Rebound phenomenon, also known as withdrawal syndrome, refers to the recurrence or deterioration of the original disease when the drug is suddenly stopped or the dosage is too fast.It refers to the phenomenon of disease reversal caused by the sudden withdrawal of drugs after the basic control of symptoms after long-term use of certain drugs to treat diseases.Common drugs of this kind include clonidine, steroid hormones, opioids, barbiturates, benzodiazepines, propranolol, etc.
Rebound phenomenon, also known as withdrawal syndrome, refers to the recurrence or deterioration of the original disease when the drug is suddenly stopped or the dosage is too fast.It refers to the phenomenon of disease reversal caused by the sudden withdrawal of drugs after the basic control of symptoms after long-term use of certain drugs to treat diseases.Drug withdrawal syndrome and rebound were first proposed during the use of adrenocortical hormone. The former refers to that when the dosage of glucocorticoid is sharply reduced or stopped, long-term use of glucocorticoid inhibits the hypothalamus pituitary adrenal cortex system, resulting in decreased secretion of corticotropin in the anterior pituitary, resulting in atrophy and dysfunction of the adrenal cortex, and even Addison's crisis,The rebound phenomenon refers to the rapid deterioration of the symptoms of the original disease due to the reduction or withdrawal of retention hormone, and the recovery of the disease even exceeds that before treatment.At present, symptoms after drug withdrawal are commonly referred to as withdrawal syndrome, including so-called withdrawal phenomenon after withdrawal of addictive drugs.[1]
Common drugs causing rebound phenomenon are as follows:
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1. Sleeping and sedative drugs
Barbiturates (such as phenobarbital, or barbital, isobaric, etc.).The former is characterized by restlessness, irregular spasm of smooth muscle, finger tremor, weakness, dizziness, visual impairment, nausea and vomiting, insomnia, weight loss, orthostatic or sitting hypotension, etc.The latter is characterized by paroxysmal spasm, alcoholic delirium, etc.Spasm may occur several times a day, and delirium may persist for 1 to several days.The syndrome caused by drug withdrawal, even if not treated, is usually expected to recover in 3-14 days, but it also leads to death.Therefore, the long-term use of barbiturates, and when the drug is pre stopped, it is appropriate to gradually reduce the dosage during 1-4 weeks of hospitalization.
Benzodiazepine anti anxiety drugs can cause addiction after long-term use, and sudden withdrawal of drugs can cause insomnia, anxiety, emotional instability and even epileptic seizures.It was reported that the patient took 10 mg diazepam three times a day for three consecutive months, and had two major convulsions within three hours after five days of drug withdrawal.Many reports indicate that withdrawal syndrome caused by diazepam withdrawal can be eliminated only after continued application of diazepam.This kind of medicine is very easy to cause insomnia rebound due to its short half-life.Temporary sleep disorder and withdrawal syndrome similar to barbital may occur when other drugs, such as chloral hydrate hypnotics, are suddenly stopped.When using such drugs, attention should be paid not to overdose, and the dosage should be slowly reduced when stopping.
Antiarrhythmias
β - receptor blockers (such as propranolol, etc.), calcium antagonists (such as nifedipine, etc.), such as sudden withdrawal after use, may cause more serious angina attacks, even myocardial infarction.This withdrawal reaction is often easy to occur in patients with effective treatment, especially those who begin to fail. After a period of treatment, the effect is significant, and it is easy to occur after drug withdrawal.
The withdrawal syndrome caused by calcium antagonists is due to the sudden withdrawal of calcium channels on the cell membrane being opened, and a large number of calcium ions rapidly pouring into the cells, making the already expanded blood vessels shrink sharply, causing coronary artery spasm and inducing angina pectoris and myocardial infarction.The therapeutic effects of β - receptor blockers are mainly to block the β - receptor of myocardium, slow down heart rate, inhibit myocardial contractility and atrioventricular conduction, improve cardiac load, reduce myocardial oxygen consumption, etc.However, long-term use of β - receptor blockers will affect many aspects of the body: for example, the number of cell membrane β - receptors increases due to feedback, and its β - receptor compensatory sensitivity to endogenous catecholamines increases;It can slow the clearance of catecholamine from blood vessels, increase the concentration of plasma, inhibit the secretion of renin and reduce its activity;The oxygen dissociation curve shifted to the right and myocardial oxygen utilization increased;It affects the level of free T 3 in blood and the life and function of platelets.If the drug is suddenly stopped, many of the above effects cannot disappear in the short term, resulting in some symptoms and signs similar to those caused by beta receptor hyperactivity, that is, drug withdrawal reaction.To deactivate beta receptors
In addition to gradually decreasing the amount of blockers, attention should be paid to the following points: ① If conditions permit, it is better for severe patients to stop taking drugs under hospital conditions.Because hospitalization is conducive to the rest of patients, reducing heart load, and also conducive to doctors' observation and treatment of possible adverse reactions after drug withdrawal; ②Use a variety of drugs, that is, beta blocker and other drugs are taken at the same time. If it is necessary to stop beta blocker, properly increase the treatment dosage of other related drugs; ③Under special circumstances, if the patient needs to have cardiac catheterization or cardiac surgery and needs to stop using beta blockers, it is not necessary to gradually stop using drugs;4 It should be specially explained to patients that they should not stop taking β - blockers without the doctor's permission to avoid serious adverse reactions.
3. Antihypertensive drugs
Almost all types of antihypertensive drugs, such as sudden drug withdrawal, can rebound, especially central antihypertensive agents, such as clonidine hydrochloride, methyldopa, and guanethiling, are prone to occur. When antihypertensive drugs are used together with beta blockers, once the drug is stopped, it is more likely to occur.The main manifestation is the sudden rise of blood pressure, which causes a series of symptoms such as dizziness, headache, fatigue, sweating, etc. Some patients can also endanger their lives due to the sudden rise of blood pressure accompanied by cardiovascular spasm, myocardial infarction, or cerebrovascular accidents.This is because the body is dependent on some antihypertensive drugs after taking them for a long time, and the reflex phenomenon occurs once the drug is suddenly stopped.Therefore, in the treatment of hypertension, when changing drugs due to long-term use of antihypertensive drugs, it is not easy to stop suddenly. It is advisable to pay attention to gradually reduce the dosage first, and then gradually stop the drug after the standby body has acquired adaptability.
Other antihypertensive drugs, such as Bendazhan, ganglion blockers, reserpine, salivary diuretics, all have withdrawal syndrome and rebound phenomenon. Most hypertensive patients must continue to use antihypertensive drugs in order to control their blood pressure. Few patients can maintain normal blood pressure after drug withdrawal.
4. Psycho nervous system drugs
Tricyclic antidepressants and lithium salts can often alleviate the symptoms of depression and mania, but can not shorten the phase of illness. Even though the symptoms disappear and normal activities resume after medication, if the drug is stopped during the phase of illness, the original symptoms can often reappear.Such drugs are represented by chlorpromazine of phenothiazines.28 female patients with chronic schizophrenia were treated with chlorpromazine and reserpine. The withdrawal symptoms were observed after drug withdrawal. On the second day, 4 patients suffered from tension, terror, insomnia, sweating and vomiting;On the third day, 13 people had coffee like disconnection symptoms;On the 4th day, 17 people felt nervous, uneasy, muscle pain, cold sweat, insomnia and nausea;On the fifth day, one person suffered from exhaustion and loss of consciousness;All these symptoms disappeared on the 10th day.
Patients who take trifluoperazine, haloperidol, imipramine, amitriptyline and other drugs to treat schizophrenia and neurosis are prone to sleep disorders, autonomic nervous disorders, vomiting, sweating, headache, dizziness, muscle spasm and other withdrawal syndromes 1-2 days after drug withdrawal.
For patients taking methamphetamine (Miantong), sudden withdrawal of the drug may cause convulsion, delirium, tremor, insomnia, restlessness, hallucination, delusion and other disconnection symptoms, so it is appropriate to gradually reduce the dosage when stopping the drug.
5. Antiepileptic drugs
It must be emphasized that patients with epilepsy must take medicine according to the doctor's instructions for a long time, and must not take medicine intermittently or automatically, because this will lead to the recurrence of epilepsy.In addition, no matter what type of epilepsy in the course of treatment, drug withdrawal must be careful.It is generally advocated that drug withdrawal should be gradually reduced only after 3-4 years of complete control of major seizures and 2-3 years of complete control of minor seizures, and no epileptic waves have appeared in EEG.Between the reduction and complete withdrawal of drugs, the major attack shall not be less than 1 year, and the minor attack shall not be less than half a year.
Nitroglycerin withdrawal syndrome
Zhang Zhiwen observed 95 patients who were treated with nitroglycerin intravenous drip for angina pectoris. Within 1 to 4 days after drug withdrawal, 34-73% of them had symptoms of drug withdrawal to varying degrees, of which 23.15% had angina pectoris aggravated, 8.42% had corresponding ST T changes in ECG, 2.11% had acute myocardial infarction, and one case died suddenly due to ventricular fibrillation after drug withdrawal for 4 days.Nitroglycerin should be given intravenously again after treatment.The main prevention measures are to use small dosage and short course of treatment as far as possible when using nitroglycerin. After stopping the use, add nitric acid vinegar drugs and slowly withdraw the drugs.
7. Adrenocortical hormone '
The withdrawal syndrome and rebound phenomenon of these drugs are caused by the decline of adrenal cortex function after withdrawal
The stronger the inhibition of glandular cortex function, the more likely it is to be caused by drugs.All cases showed general fatigue and fever, of which 80-90% had muscle joint pain and digestive tract symptoms, 70% had mental and neurological symptoms, and about 50% had shock.The method, time and dosage of glucocorticoid drugs are directly related to the emergence of withdrawal syndrome.If prednisone is taken orally for 15 to 30 mg/day, or hydrocortisone is given intravenously for more than 1 month or 200 to 100 mg/day for more than 3 days, it may cause the decrease of ACTH secretion in the anterior pituitary, resulting in pituitary adrenal atrophy and hypofunction. When the drug is suddenly stopped, it is easy to develop adrenal cortical failure and withdrawal syndrome.Special attention should be paid to the method of medication. Try to reduce the daily maintenance dose as much as possible. Use the method of gradual reduction and periodic intermittent withdrawal to avoid sudden withdrawal. With the research of chronopharmacology, the administration time of corticosteroids can be synchronized with the physiological rhythm of the human body, which can not only achieve better efficacy, but also minimize the occurrence of withdrawal syndrome.The peak of adrenocortical hormone secretion in the adrenal cortex is around 8:00 a.m., and it drops to the lowest point at midnight. Therefore, a larger dose can be given every morning.The method of daily morning administration is suitable for short-term glucocorticoids such as prednisone and hydrocortisone;The administration every other day is applicable to dexamethasone, betamethasone and other long-term glucocorticoids.Once the long-term external use of such drugs is stopped, the skin may have symptoms similar to severe contact dermatitis, and strong inflammatory response to external stimuli, especially in the face.
8. Others
If anticoagulant drugs are given for a long time, there may be rebound when they are stopped. At this time, the blood coagulation ability is increased, and the occurrence of thrombus is increased. When stopping the drug, it should be reduced by half every week.In Parkinson's disease, 36 people often take antam, bentropine and levodopa. Among them, 18 people stop taking the drug according to the method of reducing dosage per week. A total of 6 cases of dyskinesia occurred after withdrawal of the drug, and 14 cases of this symptom occurred in the other 18 people who suddenly stopped taking the drug.The long-term use of chlorphenamine butyrate, an antispasmodic drug, can cause psychological symptoms such as restlessness and hallucination.The reason may be that sudden drug withdrawal affects the metabolism of dopamine and destroys the balance of γ - aminobutyrate dopamine in the basal ganglia of the brain.
Gout treatment drugs are taken from time to time during the course of medication.It can often lead to an increase in the frequency of gout attacks, and arbitrary drug withdrawal can also increase the uric acid value in the blood, which further worsens gout.HtwoWhen the receptor antagonist cimetidine was suddenly stopped, the ulcer disease recurred quickly and seriously. Therefore, after the ulcer disappeared, most patients need to continue treatment for 4-8 weeks.It should be noted that the long-term use of codeine as an antitussive can also cause serious withdrawal symptoms after sudden withdrawal, which should be paid attention to.At present, more and more attention is being paid to the symptoms after drug withdrawal and withdrawal.[2]
prevention
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The following three points should be paid attention to to prevent the "rebound" phenomenon of drug withdrawal:
First, when stopping or replacing long-term drugs, the method of gradually reducing the dosage should be adopted.
Second, when the drug needs to be replaced, the method of slow stop can be adopted. First, new drugs can be added on the basis of the original drug, and the original drug will be gradually reduced until it is stopped.
Third, the original drug should still be available during drug withdrawal. Once rebound occurs, the drug can be used again. Generally, rebound symptoms will disappear by themselves.
summary
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When starting to use drugs to treat diseases, we should pay attention to various reactions that may occur after drug withdrawal and withdrawal.The withdrawal syndrome can be aggravated by blind and unreasonable medication, inappropriate dosage, arbitrary interruption of medication, non-compliance with medical advice, and unreasonable combination of drugs.
