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What are sedative-hypnotics? Sedative-hypnotics are drugs which depress or slow down the body's functions. Often these drugs are referred to as tranquilizers and sleeping pills or sometimes just as sedatives. Their effects range from calming down anxious people to promoting sleep. Both tranquilizers and sleeping pills can have either effect, depending on how much is taken. At high doses or when they are abused, many of these drugs can even cause unconsciousness and death. What are some of the sedative-hypnotics? Barbiturates and benzodiazepines are the two major categories of sedativehypnotics. The drugs in each of these groups are similar in chemical structure. Some well-known barbiturates are secobarbital (Seconal) and pentobarbital (Nembutal). Diazepam (Valium), chlordiazepoxide (Librium), and chlorazepate (Tranxene) are examples of benzodiazepines. A few sedativehypnotics do not fit in either category. They include methaqualone (Quaalude), ethchlorvynol (Placidyl), chloral hydrate (Noctec), and mebrobamate (Miltown). All of these drugs can be dangerous when they are not taken according to a physician's instructions. Can sedative-hypnotics cause dependence? Yes. They can cause both physical and psychological dependence. Regular use over a long period of time may result in tolerance, which means people have to take larger and larger doses to get the same effects. When regular users stop using large doses of these drugs suddenly, they may develop physical withdrawal 1|Page: Assignment in Pharmacology
symptoms ranging from restlessness, insomnia and anxiety, to convulsions and death. When users become psychologically dependent, they feel as if they need the drug to function. Finding and using the drug becomes the main focus in life. Is it true that combining sedative-hypnotics with alcohol is especially dangerous? Yes. Taken together, alcohol and sedative-hypnotics can kill. The use of barbiturates and other sedative-hypnotics with other drugs that slow down the body, such as alcohol, multiplies their effects and greatly increases the risk of death. Overdose deaths can occur when barbiturates and alcohol are used together, either deliberately or accidentally. Can sedative-hypnotics affect an unborn fetus? Yes. Babies born to mothers who abuse sedatives during their pregnancy may be physically dependent on the drugs and show withdrawal symptoms shortly after they are born. Their symptoms may include breathing problems, feeding difficulties, disturbed sleep, sweating, irritability, and fever. Many sedative-hypnotics pass through the placenta easily and have caused birth defects and behavioral problems in babies born to women who have abused these drugs during their pregnancy. What are barbiturates? Barbiturates are often called "barbs" and "downers." Barbiturates that are commonly abused include amobarbital (Amytal), pentobarbital (Nembutal), and secobarbital (Seconal). These drugs are sold in capsules and tablets or sometimes in a liquid form or suppositories. What are the effects of barbiturates when they are abused? Dinoy Edward Arlu V. BSN II-D
The effects of barbiturates are, in many ways, similar to the effects of alcohol. Small amounts produce calmness and relax muscles. Somewhat larger doses can cause slurred speech, staggering gait, poor judgment, and slow, uncertain reflexes. These effects make it dangerous to drive a car or operate machinery. Large doses can cause unconsciousness and death. How dangerous are barbiturates? Barbiturate overdose is a factor in nearly one-third of all reported drugrelated deaths. These include suicides and accidental drug poisonings. Accidental deaths sometimes occur when a user takes one dose, becomes confused and unintentionally takes additional or larger doses. With barbiturates there is less difference between the amount that produces sleep and the amount that kills. Furthermore, barbiturate withdrawal can be more serious than heroin withdrawal. What other sedative-hypnotics are abused? All the other sedative-hypnotics can be abused, including the benzodiazepines. Diazepam (Valium), chlordiazepoxide (Librium), and chlorazepate (Tranxene) are examples of benzodiazepines. These drugs are also sold on the street as downers. As with the barbiturates, tolerance and dependence can develop if benzodiazepines are taken regularly in high doses over prolonged periods of time. Other sedative-hypnotics which are abused include glutethimide (Doriden), ethchlorvynol (Placidyl), and methaqualone (Sopor, Quaalude). What is methaqualone? Methaqualone ("Sopors," "ludes") was originally prescribed to reduce anxiety during the day and as a sleeping aid. It is one of the most commonly abused drugs and can cause both physical and psychological dependence. The dangers from abusing 2|Page: Assignment in Pharmacology
methaqualone include injury or death from car accidents caused by faulty judgment and drowsiness, and convulsions, coma, and death from overdose. What are sedative-hypnotic "look-alikes"? These are pills manufactured to look like real sedative-hypnotics and mimic their effects. Sometimes look-alikes contain overthe-counter drugs such as antihistamines and decongestants, which tend to cause drowsiness. The negative effects can include nausea, stomach cramps, lack of coordination, temporary memory loss, becoming out of touch with the surroundings, and anxious behavior.
National Institute on Drug Abuse, 1984
Dinoy Edward Arlu V. BSN II-D
Alternative & Complementary Therapies for Anxiety
Adrian R White, Max H Pittler
trait anxiety. Short-term relief of anxiety may lead to dependency on the practitioner. Relaxation techniques There is a range of therapies or selflearned practices that uses physical and mental/spiritual procedures to different extents, with the aim of inducing a peaceful mental and physical state. Benson and Clipper2 emphasised the bidirectional nature of the relationship between mind and body and provided evidence of an effect of progressive muscular relaxation. Rigorous investigation of these methods faces the problem of selecting a suitable control procedure: often, trials that compare two similar techniques show little difference, so no conclusion can be made about the specific effects of either. If a therapy is found to be superior to an untreated control, this could be the result of many ‘context’ effects, such as the therapeutic relationship, instead of or in addition to any therapeutic effect. In an extensive meta-analysis of 76 controlled trials of all forms of relaxation and meditation techniques in the management of anxiety, Eppley et al.3 found overall evidence of a small but significant effect of the interventions, grouped by the type of relaxation or meditation. Psychiatric patients were specifically excluded, so the role of these therapies in generalised anxiety disorder is not known. Separate analyses of the studies that used situation- or attentioncontrol arms were not performed, so this review does not demonstrate specific effects unequivocally. There is clear evidence from more than 10 randomised controlled trials (RCTs) in healthy volunteers that muscle relaxation may lead to a significant reduction in state anxiety. Among employees, those practising regular relaxation felt more in control of their health4 and more Dinoy Edward Arlu V. BSN II-D
Anxiety is an unpleasant emotional state involving both fear and physical symptoms. It is a normal reaction to stressful events (state anxiety), but can be regarded as pathological when it is unduly severe or prolonged (trait anxiety). Anxiety may present as one symptom of a cluster of related, overlapping conditions, the most common of which are generalised anxiety disorder, phobic disorder and panic disorder. Generalised anxiety disorder is common, affecting about 2–5% of a typical western population, and may present with a range of psychological and/or physical symptoms. Conventional treatment for anxiety may include tranquillisers such as benzodiazepines for short-term use and a range of psychological therapies from superficial psychotherapy to cognitive and behaviour therapies. These conventional psychological therapies will not be considered in this review. We shall consider the effect of complementary therapies only on the psychological symptoms of anxiety. Physical disorders that may be secondary to anxiety (such as hypertension) or may be aggravated by it (such as asthma) are not the major focus of this article. Therapies for anxiety are not universally successful and, as the symptoms of anxiety are chronic and (in general) non-life-threatening, patients are likely to seek help from complementary medicine. Recent survey data suggest that anxiety is one of the most frequent conditions treated with complementary therapies.1 An important distinction must be drawn between treatments that have effects on state anxiety and those that are capable of producing lasting effects on 3|Page: Assignment in Pharmacology
able to cope with stress at work.5 In elderly patients with high anxiety, Rankin et al.6 found a significant reduction in the anxiety state compared with the effect of attention control. Medical investigations are a common cause of anxiety: Quirk and colleagues7 showed that the anxiety engendered by magnetic resonance imaging could be improved significantly more by relaxation and information than by counselling and information or by information alone. In patients with newly diagnosed cancer, relaxation with or without imagery improved anxiety as well as other aspects of mood.8 In a similar population, Bridge and colleagues9 found a significant reduction in state anxiety after relaxation compared with untreated controls, but there was no significant effect on trait anxiety. Biofeedback Biofeedback involves measuring some physical parameter (muscle tension, skin temperature, bowel activity) and using the data to alter the pitch or intensity of a visual or auditory signal, which is then fed back to the subject. With repeated practice, subjects can learn to influence the measured parameter; this is presumed to induce generalised relaxation, although Ince et al.10 have pointed out the lack of direct evidence supporting this concept. Biofeedback may have the advantage of being easier to learn than relaxation, with the disadvantage that some subjects find it difficult to continue practising relaxation in the long term without the aid of the apparatus. Fehring found biofeedback to be more effective in reducing anxiety among a group of normal students than muscle relaxation alone. These results are supported by those of several RCTs that have investigated biofeedback training for state anxiety. One clinical study measured trait anxiety in 4|Page: Assignment in Pharmacology
children who were identified by their teachers as anxious and then randomised to biofeedback or no treatment groups.12 The biofeedback group achieved significant reductions in both state and trait anxiety compared with the untreated control group. However, the actual results were poorly presented in the published report, and long-term benefit was not tested as the children were not followed up after the end of treatment. Meditation The overall effect of meditation is supported by several RCTs. The clearest of these was a trial in which the control group sat quietly for the same length of time, twice daily: meditation led to a significantly greater fall in anxiety, as measured by the State Trait Anxiety Inventory.13 In a meta-analysis of trials of all forms of relaxation and meditation techniques mentioned above, transcendental meditation proved to be clearly superior to progressive muscle relaxation and all other forms of relaxation.3 The evidence seems to point to this not being simply an effect of expectation (for example, the difference becomes greater over time), but possibly associated with the ‘effortlessness’ of the procedure. The results also suggested that methods of relaxation that involve fierce concentration seem to be less effective in reducing anxiety. Autogenic training A systematic review located eight controlled trials, all of which showed significant reduction in anxiety of the treatment groups (Kanji, White & Ernst, unpublished data). Autogenic training reduced experimentally induced anxiety in volunteer students, and it reduced anxietyrelated sickness absence in nurses when compared with untreated control groups. There were only two studies using patient Dinoy Edward Arlu V. BSN II-D
groups: autogenic training was shown to be as effective as hypnotherapy and as a particular form of transcutaneous electrical nerve stimulation in reducing anxiety in patients diagnosed with chronic hysteria. Autogenic training and hypnosis both reduced anxiety significantly in a group of young anxious patients, with no significant difference between the groups. Overall, therefore, the evidence is not conclusive. Control groups chosen were not appropriate, and autogenic training was used in combination with a variety of other therapies, which may themselves have contributed to the result. Self-hypnosis Patients undergoing coronary artery bypass surgery were randomised to receive either a self-hypnotic relaxation technique or no intervention. There were no benefits shown during surgery, but significantly greater relaxation and reduced analgesic use were noted in the treated group after surgery up to the time of discharge.14 In summarising the evidence from trials of all relaxation/meditation techniques, it seems clear that these techniques can have a positive effect, albeit small, in reducing state anxiety in normal healthy subjects. There is some evidence that they can improve patients’ overall ability to cope with conditions such as cancer. There is, however, insufficient evidence to conclude that they are of benefit in the treatment of chronic generalised anxiety. In experienced and responsible hands, these therapies are mostly safe for normal individuals: however, meditation should not be performed for longer than the stipulated time and has been associated with depersonalisation syndrome; hypnosis has been associated with false memory syndrome. These treatments should be used
with care, if at all, in patients with personality and psychotic disorders. Exercise It has been shown that exercise can reduce anxiety acutely. Measures of stress fall about 15 minutes after starting aerobic exercise and the effect lasts for 3– 4 hours after the exercise has finished. Suggested mechanisms include distraction, experience of mastery, release of endogenous opioids and reduction in muscle tension and other physical markers of stress response. There is much more doubt about its effect on trait anxiety.15 On balance, it seems that the evidence is insufficient to justify recommendation. For some time, there was concern that exercise might provoke panic attacks in susceptible individuals as a response to the symptoms of sympathetic activation. This is now known to be unfounded and, in fact, a recent well-designed and carefully performed RCT has shown that exercise may have a useful role in treating panic disorder, although the response is smaller in size and slower in onset than that seen with clomipramine.16 T’ai chi has also been shown to have a positive effect in reducing mental and emotional stress, but this was partially accounted for by the subjects’ high expectations of benefit.17 Herbal remedies Herbal remedies are among the complementary treatments most often used for anxiety.1 Extract of kava (Piper methysticum Forst.) is one of the best researched herbal remedies for this condition. However, most of the research has been published in German, and little is available in the English language. Kava extract significantly reduces anxiety when given in a dosage of 300–450 mg (standardised to 60–240 mg of kava-lactones) daily (Pittler & Ernst, unpublished data). Dinoy Edward Arlu V. BSN II-D
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Adverse effects are mild and infrequent. Stomach complaints, restlessness, drowsiness, tremor, headache and tiredness, and scaling of the skin after long-term administration, have been reported. German chamomile (Matricaria recutita L.) is also used as a treatment for anxiety. One of its active constituents, the flavonoid apigenin, may have affinity for benzodiazepine receptors, which may explain its beneficial effects. There is insufficient evidence from well-performed trials to support its clinical effectiveness. Chamomile is usually prepared as a tea and administered at a dosage of 2–4 g of dried flower heads three times daily. It is considered safe by the US Food and Drug Administration but allergic reactions to chamomile have been reported in patients with allergies to ragweed. Despite the long-standing use of lemon balm (Melissa officinalis L.) as an anxiolytic,18 there is little trial evidence supporting its clinical effectiveness for anxiety. The doses administered range from 1 to 4 g daily. No adverse effects have been reported from ingestion of lemon balm. Passion flower (Passiflora incarnata L.), skullcap (Scutellaria laterifolia L.) and valerian (Valeriana officinalis L.) are mainly used as sedatives/hypnotics but may also have beneficial effects in the treatment of anxiety.19 The last one has been a calming agent for centuries and its use as mild sedative is approved in Germany. Although it is considered safe, paradoxical reactions, including restlessness and palpitations, have been reported in a small number of patients. Other therapies Massage given twice a week for 5 weeks was shown to be superior to relaxation therapy for depressed adolescent mothers. Both groups scored 6|Page: Assignment in Pharmacology
lower anxiety, but the effect in the massage group was confirmed by objective measurement of the reduction in anxious behaviour and urinary steroid concentrations.20 In a further RCT, massage was shown to reduce anxiety in elderly institutionalised patients to a greater extent than conversation or no intervention.21 If these benefits are confirmed, it would be important to determine their duration. Aromatherapy is widely promoted for the treatment of ‘stress’, but its efficacy in this condition is not supported by goodquality clinical research. The majority of the trials of aromatherapy have investigated its effects on anxiety (as well as other outcomes) in a variety of settings/indications.22,23 Several of these studies report that anxiety scores improved in both treatment and control groups, but that there were no statistically significant differences between groups. The majority of these trials conducted are of poor methodological quality and are also poorly reported, often lacking important details. Music’s power to calm anxious minds has been used in many healthcare settings, such as operating theatres, but this does not mean that music therapy has a direct beneficial effect on patients in similar situations. Uncontrolled studies of music in coronary care units have had inconsistent results. A rigorous randomised study involving 56 patients admitted to a coronary care unit in Australia compared two or three sessions of either listening to light classical music or following relaxation instructions (breathing and feelings of heaviness, not progressive muscle relaxation, which involves isometric muscle contraction) for 30 minutes. Neither therapy had any effect on anxiety, and subjects had no benefit compared with untreated controls.24 A Dinoy Edward Arlu V. BSN II-D
number of RCTs have failed to show any beneficial effect of music on the anxiety that patients experience during various surgical procedures. However, a controlled study found that patients who listened to self-selected music tapes during sigmoidoscopy suffered less anxiety than control subjects who had no music.25 There is very little evidence from controlled clinical trials on which to form an opinion of the effectiveness of the other major complementary therapies in treating anxiety. A single study suggested that homoeopathy may have an effect in reducing agitation in children after surgery.26 Chiropractic was no better than sham chiropractic in reducing anxiety in adult hypertensive patients, although it was associated with a significant fall in blood pressure.27 There are no controlled trials of acupuncture for anxiety. In conclusion, anxiety is a problem that attracts many individuals to complementary practitioners. Encouraging results exist for short-term responses to relaxation, meditation, autogenic training, kava extract and massage. Regrettably, firm conclusions on efficacy are impossible, as many of the clinical trials have methodological flaws.
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Dinoy Edward Arlu V. BSN II-D
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