Antihistamines of different generations. What are antihistamines in simple words: classic formulations and antiallergic drugs of new generations
Question: Can antiallergic antihistamines harm a person if taken on a regular basis?
Answer: It is better to pass tests for allergens on the machine "IMEDIS Expert", and further exclude contacts with identified bioresonance test allergens. Also, if possible, it is treated by a bioresonance therapist and for many years to take homeopathic and bioresonance preparations prescribed during the treatment of bioresonance therapy, as well as during exacerbations or during the allergic season, take new-generation antihistamine drugs selected by a bioresonance test or pendulum.
You need to drink new generation antihistamines 1 time per day until the allergy symptoms disappear. If contact with the allergen cannot be avoided, then you will have to take an antihistamine (anti-allergic drug) daily, there is nowhere to go from this, alas. Upon contact with an allergen without an antiallergic drug, a severe allergic reaction can develop, which in turn can lead to death, coma, and allergies can also turn into asthma.
There are people who sit on new generations of antihistamines during their lifetime and nothing.
Of course, pills are no sweetie, and antihistamines are no exception. In a state of reaction, do not try to do without them. Allergens will need to be removed from the field of the body on time, and then it may be too late.
Antihistamines are a group of drugs whose principle of action is based on the fact that they block H1 and H2-histamine receptors. This blocking helps to reduce the reaction of the human body with a special mediator histamine. What are these medicines for? Doctors prescribe them during allergic reactions. Possessing good antipruritic, antispastic, antiserotonin and local anesthetic effects, antihistamines perfectly help with allergies, and also effectively prevent bronchospasm caused by histamine.
In accordance with the time of invention and release on sale, the whole variety of allergy remedies is classified into several levels. Antihistamines are classified into first, second, third and fourth generation drugs. The medicines included in each generation have their own specific features and properties. Their classification is based on the duration of the antihistamine effect, the available contraindications and side effects. The medicine necessary for treatment must be selected based on the characteristics of each specific case of the disease.
Generations of antihistamines
First generation antihistamines
Preparations of the 1st (first) generation include sedatives. They work at the level of H-1 receptors. The duration of their action is four to five hours, after this period it will be necessary to take a new dose of the drug, and the dose should be large enough. Sedative antihistamines, despite their strong effect, have a number of disadvantages. For example, they can provoke dry mouth, dilated pupils, blurred vision.
Drowsiness and a decrease in tone may occur, which means it is impossible to take these drugs while driving a car and other activities that require a high concentration of attention. They also enhance the effect of taking other sedatives, sleeping pills and pain medications. The effect on the body of alcohol mixed with sedatives is also enhanced. Most first generation antihistamines are interchangeable.
Their use is advisable in the event of problems of an allergic nature with respiratory system such as coughing or nasal congestion. It is worth paying attention to the fact that first-generation antihistamines fight cough well. This makes it appropriate to use them in bronchitis.
They will also be useful to those people who suffer chronic diseases associated with difficulty breathing. They are quite effective in bronchial asthma. They can also have a fairly good effect in the treatment of acute allergic reactions. So, for example, their use will be appropriate for urticaria. The most common among them are:
suprastin
diphenhydramine
diazolin
tavegil
Also often on sale you can find peritol, pipolfen and fenkarol.
Second generation antihistamines
Preparations of the 2nd (second) generation are called non-sedative. They do not have such a large list of side effects as the drugs that make up the first generation of antihistamines. These are drugs that do not cause drowsiness and do not reduce brain activity, and also do not have cholinergic effects. good effect gives their use for itching of the skin and allergic rashes.
However, their significant drawback is the cardiotoxic effect that these drugs can cause. Therefore, non-sedative drugs are prescribed only on an outpatient basis. In no case should they be taken by people suffering from heart disease. vascular system. Names of the most common non-sedative drugs:
trexil
histalong
zodak
semprex
fenistil
claritin
Third generation antihistamines
Antihistamines of the 3rd (third) generation are also otherwise called active metabolites. They have strong antihistamine properties and have virtually no contraindications. The standard set of these drugs includes:
cetrin
zyrtec
telfast
These drugs do not have a cardiotoxic effect, unlike second-generation drugs. Their use gives a positive effect in asthma and acute allergic reactions. They are also effective in the treatment of dermatological diseases. Quite often, third-generation antihistamines are prescribed by doctors for psoriasis.
New generation drugs are the most effective and harmless antihistamines. They are non-addictive, safe for the cardiovascular system, and also have a long period of action. They belong to the fourth generation of antihistamines.
Fourth generation antihistamines
Preparations of the 4th (fourth) generation have a small list of contraindications, which are mainly pregnancy and childhood, but, nevertheless, it is worth reading the instructions and consulting with a specialist before starting treatment. The list of these drugs includes:
levocetirizine
desloratadine
fexofenadine
Based on them, a larger number of drugs are produced, which, if necessary, can be purchased at a pharmacy. These include erius, xizal, lordestin, and telfast.
Forms of release of antihistamines
There are several forms of release of drugs that block histamine receptors. In most cases, their most convenient type to use are tablets and capsules. However, on the shelves of pharmacies you can also find antihistamines in ampoules, suppositories, drops and even syrups. The action of each of them is unique, so only a doctor can help you choose the most appropriate form of taking the medicine.
Treatment of children with antihistamines
As you know, children are more prone to allergic diseases than adults. A qualified allergist should select and prescribe drugs for children. Many of them in the list of their contraindications are of children's age, therefore, if necessary, from the application to the preparation of a course of treatment, it is necessary to be especially careful. Children's organisms can react quite sharply to the effects of the drug, so the child's well-being during the period of their use must be monitored very carefully. In case of side effects, the drug should be stopped immediately and consult a doctor.
For the treatment of children, both somewhat outdated medicines and more modern ones are suitable. The drugs that are part of the first generation are mainly used for urgent removal acute symptoms allergies. During long-term use, more modern means are usually used.
Antihistamines are not usually available in special "children's" forms. For the treatment of children, the same drugs are used as for adults, but in smaller doses. Drugs such as zyrtec and ketotifen are usually prescribed from the moment the child reaches the age of six months, all others - from two years. Do not forget that taking medicines by a child should be under the supervision of an adult.
In the case of an illness of a small child, the selection of antihistamines is much more complicated. For newborns, medications that have a slight sedative effect, that is, first-generation drugs, may be suitable. The most commonly used in the treatment of very young children is suprastin. It is safe for both babies and older children, as well as for nursing mothers and pregnant women. Depending on the disease and the condition of the child's body, the doctor may prescribe tavegil or Phenkarol for him, and in case of skin allergic reaction- antihistamine cream. For infants, the same drugs are suitable as for newborns.
Antihistamines during pregnancy and lactation
Due to the increased production of cortisol in the body of a woman, allergies during the childbearing period are quite rare, but, nevertheless, some women still face this problem. During pregnancy, the intake of absolutely all medications must be agreed with the doctor. This also applies to allergy remedies, which have a fairly wide range of side effects and can harm the child. The use of antihistamines is strictly prohibited in the first trimester of pregnancy; in the second and third trimesters, they can be used, observing, however, the necessary precautions.
Unintentional ingestion of the drug into the child's body is possible not only during pregnancy, but also during breastfeeding. During lactation, the use of antihistamines is highly undesirable and is prescribed only in the most urgent cases. The question of which remedy a nursing woman will use can only be decided by a doctor. Even the newest and most modern medicines can cause irreparable harm, so in any case, do not self-medicate by feeding your baby with your milk.
Side effects of antihistamines
As mentioned earlier, the body of each person is individual, and only a specialist can choose the right remedy for treatment. Taking the wrong medicine for a person and violating the dosage can seriously harm health. The harm of antihistamines can manifest itself in addition to their usual side effects such as drowsiness, runny nose and cough in violation of the timing of ovulation in women, the occurrence of allergic edema and asthma. Therefore, be sure to consult your doctor before you start drinking the medicine, and strictly follow the recommendations for taking it.
Drug treatment of allergies, antihistamines
How antihistamines work
Antihistamines of the "old" and "new" generations
What is the difference between 1st, 2nd and 3rd generation antihistamines
Fundamentals of drug therapy
There is such a substance - histamine. It is released during an allergic reaction and is responsible for the development of bad symptoms, from skin manifestations to very severe life-threatening reactions, such as anaphylactic shock. That's why antiallergic drugs are called ANTIhistamines.
They block histamine receptors and thus stop the development of allergy symptoms.
Depending on the type of reaction, antihistamines are prescribed by injection (for severe forms) and orally (for milder ones). It is understandable: if we inject the drug with the help of an intramuscular or intravenous injection, it instantly enters the bloodstream and is included in the work. And if we drink this medicine, time must pass before active substance absorbed into the blood from the gastrointestinal tract.
All anti-allergy drugs can be divided into several groups:
1. Symptomatic drugs.
2. Medicines for the treatment of chronic allergic inflammation in the affected organ.
3. Medicines for local therapy.
Symptomatic drugs are intended to alleviate the course of allergic diseases. The leading place among them belongs to drugs called antihistamines.
These agents counteract the damaging effects of the main mediator of allergic reactions, histamine. Today, doctors are armed with three generations of antihistamines that differ in their characteristics.
The selection of antihistamines is carried out individually, taking into account the nature of food allergies, the age of the child and the nature of concomitant diseases. Symptomatic drugs also, for example, include bronchodilators. They are used for asthma attacks.
Antihistamines for the treatment of chronic allergic inflammation in the affected organ are divided into non-hormonal and hormonal. The latter drugs are more powerful and effective.
The prescription of drugs in this group is carried out depending on clinical manifestations food allergies, the severity of the disease, the age of the child. It must be remembered that these drugs are generally effective only with long-term regular use.
It must be remembered that drug therapy for food allergies is a long process, you need to patiently and persistently follow medical recommendations.
We must also remember that some treatments for food allergies are absolutely contraindicated and can harm the child. So, with food allergies, treatment with herbs and many means is contraindicated. traditional medicine, and psychotherapy and reflexology, except for bioresonance treatment, almost do not give a significant effect.
Treatment with herbs and preparations based on them increases the risk of developing an allergy to plant pollen in the future. The same “service” can be provided by biologically active additives, which often contain plant components.
Antihistamines are standard therapy for atopic dermatitis. They are used as additional remedy to external treatment with severe itching and associated rashes.
Antihistamines are divided into three generations:
means of the 1st "old" generation;
means of the 2nd and 3rd generations ("new" generation).
Antihistamine drugs of the 1st "old" generation
Antihistamines of the 1st generation are more often used to treat acute reactions, in the treatment of itchy allergic dermatoses. Most of them are available in solutions in ampoules, but there are forms in tablets, syrups and powders.
Antihistamines of the 1st "old" generation (forms for oral administration)
Chloropyramine, Clemastine, Dimetindene, Quifenadine, Hifenadine, Mebhydrolin, Ketotifen.
Disadvantages of older generation antihistamines:
Incomplete connection with H1 receptors, as a result of which relatively high doses are required;
Short-term action - taking several times a day
Development of addiction - it is necessary to alternate drugs of different groups every 10-14 days
Sedative and hypnotic effect
Antihistamine drugs of the 2nd and 3rd "new" generations
Loratodin, cyterizine, fexofenadine, desloratadine.
Currently, in the treatment of atopic dermatitis, antihistamine drugs of the “new”, that is, the 2nd and 3rd generations, are widely used.
Antihistamine drugs of the 2nd and 3rd generations are used for basic and anti-relapse therapy.
Antihistamines of the "new" generation do not have sedative and hypnotic effects. They have a selective effect, causing blockade of only H1-histamine receptors. The duration of their action is up to 24 hours, so most of these drugs are prescribed once a day.
After taking most antihistamines, their residual effect may last for one week after withdrawal (this circumstance must be taken into account when conducting an allergy examination). A significant difference between the antihistamine drugs of the "new" generation is that they have not only H1-blocking action, but also anti-allergic and anti-inflammatory effects.
If long-term use is necessary, only antihistamines of the “new” generation are used.
The absence of undesirable side effects characteristic of the first antihistamines allows to significantly expand the list of indications for the appointment of modern H1-antagonists.
Benefits of 2nd generation antihistamines over 1st generation:
Rapid onset of action (from 30 minutes - acute cases);
Possibility of taking at any time of the day (including in the first half of the day) Good absorption from the digestive tract Possibility of use in children early age long duration of the antihistamine effect (up to 24 hours), which allows you to take the drug once a day.
No blockade of other types of receptors
Lack of penetration through the blood-brain barrier at therapeutic doses
Lack of connection with food intake
Non-addictive, even with long-term use (3 to 6 months)
Practically complete absence side effects associated with effects on the nervous and cardiovascular systems.
The use of antihistamine drugs in the treatment of children with atopic dermatitis.
Children after a year, as a rule, are prescribed drugs of a new generation.
The "new" generation drugs that are approved for use in children from 6 months of age are antihistamine drugs based on cetirizine (generic active ingredient).
VACCINATION
Since allergy is an immune disorder, allergic rhinitis and bronchial asthma can be treated with vaccines from allergens to which the child is hypersensitive. Indications for vaccination are determined based on the results of skin tests with allergens.
The vaccine is administered under a special scheme subcutaneously or buried under the tongue. Such treatment is applicable only in children over 5 years of age and should be carried out by an allergist.
And finally, the most interesting question: do allergy medications cause allergies? Yes! We will not go into the technical details of the complex mechanisms that can lead to this development.
Let's just say that an allergy to antihistamines is extremely rare, but it happens. There is only one way out - to change the drug.
Antihistamines are a group of drugs that perform a competitive blockade of histamine receptors in the body, which leads to inhibition of the effects mediated by it.
Histamine is a neurotransmitter that can affect the respiratory tract (causing swelling of the nasal mucosa, bronchospasm), skin (itching, blistering-hyperemic reaction), gastrointestinal tract (intestinal colic, stimulation of gastric secretion), cardiovascular system(expansion of capillary vessels, increased vascular permeability, hypotension, impaired heart rate), smooth muscle.
Strengthening its influence cause allergic reactions, so antihistamines are used to combat the manifestations of allergies. Another area of their application is symptomatic therapy / elimination of symptoms in colds.
Currently, there are three groups of drugs (according to the receptors they block):
H1 blockers - used in the treatment of allergic diseases.
H2-blockers - used in the treatment of diseases of the stomach (help reduce gastric secretion).
H3 blockers are used in the treatment of neurological diseases.
Among them, cetrin (cetirizine), phencarol (hifenadine), diphenhydramine, clemastine, suprastin stop the emission (for example, cromoglycic acid) or the action (like diphenhydramine) of histamines.
Available in the form of tablets, nasal spray, drops, including eye drops, solution in ampoules for intramuscular injection (usually for emergency therapy).
There are several generations of antihistamines. With each generation, the number and strength of side effects and the likelihood of addiction decrease, the duration of action increases.
First generation
Before buying a medicine - paracetamol, ibuprofen, antiallergic (antihistamine) drugs, cold and cold remedies, you need to know:
Paracetamol
Pain reliever, antipyretic, anti-inflammatory agent. active ingredient is paraacetaminophenol, based on which different countries many other similar drugs are produced, such as acetaminophen, panadol, efferalgan, myalgin, paramol, pilaren, etc.
Benefit. In its action, paracetamol is in many ways close to aspirin, but has less pronounced side effects. It does not reduce blood viscosity, so it is safe to use in preparation for and after surgery.
It is less likely than aspirin to cause allergic reactions and is less irritating to the stomach. Paracetamol is part of many combined drugs in combination with aspirin, analgin, caffeine, etc. It is available in the form of tablets, capsules, mixtures, syrup, "effervescent" powders (panadol, panadon).
Possible harm. When combined with alcohol, it can damage and even destroy the liver. Therefore, it, like aspirin, is dangerous for people who regularly drink alcohol. Paracetamol has a negative effect on the liver and in case of violation of the norm of its intake (in case of overdose).
Exit. Take no more than 2 g per day (4 tablets of 500 mg) - People who drink alcohol daily should stop taking paracetamol.
ibuprofen
It has an analgesic and anti-inflammatory effect. Ibuprofen is the active ingredient in drugs such as Brufen, Arthryl, Advil, Naproxen, etc. These drugs are chemically identical, but differ in the duration of the therapeutic effect.
Benefit. Help with fever, muscle and joint pain (rheumatoid arthritis, arthrosis, etc.)
Possible harm. If the body is severely dehydrated as a result of hard physical work, heat, or taking diuretics (diuretics), then ibuprofen can adversely affect the kidneys. The risk of kidney damage increases with regular use of ibuprofen.
Long-term use of ibuprofen is dangerous for the stomach. In people who constantly drink alcohol, taking ibuprofen can affect the liver.
Exit. Try to avoid dehydration. When taking ibuprofen, it is necessary to monitor the work of the kidneys. In no case should you exceed the allowable daily intake (6 tablets of ibuprofen 200 mg or 2 tablets of naproxen 220 mg).
Antiallergic (antihistamine) drugs
The drugs in this group are intended for people suffering from pollinosis (hay fever), asthma, hives or other allergic diseases.
Benefit. They relieve runny nose, sneezing, sore throat, coughing and suffocation, unbearable itching and other symptoms of these diseases.
Possible harm. Most common drugs in this group, such as suprastin, tavegil, diphenhydramine, zaditen, peritol, etc., have a sedative effect, that is, they cause drowsiness, inhibition of reactions, and general weakness. Therefore, it is dangerous to take them to car drivers, pilots, operators, dispatchers, etc., that is, people who require constant attention and quick reaction in difficult situations.
Exit. To avoid the risk, you should take a new generation of antihistamines that do not cause drowsiness and inhibition of reactions, such as claritin, kestin, which act for 12-24 hours. Sedative antihistamines are best taken in the afternoon and at night.
Remedies for the common cold
The action of drugs such as sanorin, naphthyzin, galazolin, otrivin, etc., is that they constrict blood vessels in the swollen mucous membrane of the nasal passages, as a result of which the nasal passages themselves expand.
Benefit. With a cold, the runny nose is weakened or stops, breathing through the nose is restored, and the headache disappears.
Possible harm. When taking these drugs, blood vessels are narrowed not only in the nose, as a result of which blood pressure may increase in patients with hypertension.
This is especially dangerous for hypertensive patients, since they are taken to reduce blood pressure medicines will be ineffective. In addition, drugs in this group are dangerous for those who take antidepressants such as pyrazidol, pirlindol, nialamide.
Exit. For people suffering from hypertension, common cold remedies can only be taken under the control of blood pressure. In the event of an increase in pressure, the dosage of antihypertensive drugs should be increased.
Patients with depression who take the listed antidepressants or the like, drugs in this group are contraindicated.
Complex preparations for colds used with antihistamines
Among the complex anti-cold drugs, such as askofen, citramon, sedalgin, alkaseltzer plus, bicarmint, etc. are especially known.
Benefit. Help to get rid of different symptoms diseases: from cough, runny nose, pain, fever, allergic manifestations.
Possible harm. When taking complex drugs, the so-called "unforeseen overdose" is quite often allowed.
This happens when, with a severe cold or headache, in order to increase the effectiveness of treatment, a complex cold preparation containing aspirin is added to the intake of aspirin. As a result, it may worsen peptic ulcer or even stomach bleeding occurs.
If at allergic rhinitis in addition to suprastin, take also a complex preparation containing an antihistamine, then everything together will act as a strong sleeping pill. Sometimes liver disorders are associated with a similar overdose of paracetamol or ibuprofen.
Exit. Before taking a complex preparation for a cold, you should carefully read its composition indicated on the package or in the insert, and do not take separately those medicines that are included in it.
Antiallergic drugs for children: characteristics, principle of action, benefits and harms
Diazolin (mebhydrolin);
Peritol (cyproheptadine).
In principle, the effectiveness of the above drugs has been confirmed by many years of experience, but this same experience indicates a whole bunch of side effects:
All these drugs to a greater or lesser extent affect the central nervous system, providing sedative and hypnotic effects.
Classical antihistamines dry out the mucous membranes. Dry mouth, sputum viscosity in the lungs (which is especially dangerous in acute respiratory viral infections, as it seriously increases the risk of developing pneumonia) - does not affect the child's condition in the best way.
The simultaneous use of first-generation antiallergic drugs with other drugs enhances the effect of the use of the latter. Thus, antipyretic, analgesic, hypnotic effects are enhanced. Especially dangerous is the combination of antihistamines with other drugs that actively affect the functioning of the central nervous system. In this case, the development of side effects up to fainting is possible. The combination with alcoholic beverages is highly undesirable.
The action of such drugs, although effective, is limited to 2-3 hours (some last up to 6 hours).
Of course, it does not come without advantages. Firstly, first-generation antihistamines are relatively affordable, and secondly, they are great for not long-term treatment allergies. That is, if, for example, a child ate an excessive amount of chocolate and a short-term intake of an antihistamine is required, you can safely use the same Tavegil or Fenkarol.
Most first-generation allergy remedies are forbidden to be taken orally by nursing mothers; only their local forms can be used - ointment, cream, spray. The exception is Suprastin and Fenkarol (from three months of pregnancy). Each drug has its own characteristic feature, which is important to consider when drawing up a treatment regimen. So, it is not advisable for a baby prone to constipation to use Tavegil; a child suffering from gastrointestinal diseases is prohibited from taking Suprastin; and children with impaired liver function need to be careful with the use of Phencarol.
For babies under one year old, taking first-generation antiallergic drugs is undesirable. For the little ones, there are more modern drugs are practically safe and very effective.
The principles of action of antihistamines, the second generation on the children's body
The undoubted advantage of antiallergic drugs of the second and third generation is the absence or minimization of the sedative, hypnotic, CNS inhibitory effect.
In addition, they have a number of other advantages: they do not penetrate the fetoplacental barrier (that is, such drugs can be used during pregnancy);
do not dry mucous membranes;
do not affect the mental and physical activity of the child;
have a quick and long-lasting (up to 24 hours) therapeutic effect - one tablet is enough to forget about allergy symptoms for the whole day;
in addition to antiallergic, they have antiemetic, antiulcer and other actions (some drugs); do not reduce their effectiveness with long-term use.
Perhaps the only drawback of second-generation antiallergic drugs is their ability to have a negative impact on the children's cardiovascular system. Due to the possible cardiotoxic effect, the use of such drugs is not recommended for children with various pathologies of the heart and blood vessels.
Among the most prominent representatives of the second generation:
Claritin (loratidin);
Allergy treatment, antihistamines
Diazolin dragee 50mg №20
Diazolin tab. 100mg #10
Suprastin (chloropyramine) is one of the most widely used sedative antihistamines. It has significant antihistamine activity, peripheral anticholinergic and moderate antispasmodic action.
Effective in most cases for the treatment of seasonal and year-round allergic rhinoconjunctivitis, angioedema, urticaria, atopic dermatitis, eczema, itching of various etiologies; in parenteral form - for the treatment of acute allergic conditions requiring emergency care. It does not accumulate in the blood serum, so it does not cause an overdose with prolonged use. The effect comes on quickly, but is short-lived; to increase its duration, it is combined with non-sedating H1-blockers.
Suprastin injection 2% 1ml amp. No. 5 (Egis, Hungary)
Suprastin tab. 25mg №20 (Egis, Hungary)
Chloropyramine g / x tab. 25mg #40
Tavegil (clemastine) is a highly effective antihistamine drug similar in action to diphenhydramine. It has a high anticholinergic activity, but penetrates the blood-brain barrier to a lesser extent.
In an injectable form that can be used as an additional remedy for anaphylactic shock and angioedema, for the prevention and treatment of allergic and pseudo-allergic reactions. However, there is an allergy to tavegil.
Peritol (cyproheptadine), along with antihistamine, has a significant antiserotonin effect. It is often used in some forms of migraine to increase appetite.
Peritol syrup 2mg/5ml 100ml (Egis, Hungary)
Peritol tab. 4mg №20 (Egis, Hungary)
Pipolfen (promethazine) - a pronounced effect on the central nervous system, is used as an antiemetic and to potentiate anesthesia.
Pipolphen other 25mg №20 (Egis, Hungary)
Pipolfen solution for injections 50mg 2ml amp. №10 (Egis, Hungary)
Diprazine tab. 25mg #20
Phencarol (quifenadine) - has less antihistamine activity than diphenhydramine, but is also characterized by less penetration through the blood-brain barrier, which determines the lower severity of its sedative properties. In addition, fenkarol not only blocks histamine H1 receptors, but also reduces the content of histamine in tissues. Can be used in the development of addiction to other sedative antihistamines.
Fenkarol tab. 25mg №20 (Latvia)
Second generation antihistamines (non-sedating).
Unlike the first generation, they have almost no sedative and anticholinergic effects, do not penetrate the blood-brain barrier, do not reduce mental and physical activity, are not adsorbed with food in the gastrointestinal tract, have a high affinity for H1 receptors, and have a rapid therapeutic effect. . However, for them, a cardiotoxic effect was noted to varying degrees; when they are taken, constant monitoring of cardiac activity is required (appointed on an outpatient basis). They should not be taken by patients with disorders of the cardiovascular system, elderly patients.
The effect comes on quickly and for a longer time (delayed elimination).
When using drugs in therapeutic doses, a minimal sedative effect is observed. Some particularly sensitive individuals may experience moderate drowsiness, which does not require discontinuation of the drug.
The absence of tachyphylaxis (decrease in antihistamine activity) with prolonged use.
The cardiotoxic effect occurs due to the ability to block the potassium channels of the heart muscle, the risk of a cardiotoxic effect increases when antihistamines are combined with antifungals (ketoconazole and itraconazole), macrolides (erythromycin and clarithromycin), antidepressants (fluoxetine, sertraline and paroxetine), when drinking grapefruit juice and in patients with severe hepatic impairment.
There are no parenteral forms, only enteral and local dosage forms.
The most common second-generation antihistamines are:
Trexil (terfenadine) is the first second-generation antihistamine drug that does not have an inhibitory effect on the central nervous system, but with a significant cardiotoxic effect and an increased ability to cause fatal arrhythmias.
Trexil tab. 60mg №100 (Ranbaxi, India)
Gistalong (astemizole) - one of the longest active drugs groups (up to 20 days). It is characterized by irreversible binding to H1 receptors. Virtually no sedative effect, does not interact with alcohol.
Effective for chronic allergic diseases, in an acute process, its use is impractical. But the risk of developing serious heart rhythm disturbances, sometimes fatal, increases. Due to these dangerous side effects, the sale of astemizole in the United States and some other countries has been suspended.
Astemizole tab. 10mg #10
Histalong tab. 10mg №20 (India)
Semprex (acrivastine) is a drug with high antihistamine activity with a minimally pronounced sedative and anticholinergic effect. The therapeutic effect is achieved quickly, but for a short time.
Semprex caps. 8mg №24 (GlaxoWellcome, UK)
Fenistil (dimetendene) is closest to first-generation antihistamines, but differs from them in a significantly lesser sedative effect, higher antiallergic activity and duration of action than first-generation drugs. There is a gel for external use.
Claritin (loratadine) is one of the best-selling second-generation drugs. Its antihistamine activity is higher than that of astemizole and terfenadine, due to the greater strength of binding to peripheral H1 receptors.
There is no sedative effect, it does not potentiate the effect of alcohol. It practically does not interact with other drugs and does not have a cardiotoxic effect. It can be taken by drivers, children from 1 year old.
Claritin syrup 5mg/5ml 120ml (Schering-Plough, USA)
Claritin tab. 10mg №10 (Schering-Plough, USA)
Loratadine tab. 10mg #10
Agistam tab. 10mg #12
Third generation antihistamines (metabolites).
They are active metabolites of second-generation antihistamines. They do not have a sedative and cardiotoxic effect. In this regard, the drugs are approved for use by persons whose activities require increased attention.
Zyrtec, cetrin (cetirizine) is a highly selective blocker of peripheral H1 receptors. Cetirizine is almost not metabolized in the body, the rate of its excretion depends on the function of the kidneys. It penetrates well into the skin and is effective in skin manifestations allergies.
The effect appears 2 hours after ingestion and lasts 24 hours. Do not have a sedative and cardiotoxic effect in therapeutic doses. Be wary appoint in violation of kidney function.
Cetrin tab. 10mg No. 20 (Dr. Reddy's Laboratories, India)
Telfast (fexofenadine) is a metabolite of terfenadine. Does not metabolize in the body, does not interact with drugs, does not have a sedative effect and does not affect psychomotor activity. An effective and safest drug among antihistamines.
Telfast tab. 120mg №10 (Hoechst Marion Roussel)
Telfast tab. 180mg №10 (Hoechst Marion Roussel)
Histamine pathophysiology andH 1-histamine receptors
Histamine and its effects mediated through H 1 receptors
Stimulation of H 1 receptors in humans leads to an increase in smooth muscle tone, vascular permeability, itching, slowing of atrioventricular conduction, tachycardia, activation of the branches of the vagus nerve that innervates the respiratory tract, an increase in cGMP levels, an increase in the formation of prostaglandins, etc. In table. 19-1 shows localization H 1 receptors and the effects of histamine mediated through them.
Table 19-1. Localization H 1 receptors and the effects of histamine mediated through them
The role of histamine in the pathogenesis of allergy
Histamine plays a leading role in the development of atopic syndrome. In IgE-mediated allergic reactions, a large amount of histamine enters the tissues from mast cells, causing the occurrence of the following effects by acting on H 1 receptors.
In the smooth muscles of large vessels, bronchi and intestines, activation of H1 receptors causes a change in the conformation of the Gp protein, which, in turn, leads to the activation of phospholipase C, which catalyzes the hydrolysis of inositol diphosphate to inositol triphosphate and diacylglycerols. An increase in the concentration of inositol triphosphate leads to the opening of calcium channels in the ER (“calcium depot”), which causes the release of calcium into the cytoplasm and an increase in its concentration inside the cell. This leads to the activation of calcium/calmodulin-dependent kinase of myosin light chains and, accordingly, to the contraction of smooth muscle cells. In the experiment, histamine causes a biphasic contraction of the smooth muscles of the trachea, consisting of a fast phase contraction and a slow tonic component. Experiments have shown that the fast phase of contraction of these smooth muscles depends on intracellular calcium, while the slow phase depends on the entry of extracellular calcium through slow calcium channels unblocked by calcium antagonists. Acting through H 1 receptors, histamine causes contraction of smooth muscles respiratory tract, including the bronchi. In the upper sections of the respiratory tract, there are more histamine H1 receptors than in the lower ones, which is essential in the degree of severity of bronchospasm in the bronchioles during the interaction of histamine with these receptors. Histamine induces bronchial obstruction as a result of a direct effect on the smooth muscles of the respiratory tract, reacting with histamine H 1 receptors. In addition, through H 1 receptors, histamine increases the secretion of fluid and electrolytes in the airways and causes increased mucus production and airway edema. Patients with bronchial asthma are 100 times more sensitive to histamine than healthy individuals when conducting a histamine provocation test.
In the endothelium of small vessels (postcapillary venules), the vasodilating effect of histamine is mediated through H 1 receptors in allergic reactions of the reagin type (through H 2 receptors of smooth muscle cells of venules, along the adenylate cyclase pathway). Activation of H 1 receptors leads (via the phospholipase pathway) to an increase in the intracellular level of calcium, which, together with diacylglycerol, activates phospholipase A 2, causing the following effects.
Local release of endothelium-relaxing factor. It enters neighboring smooth muscle cells and activates guanylate cyclase. As a result, the concentration of cGMP, which activates cGMP-dependent protein kinase, increases, which leads to a decrease in intracellular calcium. With a simultaneous decrease in the level of calcium and an increase in the level of cGMP, smooth muscle cells of postcapillary venules relax, which leads to the development of edema and erythema.
When phospholipase A2 is activated, the synthesis of prostaglandins, mainly the prostacyclin vasodilator, increases, which also contributes to the formation of edema and erythema.
Classification of antihistamine drugs
There are several classifications of antihistamines (histamine H1 receptor blockers), although none of them is considered generally accepted. According to one of the most popular classifications, antihistamines are divided into I and II generation drugs according to the time of creation. First-generation drugs are also commonly called sedatives (according to the dominant side effect), in contrast to second-generation non-sedative drugs. Antihistamines of the first generation include: diphenhydramine (diphenhydramine*), promethazine (diprazine*, pipolfen*), clemastine, chloropyramine (suprastin*), hifenadine (fenkarol*), sequifenadine (bicarfen*). Second generation antihistamines: terfenadine*, astemizole*, cetirizine, loratadine, ebastine, cyproheptadine, oxatomide*9, azelastine, acrivastine, mebhydroline, dimethindene.
Currently, it is customary to isolate the third generation of antihistamines. It includes fundamentally new drugs - active metabolites, which, in addition to high antihistamine activity, are characterized by the absence of a sedative effect and the cardiotoxic effect characteristic of second-generation drugs. The III generation of antihistamines include fexofenadine (telfast *), desloratadine.
In addition, according to the chemical structure, antihistamines are divided into several groups (ethanolamines, ethylenediamines, alkylamines, derivatives of alphacarboline, quinuclidine, phenothiazine *, piperazine * and piperidine *).
Mechanism of action and main pharmacodynamic effects of antihistamine drugs
Most of the antihistamines used have specific pharmacological properties, which characterizes them as a separate group. These include the following effects: antipruritic, decongestant, antispastic, anticholinergic, antiserotonin, sedative and local anesthetic, as well as the prevention of histamine-induced bronchospasm.
Antihistamines are histamine H 1 receptor antagonists, and their affinity for these receptors is much lower than that of histamine (Table 19-2). That is why these drugs are not able to displace the histamine associated with the receptor, they only block unoccupied or released receptors.
Table 19-2. Comparative effectiveness of antihistamine drugs by the degree of blockade H 1-histamine receptors
Accordingly, blockers H 1 histamine receptors are most effective in preventing allergic reactions immediate type, and in the case of a developed reaction, they prevent the release of new portions of histamine. The binding of antihistamines to receptors is reversible, and the number of blocked receptors is directly proportional to the concentration of the drug at the location of the receptor.
The molecular mechanism of action of antihistamines can be represented as a scheme: blockade of the H 1 receptor - blockade of the phosphoinositide pathway in the cell - blockade of the effects of histamine. The binding of drugs to the histamine H 1 receptor leads to a “blockade” of the receptor, i.e. prevents the binding of histamine to the receptor and the launch of a cascade in the cell along the phosphoinositide pathway. Thus, the binding of an antihistamine drug to the receptor causes a slowdown in the activation of phospholipase C, which leads to a decrease in the formation of inositol triphosphate and diacylglycerol from phosphatidylinositol, as a result, the release of calcium from intracellular depots slows down. A decrease in the release of calcium from intracellular organelles into the cytoplasm in various cell types leads to a decrease in the proportion of activated enzymes that mediate the effects of histamine in these cells. In the smooth muscles of the bronchi (as well as the gastrointestinal tract and large vessels), the activation of calcium-calmodulin-dependent kinase of myosin light chains slows down. This prevents the contraction of smooth muscles caused by histamine, especially in patients with bronchial asthma. However, in bronchial asthma, the concentration of histamine in the lung tissue is so high that modern H1-blockers are not able to block the effects of histamine on the bronchi through this mechanism. In the endothelial cells of all postcapillary venules, antihistamine drugs prevent the vasodilating effect of histamine (directly and through prostaglandins) in local and generalized allergic reactions (histamine also acts through the histamine H 2 receptors of smooth muscle cells
venule through the adenylate cyclase pathway). Blockade of histamine H 1 receptors in these cells prevents an increase in intracellular calcium levels, ultimately slowing down the activation of phospholipase A2, which leads to the development of the following effects:
Slowing down the local release of the endothelium-relaxing factor, which penetrates into neighboring smooth muscle cells and activates guanylate cyclase. Inhibition of guanylate cyclase activation reduces the concentration of cGMP, then the fraction of activated cGMP-dependent protein kinase decreases, which prevents a decrease in calcium levels. At the same time, the normalization of the level of calcium and cGMP prevents the relaxation of smooth muscle cells of postcapillary venules, that is, it prevents the development of edema and erythema caused by histamine;
A decrease in the activated fraction of phospholipase A2 and a decrease in the synthesis of prostaglandins (mainly prostacyclin), vasodilation is blocked, which prevents the occurrence of edema and erythema caused by histamine by its second mechanism of action on these cells.
Based on the mechanism of action of antihistamine drugs, these drugs should be prescribed to prevent allergic reactions of the reagin type. The appointment of these drugs in the developed allergic reaction is less effective, since they do not eliminate the symptoms of developed allergies, but prevent their occurrence. Histamine H1-receptor blockers prevent the reaction of bronchial smooth muscles to histamine, reduce itching, and prevent histamine-mediated expansion of small vessels and their permeability.
Pharmacokinetics of antihistamine drugs
The pharmacokinetics of first-generation H 1 -receptor blockers of histamine is fundamentally different from the pharmacokinetics of second-generation drugs (Table 19-3).
Penetration of the first generation antihistamines through the BBB leads to a pronounced sedative effect, which is considered a significant drawback of this group of drugs and significantly limits their use.
Antihistamines of the second generation are relatively hydrophilic and therefore do not penetrate the BBB and, therefore, do not cause a sedative effect. It is known that 80% of astemizole* is excreted 14 days after the last dose, and terfenadine* - 12 days later.
Pronounced ionization of diphenhydramine at physiological pH values and active non-specific interaction with serum
Oral albumin causes its effect on H1-histamine receptors located in various tissues, which leads to quite pronounced side effects of this drug. In the blood plasma, the maximum concentration of the drug is determined 4 hours after its administration and is equal to 75-90 ng / l (at a dose of 50 mg). The half-life is 7 hours.
The peak concentration of clemastine is reached 3-5 hours after a single oral dose of 2 mg. The half-life is 4-6 hours.
Terfenadine* is rapidly absorbed when taken orally. Metabolized in the liver. The maximum concentration in tissues is determined 0.5-1-2 hours after taking the drug, the half-life is
The maximum level of unchanged astemizole * is noted within 1-4 hours after taking the drug. Food reduces the absorption of astemizole * by 60%. The peak concentration of drugs in the blood with a single oral intake occurs after 1 hour. The half-life of the drug is 104 hours. Hydroxyastemizole and norastemizole are its active metabolites. Astemizol * penetrates the placenta, in a small amount - into breast milk.
The maximum concentration of oxatomide * in the blood is determined 2-4 hours after ingestion. The half-life is 32-48 hours. The main metabolic pathway is aromatic hydroxylation and oxidative dealkylation on nitrogen. 76% of the absorbed drug is attached to plasma albumin, from 5 to 15% is excreted in breast milk.
Table 19-3. Pharmacokinetic parameters of some antihistamine drugs
The maximum level of cetirizine in the blood (0.3 μg / ml) is determined 30-60 minutes after taking this drug at a dose of 10 mg. Renal
the clearance of cetirizine is 30 mg / min, the half-life is about 9 hours. The drug is stably associated with blood proteins.
The peak plasma concentration of acrivastin is reached 1.4-2 hours after administration. The half-life is 1.5-1.7 hours. Two-thirds of the drug is excreted unchanged by the kidneys.
Loratadine is well absorbed in the gastrointestinal tract and after 15 minutes it is determined in the blood plasma. Food does not affect the degree of absorption of drugs. The half-life of the drug is 24 hours.
Antihistamines of the 1st generation
For blockers of H 1 -receptors of histamine of the first generation, some features are characteristic.
sedative action. Most antihistamines of the first generation, easily soluble in lipids, penetrate well through the BBB and bind to the H1 receptors of the brain. Apparently, the sedative effect develops with the blockade of central serotonin and m-cholinergic receptors. The degree of development of the sedative effect varies from moderate to severe and increases when combined with alcohol and psychotropic drugs. Some drugs in this group are used as sleeping pills (doxylamine). Rarely, instead of sedation, psychomotor agitation occurs (more often in medium therapeutic doses in children and in high toxic doses in adults). Due to the sedative effect of the drugs, they cannot be used during the period of work requiring attention. All blockers of H 1 -receptors of histamine of the first generation potentiate the action of sedative and hypnotic drugs, narcotic and non-narcotic analgesics, monoamine oxidase inhibitors and alcohol.
anxiolytic action, characteristic of hydroxyzine. This effect, possibly, occurs due to the suppression of the activity of some parts of the subcortical formations of the brain by hydroxyzine.
atropine-like action. This effect is associated with the blockade of m-cholinergic receptors, most characteristic of ethanolamines and ethylenediamines. Characterized by dry mouth, urinary retention, constipation, tachycardia and blurred vision. In non-allergic rhinitis, the effectiveness of these drugs increases due to the blockade of m-cholinergic receptors. However, it is possible to increase bronchial obstruction due to an increase in the viscosity of sputum, which is dangerous in bronchial asthma. Blockers of H 1 -receptors of histamine I generation can exacerbate glaucoma and cause acute urinary retention in prostate adenoma.
Antiemetic and antihypertensive action. These effects may also be associated with the central m-anticholinergic action of these drugs. Diphenhydramine, promethazine, cyclizine*, mecli-
zine * reduce the stimulation of vestibular receptors and inhibit the function of the labyrinth, and therefore can be used for motion sickness.
Some blockers of H 1 -receptors of histamine reduce the symptoms of parkinsonism, which is due to the blockade of the central m-cholinergic receptors.
Antitussive action. Most characteristic of diphenhydramine, it is realized due to the direct action on the cough center in the medulla oblongata.
Antiserotonin action. Cyproheptadine possesses it to the greatest extent, therefore it is used for migraine.
The effect of blockade of a 1 adrenaline receptors with peripheral vasodilation is especially characteristic of drugs of the phenothiazine series. This can lead to a transient decrease in blood pressure.
Local anesthetic action is typical for most drugs in this group. The local anesthetic effect of diphenhydramine and promethazine is stronger than that of novocaine*.
Tachyphylaxis- a decrease in the antihistamine effect with long-term use, confirming the need for alternating drugs every 2-3 weeks.
Pharmacodynamics of H1-receptor blockers of histamine I generation
All blockers of H 1 -receptors of histamine of the first generation are lipophilic and, in addition to H 1 -receptors of histamine, also block m-cholinergic receptors and serotonin receptors.
When prescribing histamine receptor blockers, it is necessary to take into account the phase course of the allergic process. Histamine H1-receptor blockers should be used mainly for the prevention of pathogenetic changes in the event of a patient's alleged encounter with an allergen.
Blockers of H 1 -receptors of histamine I generation do not affect the synthesis of histamine. In high concentrations, these drugs are able to cause degranulation of mast cells and the release of histamine from them. Histamine H1 receptor blockers are more effective in preventing the action of histamine than in eliminating the effects of its influence. These drugs inhibit the response of bronchial smooth muscles to histamine, reduce itching, prevent histamine from increasing vasodilation and increase their permeability, and reduce the secretion of endocrine glands. It has been proven that H 1 -receptor blockers of histamine of the 1st generation have a direct bronchodilatory effect, and most importantly, they prevent the release of histamine from mast cells and blood basophils, which is considered the basis for the use of these drugs.
as a preventive measure. In therapeutic doses, they do not significantly affect the cardiovascular system. With forced intravenous administration, they can cause a decrease in blood pressure.
Blockers of H 1 -receptors of histamine of the 1st generation are effective in the prevention and treatment of allergic rhinitis (effectiveness is about 80%), conjunctivitis, itching, dermatitis and urticaria, angioedema, some types of eczema, anaphylactic shock, with edema caused by hypothermia. Blockers of H 1 -receptors of histamine of the first generation are used in conjunction with sympathomimetics for allergic rhinorrhea. Piperazine* and phenothiazine* derivatives are used to prevent nausea, vomiting and dizziness caused by sudden movements in Meniere's disease, vomiting after anesthesia, radiation sickness and morning vomiting in pregnant women.
Local application of these drugs takes into account their antipruritic, anesthetic and analgesic effect. It is not recommended to use them for a long time, since many of them can cause hypersensitivity and have a photosensitizing effect.
Pharmacokinetics of histamine H-receptor blockers of the 1st generation
Blockers of H 1 -receptors of histamine of the first generation differ from second-generation drugs in the short duration of action with a relatively rapid onset clinical effect. The effect of these drugs occurs, on average, 30 minutes after taking the drug, reaching a peak within 1-2 hours. The duration of action of first-generation antihistamines is 4-12 hours. metabolism and excretion by the kidneys.
Most of the first-generation H1-receptor blockers of histamine are well absorbed from the gastrointestinal tract. These drugs pass through the BBB, the placenta, and also enter breast milk. The highest concentrations of these drugs are found in the lungs, liver, brain, kidneys, spleen, and muscles.
Most blockers of H 1 -receptors of histamine I generation are metabolized in the liver by 70-90%. They induce microsomal enzymes, which, with prolonged use, can reduce their therapeutic effect, as well as the effect of other drugs. Metabolites of many antihistamines are excreted within 24 hours in the urine and only small amounts are excreted unchanged.
Side effects and contraindications to the appointment
Side effects caused by H 1 blockers of histamine receptors of the first generation are presented in Table. 19-4.
Table 19-4. Adverse drug reactions of 1st generation antihistamines
Large doses of histamine H1 receptor blockers can cause agitation and convulsions, especially in children. With these symptoms, barbiturates should not be used, as this will cause an additive effect and significant depression of the respiratory center. Cyclizine* and chlorcyclizine* are teratogenic and should not be used for vomiting in pregnant women.
Drug Interactions
Blockers of H 1 -receptors of histamine I generation potentiate the effects of narcotic analgesics, ethanol, hypnotics, tranquilizers. May enhance the effect of CNS stimulants in children. With prolonged use, these drugs reduce the effectiveness of steroids, anticoagulants, phenylbutazone (butadione *) and other drugs that are metabolized in the liver. Their combined use with anticholinergics can lead to an excessive increase in their effects. MAO inhibitors enhance the effect of antihistamine drugs. Some first-generation drugs potentiate the effect of adrenaline and norepinephrine on the cardiovascular system. Histamine H1-receptor blockers of the first generation are prescribed for the prevention of clinical symptoms of allergy, in particular, rhinitis, which often accompanies atopic bronchial asthma, for the relief of anaphylactic shock.
Antihistamines II and III generations
The second generation drugs include terfenadine *, astemizole *, cetirizine, mekvipazine *, fexofenadine, loratadine, ebastine, to the third generation of histamine H1-receptor blockers - fexofenadine (telfast *).
The following features of H 1 -receptor blockers of histamine II and III generations can be distinguished:
High specificity and high affinity for H 1 histamine receptors with no effect on serotonin and m-cholinergic receptors;
The rapid onset of the clinical effect and the duration of action, which is usually achieved by a high degree of protein binding, accumulation of the drug or its metabolite in the body and delayed excretion;
Minimal sedative effect when using drugs in therapeutic doses; some patients may experience moderate drowsiness, which is rarely the reason for discontinuation of the drug;
Lack of tachyphylaxis with prolonged use;
The ability to block potassium channels in the cells of the conduction system of the heart, which is associated with prolongation of the interval Q-T and a violation of the heart rhythm (ventricular tachycardia of the "pirouette" type).
In table. 19-5 presented Comparative characteristics some blockers of H 1 -receptors of histamine of the II generation.
Table 19-5. Comparative characteristics of H1-receptor blockers of histamine II generation
The end of the table. 19-5
Pharmacodynamics of histamine H-receptor blockers of the II generation
Astemizole * and terfenadine * do not have choline and β-adrenergic blocking activity. Astemizol * blocks α-adrenergic and serotonin receptors only in high doses. II generation histamine H1 receptor blockers have a weak therapeutic effect in bronchial asthma, since the smooth muscles of the bronchi and bronchial glands are affected not only by histamine, but also by leukotrienes, platelet activating factor, cytokines and other mediators that cause the development of the disease. The use of only blockers of H 1 -receptors of histamine does not guarantee complete relief of allergic bronchospasm.
Features of the pharmacokinetics of H 1 -receptor blockers of histamine II generation All blockers of H 1 -receptors of histamine II generation act for a long time (24-48 hours), and the time for the development of the effect is short - 30-60 minutes. About 80% of astemizole * is excreted 14 days after the last dose, and terfenadine * - after 12 days. The cumulative effect of these drugs, which occurs without changing the functions of the central nervous system, allows them to be widely used in outpatient practice in patients with hay fever, urticaria, rhinitis, neurodermatitis, etc. Blockers of H 1 -receptors of histamine of the II generation are used in the treatment of patients with bronchial asthma with individual selection of doses.
For blockers of H 1 -receptors of histamine II generation, to varying degrees, a cardiotoxic effect is characteristic, due to blocking
each potassium channel of cardiomyocytes and expressed by prolongation of the interval Q-T and arrhythmia on the electrocardiogram.
The risk of this side effect increases with the combination of antihistamines with inhibitors of the cytochrome P-450 3A4 isoenzyme (Appendix 1.3): antifungal drugs (ketoconazole and itraconazole *), macrolides (erythromycin, oleandomycin and clarithromycin), antidepressants (fluoxetine, sertraline and paroxetine) , when drinking grapefruit juice, as well as in patients with severe liver dysfunction. The combined use of the above macrolides with astemizole * and terfenadine * in 10% of cases leads to a cardiotoxic effect associated with prolongation of the interval QT. Azithromycin and dirithromycin * are macrolides that do not inhibit the 3A4 isoenzyme, and therefore do not cause interval prolongation Q-T when taken simultaneously with blockers of H 1 -receptors of histamine of the second generation.
For citation: Kareva E.N. The choice of an antihistamine drug: the view of a pharmacologist // BC. Medical review. 2016. No. 12. pp. 811-816
The article is devoted to the problem of choosing an antihistamine drug from the point of view of a pharmacologist
For citation. Kareva E.N. The choice of an antihistamine drug: the view of a pharmacologist // BC. 2016. No 12, pp. 811–816.
Antihistamines (AHPs) are the first-line therapy for most allergic diseases. They are predominantly non-prescription drugs, they have long and firmly entered our practice and have been used for more than half a century. Often the choice of these drugs is carried out empirically or even at the mercy of patients, however, there are many nuances that determine how effective this or that drug will be for a particular patient, which means that the choice of these drugs must be approached no less responsibly than, for example, the choice antibiotics.
Each specialist in his clinical practice must have encountered situations when a particular drug did not have the desired clinical effect or caused hyperergic reactions. What does it depend on and how can risks be minimized? The variability of the response to the drug is most often associated with the activity of metabolic enzymes in the patient's liver, the situation is aggravated in the case of polypharmacy (5 or more prescribed drugs at the same time). Therefore, one of the real ways to reduce the risk of an inadequate response of the body to the drug is the choice of a drug that is not metabolized in the liver. In addition, when choosing antihistamines, it is important to evaluate the following parameters: the strength and speed of the onset of the effect, the possibility of long-term use, the benefit / risk ratio (efficacy / safety), ease of use, the possibility of using comorbidities in combination with other drugs in this patient, the route of elimination , the need for dose titration, price.
To solve this problem, consider the current information on histamine and antihistamines.
Histamine and its role in the body
Histamine in the human body performs a number of physiological functions, plays the role of a neurotransmitter and is involved in many pathobiological processes (Fig. 1).
The main depot of histamine in the body is mast cells and basophils, where it is in the form of granules in a bound state. The greatest number of mast cells is localized in the skin, mucous membranes of the bronchi and intestines.
Histamine realizes its activity exclusively through its own receptors. Modern views the functional load of histamine receptors, their localization and mechanisms of intracellular signaling are given in Table 1.
In addition to physiological functions, histamine is involved in the development inflammatory process any nature. Histamine causes itching, sneezing and stimulates the secretion of the nasal mucosa (rhinorrhea), contraction of the smooth muscles of the bronchi and intestines, tissue hyperemia, dilatation of small blood vessels, increased vascular permeability to water, proteins, neutrophils, and the formation of inflammatory edema (nasal congestion).
Not only with allergic diseases, but also with any pathological processes with a pronounced inflammatory component, the level of histamine in the body is always increased. This is indicated for chronic infectious and inflammatory diseases of the respiratory and urogenital tracts, acute respiratory viral infections, influenza . At the same time, the daily amount of histamine in the urine with influenza is approximately the same as with an exacerbation of allergic diseases. Therefore, a pathogenetically justified and clinically useful step is to reduce the activity of the histamine system in conditions of its increased activity. In principle, suppressing the histaminergic activity of the body can be done either through a decrease in the amount of free histamine (inhibition of synthesis, activation of metabolism, inhibition of release from the depot), or through blockade of histamine receptor signals. In clinical practice, drugs have been used that stabilize mast cell membranes, thereby preventing the release of histamine. However, the onset of the desired action when using them has to wait a long time, and the therapeutic efficacy of this group of drugs is very moderate, so they are used exclusively for prophylactic purposes. A quick and pronounced effect is achieved when using antihistamines.
Classification of antihistamines
According to the classification adopted by the European Academy of Allergology and Clinical Immunology, all antihistamines are divided into 2 generations depending on their effect on the central nervous system.
Antihistamines of the 1st generation
First-generation H1 antagonists penetrate the blood-brain barrier (BBB) and can either stimulate or depress the CNS (Fig. 2). As a rule, the second occurs in most patients. A sedative effect when taking 1st generation antihistamines is subjectively noted by 40–80% of patients. The absence of a sedative effect in individual patients does not exclude the objective negative effect of these drugs on cognitive functions that patients may not pay attention to (the ability to drive a car, learn, etc.). Dysfunction of the central nervous system is observed even with the use of minimal doses of these drugs. The effect of first-generation antihistamines on the central nervous system is the same as when using alcohol and sedatives. Stimulation has been noted in some patients treated with conventional doses of antihistamines and is manifested by restlessness, nervousness, and insomnia. Usually, central excitation is characteristic of an overdose of first generation antihistamines, it can lead to convulsions, especially in children.
When taking AGP of the 1st generation, in addition to the sedative effect and the effect on cognitive functions, the following are observed:
short-term effect (forced intake 3-4 times a day);
rapid development of tachyphylaxis (it is necessary to change the drug every 7-10 days);
low selectivity of action: in addition to histamine H1 receptors, they block acetylcholine, adrenaline, serotonin, dopamine receptors and ion channels, causing many side effects: tachycardia, dry mucous membranes, increased sputum viscosity. They can increase intraocular pressure, disrupt urination, cause stomach pain, constipation, nausea, vomiting, and increase body weight. That's why these drugs have a number of serious limitations for use among patients with glaucoma, benign prostatic hyperplasia, cardiovascular pathology, etc.
At acute poisoning First generation antihypertensives, their central effects pose the greatest danger: the patient experiences agitation, hallucinations, ataxia, impaired coordination, convulsions, etc. Fixed, dilated pupils on a flushed face, along with sinus tachycardia, urinary retention, dry mouth and fever, are very similar to signs atropine poisoning.
In children with an overdose of 1st generation antihistamines, agitation and convulsions may occur, therefore, experts in many countries call for abandoning this group of drugs in the treatment of children or using them under strict control. In addition, the sedative effect can impair children's learning and school performance.
New antihistamines (second generation) do not penetrate the BBB, do not have a sedative effect (Fig. 2).
Note: third-generation drugs have not yet been developed. Some pharmaceutical companies present new drugs that have appeared on the pharmaceutical market as AGP III - the latest - generation. Attempts were made to classify metabolites and stereoisomers of modern AGPs to the III generation. However, it is now considered that these drugs belong to the II generation antihistamines, since there is no significant difference between them. According to the Consensus on Antihistamines, it was decided to reserve the name “third generation” to designate AHDs synthesized in the future, which will differ from known compounds in a number of basic characteristics.
Unlike older drugs, II generation antihistamines practically do not penetrate the BBB and do not cause a sedative effect, so they can be recommended to drivers, people whose work requires concentration, schoolchildren and students. The term “practically” is used here, because in very rare cases and when taking second-generation drugs, cases of sedation are possible, but this is rather an exception to the rule and depends on individual characteristics patient.
II generation antihistamines are capable of selectively blocking H1 receptors, quickly have a clinical effect with a long-term effect (for 24 hours), as a rule, are not addictive (no tachyphylaxis). Due to their higher safety profile, they are preferred in elderly patients (over 65 years of age).
Second generation antihistamines
Features of pharmacokinetics
Metabolism of II generation AGP
All II generation antihistamines are divided into 2 large groups, depending on the need for metabolic activation in the liver (Fig. 3).
The need for metabolic activation in the liver is associated with a number of problems, the main of which are the danger of drug interactions and the late onset of the maximum therapeutic effect of the drug. The simultaneous use of two or more drugs that are metabolized in the liver can lead to a change in the concentration of each of the drugs. In the case of parallel use of an inducer of drug metabolism enzymes (barbiturates, ethanol, St. With the simultaneous use of liver enzyme inhibitors (antifungal azoles, grapefruit juice, etc.), the rate of AGP metabolism slows down, which causes an increase in the concentration of the "prodrug" in the blood and an increase in the frequency and severity of side effects.
The most successful option for antihistamines are drugs that are not metabolized in the liver, the effectiveness of which does not depend on concomitant therapy, and the maximum concentration is reached in the shortest possible time, which ensures a rapid onset of action. An example of such a second-generation AGP is cetirizine.
The rate of onset of the effect of 2nd generation antihistamines
One of the most important aspects of the action of the drug is the speed of the onset of the effect.
Among the II generation antihistamines, the shortest period of reaching Cmax was observed in cetirizine and levocetirizine. It should be noted that the antihistamine effect begins to develop much earlier and is minimal for drugs that do not require prior activation in the liver, for example, for cetirizine, after 20 minutes (Table 2).
Distribution of II generation AGP
The next most important characteristic of the drug is the volume of distribution. This indicator indicates the predominant localization of the drug: in plasma, intercellular space or inside cells. The higher this indicator, the more the drug enters the tissues and inside the cells. A small volume of distribution indicates that the drug is predominantly in the vascular bed (Fig. 4). For AGP, localization in the bloodstream is optimal because its main target cells (immunocompetent blood cells and vascular endothelium) are present here.
The values of the volume of distribution (liter/kg) for second generation antihistamines in ascending order are as follows: cetirizine (0.5)< фексофенадин (5,4–5,8) < дезлоратадин (49) < эбастин (100) < лоратадин (119) (рис. 5). Малый объем распределения обеспечивает: а) высокие концентрации данного АГП на поверхности клеток-мишеней, следовательно, точно направленное действие и высокую терапевтическую эффективность; б) отсутствие накопления в паренхиматозных органах и безопасность применения.
Features of pharmacodynamics
Pharmacological effects Antihistamines are mediated by histamine receptors, selectivity for different subtypes, the strength and duration of binding to which vary between drugs. A distinctive characteristic of the second generation antihistamine cetirizine is its high affinity - the ability to permanently bind histamine H1 receptors: their employment 4 hours after taking the drug is 90%, after 24 hours - 57%, which exceeds similar indicators of other antihistamines. The most important property of antihistamines is their ability to reduce the expression of histamine H1 receptors, thereby reducing the sensitivity of tissues to histamine.
According to the strength of the antihistamine action, second-generation antihistamines can be arranged in the following order: cetirizine >> ebastine > fexofenadine >> loratadine (Fig. 6).
The antiallergic effect of individual antihistamines (cetirizine) includes the so-called additional, extra-H1 receptor action, in conjunction with which the anti-inflammatory effect of the drug is realized.
Side effects of AGP
Side effects of antihistamines include anticholinergic effects (dry mouth, sinus tachycardia, constipation, urinary retention, blurred vision), adrenolytic (hypotension, reflex tachycardia, anxiety), antiserotonin (increased appetite), central antihistamine action (sedation, increased appetite), blockade potassium channels in the heart (ventricular arrhythmia, QT prolongation). The selective action of drugs on target receptors and the ability to penetrate or not penetrate the BBB determine their effectiveness and safety.
Among the II generation AGPs, the drugs cetirizine and levocetirizine have the lowest affinity for M-cholinergic receptors, and therefore, the almost complete absence of anticholinergic action (Table 3).
Some antihistamines can cause the development of arrhythmias. "Potentially cardiotoxic" are terfenadine and astemizole. Due to the ability to cause potentially fatal arrhythmias - flutter-flicker (metabolic disorders in liver disease or against the background of CYP3A4 inhibitors), terfenadine and astemizole have been banned from use since 1998 and 1999. respectively. Among the currently available antihistamines, ebastine and rupatadine have cardiotoxicity and are not recommended for use in individuals with a prolonged QT interval, as well as those with hypokalemia. Cardiotoxicity increases when they are taken simultaneously with drugs that prolong the QT interval - macrolides, antifungal agents, calcium channel blockers, antidepressants, fluoroquinolones.
cetirizine
Cetirizine occupies a special place among the drugs of the second generation. Along with all the advantages of non-sedating antihistamines, cetirizine demonstrates properties that distinguish it from a number of new generation drugs and ensure its high clinical efficacy and safety. In particular, it has additional anti-allergic activity, a fast onset of effect, it has no danger of interaction with other medicinal substances and foodstuffs, which opens up the possibility of safe administration of the drug to patients with concomitant diseases.
The effect of cetirizine consists of the effect on both phases of allergic inflammation. The antiallergic effect includes the so-called extra-H1 receptor action: inhibition of the release of leukotrienes, prostaglandins in the nasal mucosa, skin, bronchi, stabilization of mast cell membranes, inhibition of eosinophil migration and platelet aggregation, suppression of ICAM-1 expression by epithelial cells.
Many authors, both foreign and domestic, consider cetirizine the standard of modern AGP. It is one of the most studied antihistamines, having proven its efficacy and safety in numerous clinical studies. For patients who do not respond well to other antihistamines, cetirizine is recommended. Cetirizine fully complies with the requirements for modern antihistamines.
For cetirizine, the half-life is 7-11 hours, the duration of the effect is 24 hours, after a course of treatment, the effect persists for up to 3 days, with prolonged use - up to 110 weeks, no addiction is observed. The duration of the effect of cetirizine (24 hours) is explained by the fact that the effect of antihistamines is determined not only by plasma concentration, but also by the degree of binding to plasma proteins and receptors.
Cetirizine is practically not metabolized in the liver and is excreted mainly by the kidneys, therefore it can be used even in patients with impaired liver function. But for patients with renal insufficiency, dose adjustment of the drug is required.
Cetrin - effective quality generic cetirizine at an affordable price
Currently, among the drugs of cetirizine, in addition to the original (Zyrtec), 13 generic drugs (generics) from different manufacturers are registered. The issue of interchangeability of cetirizine generics, their therapeutic equivalence is topical. original drug and choosing the optimal remedy for the treatment of allergic diseases. The stability of the therapeutic effect and the therapeutic activity of the reproduced drug are determined by the features of the technology, the quality of the active substances and the range of excipients. The quality of drug substances from different manufacturers can vary significantly. Any change in the composition of excipients may be accompanied by pharmacokinetic deviations (decrease in bioavailability and the occurrence of side effects).
A generic drug must be safe to use and equivalent to the original drug. Two drugs are considered bioequivalent (pharmacokinetically equivalent) if they, after administration by one route (for example, orally) in the same dose and regimen, have the same bioavailability (the proportion of the drug that enters the bloodstream), the time to reach the maximum concentration and the level of this concentration in the blood, half-life and area under the time-concentration curve. These properties are necessary for the manifestation of the proper efficacy and safety of the drug.
According to the recommendations of the World Health Organization, the bioequivalence of a generic should be determined in relation to the officially registered original drug.
Bioequivalence studies have been mandatory for registration of drugs since 2010. The FDA (Food and Drug Administration - Food and Drug Administration, USA) annually publishes and publishes the "Orange Book" with a list of drugs (and their manufacturers) that are considered therapeutic equivalent to original.
In addition, it is important to pay attention to compliance with international manufacturing standards (GMP) in the manufacture of drugs. Unfortunately, not all manufacturers (especially domestic ones) yet have production that meets GMP requirements, and this may affect the quality of drugs, and hence the effectiveness and safety of generics.
Thus, when choosing generics, there are a number of reliable guidelines: the authority of the manufacturer, compliance with GMP, inclusion in the FDA Orange Book. All of the above criteria are fully met by the drug Cetrin by Dr. Reddy's Laboratories Ltd. Cetrin is produced by an international pharmaceutical company whose production sites are GMP certified. It is bioequivalent to the original drug and is included in the FDA Orange Book as a drug with proven therapeutic equivalence. In addition, Tsetrin has a long successful experience of use in Russia and a large evidence base of its own.
In a comparative study of the therapeutic efficacy and pharmacoeconomics of cetirizine preparations from different manufacturers in the treatment of chronic urticaria, it was shown that the largest number patients who achieved remission were in the groups treated with Zyrtec and Cetrin, while Cetrin therapy demonstrated the best results in terms of cost-effectiveness.
A long history of the use of Cetrin in the conditions of domestic clinical practice proved its high therapeutic efficacy and safety. Cetrin is a drug that provides a practical need clinical medicine in an effective and safe antihistamine drug available to a wide range of patients.
Literature
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Historically, the term "antihistamines" means drugs that block H1-histamine receptors, and drugs that act on H2-histamine receptors (cimetidine, ranitidine, famotidine, etc.) are called H2-histamine blockers. The former are used to treat allergic diseases, the latter are used as antisecretory agents.
Histamine, this most important mediator of various physiological and pathological processes in the body, was chemically synthesized in 1907. Subsequently, it was isolated from animal and human tissues (Windaus A., Vogt W.). Even later, its functions were determined: gastric secretion, neurotransmitter function in the central nervous system, allergic reactions, inflammation, etc. Almost 20 years later, in 1936, the first substances with antihistamine activity were created (Bovet D., Staub A.). And already in the 60s, the heterogeneity of histamine receptors in the body was proven and three of their subtypes were identified: H1, H2 and H3, differing in structure, localization and physiological effects that occur during their activation and blockade. Since that time, an active period of synthesis and clinical testing of various antihistamines begins.
Numerous studies have shown that histamine, acting on the receptors of the respiratory system, eyes and skin, causes characteristic symptoms allergies, and antihistamines that selectively block the H1-type receptors are able to prevent and stop them.
Most of the antihistamines used have a number of specific pharmacological properties characterizing them as a separate group. These include the following effects: antipruritic, decongestant, antispastic, anticholinergic, antiserotonin, sedative and local anesthetic, as well as the prevention of histamine-induced bronchospasm. Some of them are not due to histamine blockade, but to structural features.
Antihistamines block the action of histamine on H1 receptors by the mechanism of competitive inhibition, and their affinity for these receptors is much lower than that of histamine. Therefore, these drugs are not able to displace histamine bound to the receptor, they only block unoccupied or released receptors. Accordingly, H1 blockers are most effective in preventing immediate allergic reactions, and in the case of a developed reaction, they prevent the release of new portions of histamine.
According to their chemical structure, most of them are fat-soluble amines, which have a similar structure. The core (R1) is represented by an aromatic and/or heterocyclic group and is linked via a nitrogen, oxygen or carbon (X) molecule to the amino group. The core determines the severity of antihistamine activity and some of the properties of the substance. Knowing its composition, one can predict the strength of the drug and its effects, such as the ability to penetrate the blood-brain barrier.
There are several classifications of antihistamines, although none of them is generally accepted. According to one of the most popular classifications, antihistamines are divided into first and second generation drugs according to the time of creation. First-generation drugs are also called sedatives (according to the dominant side effect), in contrast to non-sedative second-generation drugs. At present, it is customary to single out the third generation: it includes fundamentally new drugs - active metabolites that, in addition to the highest antihistamine activity, exhibit the absence of a sedative effect and the cardiotoxic effect characteristic of second-generation drugs (see).
In addition, according to the chemical structure (depending on the X-bond), antihistamines are divided into several groups (ethanolamines, ethylenediamines, alkylamines, derivatives of alphacarboline, quinuclidine, phenothiazine, piperazine and piperidine).
First generation antihistamines (sedatives). All of them are well soluble in fats and, in addition to H1-histamine, also block cholinergic, muscarinic and serotonin receptors. Being competitive blockers, they reversibly bind to H1 receptors, which leads to the use of rather high doses. The following pharmacological properties are most characteristic of them.
- The sedative effect is determined by the fact that most of the first generation antihistamines, easily soluble in lipids, penetrate well through the blood-brain barrier and bind to the H1 receptors of the brain. Perhaps their sedative effect consists of blocking the central serotonin and acetylcholine receptors. The degree of manifestation of the sedative effect of the first generation varies in different drugs and in different patients from moderate to severe and increases when combined with alcohol and psychotropic drugs. Some of them are used as sleeping pills (doxylamine). Rarely, instead of sedation, psychomotor agitation occurs (more often in medium therapeutic doses in children and in high toxic doses in adults). Due to the sedative effect, most drugs should not be used during tasks that require attention. All first-generation drugs potentiate the action of sedative and hypnotic drugs, narcotic and non-narcotic analgesics, monoamine oxidase inhibitors and alcohol.
- The anxiolytic effect characteristic of hydroxyzine may be due to the suppression of activity in certain areas of the subcortical region of the central nervous system.
- Atropine-like reactions associated with the anticholinergic properties of drugs are most characteristic of ethanolamines and ethylenediamines. Manifested by dry mouth and nasopharynx, urinary retention, constipation, tachycardia and visual impairment. These properties ensure the effectiveness of the discussed remedies in non-allergic rhinitis. At the same time, they can increase obstruction in bronchial asthma (due to an increase in sputum viscosity), exacerbate glaucoma and lead to infravesical obstruction in prostate adenoma, etc.
- The antiemetic and antiswaying effects are also likely to be associated with the central anticholinergic effect of the drugs. Some antihistamines (diphenhydramine, promethazine, cyclizine, meclizine) reduce the stimulation of vestibular receptors and inhibit the function of the labyrinth, and therefore can be used for motion sickness.
- A number of H1-histamine blockers reduce the symptoms of parkinsonism, which is due to central inhibition of the effects of acetylcholine.
- Antitussive action is most characteristic of diphenhydramine, it is realized through a direct action on the cough center in the medulla oblongata.
- The antiserotonin effect, which is primarily characteristic of cyproheptadine, determines its use in migraine.
- The α1-blocking effect with peripheral vasodilation, especially seen with phenothiazine antihistamines, can lead to a transient decrease in blood pressure in sensitive individuals.
- Local anesthetic (cocaine-like) action is characteristic of most antihistamines (due to a decrease in membrane permeability to sodium ions). Diphenhydramine and promethazine are stronger local anesthetics than novocaine. However, they have systemic quinidine-like effects, manifested by prolongation of the refractory phase and the development of ventricular tachycardia.
- Tachyphylaxis: Decreased antihistamine activity with long-term use, confirming the need for alternating drugs every 2-3 weeks.
- It should be noted that the first generation antihistamines differ from the second generation in the short duration of exposure with a relatively rapid onset of the clinical effect. Many of them are available in parenteral forms. All of the above, as well as low cost, determine the widespread use of antihistamines today.
Moreover, many of the qualities that were discussed allowed the “old” antihistamines to occupy their niche in the treatment of certain pathologies (migraine, sleep disorders, extrapyramidal disorders, anxiety, motion sickness, etc.) that are not associated with allergies. Many first-generation antihistamines are included in combined preparations used for colds, as sedatives, hypnotics, and other components.
The most commonly used are chloropyramine, diphenhydramine, clemastine, cyproheptadine, promethazine, phencarol, and hydroxyzine.
Chloropyramine(Suprastin) is one of the most widely used sedative antihistamines. It has significant antihistamine activity, peripheral anticholinergic and moderate antispasmodic action. Effective in most cases for the treatment of seasonal and year-round allergic rhinoconjunctivitis, angioedema, urticaria, atopic dermatitis, eczema, itching of various etiologies; in parenteral form - for the treatment of acute allergic conditions requiring emergency care. Provides a wide range of usable therapeutic doses. It does not accumulate in the blood serum, so it does not cause an overdose with prolonged use. Suprastin is characterized by a rapid onset of effect and short duration (including side effects). In this case, chloropyramine can be combined with non-sedating H1-blockers in order to increase the duration of the antiallergic effect. Suprastin is currently one of the best-selling antihistamines in Russia. This is objectively related to the proven high efficiency, controllability of its clinical effect, the availability of various dosage forms, including injections, and low cost.
Diphenhydramine, best known in our country under the name diphenhydramine, is one of the first synthesized H1-blockers. It has a fairly high antihistamine activity and reduces the severity of allergic and pseudo-allergic reactions. Due to the significant anticholinergic effect, it has an antitussive, antiemetic effect and at the same time causes dry mucous membranes, urinary retention. Due to lipophilicity, diphenhydramine gives pronounced sedation and can be used as a hypnotic. It has a significant local anesthetic effect, as a result of which it is sometimes used as an alternative for intolerance to novocaine and lidocaine. Diphenhydramine is presented in various dosage forms, including for parenteral use, which determined its widespread use in emergency therapy. However, a significant range of side effects, unpredictability of consequences and effects on the central nervous system require increased attention when using it and, if possible, the use of alternative means.
clemastine(tavegil) is a highly effective antihistamine drug similar in action to diphenhydramine. It has a high anticholinergic activity, but to a lesser extent penetrates the blood-brain barrier. It also exists in an injectable form, which can be used as an additional remedy for anaphylactic shock and angioedema, for the prevention and treatment of allergic and pseudo-allergic reactions. However, hypersensitivity to clemastine and other antihistamines with a similar chemical structure is known.
Cyproheptadine(peritol), along with antihistamine, has a significant antiserotonin effect. In this regard, it is mainly used in some forms of migraine, dumping syndrome, as an appetite enhancer, in anorexia. various genesis. It is the drug of choice for cold urticaria.
Promethazine(pipolfen) - a pronounced effect on the central nervous system determined its use in Meniere's syndrome, chorea, encephalitis, sea and air sickness, as an antiemetic. In anesthesiology, promethazine is used as a component of lytic mixtures to potentiate anesthesia.
Quifenadine(fenkarol) - has less antihistamine activity than diphenhydramine, but is also characterized by less penetration through the blood-brain barrier, which determines the lower severity of its sedative properties. In addition, fenkarol not only blocks histamine H1 receptors, but also reduces the content of histamine in tissues. May be used in the development of tolerance to other sedative antihistamines.
Hydroxyzine(atarax) - despite the existing antihistamine activity, it is not used as an antiallergic agent. It is used as an anxiolytic, sedative, muscle relaxant and antipruritic agent.
Thus, first-generation antihistamines that affect both H1- and other receptors (serotonin, central and peripheral cholinergic receptors, a-adrenergic receptors) have different effects, which determined their use in a variety of conditions. But the severity of side effects does not allow us to consider them as drugs of first choice in the treatment of allergic diseases. The experience gained with their use has made it possible to develop unidirectional drugs - the second generation of antihistamines.
Second generation antihistamines (non-sedating). Unlike the previous generation, they almost do not have sedative and anticholinergic effects, but differ in their selective action on H1 receptors. However, for them, a cardiotoxic effect was noted to varying degrees.
The following properties are the most common for them.
- High specificity and high affinity for H1 receptors with no effect on choline and serotonin receptors.
- Rapid onset of clinical effect and duration of action. Prolongation can be achieved due to high protein binding, accumulation of the drug and its metabolites in the body, and delayed elimination.
- Minimal sedative effect when using drugs in therapeutic doses. It is explained by the weak passage of the blood-brain barrier due to the peculiarities of the structure of these funds. Some particularly sensitive individuals may experience moderate drowsiness, which is rarely the reason for discontinuing the drug.
- Absence of tachyphylaxis with prolonged use.
- The ability to block the potassium channels of the heart muscle, which is associated with prolongation of the QT interval and cardiac arrhythmia. The risk of this side effect increases when antihistamines are combined with antifungals (ketoconazole and itraconazole), macrolides (erythromycin and clarithromycin), antidepressants (fluoxetine, sertraline and paroxetine), grapefruit juice, and in patients with severe liver dysfunction.
- Absence of parenteral formulations, however, some of them (azelastine, levocabastine, bamipine) are available as topical formulations.
Below are second-generation antihistamines with their most characteristic properties.
Terfenadine- the first antihistamine drug, devoid of a depressant effect on the central nervous system. Its creation in 1977 was the result of a study of both the types of histamine receptors and the features of the structure and action of existing H1-blockers, and marked the beginning of the development of a new generation of antihistamines. Currently, terfenadine is used less and less, which is associated with its increased ability to cause fatal arrhythmias associated with prolongation of the QT interval (torsade de pointes).
Astemizol- one of the longest acting drugs of the group (the half-life of its active metabolite is up to 20 days). It is characterized by irreversible binding to H1 receptors. Virtually no sedative effect, does not interact with alcohol. Since astemizole has a delayed effect on the course of the disease, it is not advisable to use it in an acute process, but it may be justified in chronic allergic diseases. Since the drug has the ability to accumulate in the body, the risk of developing serious heart rhythm disturbances, sometimes fatal, increases. Due to these dangerous side effects, the sale of astemizole in the United States and some other countries has been suspended.
Akrivastine(semprex) is a drug with high antihistamine activity with a minimally pronounced sedative and anticholinergic effect. The peculiarity of its pharmacokinetics is low level metabolism and lack of cumulation. Acrivastine is preferred in cases where there is no need for permanent antiallergic treatment due to the rapid onset of effect and short-term effect, which allows for a flexible dosing regimen.
Dimethenden(Fenistil) - is closest to the first generation antihistamines, but differs from them in a much less pronounced sedative and muscarinic effect, higher antiallergic activity and duration of action.
Loratadine(claritin) is one of the most purchased drugs of the second generation, which is quite understandable and logical. Its antihistamine activity is higher than that of astemizole and terfenadine, due to the greater strength of binding to peripheral H1 receptors. The drug is devoid of a sedative effect and does not potentiate the effect of alcohol. In addition, loratadine practically does not interact with other drugs and does not have a cardiotoxic effect.
The following antihistamines are classified as local action and are intended for the relief of local manifestations of allergies.
Levocabastin(histimet) is used as eye drops for the treatment of histamine-dependent allergic conjunctivitis or as a spray for allergic rhinitis. At topical application enters the systemic circulation in small quantities and does not have undesirable effects on the central nervous and cardiovascular systems.
Azelastine(allergodil) is a highly effective remedy for the treatment of allergic rhinitis and conjunctivitis. Used as a nasal spray and eye drops, azelastine has little to no systemic effects.
Another topical antihistamine, bamipine (soventol), in the form of a gel, is intended for use in allergic skin lesions accompanied by itching, insect bites, jellyfish burns, frostbite, sunburn, as well as mild thermal burns.
Antihistamines of the third generation (metabolites). Their fundamental difference is that they are active metabolites of antihistamines of the previous generation. Their main feature is the inability to influence the QT interval. Currently, there are two drugs - cetirizine and fexofenadine.
cetirizine(Zyrtec) is a highly selective peripheral H1 receptor antagonist. It is an active metabolite of hydroxyzine, which has a much less pronounced sedative effect. Cetirizine is almost not metabolized in the body, and the rate of its excretion depends on the function of the kidneys. Its characteristic feature is its high ability to penetrate the skin and, accordingly, its effectiveness in skin manifestations of allergies. Cetirizine neither experimentally nor clinically showed any arrhythmogenic effect on the heart, which predetermined the field of practical use of metabolite drugs and determined the creation of a new drug, fexofenadine.
Fexofenadine(telfast) is the active metabolite of terfenadine. Fexofenadine does not undergo transformations in the body and its kinetics does not change with impaired liver and kidney function. He does not enter into any drug interactions, does not have a sedative effect and does not affect psychomotor activity. In this regard, the drug is approved for use by persons whose activities require increased attention. A study of the effect of fexofenadine on the QT value showed, both in the experiment and in the clinic, the complete absence of a cardiotropic effect when using high doses and with long-term use. Along with maximum security this remedy demonstrates the ability to relieve symptoms in the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria. Thus, the pharmacokinetics, safety profile and high clinical efficacy make fexofenadine the most promising of the antihistamines at present.
So, in the doctor's arsenal there is a sufficient amount of antihistamines with different properties. It must be remembered that they provide only symptomatic relief from allergies. In addition, depending on the specific situation, you can use both different drugs and their diverse forms. It is also important for the physician to be aware of the safety of antihistamines.
| 1st generation | II generation | III generation |
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Every year the number of allergic reactions, including dermatitis, is steadily growing, which is associated with the deterioration of the environmental situation and the "unloading" of the immune system in the conditions of civilization.
Allergy - reaction hypersensitivity organism to a foreign chemical- an allergen. It can be food, pet hair, dust, drugs, bacteria, viruses, vaccines, and more.
In response to the entry of an allergen in the organs and cells of the immune system, an intensive production of a special substance, histamine, begins. This substance binds to H1 - histamine receptors and causes signs of allergy.
If you remove the provoking factor, the manifestations of allergies will pass over time, but the cells that store the memory of this substance will remain in the blood. At the next meeting with him, an allergic reaction may manifest itself with greater force.
How do antihistamines work?
These drugs bind to H1-histamine receptors and block them. Thus, histamine cannot bind to the receptors. Allergy phenomena subside: the rash turns pale, swelling and itching of the skin decrease, it becomes easier nasal breathing and the occurrence of conjunctivitis is reduced.
The first antihistamine drugs appeared in the 1930s. As science and medicine developed, the second and then the third generation of antihistamines were created. All three generations are used in medicine. The list of antihistamines is constantly updated. Analogues are produced, new forms of release appear.
Consider the most popular drugs, starting with the latest generation.
In fairness, the division into the first, second and third generations makes sense, because. substances differ in properties and side effects.
The division into the third and fourth generation is very conditional, and often carries nothing but a beautiful marketing slogan.
Sometimes these drugs are referred to both the third and fourth generations at the same time. We will not confuse you even more and call it all simpler:
Last generation - metabolites
The most modern medicines 
rstva. Distinctive feature this generation is that drugs are prodrugs. When ingested, they are metabolized - activated in the liver. Do drugs no sedative effect, also they do not affect the functioning of the heart.
Antihistamines of the new generation are successfully used to treat all types of allergies and allergic varieties of dermatitis in children, people suffering from cardiovascular diseases. Also, these funds are prescribed to people whose profession is associated with increased attention (drivers, surgeons, pilots).
Allegra (Telfast)
The active substance is fexofenadine. The drug not only blocks histamine receptors, but also reduces its production. Used for chronic urticaria and seasonal allergies. The anti-allergic effect lasts up to 24 hours after the end of the course of treatment. Not addictive.
Available only in the form of tablets. Formerly pills were called Telfast, now - Allegra. They are contraindicated in children under 12 years of age, pregnant and lactating women.
cetirizine
The effect after administration develops after 20 minutes and persists for 3 days after discontinuation of the drug. It is used to treat and prevent allergies. Cetirizine does not cause drowsiness and decreased attention. It may be used for a long time. The drug is available in the form of drops (trade name "Zirtek", "Zodak"), syrup ("Cetrin", "Zodak") and tablets.
In children's practice, it is used from 6 months in the form of drops, from 1 year in the form of syrup. From the age of 6, tablets are allowed. The dosage is determined by the doctor individually.
Pregnant women Cetirizine is strictly contraindicated. For the period of use, it is desirable to stop breastfeeding.
The medicine is prescribed for the treatment of year-round and seasonal allergies, urticaria and pruritus. The action occurs 40 minutes after administration. Available in the form of drops and tablets.
In children's practice, drops are used from the age of 2 and tablets from the age of 6. The dosage is determined by the doctor in accordance with the weight and age of the child.
The drug is contraindicated for pregnant women. Acceptance during breastfeeding is allowed.
Desloratadine
Synonyms: Lordestin, Desal, Erius.
The drug has an antihistamine and anti-inflammatory effect. Well eliminates the signs of seasonal allergies and chronic urticaria. When taken in therapeutic doses, dry mouth and headache may occur. Available in the form of syrup, tablets.
Children are prescribed from 2 years in the form of syrup. Tablets are allowed for children over 6 years of age.
Pregnant and lactating Desloratadine is contraindicated. It is possible to use it for life threatening conditions: Quincke's edema, suffocation (bronchospasm).
Antihistamines of the 3rd generation effectively eliminate the manifestations of allergies. In therapeutic doses, they do not cause drowsiness and reduce attention. However, if the recommended dosages are exceeded, dizziness, headache, and an increase in heart rate may occur.
If you have used any of their preparations, do not forget to leave a review in the comments.
Second generation - non-sedating
The drugs of this group have a pronounced antihistamine effect, the duration of which is up to 24 hours. This allows you to take them 1 time per day. Medications do not cause drowsiness or impaired attention, which is why they are called non-sedating.
Non-sedative drugs are actively used to treat:
- urticaria;
- hay fever;
- eczema;
These remedies are also used to relieve severe itching in chickenpox. There is no addiction to antiallergic drugs of the 2nd generation. They are quickly absorbed from the digestive tract. They can be taken at any time, even with meals.
Loratadine
The active substance is loratadine. The drug selectively affects H1 histamine receptors, which allows you to quickly eliminate allergies and reduce the number of side effects:
- anxiety, sleep disturbances, depression;
- frequent urination;
- constipation;
- asthma attacks are possible;
- increase in body weight.
Available in the form of tablets and syrup ( trade names"Claritin", "Lomilan"). Syrup (suspension) is convenient to dose and give to young children. The action develops 1 hour after administration.
In children, Loratadine is used from the age of 2 years in the form of a suspension. The dosage is selected by the doctor depending on the body weight and age of the child.
Loratadine is prohibited for use in the first 12 weeks of pregnancy. In extreme cases, it is prescribed under the strict supervision of a physician.
Synonym: Ebastine
This agent selectively blocks H1 histamine receptors. Does not cause drowsiness. The action occurs 1 hour after administration. The antihistamine effect persists for 48 hours.
In children, it is used from 12 years of age. Kestin has a toxic effect on the liver, causes rhythm disturbances, and reduces the heart rate. Pregnant women are contraindicated.
Synonym: Rupatadin
The medicine is used in the treatment of hives. After oral administration, it is rapidly absorbed. Simultaneous food intake enhances the effect of Rupafin. It is not used in children under 12 and pregnant women. Use during breastfeeding is possible only under strict medical supervision.
Antihistamines of the 2nd generation meet all modern requirements for medicines: high efficiency, safety, long-term effect, ease of use.
However, it should be remembered that the excess therapeutic dosage leads to the opposite effect: drowsiness appears and intensifies side effect.
First generation - sedatives
Sedative drugs are called because they cause a sedative, hypnotic, mind-depressing effect. Each representative of this group has a sedative effect expressed to varying degrees.
In addition, the first generation of drugs has a short-term anti-allergic effect - from 4 to 8 hours. They may become addictive.
However, the drugs are time-tested and often inexpensive. This explains their mass.
First generation antihistamines are prescribed to treat allergic reactions, relieve skin itching in infectious rashes, to reduce the risk of post-vaccination complications.
Along with a good anti-allergic effect, they cause a number of side effects. To reduce their risk, treatment is prescribed for 7-10 days. Side effects:
- dry mucous membranes, thirst;
- increased heart rate;
- drop in blood pressure;
- nausea, vomiting, stomach discomfort;
- increased appetite.
First-generation drugs are not prescribed to people whose activities are associated with increased attention: pilots, drivers, because. they may be distracted and muscle tone.
Suprastin
Synonyms: Chloropyramine
It is available both in the form of tablets and in ampoules. The active ingredient is chloropyramine. One of the most commonly used antiallergic drugs. Suprastin has a pronounced antihistamine effect. It is prescribed for the treatment of seasonal and chronic rhinitis, urticaria, atopic dermatitis, eczema, angioedema.
Suprastin relieves itching well, including after an insect bite. Applied in complex therapy rashes accompanied by skin itching and scratching. Available in the form of tablets, solutions for injection.
Suprastin is approved for the treatment of infants, starting from one month. The dosage is selected individually depending on the age and body weight of the child. These drugs are used in complex therapy chicken pox: to relieve itching and as a sedative. Suprastin is also included in the lytic mixture ("troychatka"), which is prescribed at a high and not knocked down temperature.
Suprastin is contraindicated for use during pregnancy and breastfeeding.
Tavegil
Synonym: clemastine
It is used in the same cases as suprastin. The drug has a strong antihistamine effect lasting up to 12 hours. Tavegil does not reduce arterial pressure, the hypnotic effect is less pronounced than that of suprastin. The medicine is available in several forms: tablets and injection.
Application in children. Tavegil has been used since 1 year. The syrup is prescribed for children from 1 year old, tablets can be used from 6 years old. The dosage is determined individually depending on the age and body weight of the child. The dose is selected by the doctor.
Tavegil is prohibited for use during pregnancy.
Synonym: Quifenadine
Fenkarol blocks H-1 histamine receptors and starts an enzyme that utilizes histamine, so the effect of the drug is more stable and long lasting. Fenkarol practically does not cause a sedative and hypnotic effect. In addition, there are indications that this drug has an antiarrhythmic effect. Phencarol is available in the form of tablets and powder for suspension.
Quifenadine (Fenkarol) is used to treat all types of allergic reactions, especially seasonal allergies. This tool is included in complex treatment parkinsonism. In surgery, it is used as part of drug preparation for anesthesia (premedication). Fencarol is used to prevent host-foreign reactions (when the body rejects foreign cells) during transfusions of blood components.
In pediatric practice, the drug is prescribed from 1 year. For children, the suspension is preferable, it has an orange flavor. If the child refuses to take the syrup, a tablet form may be prescribed. The dosage is determined by the doctor, taking into account the weight and age of the child.
Fencarol is contraindicated in the 1st trimester of pregnancy. In the 2nd and 3rd trimester, its use is possible under medical supervision.
Fenistil
Synonym: Dimetinden
The drug is used to treat all types of allergies, skin itching with chickenpox, rubella, prevention of allergic reactions. Fenistil causes drowsiness only at the beginning of treatment. After a few days, the sedative effect disappears. The medicine has a number of other side effects: dizziness, muscle spasms, dryness of the oral mucosa.
Fenistil is available in the form of tablets, drops for children, gel and emulsion. Gel and emulsion are applied externally after insect bites, contact dermatitis, sunburn. There is also a cream, but this is a completely different drug based on a different substance and it is used for "cold on the lips".
In children's practice, Fenistil in the form of drops is used from 1 meat. Up to 12 years of age, drops are prescribed, over 12 years of age, capsules are allowed. The gel is used in children from birth. The dosage of drops and capsules is selected by the doctor.
Pregnant women are allowed to use the drug in the form of a gel and drops from 12 weeks of pregnancy. From the second trimester, Fenistil is prescribed only for life-threatening conditions: Quincke's edema and acute food allergy.
Diazolin
Synonym: Mebhydrolin
The drug has low antihistamine activity. Diazolin has a fairly large number of side effects. When it is taken, dizziness, stomach pain, nausea and vomiting, increased heart rate, and frequent urination occur. But at the same time, Diazolin does not cause drowsiness. It is approved for long-term treatment in drivers and pilots.
Available in the form of tablets, powder for suspension and dragee. The duration of antiallergic action is up to 8 hours. It is taken 1-3 times a day.
In children, the drug is prescribed from 2 years of age. Up to 5 years, Diazolin in the form of a suspension is preferable; over 5 years, tablets are allowed. The dosage is selected by the doctor individually.
Diazolin is contraindicated in the first trimester of pregnancy.
Despite all the shortcomings, first-generation drugs are widely used in medical practice. They are well studied, approved for the treatment of young children. Medicines are produced in different forms: solutions for injections, suspensions, tablets, which makes it convenient to use them and select an individual dosage.
Antihistamines work well for allergic dermatitis, and (in most cases) atopic dermatitis too.
It should be remembered that drugs should be taken in a strictly defined dose, according to the instructions. Otherwise, undesirable effects may occur, even (!) an increase in an allergic reaction.
The choice of medicine and its dose should be performed by a doctor. Antiallergic treatment, especially for children and pregnant women, should be carried out under strict medical supervision.
10 comments
There are a lot of drugs, each one is better for something different. Try other drugs from the list, newer.
Well, it is best to consult a doctor, perhaps you will be prescribed an injectable form.
I have severe allergy to ragweed (but the list of allergens is not limited to this): itchy eyes, runny nose, sneezing. I started taking levocitemeresin in addition to Avamys (nasal spray). But he does not help me well, because. A strong cough has already begun, especially at night. I didn't sleep at all for one night. Now I don't know what to drink :(
Hello! My daughter (16 years old) frequent relapses allergic rhinitis. The last time the doctor prescribed a course of Desal (4 weeks) did not pass and 2 weeks later there was again nasal congestion, fever, and this time severe headaches. Thought it was low blood pressure. When they took the test, it turned out again-allergy. They started taking Desal again. Tell me, is it possible to use antihistamines so often, and what alternative and more effective treatment would you recommend?
If any one drug from at least the second generation does not help, then you need to try another active ingredient. For example, loratadine does not help my child at all. Doctors automatically prescribe it. :(They used cetrin, drank almost the entire package - everything was fine as long as the weather was damp and cold. As soon as the sun came out and all the alder-birch trees began to bloom, cetrin does not help. Where the promised effect for three days after the course of treatment is unclear.
Passed 2 courses of ASIT - so far it has not helped, alas. And drugs for ASIT are very, very expensive.
Friends say that acupuncture helps. But it is also very expensive. We need to study the issue.
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All information is presented for educational purposes. Do not self-medicate, it is dangerous! An accurate diagnosis can only be made by a doctor.
