Allergies have increased by 40% in recent years and allergy medications are used more often than ever. There are different types of allergy medication. Some are used to control acute attacks while others help prevent or lessen the severity of allergic reactions. Some of them, especially sedating antihistamines and corticosteroids, are known to produce unwanted effects which limit their use under certain conditions.
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Antihistamines work to prevent the action of histamine, a bioactive amine, on one of the histamine receptors, to block itching, swelling, redness, nasal congestion, tears in the eyes, cough, nausea and dizziness.
Histamine affects smooth muscles and blood vessels, causing smooth muscle spasms and vasodilation. Administration of antihistamines blocks most of these effects, making them the most commonly used drugs in the world.
Antihistamines are drugs that treat allergic rhinitis and other allergies. Image Credit: Studio BKK / Shutterstock
These drugs are useful for a variety of allergic conditions as well as those associated with arousal and anxiety. So, in addition to treating allergies, they have been used in various ways to treat symptoms of colds, motion sickness, nausea from other causes, skin allergies, and to induce drowsiness in tense or tense patients. anxious.
Antihistamines can be classified as sedating (first generation antihistamines) and non-sedating (second generation antihistamines). Both act on the H1 receptor, but first generation drugs also act less selectively on other receptors. The difference lies in their ability to cross the blood-brain barrier.
These drugs share a chemical structure with drugs that oppose muscarinic receptors and cholinergic receptors; certain antihypertensive drugs; and some tranquilizers. Therefore, they are not selective towards histamine receptors. They have anti-muscarinic effects, anti-alpha-adrenergic effects and anti-serotonin effects.
Sedative antihistamines readily cross the blood-brain barrier to act on central histamine receptors as well as those located at the periphery. There are approximately 64,000 neurons in the human brain that secrete histamine. These regulate a multitude of actions, namely:
- Learning and memory
- Body temperature regulation
- Regulation of heart rate and blood pressure
- Involvement in the release of stress hormones and endorphins
Central side effects
Since these actions are disturbed by sedating antihistamines, these drugs produce sedation, drowsiness, fatigue, lack of concentration, learning and memory difficulties, poor performance on exams, and difficulty at work or at work. driving due to cognitive and coordination problems. Additionally, users continue to feel tired, inattentive, forgetful, and have poor motor and sensory performance in the morning after a nighttime dose – primarily because histamine reduces the duration of therapy. REM sleep.
Anticholinergic and alpha-adrenergic side effects
In addition, sedating antihistamines also produce effects via their blockade of cholinergic and alpha-adrenergic receptors, such as urinary retention, constipation, sinus tachycardia, inhibition of intestinal motility, restlessness and worsening of the blood. narrow-angle glaucoma. They also produce or worsen dry mouth, increase appetite and induce tolerance when used beyond about 5 days.
Blurred vision, pupillary dilation, dry mouth and skin, flushing, delirium and confusion, and hyperthermia is the well-known and potentially fatal anticholinergic syndrome caused by high doses of these drugs. Many over the counter antihistamines also contain a decongestant and therefore if the user has palpitations the drug should be stopped.
Cardiac side effects
Astemizole and terfenadine are two H1 antihistamines that prolong the cardiac QT interval and can produce dangerous irregularities in the rhythm of the heart such as the characteristic “torsades de pointes” in the ventricular myocardium. Therefore, their use is currently not approved in most countries. This problem is also seen with large doses or overdoses of certain sedating antihistamines like brompheniramine, promethazine or diphenhydramine.
These drugs should be used with caution in elderly patients, as they generally have lower numbers of cholinergic neurons in the brain, have fewer cholinergic receptors, have compromised kidney and liver function, and have a less stable blood brain barrier with the drug. ‘age. Even at lower doses, they can cause dizziness, low blood pressure and sedation that lasts the next day. This can cause falls in the elderly with the risk of related injuries.
About 25% of older people (over 65) have some cognitive decline, even if it is subtle or unnoticed. These people may react badly to antihistamines with pronounced anticholinergic effects, and may show signs of dementia as a result.
Delirium or cognitive impairment are other side effects associated with the use of sedating antihistamines in the elderly. It can further lead to inappropriate treatment with antipsychotics and placement in long-term care facilities with hallucinations and other signs of agitation or aggression, caused by the anticholinergic drugs.
Doctors and other healthcare professionals, as well as older patients, should avoid these drugs now that non-sedating antihistamines are available.
Contraindications to sedative antihistamines
These drugs should be avoided in very young children and in conditions such as:
- urinary retention due to benign prostatic hyperplasia
- narrow-angle glaucoma
- cardiac disease
They should be used with caution, and only if essential, in patients with:
- xerostomia or dry mouth
- chronic obstructive pulmonary disease
- kidney disease
- liver disease
- benign prostatic hyperplasia, which is associated with chronic urinary retention
- patients on antidepressants or antiepileptics should also consult their doctor before taking antihistamines
- In patients who drink alcohol
With the availability of second generation antihistamines, older sedating antihistamines should be avoided if possible. In any case, people who are about to take exams, who are learning demanding equipment or tasks, and adults who must fly, drive, or work at any task that requires focused concentration should avoid use these drugs.
These are also called second generation H1 antihistamines and include loratadine, fexofenadine, mizolastine, ebastine, azelastine, cetirizine, desloratadine, and levocetirizine. These have no currently known cardiac side effects.
Fexofenadine and desloratidine, which, along with levocetirizine, are the most commonly used non-sedating antihistamines, cause very little sedation because they do not cross the blood-brain barrier significantly and therefore have little effect on patients. histamine receptors in the brain. Their inability to induce central sedation is due to their interaction with a pump protein, P-glycoprotein, which inhibits their translocation across the blood-brain barrier. Levocetirizine can produce sedation in a certain percentage of patients, although it should be taken in doses higher than those recommended for this.
With their lack of off-target effects, non-sedating antihistamines are much more suitable for patients who require long-term treatment. Not only are they safer, but they have a more powerful anti-allergic effect.
Non-sedating antihistamines can rarely cause acute liver damage. Although liver damage is usually mild, if it occurs, antihistamines should be stopped. Liver function is usually only slightly disturbed and returns to normal with switching to another antihistamine or stopping treatment. Fortunately, stopping these drugs quickly reverses most of these side effects, which are usually mild.
Newer antihistamines are generally safe, but should be avoided in children and during pregnancy unless they are essential.