Sedative Hypnotic Medications

8/14/2019 Sedative Hypnotic Medications

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1 | P a g e : A s s i g n m e n t i n P h a r m a c o l o g y D i n o y E d w a r d A r l u V . B S N I I - D

Sedative-HypnoticMedications

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 sedative-

hypnotics. 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 examplesof benzodiazepines. A few sedative-

hypnotics 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

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-hypnoticswith 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 unbornfetus?

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 whenthey are abused?


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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 drug-

related 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

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 theireffects. Sometimes look-alikes contain over

the-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.Source: National Institute on Drug

Abuse, 1984


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Alternative & ComplementaryTherapies for Anxiety

Adrian R White, Max H PittlerAnxiety is an unpleasant emotional

state involving both fear and physical

symptoms. It is a normal reaction tostressful 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 25% of a typical western

population, and may present with a rangeof 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

trait anxiety. Short-term relief of anxiety

may lead to dependency on the practitioner

Relaxation techniquesThere is a range of therapies or self

learned practices that uses physical and

mental/spiritual procedures to different

extents, with the aim of inducing apeaceful 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.3found 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 attention

control 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


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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 significanteffect on trait anxiety.

BiofeedbackBiofeedback 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 themeasured 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

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.

MeditationThe 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 differencebecomes 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 trainingA systematic review located eight

controlled trials, all of which showedsignificant reduction in anxiety of the

treatment groups (Kanji, White & Ernst

unpublished data). Autogenic training

reduced experimentally induced anxiety in

volunteer students, and it reduced anxiety

related sickness absence in nurses when

compared with untreated control groups

There were only two studies using patient


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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-hypnosisPatients 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 thesetechniques 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.

ExerciseIt 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 34 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 concernthat 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 Tai chi has also beenshown 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 remediesHerbal 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 300450 mg

(standardised to 60240 mg of kava-lactones

daily (Pittler & Ernst, unpublished data)


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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, theflavonoid 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 24 g of dried

flower heads three times daily. It is

considered safe by the US Food and Drug

Administration but allergic reactions tochamomile 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 therapiesMassage given twice a week for 5

weeks was shown to be superior to

relaxation therapy for depressed

adolescent mothers. Both groups scored

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 good

quality clinical research. The majority of

the trials of aromatherapy have

investigated its effects on anxiety (as well

as other outcomes) in a variety ofsettings/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.

Musics power to calm anxious mindshas 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


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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 itwas 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, asmany of the clinical trials have

methodological flaws.

Sedative Hypnotic Medications

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