Antianxiety drugs

Presented By : HANIEH NAJAFI

Anxiety is a psychological and physiological state characterized by cognitive , somatic , emotional , and behavioral components . These components combine to create an unpleasant feeling that is typically associated with uneasiness, fear , or worry . Anxiety is a normal reaction to stress . When anxiety becomes excessive, it may fall under the classification of an anxiety disorder .

Anxiety can be accompanied by physical effects such as heart palpitations , fatigue , nausea , chest pain , shortness of breath , stomachaches , or headaches . Blood pressure and heart rate are increased, sweating is increased, blood flow to the major muscle groups is increased, and immune and digestive system functions are inhibited .

Antianxiety drugs are medicines that calm and relax people with excessive anxiety, nervousness, or tension, or for short-term control of social phobia disorder or specific phobia disorder. Antianxiety are used in the treatment of stress related anxiety. They may also be used for other purposes, such as treating transient insomnia and helping patients withdraw from other medications. Anti-anxiety drugs are highly effective and some begin to work in just 30 to 90 minutes.

If used for the treatment of insomnia, they are sedativehypnotic drugs; and if used for the therapy of anxiety, they are antianxiety agents. Most sedative-hypnotic agents have anxiolytic effect but not all antianxiety agents produce sedation. Thus, anxiety is likely a specific disorder not directly related to mechanisms Producing sedation.

Anxiety state Insomnia Epilepsy Muscle spasticity Induction of amnesia As preanesthetic medication Adjunct in alcohol withdrawal For differential psychiatric diagnosis

Benzodiazepines(BZDs) Chlordiazepoxide,diazepam, oxazepam Non-benzodiazepines Buspirone, -adrenergic blocker-propranolol, zolpidem, zaleplon, clonidine Antihistamines Antidepressents Antiepileptic drug (AEDs) Atypical antipsychotics

Typical antipsychotics (eg : thioridazine)

Barbiturates meprobamate

Benzodiazepines are the most commonly used antianxiety agents. They are neither analgesics nor anesthetics. This Drugs that became popular in the 1960s as an alternative to barbiturates for treating anxiety. Benzodiazepines can relieve anxiety within 30 to 90 minutes in many patients. Because these drugs may be habit-forming, they are usually only prescribed for short periods of time when a patient is highly anxious.

Greater dose margin between anxiolysis sedation

Higher LD50 :ED50 ratio Less tolerance and dependence Less abuse potential

Rapidly absorbed from GI tract Crosses blood-brain barrier Crosses placenta and enters breast milk Metabolized by liver Metabolites active as CNS depressant

Mechanism of Action Barbiturates and benzodiazepines act similarly to produce depression of central nervous system function and behavior. Both classes of drugs enhance the ability of the inhibitory neurotransmitter, gamma aminobutyric acid (GABA), to activate a type of receptors known as GABA-A receptors. These drugs increase the effectiveness of GABA by altering the receptor so that GABA can bind more easily, an effect known as allosteric regulation. Activation of the GABA-A receptor opens an ion channel, allowing negatively charged chloride ions to enter the cell, producing an inhibition of neuronal activity.

BZDs increase the efficiency of GABA at GABA a reseptors via allosteric modulation. So do barbiturate and alcohol Barbiturate and alcohol can open the chloride channel independent of GABA-----BZDs cant.

Anxiolytic Sedative hypnotic Anticonvulsant Muscle relaxant

Most BZDs are metabolized by hepatic microsomal enzymes. Lorazepam and oxazepam are metabolized only by glucuronidation ,which is less affected bye aging and liver disease. They are the BZDs of choice in elderly or cirrhotic patients.

A history of alcohol or other sabstance abuse is relative contraindication. Warn patients about potential sedation Instruct patients to take BZD on an empty stomach and without antacids. Start low dose

If given IV ,BZDs should be given slowly (over 1-2 min ) only if ready to deal with respiratory arrest.

Antacids and food interfere with absorption. After a single dose ,BZDs lose effect by distribution more rapidly than by elimination. With repeated dosing , distribution is saturated and elimination half-life determines drug behavior.

Sedation sleepiness; depression , lightheadedness; Impairment of memory other cognitive functions motor function Disinhibition Depression

Take as directed Avoid alcohol Avoid caffeine Contraindicated in pregnancy Contraindicated in lactation Caution against driving and machinery Do not stop drug abruptly Report sleep pattern changes Menstrual irregularities

Increased CNS depression alcohol other anti-anxiety / sedative-hypnotic drug Increased BZD levels cimetidine nefazodone Decreased BZD levels carbamazepine Benzodiazepines may increase blood levels of digoxin, and reduce the efficacy of levodopa.

Confusion Muscle cramps Blurred vision Diarrhea Decreased appetite Weight loss

Hallucinations Other psychotic symptoms Delirium Seizures

antianxiety: treatment of prolonged anxiety, long duration of action, no tolerance to antianxiety effects anticonvulsant: limited use for prolonged treatment as tolerance develops to anticonvulsant effects. muscle relaxant sedative hypnotic

Diazepam anticonvulsant amnesic agent alcohol withdrawal status epilepticus

antianxiety effect without marked sedation or euphoria 5-HT1A receptor antagonist at postsynaptic sites and agonist at 5-HT1A presynaptic receptors no direct effect on GABA system little interaction with depressants except alcohol not anticonvulsant not a muscle relaxant no effect on cognitive function not a sedative-hypnotic no cross tolerance with antianxiety drugs no physical dependence and little abuse liability

Buspirone is metabolized by the liver and excreted by the kidney, and should be used with care in patients with hepatic or renal disease. The drug is classified as schedule B during pregnancy, but should not be taken during breastfeeding. Its use in children under the age of 18 years has not been studied.
4-6 week delay in therapeutic effect

Buspirone has a low incidence of side effects. Dizziness and drowsiness are the most commonly reported adverse effects. Rarely, heart problems, including congestive heart failure and myocardial infarction, have been reported.

Buspirone levels will be increased by concomitant use of erythromycin, itraconazole, and nefazadone. Use of buspirone with MAOIs should be avoided.

-Adrenergic blocker

propranolol reduces autonomic symptoms of anxiety Antidepressants imipramine in panic disorder. The dose is higher than used in the treatment of depression MAO inhibitors in agoraphobia, panic disorder, social phobia, post-traumatic stress selective serotonin reuptake inhibitors (SSRIS) and TCAS such as clomipramine in obsessive compulsive disorder

Desired onset of action. Desired duration of action. Desired period of treatment. Presence or absence of pain. Personality of patient including age. Risk of drug interactions.

Pre-surgical dosing of midazolam varies with the route of administration, the age and physical condition of the patient, and the other drugs to be used. For patients under the age of 60, who have not received narcotic analgesics, a dose of 23 mg is normally adequate. The usual dose of lorazepam is up to 4 mg, administered by intramuscular injection at least two hours prior to surgery. If the drug is given intravenously, a dose of up to 2 mg may be given 1520 minutes before surgery. Benzodiazepines should be administered 3060 minutes before exposure to the anticipated stress. Dosage should be individualized to minimize sedation. The normal dose of alprazolam is 0.250.5 mg. The usual dose of lorazepam is 23 mg. Buspirone is initially dosed at 5 mg three times a day.

Precautions and warnings apply to the use of antianxiety agents for use over long periods of time. Benzodiazepines should not be used in patients with psychosis, acute narrow-angle glaucoma, or liver disease. The drugs can act as respiratory depressants and should be avoided in patients with respiratory conditions. Because benzodiazepines are sedatives, they should be avoided in patients who must remain alert. These drugs should not be used during the second and third trimester of pregnancy. They should not be taken while breastfeeding.

Rang and Dales pharmacology .sixth edition Essntials of mecical pharmacology KD Tripathi http://www.esnips.com

http://psyweb.com/Glossary/antiax.jsp
http://www.myoptumhealth.com http://www.healthcentral.com http://en.wikipedia.org http://www.medicine.uiowa.edu

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