antagonists


There are few H3 antihistamines and for this reason, their exact effects are largely unknown.  However, in research, H3 antihistamines modulate nerve pain and may normalize the release of several neurotransmitters, including serotonin.

The only medication with known H3 activity available for patient use as an antihistamine anywhere in the world is betahistine. It is anti-vertigo drug used mostly in treatment of Meniere’s disease and other balance disorders. Betahistine actually increases release of histamine and for this reason has been associated with the risk of severe allergic events while taking it.

A 2014 paper described for the first time the H3 reverse agonist/ selective antagonist effects of two antiarrhythmic drugs, amiodarone and lorcainide. This is a very new finding and has not been investigated yet in humans; however, this behavior would explain some of the neurologic effects of these two medications.

H3 antihistamines


Thioperamide has shown promise in research as an H3 and H4 antihistamine, but is not available for patient use.

I have seen blurbs on forums and the internet in which people state that amphetamines are H3 antagonists and doxepin is an H4 antihistamine. I cannot find any evidence that this is the case. Amphetamines interact with the transport of histamine in a very complex way, and that can theoretically interfere with the ability of cells to use histamine. However, this is not the same as a true antihistamine, and the effect of amphetamines on histamine has been difficult to quantify.

Anti-inflammatory properties of H1 antihistamines

H1 antihistamines are also known to have anti-inflammatory properties. Some studies show that H1 antihistamines prevent histamine release, which is actually independent of the ability to bind H1 receptors. This effect is thought to occur by interfering with calcium activity on the cell membrane, which may be important in signaling to a cell to release histamine. However, other studies say the amount by which histamine release is reduced is not significant clinically.

H1 antihistamines have also been observed to reduce eosinophil accumulation near allergic sites. This may be due to the ability of H1 antihistamines to interfere with activation of a molecule called NF-kB. This molecule is important in production of inflammatory cytokines. NF-kB can be activated by several inflammatory molecules, including histamine and TNF. Low concentrations of cetirizine and azelastine have been shown to result in lower levels of NF-kB while also inhibiting the production of IL-1b, IL-6, IL-8, TNF and GM-CSF.

Bradykinin is a mediator released by mast cells that causes inflammation, pain and edema. H1 antihistamines such as chlorpheniramine and cetirizine have been reported to inhibit bradykinin induced formation of hives, which may mean that bradykinin triggers hitamine release, which in turn participates in hive formation. However, in testing, the amount of histamine found in these reactions was minimal. This implies that H1 antihistamines may be able to inhibit bradykinin action in another way. H1 antihistamines have also inhibited weal and flare responses by methacholine and platelet activating factor (PAF).


Church, Diana S., Church, Martin K. Pharmacology of antihistamines. World Allergy Organization Journal 2011, 4 (Suppl 3): S22-S27.

Leurs, R., et al. H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects. Clinical and Experimental Allergy 32 (2002): 489-498.

Pharmacology of H1 antihistamines

H1 receptors are a type of G-protein-coupled-receptors (GPCRs), and exist in two different conformational states. A conformation is a shape, and the way a receptor is shaped affects its activity. One of the H1 receptor conformations makes it active, so it is effectively the “on” position. The other makes it inactive, so it is effectively the “off” position.

When histamine binds to the H1 receptor, it keeps the receptor in the “on” position. This causes many things to occur. If too many H1 receptors are bound in the “on” position for too long, it can cause airway constriction, difficulty breathing, dilation of blood vessels, hiving, pain and itching, among other symptoms.

In pharmacology, two terms are used to describe the effect a substance has when it binds to a receptor. An agonist fully activates the receptor it binds to. Histamine is an agonist of the H1 receptor because when it binds the receptor, it activates it and thus turns it on. An antagonist binds the receptor but doesn’t turn it on (which is not the same as turning it off). By the antagonist binding the receptor, it prevents histamine from binding there are turning it on.

The medications we use to mediate H1 receptor actions, like diphenhydramine or cetirizine, are often called H1 antagonists, but this is a misnomer. All known medications that act on H1 receptors are more correctly classed as H1 reverse agonists, which is a trickier concept. Basically this means that when these medications bind the H1 receptor, they turn it off. In turn, this prevents a series of actions that are executed by the action of histamine.

First generation H1 antihistamines have a wide ranging group of effects. I have described receptors in the past as being like locks, and the substances that bind them (called ligands) are like keys. In this analogy, first generation H1 antihistamines like diphenhydramine would be like a master key. They are capable of binding to many receptors, including muscarinic, serotonin and a-adrenergic receptors. They also cross the blood-brain barrier. Histamine is an important neurotransmitter with a lot of activity of the brain. By crossing into the brain, these first generation H1 antihistamines can interfere with the sleep-wake cycle, learning, memory, fluid balance, regulation of body temperature, regulation of the cardiovascular system, and stress release of ACTH and b-endorphin from the pituitary.

During the day, first generation H1 antihistamines often cause sleepiness, sedation, drowsiness, fatigue and impaired concentration and memory, even at recommended doses. At night, they delay the onset and reduce the duration of REM sleep. This in turn causes a lower quality sleep, with decreases in attention, vigilance and working memory still observable in the morning.

Second generation H1 antihistamines have largely dealt with the issues present in first generation formulations. Unlike first generation medications, they bind with excellent specificity to the H1 receptor, rather than binding promiscuously. They demonstrate very limited penetration of the blood brain barrier so there is little associated sedation. Desloratadine in the most potent antihistamine, followed by levocetirizine and then fexofenadine.

H1 antihistamines are universally well absorbed with the exception of fexofenadine, which relies on a unique transport mechanism that can be more variable. Studies have shown that in adults, the maximum inhibition of allergic response occurs about four hours after taking levocetirizine, fexofenadine or desloratadine. Loratadine requires metabolism to release the active portion of the molecule, and thus can take hours longer to become efficacious. Fexofenadine has a shorter duration of action at about 8.5 hours, compared to 19 hours for cetirizine at a typical dose.


Church, Diana S., Church, Martin K. Pharmacology of antihistamines. World Allergy Organization Journal 2011, 4 (Suppl 3): S22-S27.

Leurs, R., et al. H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects. Clinical and Experimental Allergy 32 (2002): 489-498.

A comprehensive list of antihistamines: H1 receptor (part 2)

Chloropyramine is a first generation H1 antagonist. It is used for allergic eye and nasal symptoms, bronchial asthma, Quincke’s edema, and allergic reactions to food, medications and insect bites. It is available in several European countries as an oral or IV/IM preparation for emergent situations. It has the typical anticholinergic side effects seen in older H1 antihistamines. It is available under several names, including Allergosan, Suprastin, Supralgon and Avapena, in several countries, including Georgia, Hungary, Lithuania, Latvia, Russia, Croatia, Serbia, Bosnia and Herzegovina, Bulgaria and Mexico.

Chlorpheniramine is a first generation H1 alkylamine antihistamine. It is less sedating than other first generation antihistamines. It is sometimes used off label as an antidepressant and anti-anxiety medication as it has serotonin-norepinephrine reuptake inhibiting properties. It is available alone and in various combinations in the US, Canada, throughout Europe and Asia.

Chlorphenoxamine, more commonly known as Systral, is a medication with structural similarities to diphenhydramine. It is mostly used as an anti-Parkinsonian drug and is available in Latin American and Caribbean countries, as well as some European countries and Thailand.

Cinnarizine is an H1 antagonist that functions as both an antihistamine and also as a calcium channel blocker. It is a piperazine derivative. It improves blood flow to the brain and is used for cerebral apoplexy, cerebral symptoms following trauma and cerebral arteriosclerosis. It is also used for nausea and vomiting due to several causes. It is also antiserotinergic and antidopaminergic. Due to its action of dopamine receptors, it can cause parkinsonism if used frequently. It is not available in the US or Canada, but is available under a number of names in many countries, including Brazil, Peru, Philippines, Malaysia, China, Bangladesh, India, and Israel, among several others.

Clemastine is an H1 anthistamine. Though it can be sedating, it has fewer side effects than several other H1 medications. It is also a functional inhibitor of acid sphingomyelinase. It is available in many countries without prescription under brand names such as Tavist, Tavegil or Agasten. It is particularly effective for itching.

Cyclizine is an H1 antihistamine mostly used for nausea, vomiting and dizziness from motion sickness or medications, such as anesthesia. It is also used to potentiate the effects of opiates and opioids. It is a piperazine derivative and is available in the US and UK as IM/IV and oral formulations.

Cyproheptadine is a first generation H1 antihistamine. It is also antiserotonergic and for this reason is used to manage serotonin syndrome. It has a variety of unusual uses, including as a local anesthetic, to treat nightmares in children and due to PTSD, for hyperhidrosis, and to prevent migraine.

Dexbrompheniramine is a widely available medication with structural similarities to chlorpheniramine. It is used to manage general allergic symptoms. It is available in the US and Canada as Drixoral.

Dexchlorpheniramine is the one form of the drug chlorpheniramine. It is available in the US and Canada as Polaramine.