Anxiolytic2003.lec.new Microsoft Office Power Point Presentation

ANXIOLYTIC AND HYPNOTIC DRUGS .

anxiolytic agents An anxiolytic or antianxiety agent is a drug prescribed for the treatment of symptoms of anxiety.

Anxiety disorders as recognised clinically include • •

• • •  

generalised anxiety disorder (excessive anxiety lacking any clear reason) 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 (recall of past stressful experiences) obsessive compulsive disorder (e.g. fear of contamination).

CLASSIFICATION OF ANXIOLYTIC AND HYPNOTIC DRUGS

• • • • • • • •

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

Benzodiazepines Act by binding to GABAA receptor, thus enhancing the inhibitory effect of GABA. Anxiolytic effects are mediated by GABAA receptors containing the α2 subunit, while sedation occurs through those with the α1 subunit.

Effects of 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}

Effects of Benzodiazepines • 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.

• muscle relaxation and loss of motor coordination ( clonazepam) • suppression of convulsions (antiepileptic effect) (e.g. Clonazepam ,

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

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

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

BUSPIRONE   Buspirone is a partial agonist at 5HT1A receptors is used to treat various anxiety disorders. It also binds to dopamine receptors (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.

side effects of Buspirone • 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

Barbiturates Barbiturates are Non-selective central nervous system depressants (Act partly by enhancing action of GABA)that produce effects ranging from sedation and reduction of anxiety to unconsciousness and death from respiratory and cardiovascular failure-therefore dangerous in overdose

Barbiturates use as sedative/hypnotic agents is no longer recommended. Barbiturates that remain in clinical use include: • phenobarbital , to treat epilepsy • thiopental, used as an intravenous anaesthetic agent .

Barbiturates 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.

Sedative antihistamines 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.

Antidepressants 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.

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.

zolpidem • Zolpidem It is a short-acting nonbenzodiazepine hypnotic that potentiates inhibitory neurotransmitter GABA, by binding to GABAA receptors. It works quickly (usually within 15 minutes) • It was recommended that zolpidem be used for short periods of time using the lowest effective dose for improving sleep quality.

Side effects of zolpidem • zolpidem is associated with drug tolerance, drug dependence, rebound insomnia and CNS related adverse effects. • amnesia • Hallucinations • motor coordination

Drug interaction with anxiolytic or hypnotic drugs • Cimetidine metabolism of benzodiazepines inhibited by cimetidine • Rifampicin metabolism of benzodiazepines possibly accelerated by rifampicin • Theophylline effects of benzodiazepines possibly reduced by theophylline • enhanced hypotensive effect when anxiolytics and hypnotics given with

Drug interaction with anxiolytic or hypnotic drugs • Anaesthetics, General /increased sedative effect when anxiolytics and hypnotics given with general anaesthetics • Digoxin\ alprazolam increases plasma concentration of digoxin (increased risk of toxicity) • Valproate \clobazam possibly increases plasma concentration of valproate • Omeprazole /metabolism of diazepam possibly inhibited by omeprazole

Drug interaction with anxiolytic or hypnotic drugs barbiturates accelerate the metabolism of some drugs including • Chloramphenicol • Corticosteroids • Coumarins • Digitoxin • Doxycycline

Drug interaction with anxiolytic or hypnotic drugs barbiturates accelerate the metabolism of some drugs including: • • • •

Metronidazole Progestogens &oestrogenes Propranolol Clonazepam

• Rifampicin  

Drug interaction with anxiolytic or hypnotic drugs • Folates plasma concentration of phenobarbital possibly reduced by folates • Valproate plasma concentration of phenobarbital increased by valproate (also plasma concentration of valproate reduced) • Alcohol increased sedative effect when barbiturates given with alcohol

sedatives and dental procedures • The benefits of using sedatives befor dental procedures involves performing dental treatment on a patient in an environment that’s stress- and anxiety-free

sedatives and dental procedures…cont.

• 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.

sedatives and dental procedures…cont.

• 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 ...

sedatives and dental procedures…cont.

• In children anxiolytic treatment should be used only to relieve acute anxiety (and related insomnia) caused by fear (e.g. before surgery).