Are there long term side effects of antihistamine usage?
Astemizole
Astemizole (marketed under the brand name Hismanal, developmental code R43512) was a second-generation antihistamine drug that has a long duration of action. Astemizole was discovered by Janssen Pharmaceutica in 1977. It has been withdrawn from the market in most countries because of rare but potentially fatal side effects (QTc interval prolongation and related arrhythmias due to hERG channel blockade).
Ethisterone
Side effects of ethisterone include symptoms of masculinization such as acne and hirsutism among others.
Iprindole
Anticholinergic side effects such as dry mouth and constipation are either greatly reduced in comparison to imipramine and most other TCAs or fully lacking with iprindole. However, it still has significant antihistamine effects and therefore can produce sedation, though this is diminished relative to other TCAs similarly. Iprindole also lacks significant alpha-blocking properties, and hence does not pose a risk of orthostatic hypotension.
Thiazinamium metilsulfate
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.
Prodrug
Terfenadine, the first non-sedating antihistamine, had to be withdrawn from the market because of the small risk of a serious side effect.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.
Side effects of bicalutamide
Combination of bicalutamide with medical (i.e., a analogue) or surgical castration modifies the side effect profile of bicalutamide. Some of its side effects, including breast pain/tenderness and gynecomastia, are far less likely to occur when the drug is combined with a analogue, while certain other side effects, including hot flashes, depression, fatigue, and sexual dysfunction, occur much more frequently in combination with a analogue. It is thought that this is due to the suppression of estrogen levels (in addition to androgen levels) by analogues, as estrogens may compensate for various negative central effects of androgen deprivation. If bicalutamide is combined with a analogue or surgical castration, the elevation of androgen and estrogen levels in men caused by bicalutamide will be prevented and the side effects of excessive estrogens, namely gynecomastia, will be reduced. However, due to the loss of estrogen, bone loss will accelerate and the risk of osteoporosis developing with long-term therapy will increase.
Anaphylaxis
Antihistamines (both H1 and H2), while commonly used and assumed effective based on theoretical reasoning, are poorly supported by evidence. A 2007 Cochrane review did not find any good-quality studies upon which to base recommendations and they are not believed to have an effect on airway edema or spasm. Corticosteroids are unlikely to make a difference in the current episode of anaphylaxis, but may be used in the hope of decreasing the risk of biphasic anaphylaxis. Their prophylactic effectiveness in these situations is uncertain. Nebulized salbutamol may be effective for bronchospasm that does not resolve with epinephrine. Methylene blue has been used in those not responsive to other measures due to its presumed effect of relaxing smooth muscle.
Effects of long-term benzodiazepine use
Daily users of benzodiazepines are also at a higher risk of experiencing psychotic symptomatology such as delusions and hallucinations. A study found that of 42 patients treated with alprazolam, up to a third of long-term users of the benzodiazepine drug alprazolam (Xanax) develop depression. Studies have shown that long-term use of benzodiazepines and the benzodiazepine receptor agonist nonbenzodiazepine Z drugs are associated with causing depression as well as a markedly raised suicide risk and an overall increased mortality risk.
Interstitial cystitis
The antihistamine hydroxyzine failed to demonstrate superiority over placebo in treatment of IC patients in a randomized, controlled, clinical trial. 
Amitriptyline has been shown to be effective in reducing symptoms such as chronic pelvic pain and nocturia in many patients with IC/BPS with a median dose of 75 mg daily. In one study, the antidepressant duloxetine was found to be ineffective as a treatment, although a patent exists for use of duloxetine in the context of IC, and is known to relieve neuropathic pain. The calcineurin inhibitor cyclosporine A has been studied as a treatment for interstitial cystitis due to its immunosuppressive properties. A prospective randomized study found cyclosporine A to be more effective at treating IC symptoms than pentosan polysulfate, but also had more adverse effects.
Tetrahydrogestrinone
Side effects from prolonged use are likely to include infertility in both men and women, as well as other steroid side effects such as acne and hirsutism. Unlike most other anabolic steroids, THG also binds with high affinity to the glucocorticoid receptor, and while this effect may cause additional weight loss, it is also likely to cause additional side effects such as immunosuppression that are not seen with most other steroids.
Finasteride
Men in the U.S. and Canada concerned about persistent sexual side effects "coined the phrase 'post-finasteride syndrome', which they say is characterized by sexual, neurological, hormonal and psychological side effects that can persist in men who have taken finasteride for hair loss or an enlarged prostate". In 2016, Merck was a defendant in approximately 1,370 product liability lawsuits which had been filed by customers alleging they have experienced persistent sexual side effects following cessation of treatment with finasteride.
Effects of long-term benzodiazepine use
A study of 50 patients who attended a benzodiazepine withdrawal clinic found that long-term use of benzodiazepines causes a wide range of psychological and physiological disorders. It was found that, after several years of chronic benzodiazepine use, a large portion of patients developed various mental and physical health problems including agoraphobia, irritable bowel syndrome, paraesthesiae, increasing anxiety, and panic attacks, which were not preexisting. The mental health and physical health symptoms induced by long-term benzodiazepine use gradually improved significantly over a period of a year following completion of a slow withdrawal. Three of the 50 patients had wrongly been given a preliminary diagnosis of multiple sclerosis when the symptoms were actually due to chronic benzodiazepine use. Ten of the patients had taken drug overdoses whilst on benzodiazepines, despite the fact that only two of the patients had any prior history of depressive symptomatology. After withdrawal, no patients took any further overdoses after 1 year post-withdrawal. The cause of the deteriorating mental and physical health in a significant proportion of patients was hypothesised to be caused by increasing tolerance where withdrawal-type symptoms emerged, despite the administration of stable prescribed doses. Another theory is that chronic benzodiazepine use causes subtle increasing toxicity, which in turn leads to increasing psychopathology in long-term users of benzodiazepines.
Dopamine
However, the widespread use of antipsychotic drugs has long been controversial. There are several reasons for this. First, antipsychotic drugs are perceived as very aversive by people who have to take them, because they produce a general dullness of thought and suppress the ability to experience pleasure. Second, it is difficult to show that they act specifically against psychotic behaviors rather than merely suppressing all types of active behavior. Third, they can produce a range of serious side effects, including weight gain, diabetes, fatigue, sexual dysfunction, hormonal changes, and a type of serious movement disorder known as tardive dyskinesia. Some of these side effects may continue long after the cessation of drug use, or even permanently.
Opioid
Tolerance to nausea occurs within 7–10 days, during which antiemetics ("e.g." low dose haloperidol once at night) are very effective. Due to severe side effects such as tardive dyskinesia, haloperidol is now rarely used. A related drug, prochlorperazine is more often used, although it has similar risks. Stronger antiemetics such as ondansetron or tropisetron are sometimes used when nausea is severe or continuous and disturbing, despite their greater cost. A less expensive alternative is dopamine antagonists such as domperidone and metoclopramide. Domperidone does not cross the blood–brain barrier and produce adverse central antidopaminergic effects, but blocks opioid emetic action in the chemoreceptor trigger zone. (The drug is not available in the U.S.) Some antihistamines with anticholinergic properties ("e.g." orphenadrine or diphenhydramine) may also be effective. The first-generation antihistamine hydroxyzine is very commonly used, with the added advantages of not causing movement disorders, and also possessing analgesic-sparing properties. Δ-tetrahydrocannabinol relieves nausea and vomiting; it also produces analgesia that may allow lower doses of opioids with reduced nausea and vomiting.
Histidine decarboxylase
Antihistamines are a class of medications designed to reduce unwanted effects of histamine in the body. Typical antihistamines block specific histamine receptors, depending on what physiological purpose they serve. For example, diphenhydramine (Benadryl™), targets and inhibits the H1 histamine receptor to relieve symptoms of allergic reactions. Inhibitors of histidine decarboxylase can conceivably be used as atypical antihistamines. Tritoqualine, as well as various catechins, such as epigallocatechin-3-gallate, a major component of green tea, have been shown to target HDC and histamine-producing cells, reducing histamine levels and providing anti-inflammatory, anti-tumoral, and anti-angiogenic effects.
Drug-induced QT prolongation
Drug-induced QT prolongation is seen with a QT interval above 450 ms on the ECG and is usually a result of treatment by anti-arrhythmic drugs, such as amiodarone and sotalol, or a number of other drugs that have been reported to cause this problem (e.g., cisapride). Some antipsychotic drugs, such as haloperidol and ziprasidone, have a prolonged QT interval as a rare side-effect. Antihistamines, erythromycin, and ciprofloxacin may also cause drug-induced LQT. Genetic mutations may make one more susceptible to drug-induced LQT. It is associated with hypokalaemia, hypocalcaemia and hypothermia and may lead to torsades de pointes.
Antihistamine
Antihistamines suppress the histamine-induced wheal response (swelling) and flare response (vasodilation) by blocking the binding of histamine to its receptors or reducing histamine receptor activity on nerves, vascular smooth muscle, glandular cells, endothelium, and mast cells.
Hashish
It has been claimed that the user’s psychological and physiological needs will influence the response and that the user must cooperate with and facilitate the effects. Therefore, the effect of the physical and interpersonal setting is strong and usually controls the underlying tone of the experience. Generally the intensification of sensation and increased clarity of perception have been reported. Short lived adverse effects have also been reported, including psychotic states following heavy consumption. Regular users are at risk of dependence. Especially people with major mental illnesses e.g. schizophrenia are vulnerable as hashish provokes relapse and aggravates existing symptoms.
Finasteride
The 2010 Cochrane review found that compared with placebo, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder for the first year of treatment; the rates of these effects became indistinguishable from placebo after 2–4 years and these side effects usually got better over time. Another 2010 review found that when used for hair loss finasteride increased rates of sexual problems. A 2016 meta-analysis found that sexual dysfunction, including erectile dysfunction, loss of libido, and reduced ejaculate, may occur in 3.4 to 15.8% of men treated with finasteride or dutasteride. This adverse effect has been linked to lower quality of life and can cause stress in relationships.
Angioedema
In allergic angioedema, avoidance of the allergen and use of antihistamines may prevent future attacks. Cetirizine is a commonly prescribed antihistamine for angioedema. Some patients have reported success with the combination of a nightly low dose of cetirizine to moderate the frequency and severity of attacks, followed by a much higher dose when an attack does appear. Severe angioedema cases may require desensitization to the putative allergen, as mortality can occur. Chronic cases require steroid therapy, which generally leads to a good response. In cases where allergic attack is progressing towards airway obstruction, epinephrine may be life-saving.
Loratadine
Antihistamines should be discontinued about 48 hr prior to skin allergy tests, since these drugs may prevent or diminish otherwise-positive reactions to dermal activity indicators.
5-HT3 antagonist
There are few side effects related to the use of 5-HT antagonists; the most common are constipation or diarrhea, headache, and dizziness. Unlike antihistamines with antiemetic properties such as cyclizine, 5-HT antagonists do not produce sedation, nor do they cause extrapyramidal effects, as phenothiazines (such as prochlorperazine) sometimes do.
Nonbenzodiazepine
Long-term use is not recommended as tolerance and addiction can occur. A survey of patients using nonbenzodiazepine Z drugs and benzodiazepine hypnotic users found that there was no difference in reports of adverse effects that were reported in over 41% of users and, in fact, Z drug users were more likely to report that they had tried to quit their hypnotic drug and were more likely to want to stop taking Z drugs than benzodiazepine users. Efficacy also did not differ between benzodiazepine and Z drug users.
Effects of long-term benzodiazepine use
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).
Analgesic
The use of adjuvant analgesics is an important and growing part of the pain-control field and new discoveries are made practically every year. Many of these drugs combat the side-effects of opioid analgesics, an added bonus. For example, antihistamines including orphenadrine combat the release of histamine caused by many opioids. Stimulants such as methylphenidate, caffeine, ephedrine, dextroamphetamine, methamphetamine, and cocaine work against heavy sedation and may elevate mood in distressed patients as do the antidepressants. The use of medicinal cannabis remains a debated issue.
QT interval
Prolongation of the QT interval may be due to an adverse drug reaction. Many drugs, such as haloperidol, vemurafenib, ziprasidone, methadone and sertindole, can prolong the QT interval. Some antiarrhythmic drugs, like amiodarone or sotalol, work by getting a pharmacological QT prolongation. Also, some second-generation antihistamines, such as astemizole, have this effect. In addition, high blood alcohol concentrations prolong the QT interval. A possible interaction between selective serotonin reuptake inhibitors and thiazide diuretics is associated with QT prolongation. Macrolide and fluoroquinolone antibiotics are also suspected to prolong the QT interval. It was discovered recently that azithromycin is associated with an increase in cardiovascular death.
List of long term side effects of antipsychotics
Many patients will not develop these side effects, although there is still a significant possibility of risks associated with Antipsychotic usage.
Bamipine
Side effects are typical of an old (first-generation) antihistamine: tiredness in adults, agitation in children, mydriasis (dilation of the pupils). These effects are rare when bamipine is applied topically as an ointment. Allergic and hypersensitivity reactions are also rare. Acute eczema can be worsened by bamipine ointment.
Constipation
Many medications have constipation as a side effect. Some include (but are not limited to) opioids, diuretics, antidepressants, antihistamines, antispasmodics, anticonvulsants, tricyclic antidepressants, antiarrythmics, beta-adrenoceptor antagonists, anti-diarrheals, 5-HT3 receptor antagonists such as ondansetron, and aluminum antacids. Certain calcium channel blockers such as nifedipine and verapamil can cause severe constipation due to dysfunction of motility in the rectosigmoid colon. Supplements such as calcium and iron supplements can also have constipation as a notable side effect.
Hives
Non-sedating antihistamines that block the histamine H1 receptors are the first line of therapy. First generation antihistamines such as diphenhydramine or hydroxyzine block both central and peripheral H1 receptors and can be sedating. Second generation antihistamines such as loratadine, cetirizine, or desloratadine selectively antagonize the peripheral H1 receptors and are less sedating, less anticholinergic, and generally preferred over the first generation antihistamines.
People who don’t respond to the maximum dose of H1 antihistamines may benefit from increasing the dose, then to switching to another non-sedating antihistamine, then to adding a leukotriene antagonist, then to using an older antihistamine, then to using systemic steroids and finally to using ciclosporin or omalizumab.
Antihistamine
Antihistamines are drugs which treat allergic rhinitis and other allergies. Antihistamines can give relief when a person has nasal congestion, sneezing, or hives because of pollen, dust mites, or animal allergy. Typically people take antihistamines as an inexpensive, generic, over-the-counter drug with few side effects. 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. Antihistamines are usually for short-term treatment. Chronic allergies increase the risk of health problems which antihistamines might not treat, including asthma, sinusitis, and lower respiratory tract infection. Doctors recommend that people talk to them before any longer term use of antihistamines.
Norgestimate
Side effects associated with the combination of estradiol and norgestimate in postmenopausal women, with greater than or equal to 5% incidence over one year, include headache (23%), upper respiratory tract infection (21%), breast pain (16%), back pain (12%), abdominal pain (12%), flu-like symptoms (11%), arthralgia (9%), vaginal bleeding (9%), dysmenorrhea (8%), sinusitis (8%), vaginitis (7%), pharyngitis (7%), fatigue (6%), pain (6%), nausea (6%), viral infection (6%), flatulence (5%), tooth disorder (5%), myalgia (5%), dizziness (5%), depression (5%), and coughing (5%).
Lorazepam
Many beneficial effects of lorazepam (e.g., sedative, muscle relaxant, anti-anxiety, and amnesic effects) may become adverse effects when unwanted. Adverse effects can include sedation and low blood pressure; the effects of lorazepam are increased in combination with other CNS depressant drugs. Other adverse effects include confusion, ataxia, inhibiting the formation of new memories, and hangover effects. With long-term benzodiazepine use it is unclear whether cognitive impairments fully return to normal after stopping lorazepam use; cognitive deficits persist for at least six months after withdrawal, but longer than six months may be required for recovery of cognitive function. Lorazepam appears to have more profound adverse effects on memory than other benzodiazepines; it impairs both explicit and implicit memory. In the elderly, falls may occur as a result of benzodiazepines. Adverse effects are more common in the elderly, and they appear at lower doses than in younger patients. Benzodiazepines can cause or worsen depression. Paradoxical effects can also occur, such as worsening of seizures, or paradoxical excitement; paradoxical excitement is more likely to occur in the elderly, children, those with a history of alcohol abuse, and in people with a history of aggression or anger problems. Lorazepam's effects are dose-dependent, meaning the higher the dose, the stronger the effects (and side effects) will be. Using the smallest dose needed to achieve desired effects lessens the risk of adverse effects. Sedative drugs and sleeping pills, including lorazepam, have been associated with an increased risk of death.
Adverse effect
Most drugs have a large list of nonsevere or mild adverse effects which do not rule out continued usage. These effects, which have a widely variable incidence according to individual sensitivity, include nausea, dizziness, diarrhea, malaise, vomiting, headache, dermatitis, dry mouth, etc. These can be considered a form of pseudo-allergic reaction, as not all users experience these effects; many users experience none at all.
Simvastatin
Common side effects (>1% incidence) may include indigestion and eczema. Rare side effects include joint pain, memory loss, and muscle cramps. Cholestatic hepatitis, hepatic cirrhosis, rhabdomyolysis (destruction of muscles and blockade of renal system), and myositis have been reported in patients receiving the drug chronically. Serious allergic reactions to simvastatin are rare. If the following signs of a serious allergic reaction occur, seek medical attention immediately: rash, hoarsness itching/swelling, dizziness, or difficulty swallowing/breathing.
Hydroxyzine
Hydroxyzine, sold under the brand names Atarax among others, is a medication of the antihistamine type. It is used in the treatment of itchiness, anxiety, and nausea, including that due to motion sickness. It is used either by mouth or injection into a muscle.
Common side effects include sleepiness, headache, and a dry mouth. Serious side effects may include QT prolongation. It is unclear if use during pregnancy or breastfeeding is safe. Hydroxyzine works by blocking the effects of histamine. It is in the piperazine family of chemicals.
It was first made by Union Chimique Belge in 1956 and was approved for sale by Pfizer in the United States later that year. In the United Kingdom 28 doses cost less than a pound. In the United States the wholesale cost in 2018 was about 0.05 USD per dose. In the United States about 8 million prescriptions were written for hydroxyzine in 2016.
Dihydrocodeine
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.
Protriptyline
Protriptyline shares side effects common to all TCAs. The most frequent of these are dry mouth, constipation, urinary retention, increased heart rate, sedation, irritability, dizziness, decreased coordination, anxiety, blood disorders, confusion, decreased libido, dizziness, flushing, headache, impotence, insomnia, low blood pressure, nightmares, rapid or irregular heartbeat, rash, seizures, sensitivity to sunlight, stomach and intestinal problems. Other more complicated side effects include; chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling; sudden numbness or weakness, especially on one side of the body; sudden headache, confusion, problems with vision, speech, or balance; hallucinations, or seizure (convulsions); easy bruising or bleeding, unusual weakness; restless muscle movements in your eyes, tongue, jaw, or neck; urinating less than usual or not at all; extreme thirst with headache, nausea, vomiting, and weakness; or feeling light-headed or fainting.
Dry mouth, if severe to the point of causing difficulty speaking or swallowing, may be managed by dosage reduction or temporary discontinuation of the drug. Patients may also chew sugarless gum or suck on sugarless candy in order to increase the flow of saliva. Some artificial saliva products may give temporary relief. 
Men with prostate enlargement who take protriptyline may be especially likely to have problems with urinary retention. Symptoms include having difficulty starting a urine flow and more difficulty than usual passing urine. In most cases, urinary retention is managed with dose reduction or by switching to another type of antidepressant. In extreme cases, patients may require treatment with bethanechol, a drug that reverses this particular side effect.
Antihistamine
Most studies of antihistamines reported on people who are younger, so the effects on people over age 65 are not as well understood. Older people are more likely to experience drowsiness from antihistamine use than younger people. Also, most of the research has been on white people and other ethnicities are not as represented in the research. The evidence does not report how antihistamines affect women differently than men. Different studies have reported on antihistamine use in children, with various studies finding evidence that certain antihistamines could be used by children 2 years of age, and other drugs being safer for younger or older children.
List of long term side effects of antipsychotics
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.
Hyoscyamine
Side effects include dry mouth and throat, increased appetite leading to weight gain, eye pain, blurred vision, restlessness, dizziness, arrhythmia, flushing, and faintness. An overdose will cause headache, nausea, vomiting, and central nervous system symptoms including disorientation, hallucinations, euphoria, sexual arousal, short-term memory loss, and possible coma in extreme cases. The euphoric and sexual effects are stronger than those of atropine but weaker than those of Hyoscine, as well as dicycloverine, orphenadrine, cyclobenzaprine, trihexyphenidyl, and ethanolamine antihistamines like phenyltoloxamine. It can also act as a diuretic.
Xylazine
Xylazine administration can lead to diabetes mellitus and hyperglycemia. Other possible side effects that can occur are areflexia, asthenia, ataxia, blurred vision, disorientation, dizziness, drowsiness, dysarthria, dysmetria, fainting, hyporeflexia, slurred speech, somnolence, staggering, coma, apnea, shallow breathing, sleepiness, premature ventricular contraction, tachycardia, miosis, and dry mouth. Rarely, hypotonia, dry mouth, urinary incontinence and nonspecific electrocardiographic ST segment changes occur. It has been reported that the duration of symptoms after human overdose is 8 to 72 hours. Further research is necessary to categorize the side effects that occur when xylazine is used in conjunction with heroin and cocaine.
Antihistamine
Currently most people who use an antihistamine to treat allergies use a second generation drug.
Antihistamine
H-antihistamines, like H-antihistamines, occur as inverse agonists and neutral antagonists. They act on H histamine receptors found mainly in the parietal cells of the gastric mucosa, which are part of the endogenous signaling pathway for gastric acid secretion. Normally, histamine acts on H to stimulate acid secretion; drugs that inhibit H signaling thus reduce the secretion of gastric acid.
Belimumab
Common adverse effects reported with belimumab include nausea, diarrhea, and fever, as well as hypersensitivity and infusion-site reactions, which were severe in 0.9% of patients. Regulatory agencies recommend that patients be treated with an antihistamine prior to a belimumab infusion.
Anabolic steroid
A 2005 review in "CNS Drugs" determined that "significant psychiatric symptoms including aggression and violence, mania, and less frequently psychosis and suicide have been associated with steroid abuse. Long-term steroid abusers may develop symptoms of dependence and withdrawal on discontinuation of AAS". High concentrations of AAS, comparable to those likely sustained by many recreational AAS users, produce apoptotic effects on neurons, raising the specter of possibly irreversible neurotoxicity. Recreational AAS use appears to be associated with a range of potentially prolonged psychiatric effects, including dependence syndromes, mood disorders, and progression to other forms of substance abuse, but the prevalence and severity of these various effects remains poorly understood. There is no evidence that steroid dependence develops from "therapeutic" use of AAS to treat medical disorders, but instances of AAS dependence have been reported among weightlifters and bodybuilders who chronically administered supraphysiologic doses. Mood disturbances (e.g. depression, [hypo-]mania, psychotic features) are likely to be dose- and drug-dependent, but AAS dependence or withdrawal effects seem to occur only in a small number of AAS users.
Migraine treatment
In recommended doses, the side effects of paracetamol are mild to non-existent. In contrast to aspirin, it is not a blood thinner (and thus may be used in patients where coagulation is a concern), and it does not cause gastric irritation. Compared to Ibuprofen—which can have adverse effects that include diarrhea, vomiting, and abdominal pain—paracetamol is well tolerated with fewer side effects. Prolonged daily use increases the risk of upper gastrointestinal complications such as stomach bleeding, and may cause kidney or liver damage. Paracetamol is metabolized by the liver and is hepatotoxic; side effects may be more likely in chronic alcoholics or patients with liver damage.
Histamine
First-generation H antihistamines (i.e., antagonists of histamine receptor H) are capable of crossing the blood–brain barrier and produce drowsiness by antagonizing histamine H receptors in the tuberomammillary nucleus. The newer class of second-generation H antihistamines do not readily permeate the blood–brain barrier and thus are less likely to cause sedation, although individual reactions, concomitant medications and dosage may increase the likelihood of a sedating effect. In contrast, histamine H receptor antagonists increase wakefulness. Similar to the sedative effect of first-generation H antihistamines, an inability to maintain vigilance can occur from the inhibition of histamine biosynthesis or the loss (i.e., degeneration or destruction) of histamine-releasing neurons in the TMN.
Ergogenic use of anabolic steroids
Anabolic steroid users tend to be disillusioned by the portrayal of anabolic steroids as deadly in the media and in politics. According to one study, anabolic steroid users also distrust their physicians, and in the sample, 56% had not disclosed their anabolic steroid use to their physicians. Another 2007 study showed that while 66% of individuals using anabolic steroids for non-medical purposes were willing to seek medical supervision for their steroid use, 58% lacked trust in their physicians, 92% felt that the medical community's knowledge of non-medical anabolic steroid use was lacking, and 99% felt that the public has an exaggerated view of the side effects of anabolic steroid use. A 2006 study has showed that long-term anabolic steroid users were more likely to have symptoms of muscle dysmorphia and also showed stronger endorsement of more traditional male roles.
Anticholinergic
Acute anticholinergic syndrome is reversible and subsides once all of the causative agent has been excreted. Reversible Acetylcholinesterase inhibitor agents such as physostigmine can be used as an antidote in life-threatening cases. Wider use is discouraged due to the significant side effects related to cholinergic excess including: seizures, muscle weakness, bradycardia, bronchoconstriction, lacrimation, salivation, bronchorrhea, vomiting, and diarrhea. Even in documented cases of anticholinergic toxicity, seizures have been reported after the rapid administration of physostigmine. Asystole has occurred after physostigmine administration for tricyclic antidepressant overdose, so a conduction delay (QRS > 0.10 second) or suggestion of tricyclic antidepressant ingestion is generally considered a contraindication to physostigmine administration.
Recreational use of dextromethorphan
A formal survey of dextromethorphan users showed that more than half of users reported experience of the following withdrawal-symptoms individually for the first week after long-term/addictive dextromethorphan use: fatigue, apathy, flashbacks, and constipation. Over a quarter reported insomnia, nightmares, anhedonia, impaired memory, attention deficit and decreased libido. Rarer side effects included panic attacks, impaired learning, tremor, jaundice, urticaria (hives) and myalgia. DXM has also been "known to increase the frequency of complex partial seizures in epileptics by 25% compared to placebo." Frequent and long-term usage at high doses could possibly lead to toxic psychosis and other permanent psychological problems. It is important to note that medical DXM use has not been shown to cause the above issues.
Lovastatin
Lovastatin is usually well tolerated, with the most common side effects being, in approximately descending order of frequency: creatine phosphokinase elevation, flatulence, abdominal pain, constipation, diarrhoea, muscle aches or pains, nausea, indigestion, weakness, blurred vision, rash, dizziness and muscle cramps. As with all statin drugs, it can rarely cause myopathy, hepatotoxicity (liver damage), dermatomyositis or rhabdomyolysis. This can be life-threatening if not recognised and treated in time, so any unexplained muscle pain or weakness whilst on lovastatin should be promptly mentioned to the prescribing doctor. Other uncommon side effects that should be promptly mentioned to either the prescribing doctor or an emergency medical service include:
Post-acute-withdrawal syndrome
After long-term use of dopamine agonists, a withdrawal syndrome may occur during dose reduction or discontinuation with the following possible side effects: anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. For some individuals, these withdrawal symptoms are short-lived and make a full recovery, for others a protracted withdrawal syndrome may occur with withdrawal symptoms persisting for months or years.
Allergen
In the case of nasal symptoms, antihistamines are normally the first option. They may be taken together with pseudoephedrine to help relieve a stuffy nose and they can stop the itching and sneezing. Some over-the-counter options are Benadryl and Tavist. However, these antihistamines may cause extreme drowsiness, therefore, people are advised to not operate heavy machinery or drive while taking this kind of medication. Other side effects include dry mouth, blurred vision, constipation, difficulty with urination, confusion, and light-headedness.
NS5B inhibitor
Comparing virological response of NS5B inhibitors to previous therapy of chronic hepatitis C with the combination of interferon and ribavirin, it was possible to observe a significant difference in efficacy and safety. The efficacy rate of interferon plus ribavirin varied within 44-46% while it increases up to 90% by direct acting antivirals such as NS5B inhibitors/ Data on the frequency of side effects may vary between researches for both drug categories. Nevertheless, there is a significant difference between the safety profiles of NS5B inhibitors, particularly sofosbuvir and the combination of interferon and ribavirin. Comparing interferon containing therapies, sofosbuvir does not cause neutropenia, thrombocytopenia, or any other serious adverse effects. Common side effects associated with sofosbuvir are headache, tiredness, insomnia, dizziness, itching, infections of upper respiratory tract, rashes, back pain, anemia, and lymphopenia. With the advent of direct acting antivirals, the duration of the hepatitis treatment has also been impressively reduced. Severity of adverse effects is strongly associated with duration of therapy and the dose used for hepatitis C treatment. Therefore, direct actung antivirals have become the initial treatment ised for most patients with chronic hepatitis C.
Allylestrenol
Side effects of allylestrenol are few and have not been well-defined, but are assumed to be similar to those of related medications (i.e., other progestins). When used at high dosages in the treatment of BPH in men, allylestrenol can cause symptoms of hypogonadism and sexual dysfunction. The medication indeloxazine may be able to counteract allylestrenol-associated sexual dysfunction. Allylestrenol has no androgenic or other off-target hormonal side effects.
Azithromycin
Most common adverse effects are diarrhea (5%), nausea (3%), abdominal pain (3%), and vomiting. Fewer than 1% of people stop taking the drug due to side effects. Nervousness, skin reactions, and anaphylaxis have been reported. Clostridium difficile has been reported with use of azithromycin. Azithromycin does not affect the efficacy of birth control unlike some other antibiotics such as rifampin. Hearing loss has been reported.
Effects of long-term benzodiazepine use
Long-term benzodiazepine use may lead to the creation or exacerbation of physical and mental health conditions, which improve after 6 or more months of abstinence. After a period of about 3 to 6 months of abstinence after completion of a gradual-reduction regimen, marked improvements in mental and physical wellbeing become apparent. For example, one study of hypnotic users gradually withdrawn from their hypnotic medication reported after 6 months of abstinence that they had less severe sleep and anxiety problems, were less distressed, and had a general feeling of improved health. Those having remained on hypnotic medication had no improvements in their insomnia, anxiety, or general health ratings. A study found that individuals having withdrawn from benzodiazepines showed a marked reduction in use of medical and mental health services.
Depressant
In general, benzodiazepines are safe and effective in the short term, although cognitive impairments and paradoxical effects such as aggression or behavioral disinhibition occasionally occur. A minority react reverse and contrary to what would normally be expected. For example, a state of panic may worsen considerably following intake of a benzodiazepine. Long-term use is controversial due to concerns about adverse psychological and physical effects, increased questioning of effectiveness, and, because benzodiazepines are prone to cause tolerance, physical dependence, and, upon cessation of use after long-term use, a withdrawal syndrome. Due to adverse effects associated with the long-term use of benzodiazepines, withdrawal from benzodiazepines, in general, leads to improved physical and mental health. The elderly are at an increased risk of suffering from both short- and long-term adverse effects.
Doxylamine
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.
Butriptyline
Butriptyline has potent antihistamine effects, resulting in sedation and somnolence. It also has potent anticholinergic effects, resulting in side effects like dry mouth, constipation, urinary retention, blurred vision, and cognitive/memory impairment. The drug has relatively weak effects as an alpha-1 blocker and has no effects as a norepinephrine reuptake inhibitor, so is associated with little to no antiadrenergic and adrenergic side effects.
Gabapentin
The most common side effects of gabapentin include dizziness, fatigue, drowsiness, ataxia, peripheral edema (swelling of extremities), nystagmus, and tremor. Gabapentin may also produce sexual dysfunction in some patients, symptoms of which may include loss of libido, inability to reach orgasm, and erectile dysfunction. Gabapentin should be used carefully in people with kidney problems due to possible accumulation and toxicity.
Antidepressant
Sexual side-effects are also common with SSRIs, such as loss of sexual drive, failure to reach orgasm, and erectile dysfunction. Although usually reversible, these sexual side-effects can, in rare cases, last for months or years after the drug has been completely withdrawn.
Mizolastine
Mizolastine (Mizollen) is a once-daily, non-sedating antihistamine. It blocks H receptors and is commonly fast-acting. It does not prevent the actual release of histamine from mast cells, it just prevents it binding to receptors. Side effects can include dry mouth and throat.
Histamine
Libido loss and erectile failure can occur during treatment with histamine H receptor antagonists such as cimetidine, ranitidine, and risperidone. The injection of histamine into the corpus cavernosum in men with psychogenic impotence produces full or partial erections in 74% of them. It has been suggested that H antagonists may cause sexual difficulties by reducing the uptake of testosterone.
Cimetidine
Reported side effects of cimetidine include diarrhea, rashes, dizziness, fatigue, constipation, and muscle pain, all of which are usually mild and transient. It has been reported that mental confusion may occur in the elderly. Because of its hormonal effects, cimetidine rarely may cause sexual dysfunction including loss of libido and erectile dysfunction and gynecomastia (0.1–0.2%) in males during long-term treatment. Rarely, interstitial nephritis, urticaria, and angioedema have been reported with cimetidine treatment. Cimetidine is also commonly associated with transient raised aminotransferase activity; hepatotoxicity is rare.
Recreational drug 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.
Aminoglutethimide
AG has many side effects and is a relatively toxic medication, although its side effects are described as usually relatively mild. The side effects of AG include lethargy, fatigue, weakness, malaise, drowsiness, somnolence, depression, apathy, sleep disturbances, stomach discomfort, nausea, vomiting ataxia, joint aches and pains, fever, skin rash, hypotension or hypertension, high cholesterol levels, virilization, hypothyroidism, thyroid abnormalities, elevated liver enzymes, jaundice, hepatotoxicity, weight gain, leg cramps, personality changes, blood dyscrasias, and adrenal insufficiency (e.g., hyponatremia, hypoglycemia, others). Lethargy is the most common side effect and has been found to occur in 31 to 70% of people treated with AG. It is the most common reason for discontinuation of AG. Skin rash and hypotension have both been observed in about 15% of people. At least one side effect will occur in 45 to 85% of people. Severe toxicity is seen in 10% of people, including circulatory collapse thought to be due to adrenal insufficiency. Hematological and bone marrow toxicity, including marked depression of white blood cell count, platelets, or both, occurs rarely, with an incidence of about 0.9%. It is usually seen within the first 7 weeks of treatment and resolves within 3 weeks following discontinuation. AG is discontinued in 5 to 10% of people due to intolerable side effects. The central nervous system side effects of AG are due to its nature as an anticonvulsant and relation to glutethimide.
Cold urticaria
Allergy medications containing antihistamines such as diphenhydramine (Benadryl), cetirizine (Zyrtec), loratidine (Claritin), cyproheptadine (Periactin), and fexofenadine (Allegra) may be taken orally to prevent and relieve some of the hives (depending on the severity of the allergy). For those who have severe anaphylactic reactions, a prescribed medicine such as doxepin, which is taken daily, should help to prevent and/or lessen the likelihood of a reaction and thus, anaphylaxis. There are also topical antihistamine creams which are used to help relieve hives in other conditions, but there is not any documentation stating it will relieve hives induced by cold temperature.
Benzodiazepine
The main problem of the chronic use of benzodiazepines is the development of tolerance and dependence. Tolerance manifests itself as diminished pharmacological effect and develops relatively quickly to the sedative, hypnotic, anticonvulsant, and muscle relaxant actions of benzodiazepines. Tolerance to anti-anxiety effects develops more slowly with little evidence of continued effectiveness beyond four to six months of continued use. In general, tolerance to the amnesic effects does not occur. However, controversy exists as to tolerance to the anxiolytic effects with some evidence that benzodiazepines retain efficacy and opposing evidence from a systematic review of the literature that tolerance frequently occurs and some evidence that anxiety may worsen with long-term use. The question of tolerance to the amnesic effects of benzodiazepines is, likewise, unclear. Some evidence suggests that partial tolerance does develop, and that, "memory impairment is limited to a narrow window within 90 minutes after each dose".
Norethisterone
High-dosage norethisterone has been used to suppress menstruation in women with severe intellectual disability who were incapable of handling their own menses. A study of 118 nulliparous women treated with 5 mg/day norethisterone for a period of 2 to 30 months found that the drug was effective in producing amenorrhea in 86% of the women, with breakthrough bleeding occurring in the remaining 14%. Side effects including weight gain, hirsutism, acne, headache, nausea, and vomiting all did not appear to increase in incidence and no "disturbing side effects" were noted in any of the women. Another study of 5 mg/day norethisterone in 132 women also made no mention of androgenic side effects. These findings suggest little to no risk of androgenic side effects with norethisterone at a dosage of 5 mg/day. A study of 194 women treated with 5 to 15 mg/day NETA for a median duration of 13 months of therapy to suppress symptoms of endometriosis observed no side effects in 55.2% of patients, weight gain in 16.1%, acne in 9.9%, mood lability in 8.9%, hot flashes in 8.3%, and voice deepening in two women (1.0%).
Orphenadrine
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.
Dapoxetine
The most common effects when taking dapoxetine are nausea, dizziness, dry mouth, headache, diarrhea, and insomnia. Discontinuation due to adverse effects is dose related. According to McMahon in recent study in Asia, the rate of discontinuation is 0.3%, 1.7%, and 5.3% of 1067 studied subjects with placebo, dapoxetine 30 mg, and dapoxetine 60 mg respectively. Unlike other SSRIs used to treat depression, which have been associated with high incidences of sexual dysfunction, dapoxetine is associated with low rates of sexual dysfunction. Taken as needed, dapoxetine has very mild adverse effects of decreased libido (<1%) and erectile dysfunction (<4%).
Doxepin
Antidepressant doses of doxepin are defined as 25 to 300 mg/day, although are typically above 75 mg/day. Antihistamine doses, including for dermatological uses and as a sedative/hypnotic for insomnia, are considered to be 3 to 25 mg, although higher doses between 25 and 50 mg and in some cases even up to 150 mg have been used to treat insomnia. At low doses, below 25 mg, doxepin is a pure antihistamine. At antidepressant doses of above 25 mg, doxepin has significant antiadrenergic, antiserotonergic, and anticholinergic effects, and these activities contribute to its side effects.
Testosterone (medication)
A subsequent 2017 systematic review and meta-analysis of over 3,000 postmenopausal women similarly found that transdermal testosterone therapy was effective in improving multiple domains of sexual function in the short-term treatment of HSDD. Androgenic adverse effects such as acne and hirsutism were significantly greater in incidence, while no significant differences in "increase in facial hair, alopecia, voice deepening, urinary symptoms, breast pain, headache, site reaction to the patch, total adverse events, serious adverse events, reasons for withdrawal from the study, and the number of women who completed the study" were seen relative to the controls.
Side effects of cyproterone acetate
The side effects of cyproterone acetate (CPA), a steroidal antiandrogen and progestin, including its frequent and rare side effects, have been studied and characterized. It is generally well-tolerated and has a mild side-effect profile, regardless of dosage, when it used as a progestin or antiandrogen in combination with an estrogen such as ethinylestradiol or estradiol valerate in women. Side effects of CPA include hypogonadism and associated symptoms such as demasculinization, sexual dysfunction, infertility, and osteoporosis; breast changes such as breast tenderness, enlargement, and gynecomastia; emotional changes such as fatigue and depression; and other side effects such as vitamin B12 deficiency, weak glucocorticoid effects, and elevated liver enzymes. Weight gain can occur with CPA when it is used at high doses. Some of the side effects of CPA can be improved or fully prevented if it is combined with an estrogen to prevent estrogen deficiency. Little quantitative data are available on many of the potential side effects of CPA.
Antihistamine
The first generation of antihistamine drugs became available in the 1930s. This marked the beginning of medical treatment of nasal allergies. Research into these drugs led to the discovery that they were H1 antagonists and also to the development of H2 antagonists, where H1 antihistamines affected the nose and the H2 antihistamines affected the stomach. This history has led to contemporary research into drugs which are H3 receptor antagonist and which affect the Histamine H4 receptor.
Histamine dihydrochloride
It is also a FDA-approved active ingredient for topical analgesic use and is available in such products as GOLDEN CREME and Australian Dream Cream, which are used for the temporary relief of minor aches and pains of muscles and joints associated with arthritis, simple backache, bruises, sprains, and strains.
Histamine dihydrochloride is administered in conjunction with low doses of the immune-activating cytokine interleukin-2 (IL-2) in the post-remission phase of AML, i.e. when patients have completed the initial chemotherapy. This combination has been reported to significantly reduce the risk of relapse in AML. The effect is particularly pronounced in patients in their first remission who are below the age of 60.
Opioid
Itching tends not to be a severe problem when opioids are used for pain relief, but antihistamines are useful for counteracting itching when it occurs. Non-sedating antihistamines such as fexofenadine are often preferred as they avoid increasing opioid induced drowsiness. However, some sedating antihistamines such as orphenadrine can produce a synergistic pain relieving effect permitting smaller doses of opioids be used. Consequently, several opioid/antihistamine combination products have been marketed, such as "Meprozine" (meperidine/promethazine) and "Diconal" (dipipanone/cyclizine), and these may also reduce opioid induced nausea.
Diazepam
Use of diazepam should be avoided, when possible, in individuals with:Adverse effects of benzodiazepines such as diazepam include anterograde amnesia, confusion (especially pronounced in higher doses) and sedation. The elderly are more prone to adverse effects of diazepam, such as confusion, amnesia, ataxia, and hangover effects, as well as falls. Long-term use of benzodiazepines such as diazepam is associated with drug tolerance, benzodiazepine dependence, and benzodiazepine withdrawal syndrome. Like other benzodiazepines, diazepam can impair short-term memory and learning of new information. While benzodiazepine drugs such as diazepam can cause anterograde amnesia, they do not cause retrograde amnesia; information learned before using benzodiazepines is not impaired. Tolerance to the cognitive-impairing effects of benzodiazepines does not tend to develop with long-term use, and the elderly are more sensitive to them. Additionally, after cessation of benzodiazepines, cognitive deficits may persist for at least six months; it is unclear whether these impairments take longer than six months to abate or if they are permanent. Benzodiazepines may also cause or worsen depression. Infusions or repeated intravenous injections of diazepam when managing seizures, for example, may lead to drug toxicity, including respiratory depression, sedation and hypotension. Drug tolerance may also develop to infusions of diazepam if it is given for longer than 24 hours. Adverse effects such as sedation, benzodiazepine dependence, and abuse potential limit the use of benzodiazepines. Sedatives and sleeping pills, including diazepam, have been associated with an increased risk of death.
Amphetamine
At normal therapeutic doses, the most common psychological side effects of amphetamine include increased alertness, apprehension, concentration, initiative, self-confidence, and sociability, mood swings (elated mood followed by mildly depressed mood), insomnia or wakefulness, and decreased sense of fatigue. Less common side effects include anxiety, change in libido, grandiosity, irritability, repetitive or obsessive behaviors, and restlessness; these effects depend on the user's personality and current mental state. Amphetamine psychosis (e.g., delusions and paranoia) can occur in heavy users. Although very rare, this psychosis can also occur at therapeutic doses during long-term therapy. According to the USFDA, "there is no systematic evidence" that stimulants produce aggressive behavior or hostility.
Hives
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.
Clozapine
Clozapine may cause side effects, some of which are serious and potentially fatal. Common side effects include constipation, bed-wetting, night-time drooling, muscle stiffness, sedation, tremors, orthostatic hypotension, hyperglycemia, and weight gain. The risk of developing extrapyramidal symptoms, such as tardive dyskinesia is below that of typical antipsychotics; this may be due to clozapine's anticholinergic effects. Extrapyramidal symptoms may subside somewhat after a person switches from another antipsychotic to clozapine.
Cyproheptadine
Cyproheptadine, sold under the brand name Periactin among others, is a first-generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties.Adverse effects include:
Gastric decontamination measures such as activated charcoal are sometimes recommended in cases of overdose. The symptoms are usually indicative of CNS depression (or conversely CNS stimulation in some) and excess anticholinergic side effects. The LD in mice is 123 mg/kg and 295 mg/kg in rats.
Temazepam
Chronic or excessive use of temazepam may cause drug tolerance, which can develop rapidly, so this drug is not recommended for long-term use. In 1979, the Institute of Medicine (USA) and the National Institute on Drug Abuse stated that most hypnotics lose their sleep-inducing properties after about three to 14 days. In use longer than one to two weeks, tolerance will rapidly develop towards the ability of temazepam to maintain sleep, resulting in a loss of effectiveness. Some studies have observed tolerance to temazepam after as little as one week's use. Another study examined the short-term effects of the accumulation of temazepam over seven days in elderly inpatients, and found little tolerance developed during the accumulation of the drug. Other studies examined the use of temazepam over six days and saw no evidence of tolerance. A study in 11 young male subjects showed significant tolerance occurs to temazepam's thermoregulatory effects and sleep inducing properties after one week of use of 30-mg temazepam. Body temperature is well correlated with the sleep-inducing or insomnia-promoting properties of drugs.
Diphenhydramine
Diphenhydramine is an antihistamine mainly used to treat allergies. It is also used for insomnia, symptoms of the common cold, tremor in parkinsonism, and nausea. It is used by mouth, injection into a vein, and injection into a muscle. Maximal effect is typically around two hours after a dose, and effects can last for up to seven hours.
Common side effects include sleepiness, poor coordination, and an upset stomach. Its use is not recommended in babies. There is no clear risk of harm when used during pregnancy; however, use during breastfeeding is not recommended. It is a first generation H-antihistamine and works by blocking certain effects of histamine. Diphenhydramine is also an anticholinergic.
Diphenhydramine was first made by George Rieveschl and came into commercial use in 1946. It is available as a generic medication. The wholesale price in the developing world is about per dose. In the United States, it costs less than for a typical month’s supply. It is sold under the trade name Benadryl, among others.
Management of prostate cancer
Each treatment has disadvantages that limit its use in certain circumstances. Although orchiectomy is a low-risk surgery, the psychological impact of removing the testicles can be significant, and sterility is certain. The loss of testosterone can cause hot flashes, weight gain, loss of libido, enlargement of the breasts (gynecomastia), impotence, penile atrophy, and osteoporosis. GnRH agonists eventually cause the same side effects as orchiectomy but may cause worse symptoms at the beginning of treatment. When GnRH agonists are first used, testosterone surges can lead to increased bone pain from metastatic cancer, so antiandrogens or abarelix is often added to blunt these side effects. Estrogens are not commonly used because they increase the risk for cardiovascular disease and blood clots. In general, the antiandrogens do not cause impotence, and usually cause less loss of bone and muscle mass. Ketoconazole can cause liver damage with prolonged use, and aminoglutethimide can cause skin rashes.
Thioridazine
Thioridazine prolongs the QTc interval in a dose-dependent manner. It produces significantly less extrapyramidal side effects than most first-generation antipsychotics. Its use, along with the use of other typical antipsychotics, has been associated with degenerative retinopathies. It has a higher propensity for causing anticholinergic side effects coupled with a lower propensity for causing extrapyramidal side effects and sedation than chlorpromazine, but also has a higher incidence of hypotension and cardiotoxicity. It is also known to possess a relatively high liability for causing orthostatic hypotension compared to other antipsychotics. Similarly to other first-generation antipsychotics it has a relatively high liability for causing prolactin elevation. It is moderate risk for causing weight gain. As with all antipsychotics thioridazine has been linked to cases of tardive dyskinesia (an often permanent neurological disorder characterised by slow, repetitive, purposeless and involuntary movements, most often of the facial muscles, that is usually brought on by years of continued treatment with antipsychotics, especially the first-generation (or "typical") antipsychotics such as thioridazine) and neuroleptic malignant syndrome (a potentially fatal complication of antipsychotic treatment). Blood dyscrasias such as agranulocytosis, leukopenia and neutropenia are possible with thioridazine treatment.
Insomnia
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. 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. A further problem is, with regular use of short-acting sleep aids for insomnia, daytime rebound anxiety can emerge. 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. 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.
Statin
Other possible adverse effects include neuropathy, pancreatic and liver dysfunction, and sexual dysfunction. The rate at which such events occur has been widely debated, in part because the risk/benefit ratio of statins in low-risk populations is highly dependent on the rate of adverse events. A Cochrane meta-analysis of statin clinical trials in primary prevention found no evidence of excess adverse events among those treated with statins compared to placebo. Another meta-analysis found a 39% increase in adverse events in statin treated people relative to those receiving placebo, but no increase in serious adverse events. The author of one study argued that adverse events are more common in clinical practice than in randomized clinical trials. A systematic review concluded that while clinical trial meta-analyses underestimate the rate of muscle pain associated with statin use, the rates of rhabdomyolysis are still "reassuringly low" and similar to those seen in clinical trials (about 1–2 per 10,000 person years). A systematic review co-authored by Ben Goldacre concluded that only a small fraction of side effects reported by people on statins are actually attributable to the statin.
Dihydrotestosterone
5α-Reductase inhibitors are overall well-tolerated and show a low incidence of adverse effects. Sexual dysfunction, including erectile dysfunction, loss of libido, and reduced ejaculate volume, may occur in 3.4 to 15.8% of men treated with finasteride or dutasteride. A small increase in the risk of affective symptoms including depression, anxiety, and self-harm may be seen. Both the sexual dysfunction and affective symptoms may be due partially or fully to prevention of the synthesis of neurosteroids like allopregnanolone rather necessarily than due to inhibition of DHT production. A very small risk of gynecomastia has been associated with 5α-reductase inhibitors (1.2 to 3.5%). Based on reports of 5α-reductase type II deficiency in males and the effectiveness of 5α-reductase inhibitors for hirsutism in women, reduced body and/or facial hair growth is a likely potential side effect of these drugs in men. There are very few studies evaluating the side effects of 5α-reductase inhibitors in women. However, due to the known role of DHT in male sexual differentiation, 5α-reductase inhibitors may cause birth defects such as ambiguous genitalia in the male fetuses of pregnant women. As such, they are not used in women during pregnancy.
Amphetamine
Reviews of clinical stimulant research have established the safety and effectiveness of long-term continuous amphetamine use for the treatment of ADHD. Randomized controlled trials of continuous stimulant therapy for the treatment of ADHD spanning 2 years have demonstrated treatment effectiveness and safety. Two reviews have indicated that long-term continuous stimulant therapy for ADHD is effective for reducing the core symptoms of ADHD (i.e., hyperactivity, inattention, and impulsivity), enhancing quality of life and academic achievement, and producing improvements in a large number of functional outcomes across 9 categories of outcomes related to academics, antisocial behavior, driving, non-medicinal drug use, obesity, occupation, self-esteem, service use (i.e., academic, occupational, health, financial, and legal services), and social function. One review highlighted a nine-month randomized controlled trial of amphetamine treatment for ADHD in children that found an average increase of 4.5 IQ points, continued increases in attention, and continued decreases in disruptive behaviors and hyperactivity. Another review indicated that, based upon the longest follow-up studies conducted to date, lifetime stimulant therapy that begins during childhood is continuously effective for controlling ADHD symptoms and reduces the risk of developing a substance use disorder as an adult.
Norethisterone
At contraceptive and hormone replacement dosages (0.35 to 1 mg/day), norethisterone has essentially progestogenic side effects only. In most clinical studies of norethisterone for contraception or menopausal hormone therapy, the drug has been combined with an estrogen, and for this reason, it is difficult to determine which of the side effects were caused by norethisterone and which of them were caused by estrogen in such research. However, NETE, an intramuscularly administered prodrug of norethisterone which is used as a long-acting contraceptive, is used without an estrogen, and hence can be employed as a surrogate for norethisterone in terms of understanding its effects and tolerability. In clinical studies, the most common side effect with NETE has been menstrual disturbances, including prolonged bleeding or spotting and amenorrhea. Other side effects have included periodic abdominal bloating and breast tenderness, both of which are thought to be due to water retention and can be relieved with diuretics. There has been no association with weight gain, and blood pressure, blood clotting, and glucose tolerance have all remained normal. However, a decrease in cholesterol has been observed.
Benzodiazepine
The short-term use of benzodiazepines adversely affects multiple areas of cognition, the most notable one being that it interferes with the formation and consolidation of memories of new material and may induce complete anterograde amnesia. However, researchers hold contrary opinions regarding the effects of long-term administration. One view is that many of the short-term effects continue into the long-term and may even worsen, and are not resolved after stopping benzodiazepine usage. Another view maintains that cognitive deficits in chronic benzodiazepine users occur only for a short period after the dose, or that the anxiety disorder is the cause of these deficits.
Benzodiazepine
A major disadvantage of benzodiazepines that tolerance to therapeutic effects develops relatively quickly while many adverse effects persist. Tolerance develops to hypnotic and myorelexant effects within days to weeks, and to anticonvulsant and anxiolytic effects within weeks to months. Therefore, benzodiazepines are unlikely to be effective long-term treatments for sleep and anxiety. While BZD therapeutic effects disappear with tolerance, depression and impulsivity with high suicidal risk commonly persist. Several studies have confirmed that long-term benzodiazepines are not significantly different from placebo for sleep or anxiety. This may explain why patients commonly increase doses over time and many eventually take more than one type of benzodiazepine after the first loses effectiveness. Additionally, because tolerance to benzodiazepine sedating effects develops more quickly than does tolerance to brainstem depressant effects, those taking more benzodiazepines to achieve desired effects may suffer sudden respiratory depression, hypotension or death. Most patients with anxiety disorders and PTSD have symptoms that persist for at least several months, making tolerance to therapeutic effects a distinct problem for them and necessitating the need for more effective long-term treatment (e.g., psychotherapy, serotonergic antidepressants).
Effects of long-term benzodiazepine use
The effects of long-term benzodiazepine use include drug dependence and neurotoxicity as well as the possibility of adverse effects on cognitive function, physical health, and mental health. Benzodiazepines are generally effective when used therapeutically in the short term, but even then the risk of dependency can be significantly high. Most of the problems associated with benzodiazepines result from their long-term use. There are significant physical, mental and social risks associated with the long-term use of benzodiazepines. Although anxiety can temporarily increase as a withdrawal symptom, there is evidence that a reduction or withdrawal from benzodiazepines can lead in the long run to a reduction in anxiety symptoms. Due to these increasing physical and mental symptoms from long-term use of benzodiazepines, slowly withdrawing from benzodiazepines is recommended for many long-term users. Not everyone, however, experiences problems with long-term use.
Benzodiazepine
The long-term effects of benzodiazepine use can include cognitive impairment as well as affective and behavioural problems. Feelings of turmoil, difficulty in thinking constructively, loss of sex-drive, agoraphobia and social phobia, increasing anxiety and depression, loss of interest in leisure pursuits and interests, and an inability to experience or express feelings can also occur. Not everyone, however, experiences problems with long-term use. Additionally, an altered perception of self, environment and relationships may occur.
Mifepristone
Nearly all women using the mifepristone/misoprostol regimen experienced abdominal pain, uterine cramping, and vaginal bleeding or spotting for an average of 9–16 days. Up to 8% of women experienced some type of bleeding for 30 days or more. Other less common side effects included nausea, vomiting, diarrhea, dizziness, fatigue, and fever. Pelvic inflammatory disease is a very rare but serious complication. Excessive bleeding and incomplete termination of a pregnancy require further intervention by a doctor (such as vacuum aspiration). Between 4.5 and 7.9% of women required surgical intervention in clinical trials. Mifepristone is contraindicated in the presence of an intrauterine device, as well as with ectopic pregnancy, adrenal failure, hemorrhagic disorders, inherited porphyria, and anticoagulant or long-term corticosteroid therapy.
Physostigmine
It has been shown to improve long term memory, and was once explored as a therapy for Alzheimer's disease, but in clinical trials it was not shown to confer convincing benefits, and it led to very common moderate to severe side-effects such as nausea, vomiting, diarrhea, loss of appetite (anorexia), abdominal pain, and tremors, resulting in a high rate of withdrawal. Physostigmine's poor tolerability led to it being abandoned in favor of later acetylcholinesterase inhibitors, three of which are currently in use: donepezil, galantamine, and rivastigmine. Recently, it has begun to be used in the treatment of orthostatic hypotension.
Terbinafine
Many side effects and adverse drug reactions have been reported with oral terbinafine hydrochloride possibly due to its extensive biodistribution and the often extended durations involved in antifungal treatment (longer than two months). A comprehensive list of adverse events associated with terbinafine use includes:
Tubocurarine chloride
Tubocurarine has a time of onset of around 5 minutes which is relatively slow among neuromuscular-blocking drugs, and has a duration of action of 60 to 120 minutes. It also causes histamine release, now a recognized hallmark of the tetrahydroisioquinolinium class of neuromuscular blocking agents. Histamine release is associated with bronchospasms, hypotension, salivary secretions, making it dangerous for asthmatics, children, and those who are pregnant or lactating. However, the main disadvantage in the use of tubocurarine is its significant ganglion-blocking effect, that manifests as hypotension, in many patients; this constitutes a relative contraindication to its use in patients with myocardial ischaemia.