Brain steal syndrome. Rebound syndrome: one of the phenomena of addiction withdrawal Coronary steal syndrome
Drug interaction is a change in the pharmacological effect of one or more drugs when used simultaneously or sequentially (increased effect - synergists, decreased effect - antagonists).
Aspects of pharmacotherapy
1. selection of drugs for joint use (to enhance the therapeutic effect and reduce side effects, it is advisable to prescribe drugs with different mechanisms of action);
2. achieving selectivity of action:
Structure modification - synthesis of drugs similar to natural biologically active substances (hormones, enzymes);
Selective delivery of drugs - improving the technology of manufacturing dosage forms with targeted delivery of drugs to the affected organ.
Quantitative aspects of pharmacotherapy:
1. drug doses;
2. breadth of therapeutic action - the range between the minimum toxic and minimum therapeutic dose;
3. The effectiveness of a drug is the ability of a drug to provide the maximum possible effect.
Synergy - a type of drug interaction characterized by an increase in the pharmacological effect or side effect of one or more drugs.
Types of synergy:
1. sensitizing effect of drugs(interaction formula - 0 + 1 = 1.5) - enhancing the pharmacological effect of only one of the combination of drugs (polarizing mixture - glucose and insulin enhance the effect of potassium, ascorbic acid enhances the effect of iron);
2. additive effect of drugs(interaction formula - 1 + 1 = 1.75) - a type of interaction in which the pharmacological effect of a combination of drugs is greater than the effect of each individual drug included in the combination, but less than the mathematical sum of their effect (salbutamol + theophylline);
3. summation of effect(interaction formula - 1 + 1 = 2) - type of interaction in which the pharmacological effect of a combination of drugs is equal to the mathematical sum of the effects of each of the jointly prescribed drugs (ethacrynic acid + furosemide);
4. potentiation of effect(interaction formula - 1 + 1 = 3) - a type of interaction in which the pharmacological effect of a combination of drugs is greater than the mathematical sum of the effects of each individual drug (prednisolone + norepinephrine, prednisolone + aminophylline).
Antagonism of drugs(interaction formula - 1 + 1 = 0.5) - weakening or blocking the pharmacological action of one or more drugs included in the combination of drugs (nitrates + β 1 -blockers - reduction of reflex tachycardia caused by nitrates; astringents and laxatives; hypotensive and hypertensive facilities).
Synergism and antagonism have both positive and harmful effects on the patient’s body (aminoglycosides + loop diuretics - mutual enhancement of ototoxic side effects; tetracyclines + aminoglycosides - leveling of antimicrobial activity).
Pharmaceutical or physicochemical interaction - This is an interaction characterized by physicochemical processes that occur during the joint use of drugs before their introduction into the patient’s body (in a syringe, in a dropper, at the injection site, in the lumen of the gastrointestinal tract). Combinations are not compatible: sodium bicarbonate + valerian + papaverine; lily of the valley + motherwort + hawthorn extract; aminophylline + diphenhydramine; aminophylline + strophanthin; cholestyramine + indirect anticoagulants or cardiac glycosides or acetylsalicylic acid. Physico-chemical interaction can occur without external signs, but the formation of a precipitate in solutions, a change in their color, and the release of gas are possible.
Pharmacodynamic interaction- this is the interaction of drugs at the receptor level.
Types of interaction at the receptor level:
1. competition of drugs for binding to the receptor (atropine - pilocarpine);
2. change in the kinetics of drug binding at the receptor level - a change in the transport or distribution of another drug by one drug (sympatholytic octadin - tricyclic antidepressants);
3. interaction of drugs at the level of mediators (three types of influence):
Blockade by one drug of subsequent stages of action of another drug at the level of one biological process (methyldopa - pentamine);
Violation by one drug of the possible interaction of a mediator with a receptor (prozerin - atropine);
Violation by one drug of the metabolic pathways, distribution, binding or transport of a mediator involved in the implementation of the effect of another drug (ephedrine - antidepressant nialamide);
4. change in receptor sensitivity under the influence of a combination of drugs (fluorotane - adrenaline, cardiac glycosides - β-blockers).
Physiological interaction- interaction of drugs at the level of the physiological systems of the body through a complex therapeutic effect on different parts of the pathogenesis of the same pathological process (for hypertension - diuretics + calcium antagonists + ACE inhibitors; combined contraceptives).
Pharmacokinetic interaction - a change by one drug in the plasma concentration of another drug due to a change in the rate of its absorption, distribution, binding to plasma proteins, metabolism and/or excretion.
Features of drug interaction at the site of absorption. The interaction of drugs mainly occurs through the enteral route of administration, but is also possible through the parenteral route.
Factors influencing the interaction of drugs in the gastrointestinal tract:
1. changes in the pH of gastric juice (antacids - decreased absorption of indirect anticoagulants, non-steroidal anti-inflammatory drugs, sulfonamides, barbiturates);
2. the presence of cations in the gastrointestinal tract (the presence of cations Ca ++, Fe ++, Al +++, Mg ++ in the intestine slows down the absorption of many drugs; ferrous sulfate - tetracyclines, drinking paracetamol with milk);
3. direct interaction of drugs in the lumen of the gastrointestinal tract (cholestyramine - indirect anticoagulants);
4. impaired gastrointestinal motility (drugs, anticholinergics, antidepressants slow down the evacuation of gastric contents and intestinal motility and change the rate of absorption of many drugs; slowing intestinal motility increases the concentration of cardiac glycosides and glucocorticosteroids in the blood; laxatives reduce the effect of many drugs);
5. peculiarities of blood supply to the gastrointestinal tract (in case of heart failure - decreased absorption of drugs);
6. interaction of drugs with food (captopril, acetylsalicylic acid together with food - decreased effect; propranolol, lobetalol - increased effect; spicy seasonings that irritate the gastrointestinal mucosa of drugs - decreased effect).
When administered parenterally, the effect of novocaine in combination with adrenaline is enhanced.
Features of drug interaction at the distribution level.
Factors influencing the interaction of drugs:
1. blood flow speed (in heart failure, cardiac glycosides enhance the effect of diuretics; reduce the effect of diuretics in hypotension);
2. state of the microcirculatory bed;
9. drug resistance;
10. Paramedicinal side effects of drugs.
4. According to the severity of the current:
1. fatal, i.e. that can lead to death (for example, anaphylactic shock);
2. severe, requiring immediate drug withdrawal and corrective measures;
3. moderate severity, not requiring corrective measures (only drug withdrawal is necessary, for example, for urticaria);
4. mild, not requiring drug withdrawal (for example, the sedative effect of clonidine).
Side effects of drugs associated with their pharmacological properties occurs when taking a drug in a therapeutic dose due to the effect of the drug on various receptors of organs and tissues of the body (propranolol - bronchospasm, nifedipine - constipation, cardiac glycosides - increased peripheral resistance).
Toxic complications caused by relative and absolute overdose of drugs, are characterized by an excessive increase in the concentration of drugs in the blood plasma and/or organs and tissues due to taking an excessive amount of the drug or a violation of its pharmacokinetics (decreased binding to protein, slower biotransformation, decreased excretion, etc.).
Types of toxic effects of drugs:
1. local action (abscess, phlebitis);
2. general (generalized, systemic) effect - manifests itself in case of drug overdose, in case of accumulation of individual drugs in a therapeutic dose, in case of disturbance of the functional state of the excretory organ;
3. organ-specific action:
Neurotoxic (lomefloxacin, cycloserine);
Hepatotoxic (lincosamides);
Nephrotoxic (aminoglycosides, crizanol, bijoquinol, bismoverol);
Ototoxic (aminoglycosides);
Hematotoxic (cytostatics);
Ophthalmotoxic (amiodarone);
Mutagenic effect (immunosuppressants);
Oncogenic effect.
Side effects of drugs caused by increased tissue sensitivity manifested by idiosyncrasy and allergic reactions.
Idiosyncrasy- this is a congenital hypersensitivity to drugs, usually caused by hereditary enzymopathies and develops upon the first dose of drugs.
Allergic reactions - immunopathological reactions that develop after repeated use of drugs in sensitized people.
Types of allergic reactions:
1. immediate hypersensitivity reactions (reagin type with the participation of IgE interacting with mast cell receptors that secrete biologically active substances: histamine, bradykinin, prostaglandin, serotonin): anaphylactic shock, Quincke's edema, acute urticaria, etc. - vaccines, serums, local anesthetics, penicillin;
2. cytotoxic reactions (formation of antibodies to “drug + protein” complexes on the membranes of blood cells): thrombocytopenia, hemolytic anemia - penicillins, cephalosporins, quinidine, salicylates;
3. immunocomplex reactions (formation of immune complexes with the participation of IgM and IgG in vascular endothelial cells): vasculitis, alveolitis, nephritis, serum sickness;
4. delayed-type hypersensitivity reactions (formation of sensitized T-lymphocytes with the presence of antigen-specific receptors and the release of biologically active substances (lymphokinins) when drugs interact with them): Mantoux and Pirquet allergy tests, etc.
Classification of allergic reactions:
1. According to the intensity of clinical manifestations:
1. fatal (deadly): anaphylactic shock;
2. severe: Morgagni-Adams-Stokes syndrome - quinidine;
3. moderate severity: attack of bronchial asthma - aspirin;
4. lungs.
2. By time of occurrence:
1. acute (seconds - hours): anaphylactic shock, Quincke's edema;
2. subacute (hours - 2 days): thrombocytopenia;
3. slow or delayed (days): serum sickness.
Side effects of drugs caused by changes in the functional state of the body, occurs in patients suffering from diseases of any organs when drugs are prescribed in therapeutic doses (cardiac glycosides - arrhythmias in myocardial infarction; anticholinergics, morphine - acute urinary retention in prostate adenoma; in diseases of the liver and kidneys - various side effects).
Drug withdrawal syndrome occurs when a person suddenly stops taking certain drugs for a long time (clonidine - hypertensive crisis, propranolol, neodicoumarin, nitrates - deterioration of the patient's condition).
Steal syndrome is characterized by a parallel deterioration in the functional state of other organs or systems of the body along with an improvement in the condition of the main organ (chime - an attack of angina in atherosclerosis of the coronary arteries).
Rebound syndrome characterized by a change in the pharmacological effect to the opposite (urea - tissue edema).
Drug addiction characterized by a pathological need to take drugs.
There are mental and physical drug dependence.
Mental dependence - state , characterized by an unmotivated need to take any drug in order to prevent mental discomfort due to stopping taking the drug, but not accompanied by the development of abstinence.
Physical dependence - a condition characterized by the development of withdrawal syndrome due to cessation of taking a drug (psychotropic drugs) or after the administration of its antagonist. Withdrawal (withdrawal syndrome) is characterized by symptoms: anxiety, depression, loss of appetite, abdominal cramps, headache, sweating, lacrimation, sneezing, fever, goose bumps.
Drug resistance- a condition characterized by the absence of a pharmacological effect, even when a toxic dose of drugs is prescribed.
Paramedicinal action of drugs is not due to their pharmacological properties, but to the patient’s emotional, psychogenic reaction to a particular drug (replacing Corinfar with Adalat - dizziness, weakness).
4.6. Steal syndromeIn the broad sense of the word, “steal” syndrome is understood as this type of side effect when a drug that improves the functional state of an organ causes a parallel deterioration in the functional state of other organs or systems of the body. Most often, the “steal” syndrome is observed at the level of the circulatory bloodstream in cases where expansion under the influence of vasodilators of some vascular areas and, consequently, improvement of blood flow in them, leads to deterioration of blood flow in other adjacent vascular areas. This particular type of side effect of drugs can be considered using the example of coronary “steal” syndrome.
Coronary steal syndrome develops in cases where two branches of the coronary artery arising from the same main vessel, for example, from the left coronary artery, have different degrees of stenosis (narrowing). In this case, one of the branches is slightly affected by atherosclerosis and retains the ability to expand or contract in response to changes in the myocardial oxygen demand. The other branch is significantly affected by the atherosclerotic process and therefore is constantly expanded to the maximum, even with low myocardial oxygen demand. In this situation, prescribing to the patient any arterial vasodilator, for example, dipyridamole, can cause a deterioration in the nutrition of that area of the myocardium that is supplied with blood by the coronary artery affected by atherosclerosis, i.e. provoke an attack of angina (Fig. 10).
Rice. 10. Scheme of development of coronary “steal” syndrome: A, B, A", I" -Diameters of the coronary artery
A branch of the coronary artery affected by atherosclerosis A expanded as much as possible in order to ensure adequate blood supply to the area of the myocardium irrigated by it (see Fig. 10, A). After the administration of a coronary agent, i.e. With a drug that dilates the coronary arteries, for example, dipyridamole, the coronary vessels dilate and, therefore, the volumetric velocity of coronary blood flow through them increases. However, the vessel A was previously already maximally expanded (diameter A equal to diameter L"). The vessel located nearby expands (diameter B less than diameter B"), resulting in the volumetric velocity of blood flow in the vessel B" increases, and in the vessel A", according to the laws of hydrodynamics, it decreases significantly. In this case, a situation is possible when the direction of blood through the vessel A" will change and it will begin to flow into the vessel B"(see Fig. 10, 6).
4.7. Rebound syndrome
“Rebound” syndrome is a type of side effect of a drug when, for some reason, the effect of the drug is reversed. For example, the osmotic diuretic drug urea, due to an increase in osmotic pressure, causes the transition of fluid from edematous tissues into the bloodstream, sharply increases blood circulation volume (BCV), which entails an increase in blood flow in the glomeruli of the kidneys and, as a result, greater filtration of urine. However, urea can accumulate in the tissues of the body, increase the osmotic pressure in them and, ultimately, cause the reverse transfer of fluid from the circulatory bed into the tissues, i.e. do not reduce, but increase their swelling.
4.8. Drug addiction
Drug dependence is understood as a type of side effect of drugs, which is characterized by a pathological need to take drugs, usually psychotropic ones, in order to avoid withdrawal syndrome or mental disorders that occur when taking these drugs abruptly. There are mental and physical drug dependence.
Under mental dependence understand the patient’s condition, characterized by an unmotivated need to take any drug, often psychotropic, in order to prevent mental discomfort due to stopping the drug, but not accompanied by the development of abstinence.
Physical dependence is a patient’s condition characterized by the development of abstinence syndrome due to discontinuation of a drug or after the administration of its antagonist. Under withdrawal or withdrawal syndrome understand the patient’s condition that occurs after stopping the use of any psychotropic drug and is characterized by anxiety, depression, loss of appetite, cramping abdominal pain, headache, trembling, sweating, lacrimation, sneezing, goose bumps, increased body temperature, etc. .
4.9. Drug resistance
Drug resistance is a condition in which there is no effect from taking a drug, which cannot be overcome by increasing the dose and persists even when a dose of the drug is prescribed that always causes side effects. The mechanism of this phenomenon is not always clear; it is possible that it is not based on the patient’s body’s resistance to any drug, but on a decrease in individual sensitivity to the drug, due to the genetic or functional characteristics of a particular patient.
4.10. Paramedicinal effects of drugs
The paramedicinal effect of drugs is not due to their pharmacological properties, but to the emotional, psychogenic reaction of the patient to a particular drug.
For example, the patient has been taking a calcium ion antagonist for a long time nifedipine, produced by AWD (Germany) under the name "Corinthard". At the pharmacy where he usually bought this drug, the drug produced by AWD was not available, and
The patient was offered nifedipine called "adalat" produced by Bayer (Germany). However, taking Adalat caused the patient severe dizziness, weakness, etc. In this case, we can talk not about the own side effects of nifedipine, but about a paramedicinal, psychogenic reaction that arose in the patient subconsciously due to the reluctance to exchange Corinfar for a similar drug.
CHAPTER 5 DRUG INTERACTIONS
IN In practical health care conditions, doctors very often have to deal with a situation where the same patient has to prescribe several drugs at the same time. This is largely due to two fundamental reasons.
L Currently, no one doubts that effective therapy for many diseases can only be achieved with the combined use of drugs. (For example, hypertension, bronchial asthma, gastric ulcer, rheumatoid arthritis and many, many others.)
2. Due to the increasing life expectancy of the population, the number of patients suffering from concomitant pathology, which includes two, three or more diseases, is constantly increasing, which, accordingly, requires the prescription of several drugs simultaneously and/or sequentially.
The simultaneous prescription of several drugs to one patient is called polypharmacy. Naturally, polypharmacy can be rational, i.e. useful for the patient, and vice versa, harm him.
As a rule, in practical conditions, the prescription of several drugs simultaneously for the treatment of one specific disease has 3 main goals:
increasing the effectiveness of therapy;
reducing the toxicity of drugs by reducing the doses of combined drugs;
prevention and correction of side effects of drugs.
At the same time, combined drugs can affect both the same parts of the pathological process and different parts of the pathogenesis.
For example, a combination of two antiarrhythmics ethmosin and disopyramide, which belong to class IA antiarrhythmic drugs, i.e. drugs that have similar mechanisms of action and realize their pharmacological effects at the level of the same link in the pathogenesis of cardiac arrhythmias, provide
produces a high level of antiarrhythmic effect (66-92% of patients). Moreover, this high effect is achieved in most patients when using drugs in doses reduced by 50%. It should be noted that with monotherapy (therapy with one drug), for example, supraventricular extrasystole, disopyramide at the usual dose was active in 11% of patients, and ethmozin - in 13%, and with monotherapy at half the dose, a positive effect could not be achieved in any from patients.
In addition to influencing one link of the pathological process, a combination of drugs is very often used to correct different links of the same pathological process. For example, in the treatment of hypertension, a combination of calcium channel blockers and diuretics may be used. Calcium channel blockers have powerful vasodilating (vasodilating) properties, mainly in relation to peripheral arterioles, reducing their tone and, thereby, helping to reduce blood pressure. Most diuretics lower blood pressure by increasing the excretion (removal) of Na + ions in the urine, reducing blood volume and extracellular fluid, and reducing cardiac output, i.e. two different groups of drugs, acting on different parts of the pathogenesis of hypertension, enhance the effectiveness of antihypertensive therapy.
An example of combining drugs to prevent side effects is the prescription of nystatin to prevent the development of candidiasis (fungal infections of the mucous membranes) during long-term treatment with antibiotics of the penicillin, tetracycline, neomycin group, etc., or the prescription of drugs containing K + ions to prevent the development of hypokalemia during treatment with cardiac glycosides in patients with heart failure.
Knowledge of the theoretical and practical aspects of the interaction of drugs with each other is necessary for every practical medical worker, since, on the one hand, they allow, through a rational combination of drugs, to enhance the effect of the therapy, and on the other hand, to avoid complications that arise when using irrational combinations of drugs, as a result of which their side effects intensify, including death.
So, drug interaction is understood as a change in the pharmacological effect of one or more drugs when used simultaneously or sequentially. The result of such interaction may be an increase in pharmacological effects, i.e. the combined drugs are synergists, or a decrease in the pharmacological effect, i.e. interacting drugs are antagonists.
Temporary improvement can be obtained by reducing myocardial oxygen demand with medications ( β-blockers) or by improving coronary blood flow ( nitrates, calcium antagonists). However, repeated ischemic episodes may occur.
The only real way to treat hibernating myocardium is timely revascularization, performed before the development of irreversible morphological changes in the myocardium.
Fixed and dynamic obstruction of the coronary arteries
Fixed Coronary obstruction causes a permanent decrease in blood flow, usually corresponding to the degree of atherosclerotic narrowing of the coronary arteries. Clinical manifestations of myocardial ischemia in patients with fixed coronary obstruction, as a rule, develop when the coronary artery narrows in excess of 70%.
Dynamic obstruction is associated: (1) with increased tone and spasm of the coronary artery, (2) thrombus formation. The addition of a dynamic component of obstruction leads to episodes of ischemia even with hemodynamically insignificant narrowing of the coronary artery.
To characterize the severity of coronary obstruction, not only the degree of narrowing of the coronary arteries at rest, but also the severity of the decrease in coronary reserve is of great importance. Coronary reserve refers to the ability of the coronary vessels to dilate and, as a result, increase blood flow when the load on the heart increases.
The development of dynamic obstruction in atherosclerotic lesions of the coronary vessels is caused by impaired reactivity of the coronary arteries and activation of thrombogenic mechanisms. These processes are facilitated by systemic endothelial dysfunction, which occurs, for example, with hyperhomocysteinemia, diabetes mellitus, dyslipoproteinemia and other diseases.
Impaired reactivity of coronary arteries affected by atherosclerosis is caused by the following mechanisms:
Reduced formation of vasodilators;
Reduced bioavailability of vasodilators;
Damage to smooth muscle cells of the coronary vessels.
Increased thrombogenicity in atherosclerotic damage to the coronary arteries and ischemia is explained by the following factors:
Increased formation of thrombogenic factors (tissue thromboplastin, plasminogen activator inhibitor, von Willebrand factor, etc.);
Reducing the formation of atrombogenic factors (antithrombin III, proteins C and S, prostacyclin, NO, tissue plasminogen activator, etc.).
The significance of dynamic obstruction increases with endothelial damage and destabilization of the atherosclerotic plaque, which leads to platelet activation, the development of local spasm and acute thrombotic occlusive complications, in particular acute coronary syndrome.
Thus, atherosclerotic lesions of the coronary vessels, in addition to a mechanical reduction in the lumen of the vessel (fixed obstruction), can be the cause of dynamic obstruction.
The phenomenon of stealing
The phenomenon of coronary steal consists of a sharp decrease in coronary blood flow in the myocardial zone, supplied with blood from a partially or completely obstructed coronary artery with an increase in the number of vasodilators, as well as with physical activity.
The steal phenomenon occurs as a result of blood flow redistribution and can form either within the basin of one epicardial artery (intracoronary steal), or between the blood supply basins of different coronary arteries in the presence of collateral blood flow between them (intercoronary steal).
With intracoronary steal at rest, there is a compensatory maximum expansion of the arteries of the subendocardial layer with a loss of their sensitivity to vasodilators, while the arteries of the epicardial (outer) layer still retain the ability to expand under the influence of vasodilators. With physical exertion or the predominance of humoral vasodilators, rapid expansion of the epicardial arteries occurs. This leads to a decrease in resistance in the segment “poststenotic area - epicardial arterioles” and a redistribution of blood flow in favor of the epicardium with depletion of the subendocardial blood supply.
Rice. 1.9. Mechanism of intracoronary steal phenomenon
(according to Gewirtz N., 2009).
For intercoronary steal phenomenon a “donor” section of the heart is distinguished, which receives blood from a normal artery, and an “acceptor” section, which lies in the vascularization zone of the stenotic artery. At rest, the “donor” region supplies blood to the “acceptor” region due to collaterals. Under these conditions, the arterioles of the “acceptor” region are in a state of submaximal dilatation and are practically insensitive to vasodilators, and the arteries of the “donor” region fully retain the ability to dilate. The occurrence of a vasodilator stimulus leads to dilation of the arterioles of the “donor” region and a redistribution of blood flow in its favor, which causes ischemia of the acceptor region. The more developed the collaterals between the normal and ischemic parts of the heart, the greater the likelihood of intercoronary steal.
Rice. 1.9. The mechanism of the intercoronary steal phenomenon
Steal syndrome is the general name of clinical syndromes caused by unfavorable redistribution of blood between organs and tissues through collaterals, leading to the occurrence or worsening of ischemia. Thus, with occlusion of the superior mesenteric artery, which has anastomoses with the celiac trunk system, mesenteric steal syndrome can be observed: the outflow of blood through the anastomoses causes ischemia of the organs supplied by the branches of the celiac trunk, clinically manifested by abdominal pain. Abdominal pain when walking, which goes away at rest, in patients with damage to the iliac and mesenteric arteries can arise as a result of an actively functioning mesenteric-ilio-femoral collateral circulation. Cerebral steal syndrome with the development of ischemia of a section of brain tissue occurs as a result of worsening circulatory failure in the affected vascular system due to the redistribution of blood flow in favor of the adjacent, usually more intact vascular system. For example, when the subclavian artery is blocked at a certain level, the blood supply in the affected arm is compensated by the vertebral artery on the opposite side, which leads to the development of brain steal syndrome. In this case, with an increase in the functional load on the hand, dizziness, imbalance, and transient visual impairment occur. Worsening of ischemia in the affected area of brain tissue is also possible with the use of vasodilating drugs that affect hl. arr. on intact vessels (eg, papaverine). In angina pectoris, coronary steal syndrome can also develop with the use of certain medications. For example, dipyridamole, expanding the preem. unaffected vessels of the heart, impairs blood supply to the ischemic area of the myocardium. Its intravenous administration is used for diagnostic purposes to provoke myocardial ischemia, detected using radionuclide testing.
The clinical picture is usually characterized by symptoms of vertebrobasilar vascular insufficiency and symptoms of ischemia of the upper limb.
The dominant one, as a rule, is cerebrovascular insufficiency, which usually manifests itself as short-term paroxysmal crises lasting several minutes: headache, dizziness, short-term attacks of loss of consciousness, darkening of the eyes, loss of visual fields, sensation of objects rotating, paresthesia, unsteady gait, dysarthria . The attacks usually pass without leaving permanent neurological damage.
It is typical for the condition to worsen or for brain symptoms to appear when blood flow to the upper limb increases, for example after exercising the upper limb.
Signs of ischemia of the upper extremities are usually mildly expressed in the form of fatigue, weakness, numbness, chilliness, and moderate pain when loading the extremities.
During clinical examination, neurological symptoms are usually not detected, but signs of arterial insufficiency of the upper extremities are detected - decreased skin temperature, decreased blood pressure, noise in the neck during auscultation.
The exact topical diagnosis and the nature of blood flow reversal are established using angiography.
Differential diagnosis is aimed at establishing the cause that caused vertebrobasilar vascular insufficiency: occlusive vascular lesions, pathological tortuosity, anomaly, compression of the vertebral artery or still syndrome. This is necessary for choosing a method of surgical treatment. In addition, it is important to identify possible multiple lesions of the brachiocephalic arteries.
It is necessary to exclude intracranial tumors, cerebral hemorrhage, intracranial aneurysms, embolism of cerebral vessels and extracranial arteries, Meniere's syndrome, eye diseases, spondylosis and other pathologies of the cervical spine.
Aortoarteriography data, as well as other clinical and special research methods (radiography of the skull and cervical spine, examination of the fundus and neurological status) are of decisive importance for establishing a diagnosis.
Rebound syndrome develops against the background of long-term use of drugs of various groups and its subsequent abrupt withdrawal. Usually, with a gradual reduction in dosage until the drug is completely stopped, the phenomenon of drug withdrawal does not occur, but for some groups of drugs there are certain risks even against the background of a systematic dose reduction. These include antihistamines, hormonal drugs and antidepressants.
Spectrum of medications
Features of the phenomenon
The first information about drug withdrawal syndrome and the adverse effects of a significant decrease in active substances in the blood plasma dates back to the early days of medicine. Disputes about the connection between the deterioration of the patient’s health and drug withdrawal still continue to this day. Rebound syndrome involves disinhibition of regulatory mechanisms. If, while taking medications, various pathogenic reactions were suppressed, then after interrupting the course, a pronounced exacerbation of these reactions occurs. Many experts synonymize the concepts of “rebound phenomenon” and “withdrawal syndrome”, but these concepts clearly cannot be combined, since they have completely different mechanisms of action:
- withdrawal phenomenon - failure of organs, tissues or systems as a result of cessation of drug replacement therapy;
- "ricochet" syndrome (recoil, reverse) - exacerbation of reactions of organs or systems in their pathology against the background of withdrawal of drug therapy.
Rebound syndrome is more a type of withdrawal phenomenon than a synonym. Despite this, many clinicians quite naturally combine both terms into one and give it equal meaning. Withdrawal syndrome occurs with long-term drug correction of mental illness or metabolic disorders. Such reactions often occur after discontinuation of medications that have a suppressive or depressing effect on the body to varying degrees.
Aspects of drug treatment
An important point in organizing the management of an individual patient is the choice of medications that will activate the necessary receptors, inhibit pathogenic phenomena or conditions, and also improve the patient’s well-being. The algorithm for any purpose includes the following nuances:
- choice of pharmacological group;
- selection of a representative of the pharmacological group;
- generics (analogs) or originals;
- drawing up an adequate dosage.
The algorithm is entirely based on laboratory and instrumental studies on a specific disease, general complaints of the patient, and his clinical history. The general somatic status of the patient, his age, psycho-physical development and psycho-emotional state are taken into account. When taking certain drugs for a long time, it is important to take into account the financial capabilities of the patient. For example, if a patient is forced to take an expensive original drug for life, and he does not always have the opportunity to provide himself with it, then systematic interruptions in taking it can affect the treatment and general condition, up to the development of “rebound” syndrome.
Development factors
There are a number of specific factors that are not associated with the usual understanding of the “rebound” syndrome, but occur in clinical practice. In prevailing cases, a similar phenomenon is observed when taking drugs that have a short half-life and elimination from the body. The intensity of the syndrome in this case depends on the speed of elimination of the active substance from the blood plasma. The condition can also develop when the drugs themselves do not have any effect on the existing problem. Such addiction occurs with long-term ineffective use of a group of cardiological drugs, in which nitrates predominate. With intermittent treatment, a pathological condition occurs quite often due to self-prescription, inadequate dosage and lack of discipline of the patient. There is another type of intermittent therapy, when the syndrome can occur in the interval between taking subsequent doses (for example, if the next dose should be taken 5 hours after the first, then the phenomenon may occur during this time period). In extremely rare cases, rebound syndrome has been described as a result of the primary and only dose of a drug due to a rapid decrease in its concentration in the blood.
Important! The method of administration is also a presumptive factor in the development of the phenomenon of drug withdrawal. Thus, with intravenous (parenteral) administration, pathology develops much more often. With oral administration and other methods of absorption of medications by the body, the concentration of the active substance in the blood plasma decreases gradually.
Etiological factors
Withdrawal syndrome is quite complex due to the difficulty of instantly rebuilding the body to exist without medications. Substances that provoke addiction are often classified as psychoactive, which is why many patients experience nervous disorders and emotional instability. Such conditions can cause deep depression. Antidepressants belong to this group of drugs and cause persistent disturbances of consciousness and psyche. Cancellation of hormonal drugs often leads to hormonal imbalances and metabolic disorders. The main causes of recoil syndrome are:
- incorrect dosage prescription;
- mental illness of the patient;
- drug replacement of the function of an organ or system;
- other drug addictions (toxic, alcoholic, etc.).
This is interesting! Only in gynecology is withdrawal syndrome a positive thing. In the absence of pregnancy for a long time, women are prescribed hormonal medications, which are then discontinued. Against the background of withdrawal syndrome, a hormonal surge occurs, ovulation is stimulated, which significantly increases a woman’s chances of becoming pregnant. When the drug course is interrupted, withdrawal syndrome occurs, which does not depend on the reduction in the effect of the active substances.
Signs and manifestations
The symptomatic complex of withdrawal syndrome develops according to the scenario of a concomitant disease. With mental disorders and long-term use of antidepressants, patients experience an exacerbation of existing pathologies. The same applies to hormonal diseases. Among the main general symptoms are:
- decreased performance;
- depression and apathy;
- emotional disorders;
- deterioration of health according to the main diagnosis;
- development of depressive syndrome;
- decreased function of internal organs and systems;
- sweating and shortness of breath;
- tachycardia, trembling of limbs.
Apathy and indifference when withdrawing from psychoactive drugs
Important! The psychological factor in withdrawal syndrome plays an important role, since often the very thought of stopping the drug contributes to fixation on this event. During the period of the “rebound phenomenon,” addiction to the drug replaces all other primary needs (sexual intimacy, communication, nutrition).
Signs of hormonal withdrawal
Recoil syndrome after discontinuation of hormonal medications provokes the development of some specific symptoms. After long-term treatment with glucocorticosteroids, a decrease in adrenal function, a decrease in cardiac ejection fraction, and even cardiac arrest occur. Today, rebound syndrome after interrupting the course can be avoided by following clear patterns. It is necessary to discontinue drugs of this group with a gradual dose reduction.
Signs of antidepressant withdrawal
Treatment of psychodependent conditions is always associated with the risk of withdrawal syndrome, since antidepressants directly affect the human autonomic system, controls brain receptors and behavioral reactions. Among the main symptoms are:
- insomnia and anxiety;
- convulsive syndrome:
- tremor of the limbs;
- increased heart rate.
Important! Today, this often occurs due to the patient’s lack of discipline in following the medication regimen. With adequate dosage and proper medical management of the patient, such phenomena occur less and less often. Despite this, it is worth remembering that withdrawal symptoms can develop in an aggressive manner, even leading to death.
Preventive actions
Prevention consists of choosing a specialized doctor and following all the rules for taking prescribed medications. It is important not to self-medicate and get carried away with the uncontrolled use of any medications. This is especially true for patients with a burdened clinical history.
Consultation with a doctor regarding the drug dosage regimen
Some patients are forced to take certain replacement drugs for life to replenish the lost function of organs, tissues or systems. Rebound syndrome is a dependence on a drug with severe symptoms of an existing pathology. The condition requires correction by prescribing similar, milder medications, herbal teas, vitamin complexes, or by simply waiting. In case of any troubling conditions, you should contact a specialist.
