Withdrawal Reactions

Seizure disorders are generally categorized as idiopathic or acquired. Idiopathic seizures have no known cause acquired seizure disorders have a known cause, including high fever, electrolyte imbalances, uremia, hypoglycemia, hypoxia, brain tumors, and some drug withdrawal reactions. Once the cause is removed (if it can be removed), the seizures theoretically cease. 

Increasingly, detoxification is being done on an ambulatory basis, which is much less costly than inpatient detoxification (Hayashida et al. 1989). Inpatient detoxification is indicated for patients with serious medical or surgical illness and for those with a past history of adverse withdrawal reactions or with current evidence of more serious withdrawal reactions (e.g., dehrium tremens) (Feldman et al. 1975). 

Busto U, Sellers EM, Naranjo CA, et al Withdrawal reaction after long-term therapeutic use of benzodiazepines. N Engl] Med 315 854-859, 1986a... 

The use of duloxetine in stress urinary incontinence is complicated by (1) the potential for multiple clinically relevant drug-drug interactions with cytochrome P-450 2D6 and 1A2 inhibitors, (2) withdrawal reactions if abruptly discontinued, (3) high rates of nausea and other side effects, (4) the hepa-totoxicity that contraindicates its use in patients with any degree of hepatic impairment, and (5) its mild hypertensive effect. 

Despite public misconceptions, there is little firm evidence that the typical and atypical antidepressants produce dependence in clinical users. A review of 21 case reports of antidepressant addiction revealed that 12 were associated with tranylcypromine, although 8 of these 12 had a previous history of substance misuse (Haddad, 1999). Tranylcypromine s structural similarity to amphetamine may account for the significant number of reports of its addictive potential, but even here the term (mild) discontinuation reaction rather than withdrawal reaction should be used to allay any concerns patients might have (Haddad, 1999). 

If the R group of Cp2TiR was not electron-withdrawing, reaction with CO resulted in the formation of an acyl compound. However, isolation of the initially formed CO adduct, Cp2Ti(CO)(R), was unsuccessful in these cases. 

Adverse effects of /3-blockade include hypotension, heart failure, bradycardia, heart block, bronchospasm, altered glucose metabolism, fatigue, malaise, and depression. Abrupt withdrawal in patients with angina has been associated with increased severity and number of pain episodes and MI. Tapering of therapy over about 2 days should minimize the risk of withdrawal reactions if therapy is to be discontinued. 

It is important to be aware of possible adverse drug withdrawal events (ADWE). These events may be caused by physiological withdrawal reaction, but it is also possible that the underlying disease is worsened. An example of ADWE is delirium or seizures that may occur after abrupt discontinuing of benzodiazepines or alcohol. 

Group 1 Dose-related reactions Group 2 Non-dose-related reactions Group 3 Dose- and time-related reactions Group 4 Time-related reactions Group 5 Withdrawal reactions Group 6 Treatment failure. 

Drug withdrawal reactions - tricyclic antidepressants, monoamine oxidase inhibitors, benzodiazepines, barbiturates, alcohol, opioids. 

Auditory hallucinations consist typically of voices making derogatory personal statements may also occur. They are frightening and may prompt aggressive and violent behaviour (O Brien Woody, 1994). The hallucinations in these drug-induced states in chronic users occur in an otherwise clear consciousness, but similar hallucinations occur in the delirium which may follow acute intoxication with these drugs or in their withdrawal reactions. 

It does not cause cognitive impairment and has a low potential for abuse. It does not show withdrawal reactions and has no anticonvulsive, hypnotic, muscle relaxant and sedative effects. The anxiolytic effect gradually evolves over 1-3 weeks, it does not potentiate the sedative effects of alcohol and is indicated for the short-term management of generalized anxiety disorder. 

Drowsiness, disinhibi-tion, agitation, confusion depression Withdrawal reactions Potential risk for abuse and dependence Less risk for rebound and withdrawal reactions Same as other benzodiazepines Higher risk for rebound and withdrawal reactions... 

Benzodiazepines have a low abuse potential when they are properly prescribed and their use is supervised (American Psychiatric Association 1990). However, physical dependence often occurs when benzodiazepines are taken at higher-than-usual doses or for prolonged periods. If benzodiazepines are discontinued precipitously, withdrawal effects (including hyperpyrexia, seizures, psychosis, and even death) may occur. Signs and symptoms of withdrawal may include tachycardia, increased blood pressure, muscle cramps, anxiety, insomnia, panic attacks, impairment of memory and concentration, perceptual disturbances, and delirium. In addition, withdrawal-related derealization, hallucinations, and other psychotic symptoms have been reported. These withdrawal symptoms may begin as early as the day after discontinuation of the benzodiazepine, and they may continue for weeks to months. Evidence indicates that withdrawal reactions associated with shorter-half-life benzodiazepines peak more rapidly and more intensely. 

Lee s progress through the detoxification was uneventful, with poor sleep the most troublesome aspect. He was pleasantly surprised with the low level of withdrawal discomfort, compared to his own attempts to come off heroin without medication. He and his parents followed the instructions carefully, and in all Lee used about three-quarters of the available medication, apart from the sleeping tablets, which were all necessary. Nine days after his last use of heroin naltrexone was instituted, with no withdrawal reaction. 

Hollister LE, Motzenbecker FP, Degan RO. Withdrawal reactions from chlordiazepoxide ( librium ). Psychopharmacology 1961 2 63-68. 

A hypertensive crisis in a 29-year-oid man after abrupt discontinuation of risperidone is the only report to date of any serious withdrawal reaction that we are aware of (484). Although the episode was attributed to risperidone s a -blocking effect, this is debatable because the hypertension was first detected within hours of discontinuation, the patient had been given multiple drugs, and he used cannabis in the hospital. 

Paroxetine at low concentration is dependent on CYP 2D6 for its clearance. However, this enzyme is almost completely saturated by paroxetine at low concentrations, which accounts for the nonlinear pharmacokinetics of paroxetine and why its half-life goes from 10 to 20 hours when the dose is advanced from 10 to 20 mg per day. At higher concentrations, paroxetine is most likely dependent on CYP 3A3/4 for its clearance. This dose-dependent change in the clearance of paroxetine probably accounts for the higher incidence of withdrawal reactions with this SSRI than might otherwise be expected for a drug with a half-life of 20 hours at steady-state on 20 mg per day (296, 297). 

Although some studies have found little or no evidence, there is now a large body of data indicating that continuous use of a BZD, even at therapeutic doses, will result in withdrawal symptoms in some patients (214, 215). It also has been reasonably well-established that the longer a BZD is taken, even in therapeutic doses, the greater the likelihood of withdrawal reactions when it is discontinued, especially abruptly (3). The most commonly reported withdrawal symptoms include the following ... 

There is considerable overlap between the symptoms of the post-withdrawal syndrome and the actual withdrawal reaction, but the symptoms of post-withdrawal are much more like those of clinical anxiety feelings of tension and threat, and bodily feelings such as unsteadiness, shaking, palpitations and gastrointestinal symptoms are prominent. Symptoms that develop as secondary complications of anxiety, such as agoraphobia, may also be present. 

Should obviate the risk of moderate to severe withdrawal reactions by gradual discontinuation of use of these drugs in all patients with known or suspected long-term, heavy BZD use (2)... 

The nosology of anxiety disorders has changed considerably over the past 40 years (141). Such disorders were not mentioned in the original DSM. In DSM-II, problems with anxiety were considered a subset of behavioral disorders and were restricted to overanxious and withdrawing reactions. The DSM-III defined three types of anxiety disorders in children and adolescents overanxious, avoidant, and separation disorder. The DSM-III also acknowledged that children and adolescents could meet adult criteria for simple phobias, panic disorder, posttraumatic stress disorder, and obsessive-compulsive disorder (OCD). In DSM-IV ( 45), generalized anxiety disorder (GAD) and social phobia (or social anxiety disorder with childhood onset) replaced overanxious disorder and avoidant disorder, respectively. 

Abrupt alcohol withdrawal leads to a characteristic syndrome of motor agitation, anxiety, insomnia, and reduction of seizure threshold. The severity of the syndrome is usually proportionate to the degree and duration of alcohol abuse. However, this can be greatly modified by the use of other sedatives as well as by associated factors (eg, diabetes, injury). In its mildest form, the alcohol withdrawal syndrome of tremor, anxiety, and insomnia occurs 6-8 hours after alcohol consumption is stopped (Figure 23-2). These effects usually abate in 1-2 days. In some patients, more severe withdrawal reactions occur, with patients at risk of hallucinations or generalized seizures during the first 1-3 days of withdrawal. Alcohol withdrawal is one of the most common causes of seizures in adults. Several days later, individuals can develop the syndrome of delirium tremens, which is characterized by total disorientation, hallucinations, and marked abnormalities of vital signs. 

Naltrexone Nonselective competitive antagonist of opioid receptors Reduced risk of relapse in individuals with alcoholism Available as an oral or long-action parenteral formulation Toxicity Gastrointestinal effects and liver toxicity will precipitate a withdrawal reaction in individuals physically dependent on opioids and will prevent the analgesic effect of opioids... 

As users who run out of supply usually fail to experience serious abstinence reactions, it has often been denied that cannabis is addictive. Nevertheless, a relatively high proportion of users persist in continued use, often in spite of negative consequences. The persistence is often explained by a disinclination to face the world without the drug rather than by strong cannabis euphoria or fear of withdrawal reactions. 

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