Anxolticsnew Microsoft Office Word Document (3)

2009

ANXIOLYTIC AND HYPNOTIC DRUGS Anxiety disorders as recognised clinically include: • generalised anxiety disorder (an ongoing state of excessive anxiety lacking any clear reason or focus) • panic disorder (sudden attacks of overwhelming fear occur in association with marked somatic symptoms, such as sweating, tachycardia, chest pains, trembling and choking). • phobias (strong fears of specific objects or situations, e.g. snakes, open spaces, flying, social interactions) • post-traumatic stress disorder (anxiety triggered by recall of past stressful experiences) •

obsessive compulsive disorder (compulsive ritualistic behaviour driven by irrational anxiety, e.g. fear of contamination).

It should be stressed that the treatment of such disorders generally involves psychological approaches as well as drug treatment.

CLASSIFICATION OF ANXIOLYTIC AND HYPNOTIC DRUGS The main groups of drugs are as follows: 1. 2. 3. 4. 5. 6. 7. 8.

Benzodiazepines. Buspirone. Barbiturates β-Blockers Sedative antihistamines Antidepressants antiepileptic drugs Zolpidem.( for insomnia) 1

Benzodiazepines. This is the most important group, used as anxiolytic and hypnotic agents. Anxiolytics, particularly the benzodiazepines, have been termed ‘minor tranquillisers’. 1. Buspirone. This 5-HT1A receptor agonist is anxiolytic but not appreciably sedative. 2. β-Adrenoceptor antagonists (e.g. propranolol ) These are used to treat some forms of anxiety, particularly where physical symptoms such as sweating, tremor and tachycardia are troublesome. Their effectiveness depends on block of peripheral sympathetic responses rather than on any central effects. They are sometimes used by actors and musicians to reduce the symptoms of stage fright. 3. Barbiturates. These are now largely obsolete, superseded by benzodiazepines. Their use is now confined to anaesthesia and the treatment of epilepsy . 4. 5. Sedative antihistamines such as diphenhydramine & promethazine, are sometimes used as sleeping pills, intended to improve children's sleep patterns.they have antagonistic effect on H1 –receptor in the brain. 6. 7. Antidepressants as Selective serotonin reuptake inhibitors such as fluoxetine and sertraline are used to treat certain anxiety disorders.Their action in this context appears to be independent of their antidepressant effects. 8. 9. Various drugs that enhance the effects of 2

GABA, developed primarily as antiepileptic drugs ,may also be effective in treating anxiety disorders ,They include gabapentin , and valproate. 10. This hypnotic acts similarly to benzodiazepines, although chemically distinct, but lacks appreciable anxiolytic activity.It is approved for the short-term (usually about two to six weeks) treatment of insomnia.

11. Zolpidem.

Benzodiazepines Benzodiazepines cause: 1. reduction of anxiety and aggression 2.sedation, leading to improvement of insomnia Although { long-term use of benzodiazepines as sleeping pills is undesirable, owing to tolerance, dependence and 'hangover' effects}.

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3 Benzodiazepines decrease the time taken to get to sleep, and increase the total duration of sleep, Both effects tend to decline when benzodiazepines are taken regularly for 1-2 weeks. Long-acting drugs such as nitrazepam are no longer used as hypnotics. 4.muscle relaxation and loss of motor coordination ( clonazepam) 5.suppression of convulsions (antiepileptic effect) (e.g. Clonazepam , diazepam ).

Side effects of benzo.. These may be divided into: 1. toxic effects resulting from acute overdosage 2. unwanted effects occurring during normal therapeutic use 3. tolerance and dependence 4. the appearance of a benzodiazepine withdrawal syndrome when the benzodiazepines are stopped or the dose is reduced after long-term usage. 3

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The withdrawal symptoms may include anxiety & irritability sweating tremor sleep disorders

Side effects of benzo.. 1. Drowsiness & confusion 2. amnesia . 3. impaired coordination, which considerably affects manual skills such as driving performance.

Buspirone Buspirone is a partial agonist at 5-HT1A receptors is used to treat various anxiety disorders. It also binds to dopamine receptors, but it is likely that its 5-HT-related actions are important in relation to anxiety suppression (e.g. ipsapirone). However, buspirone takes days or weeks to produce its effect in humans,. Buspirone is ineffective in controlling panic attacks or severe anxiety states. Buspirone has side effects quite different from those of benzodiazepines. It does not cause sedation or motor incoordination, nor have withdrawal effects been reported. side effects are nausea, dizziness, headache and restlessness, which generally seem to be less troublesome than the side effects of benzodiazepines.

BARBITURATES

Barbiturates that remain in clinical use include phenobarbital, still occasionally used to treat epilepsy ,and thiopental, which is widely used as an intravenous anaesthetic agent . use as sedative/hypnotic agents is no longer recommended. Barbiturates are Non-selective central nervous system depressants that produce 4

effects ranging from sedation and reduction of anxiety to unconsciousness and death from respiratory and cardiovascular failure-therefore dangerous in overdose. Act partly by enhancing action of GABA, but less specific than benzodiazepines.

Barbiturates induce a high degree of tolerance and dependence. They also strongly induce the synthesis of hepatic cytochrome P450 and conjugating enzymes, and thus increase the rate of metabolic degradation of many other drugs.

OTHER POTENTIAL ANXIOLYTIC DRUGS Antidepressants: Selective serotonin reuptake inhibitors such as fluoxetine and sertraline are used to treat certain anxiety disorders( including obsessive compulsive disorder and panic). Their action in this context appears to be independent of their antidepressant effects.

antiepileptic drugs : Various drugs that enhance the effects of GABA, developed primarily as antiepileptic drugs ,may also be effective in treating anxiety disorders ,They include gabapentin, and valproate.

Drug interaction with anxiolytic or hypnotic drugs C h l o r a 5

m p h e n i c o l b a r b i t u r a t e s a c c e l e r a t e m 6

e t a b o l i s m o f c h l o r a m p h e n i c o l . Corticosteroids barbiturates accelerate metabolism of corticosteroids . Coumarins 7

barbiturates accelerate metabolism of coumarins . Digitoxin barbiturates accelerate metabolism of digitoxin . Doxycycline barbiturates accelerate metabolism of doxycycline . Metronidazole barbiturates accelerate metabolism of metronidazole . Progestogens &oestrogenes barbiturates accelerate metabolism of prog& oestro..( reduced contraceptive effect( Propranolol barbiturates possibly reduce plasma concentration of propranolol Clonazepam phenobarbital often reduces plasma concentration of clonazepam Folates plasma concentration of phenobarbital possibly reduced by folates Rifampicin phenobarbital possibly reduces plasma concentration of rifampicin Valproate plasma concentration of phenobarbital increased by valproate (also plasma concentration of valproate reduced) Alcohol increased sedative effect when barbiturates given with alcohol .

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Notes on hypnotics ('sleeping tablets') : The cause of insomnia should be established before administering hypnotic drugs. Common causes include alcohol or other drug misuse and physical or psychiatric disorder (especially depression). Tricyclic antidepressants cause drowsiness, so can kill two birds with one stone if taken at night by depressed patients with sleep disturbance. Optimal treatment of chronic insomnia is often by changing behaviour (e.g. increasing exercise, staying awake during the day) rather than with drugs.

sedatives /anxiolytics and dental procedures 9

Some anxious patients may benefit from the use of a hypnotic for 1 to 3 nights before the dental appointment. Hypnotics do not relieve pain, and if pain interferes with sleep an appropriate analgesic should be given. Diazepam , nitrazepam or temazepam are used at night for dental patients. Temazepam is preferred when it is important to minimise any residual effect the following day. Diazepam and temazepam are effective anxiolytics for dental treatment in adults, but they are less suitable for children. Diazepam has a longer duration of action than temazepam. When given at night diazepam is associated with more residual effects the following day; patients should be very carefully warned not to drive . In children anxiolytic treatment should be used only to relieve acute anxiety (and related insomnia) caused by fear (e.g. before surgery). Benzodiazepines can alleviate anxiety at doses that do not necessarily cause excessive sedation and they are of particular value during short procedures or during operations under local anaesthesia (including dentistry). Amnesia reduces the likelihood of any unpleasant memories of the procedure . Benzodiazepines have no analgesic effect so an opioid analgesic may sometimes be required for pain.

Anxiolytics diminish tension, anxiety and panic, and may benefit anxious patients. However, their use is no substitute for sympathy and reassurance of the patient.

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