Anti-Anxiety Drugs

ANTIANXIETY DRUGS

Anxiety

• It is emotional state, unpleasant in nature, associated with uneasiness, discomfort and

fear about some defined or undefined future threat.

• Some degree anxiety is a part of normal life.

• Treatment is needed when it is disproportionate to situation and excessive

• It is the subjectively unpleasant feelings of dread over something unlikely to happen,

such as the feeling of imminent death

• It is often accompanied by muscular tension, restlessness, fatigue, and problems in

concentration. Anxiety can be appropriate, but when it is too much and continues too
long, the individual may suffer from an anxiety disorder

• Common physical symptoms of anxiety include: Sweating, Stomach upset or

dizziness, Frequent urination or diarrhea, Shortness of breath, Tremors and twitches,
Muscle tension , Headaches, Fatigue, Insomnia

Type of disorders

• If constant worries and fears distract from day-to-day activities or if troubled by a

persistent feeling that something bad is going to happen, be suffering from
generalized anxiety disorder (GAD).

• Panic disorder is characterized by repeated, unexpected panic attacks, as well as fear

of experiencing another episode

• Obsessive-compulsive disorder (OCD) is characterized by unwanted thoughts or

behaviors that seem impossible to stop or control.

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• A phobia is an unrealistic or exaggerated fear of a specific object, activity, or situation

that in reality presents little to no danger. Common phobias include fear of animals
such as snakes and spiders, fear of flying, and fear of heights

• Fear of being seen negatively by others and humiliated in public, you may have social
anxiety disorder also known as social phobia.

• Post-traumatic stress disorder (PTSD) is an extreme anxiety disorder that can occur
in the aftermath of a traumatic or life-threatening event.

Antianxiety Drugs

• These drugs are mild CNS depressants which are aimed to control the symptoms of
anxiety, without interfering with normal or mental or physical functions.

• They are more closely resemble sedative hypnotics

• They do not control thought disorder of schizophrenia

• Do not produce extrapyramidal side effects

• They have anticonvulsant activity

• They produce physical dependence and carry abuse liability

Classification

1. Benzodiazepines – Diazepam, Chlordiazepoxide, Oxazepam, lorazepam, alprazolam,

chlonazepam

2. Azapirones- Buspirone, Gepirone , ispapirone

3. Sedative antihistaminic-Hydroxyzine

4. Beta blockers- Propranolol

Benzodiazepines

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• The overall action of all BZD is similar but differences in time course of action but
exert relatively selective anxiolytics, hypnotic muscle relaxant and anticonvulsant
effect

• when anesthetic dose of diazepam is administered i.v. some degree of awareness is

maintained

• The antianxiey action of BZD is probable not dependent on sedative property

• They increase onset of sleep, reduce intermittent awakening and increase total sleep
time

• They tend to shorten REM phase but more REM cycles may occur so that overall effect
on REM sleep is less marked

• Night terror and body movements during sleep are reduced and feeling of refreshing
sleep

• Some degree of tolerance is developed on repeated use.

Mechanism of Action

• BZD produce centrally mediated skeletal muscle relaxation without impairing

voluntary activity.

• Very high doses depress neuromuscular transmission, given Ip diazepam causes

analgesia.

• Decrease nocturnal gastric secretion and prevents ulcers.

• Site and mechanism

• BZD act on midbrain ascending reticular formation and on limbic system. Muscle
relaxation is produced.

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 Anti-Anxiety Drugs

• BZD act by enhancing presynaptic/post synaptic inhibition through a specific BZD

receptor which is a n integral part of the GABA-receptor Cl channel complex

• Benzodiazepines work by increasing the efficiency of a natural brain chemical, GABA,

to decrease the excitability of neurons

• This reduces the communication between neurons and, therefore, has a calming effect
on many of the functions of the brain

• The GABAA receptor is a protein complex located in the synapses of neurons. All
GABAA receptors contain an ion channel that conducts chloride ions across neuronal
cell membranes and two binding sites for the neurotransmitter gamma-aminobutyric
acid (GABA), while a subset of GABAA receptor complexes also contain a single
binding site for benzodiazepines

Pharmacokinetics

• Differences in pharmacokinetic amount BZDs as they differ in lipid solubility.

• Oral absorption of some is rapid while that of other is low.

• Absorption from i.m. site is irregular except for lorazepam

• Plasma protein binding also varies markedly

• Widely distributed in body

• Relatively short duration of action obtained with single dose of a drug

• Metabolized in liver by dealkylation and hydroxylation to many metabolites some of

which may be active

• BZD and their metabolites are secreted in urine as glucuronide conjugates.

• BZD cross placenta and secreted in milk.

Adverse Effect

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• BZD are relatively safe drugs

• Side effect of hypnotic doses are dizziness, vertigo, ataxia, disorientation, amnesia
prolongation of reaction time

• Impairment of psychomotor skill

• Hangover weakness, blurring of vision, dry mouth

• Tolerance to the sedative effects develops gradually but there is little tendency to
increase the dose

• Cross tolerance to alcohol and other CNS depressants occurs.

Interactions

• BZD synergies with alcohol and other CNS depressants leading to excessive
impairment

• Concurrent use with Sod. Valproate has provoked psychotic symptoms

• Cimetidine, Isoniazide and oral contraceptives also

Uses

• As hypnotic-in insomnia

• To reduce nocturnal awakenings, to provide anxiolytics effect, to shorten sleep

latency

• Chronic insomnia -alcoholic, diseases such s pain, COPD, . Measures like anabolic
exercise

• Short term insomnia-stress, illness

• Transient insomnia-overnight train, new place, unusual pattern of work, shift

workers, intercontinental travel-jetlag etc

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Other uses

• Anxiolytics

• Emergency control of status epileptics, tetanus

• Muscle relaxant

• Preanesthetic medication to cause sedation

• Alcohol withdrawal

• Electrical cardio version of arrhythmia, cardiac catheterization, endoscopies and

many minor procedure

• Along with analgesics, NSAIDs, spasmolytics, antiulcer

Buspirone

• It does not produce sedation or cognitive/functional impairment

• Does not interact with BZD receptor or modify GABAergic transmission

• Does not produce tolerance or physical dependence

• Does not suppress BZD or barbiturate withdrawal syndrome

• Has no muscle relaxant or anticonvulsant activity

• It relieves mild to moderate generalized anxiety but is ineffective in sever cases

• Effect develops slowly and last for 2 weeks

• It is rapidly absorbed undergoes first pass metabolism, one metabolite is active and
excretion occurs both in urine and feces, half life is 2-3.5 hrs

• Side effects are dizziness, nausea, headache, excitement

• May cause rise in BP but no CNS depression

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• Dose 5-15 mg

Hydroxyzine

• Due to its antagonistic effects on several receptor systems in the brain, hydroxyzine
is claimed to have strong anxiolytic and mild antiobsessive as well as antipsychotic
properties

• Because of its antihistamine effects it can also be used for the treatment of severe
cases of itching, hyperalgesia and motion sickness-induced nausea, it has also been
used in some cases to relieve the effects of opioid withdrawal

• Hydroxyzine has been used to potentiate the analgesia of opioids and to alleviate
some of their side effects, such as itching, nausea, and vomiting.

• Hydroxyzine is prescribed when the onset of an organic disease state manifests

through anxiety, as generalized anxiety disorder, or in other more serious cases as
psychoneurosis, and is therefore prescribed as a means of regulating normal function.

• Mechanism of action is as a potent H1 receptor inverse agonistUnlike many other first-

generation antihistamines, it has very low affinity for the mACh receptors

Contraindications

• Pregnancy-fetal abnormalities

• Hypersensitivity

• intravenous (IV) injection, as it has shown to cause hemolysis

• With antidepressant causing CNS effects

• long-term prescription of hydroxyzine can lead to tardive dyskinesia (movement

disorder)

Adverse effects

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• deep sleep, incoordination, sedation, calmness, and dizziness have been reported in
children and adults, as well as others such as hypotension tinnitus, and headaches

• hallucinations or confusion have been observed in rare cases

Uses

• Antiallergic

• Antianxiety

• Antipsychotic

• Itching

• Hyperalgesia

• Motion sickness

• Opiod withdrawal

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