Instruct: Given a question, retrieve documents that can help answer the question.
Query: Are there long term side effects of antihistamine usage?
Antihistamines are drugs which treat allergic rhinitis and other allergies.[1] Antihistamines can give relief when a person has nasal congestion, sneezing, or hives because of pollen, dust mites, or animal allergy.[1] Typically people take antihistamines as an inexpensive, generic, over-the-counter drug with few side effects.[1] As an alternative to taking an antihistamine, people who suffer from allergies can instead avoid the substance which irritates them. However, this is not always possible as some substances, such as pollen, are carried in the air, thus making allergic reactions caused by them generally unavoidable.[1] Antihistamines are usually for short-term treatment.[1] Chronic allergies increase the risk of health problems which antihistamines might not treat, including asthma, sinusitis, and lower respiratory tract infection.[1] Doctors recommend that people talk to them before any longer term use of antihistamines.[1]
The benzodiazepine and nonbenzodiazepine hypnotic medications also have a number of side-effects such as day time fatigue, motor vehicle crashes and other accidents, cognitive impairments, and falls and fractures. Elderly people are more sensitive to these side-effects.[113] Some benzodiazepines have demonstrated effectiveness in sleep maintenance in the short term but in the longer term benzodiazepines can lead to tolerance, physical dependence, benzodiazepine withdrawal syndrome upon discontinuation, and long-term worsening of sleep, especially after consistent usage over long periods of time. Benzodiazepines, while inducing unconsciousness, actually worsen sleep as—like alcohol—they promote light sleep while decreasing time spent in deep sleep.[114] A further problem is, with regular use of short-acting sleep aids for insomnia, daytime rebound anxiety can emerge.[115] Although there is little evidence for benefit of benzodiazepines in insomnia compared to other treatments and evidence of major harm, prescriptions have continued to increase.[116] This is likely due to their addictive nature, both due to misuse and because—through their rapid action, tolerance and withdrawal—they can "trick" insomniacs into thinking they are helping with sleep. There is a general awareness that long-term use of benzodiazepines for insomnia in most people is inappropriate and that a gradual withdrawal is usually beneficial due to the adverse effects associated with the long-term use of benzodiazepines and is recommended whenever possible.[117][118]
Since many of the uses of antihistamines involve conditions such as rashes, which should be treatable by local application, there is some rationale for developing drugs for topical use. The known side effects of antihistamines could in principle be avoided if the drug were functionalized to avoid systemic absorption. The known poor absorption of quat salts make such derivatives attractive for nonabsorbable antihistamines for topical use.
This is a general list of long-term side effects associated with Antipsychotic (neuroleptic) medication.
Not much published research exists which compares the efficacy and safety of the various antihistamines available.[1] The research which does exist are mostly short term studies or studies which look at too few people to make general assumptions.[1] Another gap in the research is in information reporting the health effects for individuals with long term allergies to take antihistamines for a long period of time.[1] Newer antihistamines have been demonstrated to be effective in treating hives.[1] However, there is not research comparing the relative efficacy of these drugs.[1]
Clemastine, also known as meclastin, is an antihistamine and anticholinergic. Unlike loratadine or fexofenadine, clemastine is a sedating antihistamine; however, it exhibits fewer other side effects than most of the widely used antihistamines. Clemastine is also classified as an antipruritic (i.e., it stops itching).
As an alternative to taking prescription drugs, some evidence shows that an average person seeking short-term help may find relief by taking over-the-counter antihistamines such as diphenhydramine or doxylamine.[92] Diphenhydramine and doxylamine are widely used in nonprescription sleep aids. They are the most effective over-the-counter sedatives currently available, at least in much of Europe, Canada, Australia, and the United States, and are more sedating than some prescription hypnotics.[93] Antihistamine effectiveness for sleep may decrease over time, and anticholinergic side-effects (such as dry mouth) may also be a drawback with these particular drugs. While addiction does not seem to be an issue with this class of drugs, they can induce dependence and rebound effects upon abrupt cessation of use. However, people whose insomnia is caused by restless legs syndrome may have worsened symptoms with antihistamines.[94]
Mast cell stabilizers can help people with allergic conjunctivitis. They tend to have delayed results, but they have fewer side-effects than the other treatments and last much longer than those of antihistamines. Some people are given an antihistamine at the same time so that there is some relief of symptoms before the mast cell stabilizers becomes effective. Doctors commonly prescribe lodoxamide and nedocromil as mast cell stabilizers, which come as eye drops.
At very low doses, doxepin has not shown discontinuation or withdrawal effects nor rebound insomnia. Sustained effectiveness without apparent tolerance was demonstrated in clinical studies of up to 12 weeks duration. This appears to be in contrast to over-the-counter antihistamines like diphenhydramine and doxylamine and all other first-generation antihistamines, which are associated with rapid development of tolerance and dependence (by day 3 or 4 of continuous dosing) and loss of hypnotic effectiveness. It is for this reason that, unlike doxepin, they are not recommended for the chronic management of insomnia and are advised for only short-term treatment (i.e., 1 week). It is not entirely clear why doxepin and first-generation antihistamines are different in this regard, but it has been suggested that it may have to do with the lack of selectivity for the H receptor of the latter or may have to do with the use of optimal doses. Unlike very-low-dose doxepin, most first-generation antihistamines also have marked anticholinergic activity as well as associated side effects such as dry mouth, constipation, urinary retention, and confusion. This is particularly true in older people, and antihistamines with concomitant anticholinergic effects are not recommended in adults over the age of 65. Anticholinergic activity notably may interfere with the sleep-promoting effects of H receptor blockade.
Orphenadrine has the side effects of the other common antihistamines in large part. Stimulation is somewhat more common than with other related antihistamines, and is especially common in the elderly. Common side effects include dry mouth, dizziness, drowsiness, upset stomach or vomiting, constipation, urine retention, blurred vision, and headache. Its use in Parkinson's is especially limited by these factors.
Triprolidine is an over-the-counter antihistamine with anticholinergic properties. It is used to combat the symptoms associated with allergies and is sometimes combined with other cold medications designed to provide general relief for flu-like symptoms. Like many antihistamines, the most common side effect is drowsiness.
Terfenadine, the first non-sedating antihistamine, had to be withdrawn from the market because of the small risk of a serious side effect. However, terfenadine was discovered to be the prodrug of the active molecule, fexofenadine, which does not carry the same risks as the parent compound. Therefore, fexofenadine could be placed on the market as a safe replacement for the original drug. Loratadine, another non-sedating antihistamine, is the prodrug of desloratadine, which is largely responsible for the antihistaminergic effects of the parent compound. However, in this case the parent compound does not have the side effects associated with terfenadine, and so both loratadine and its active metabolite, desloratadine, are currently marketed.
This is only a list of long term side effects, and many consumers of these drugs may experience a decline in these side effects over time if they continue to take their medicine.
Itching and flushing and other effects of blood vessel dilation are also common side-effects, due to histamine release in response to the drug using one or more types of receptors in the CNS or other responses elsewhere in the body. First-generation antihistamines such as tripelennamine (Pyrabenzamine), clemastine (Tavist), hydroxyzine (Atarax), diphenhydramine (Benadryl), cyproheptadine (Periactin), brompheniramine (Dimetapp), chlorphenamine (Chlor-Trimeton), doxylamine (NyQuil) and phenyltoloxamine (Percogesic Original Formula) not only combat the histamine-driven side-effects, but are analgesic-sparing (potentiating) in various degrees. The antihistamine promethazine (Phenergan) may also have a positive effect on hepatic metabolism of dihydrocodeine as it does with codeine. Higher doses of promethazine may interfere with most other opioids with the exception of the pethidine family (Demerol and the like) by this or other unknown mechanisms.
Doxylamine succinate is a potent anticholinergic and has a side-effect profile common to such drugs, including dry mouth, ataxia, urinary retention, drowsiness, memory problems, inability to concentrate, hallucinations, psychosis, and a marked increased sensitivity to external stimuli. Like many hypnotics, it should not be combined with other antihistamines, such as cetirizine (Zyrtec) or diphenhydramine (Benadryl), as this combination can increase the risk of serious side effects. Using doxylamine over a long period of time is not recommended. However, the drug is not addictive, and withdrawal effects are unlikely to be experienced with prolonged use.
Antihistamines (or "histamine antagonists") inhibit the release or action of histamine. "Antihistamine" can be used to describe any histamine antagonist, but the term is usually reserved for the classical antihistamines that act upon the H histamine receptor. Antihistamines are used as treatment for allergies. Allergies are caused by an excessive response of the body to allergens, such as the pollen released by grasses and trees. An allergic reaction causes release of histamine by the body. Other uses of antihistamines are to help with normal symptoms of insect stings even if there is no allergic reaction. Their recreational appeal exists mainly due to their anticholinergic properties, that induce anxiolysis and, in some cases such as diphenhydramine, chlorpheniramine, and orphenadrine, a characteristic euphoria at moderate doses. High dosages taken to induce recreational drug effects may lead to overdoses. Antihistamines are also consumed in combination with alcohol, particularly by youth who find it hard to obtain alcohol. The combination of the two drugs can cause intoxication with lower alcohol doses.
The long-term use of benzodiazepines may have a similar effect on the brain as alcohol, and are also implicated in depression, anxiety, post-traumatic stress disorder (PTSD), mania, psychosis, sleep disorders, sexual dysfunction, delirium, and neurocognitive disorders. However a 2016 study found no association between long-term usage and dementia. As with alcohol, the effects of benzodiazepine on neurochemistry, such as decreased levels of serotonin and norepinephrine, are believed to be responsible for their effects on mood and anxiety. Additionally, benzodiazepines can indirectly cause or worsen other psychiatric symptoms (e.g., mood, anxiety, psychosis, irritability) by worsening sleep (i.e., benzodiazepine-induced sleep disorder).
Hallucinations and possibly delirium resembling the effects of Datura stramonium can result if the drug is taken in much higher than therapeutical dosages. Antihistamines are widely available over the counter at drug stores (without a prescription), in the form of allergy medication and some cough medicines. They are sometimes used in combination with other substances such as alcohol.
The most common unsupervised use of antihistamines in terms of volume and percentage of the total is perhaps in parallel to the medicinal use of some antihistamines to stretch out and intensify the effects of opioids and depressants. The most commonly used are hydroxyzine, mainly to stretch out a supply of other drugs, as in medical use, and the above-mentioned ethanolamine and alkylamine-class first-generation antihistamines, which are - once again as in the 1950s - the subject of medical research into their anti-depressant properties.
A systematic review of 30 trials, with 17 different treatment comparisons found that all topical antihistamines and mast cell stabilizers included for comparison were effective in reducing symptoms of seasonal allergic conjunctivitis. There was not enough evidence to determine differences in long-term efficacy among the treatments.
Treatment guidelines for the management of chronic hives have been published. According to the 2014 American practice parameters, treatment involves a step wise approach. Step 1 consists of second generation, H1 receptor blocking antihistamines. Systemic glucocorticoids can also be used for episodes of severe disease but should not be used for long term due to their long list of side effects. Step 2 consists of increasing the dose of the current antihistamine, adding other antihistamines, or adding a leukotriene receptor antagonist such as montelukast. Step 3 consists of adding or replacing the current treatment with hydroxyzine or doxepin. If the individual doesn't respond to steps 1–3 then they are considered to have refractory symptoms. At this point, anti-inflammatory medications (dapsone, sulfasalazine), immunosuppressants (cyclosporin, sirolimus) or other medications like omalizumab can be used. These options are explained in more detail below.
Many patients will not develop these side effects, although there is still a significant possibility of risks associated with Antipsychotic usage.
Antihistamine drugs can have undesirable side-effects, the most notable one being drowsiness in the case of oral antihistamine tablets. First-generation antihistamine drugs such as diphenhydramine cause drowsiness, while second- and third-generation antihistamines such as cetirizine and loratadine are less likely to.
Rupatadine is a non-sedating antihistamine. However, as in other non sedating second-generation antihistamines, the most common side effects in controlled clinical studies were somnolence, headaches and fatigue.
Cyclosporine A, an immunosuppressive agent, has apparently halted destruction of beta cells (on the basis of reduced insulin usage), but its kidney toxicity and other side effects make it highly inappropriate for long-term use.
Hydroxyzine's predominant mechanism of action is as a potent and selective histamine H receptor inverse agonist. This action is responsible for its antihistamine and sedative effects. Unlike many other first-generation antihistamines, hydroxyzine has very low affinity for the muscarinic acetylcholine receptors, and in accordance, has low or no propensity for producing anticholinergic side effects. In addition to its antihistamine activity, hydroxyzine has also been shown to act more weakly as an antagonist of the serotonin 5-HT receptor, the dopamine D receptor, and the α-adrenergic receptor. The weak antiserotonergic effects of hydroxyzine likely underlie its usefulness as an anxiolytic, as other antihistamines without such properties have not been found to be effective in the treatment of anxiety.