ANTI-ANXIETY DRUGS

Unlike the antipsychotic drugs, these drugs are used to treat anxiety or neurosis. They are not used
to treatment of psychosis. These drugs, therefore, are known as antianxiety drugs or minor tranquilizers.
They are also known as anxiolytics.
There ae two types of anxiety – primary and secondary. Primary anxiety is not caused by a medical
condition or by drug use; secondary anxiety is related to selected drug use or medical or psychiatric
disorders. The anxiolytics are not usually given for secondary anxiety unless the medical problem is
untreatable, severe, and causing disability. In this case, the drug could be given for a short period to
alleviate any acute anxiety attacks. Long term use of anxiolytics is discouraged because tolerance
develops within weeks or months, depending on the drug. Drug tolerance can occur in less than 2-3
months for meprobamate and phenobarbital.
Some symptoms of a severe or acute attack of anxiety include dyspnea (difficulty of breathing),
choking sensation, chest pain, heart palpitations, dizziness, faintness, sweating, trembling and shaking,
and fear of losing control. Nonpharmacologic measures might include using relaxation technique,
psychotherapy, or support groups.
▪ Antianxiety drugs have sedative and hypnotic properties and possess some central skeletal muscle
relaxant activity.
▪ They have a habituation and physical dependence lability.
▪ Generally, the antianxiety drugs have a lower incidence of adverse effects than the antipsychotic
drugs.

MEPROBAMATE
▪ A propyl alcohol derivative (propanediol derivatives). At one time, Meprobamate was widely used
antianxiety drugs; however, it has largely been replaced by the benzodiazepines.
▪ Well absorbed from the GIT, and its peak, serum concentration is reached in about 1 ½ hours.
Metabolism occurs in the liver, and the inactive metabolites are excreted via the kidney.
▪ It depresses the CNS in a fashion like that of the barbiturates, especially phenobarbital, but
meprobamate is shorter acting.
▪ It can promote sleep, but, like phenobarbital, it decreases the REM phase.
▪ The skeletal muscle relaxant activity demonstrated by meprobamate is probably a combination of its
sedative effect and specific central muscle relaxant activity
▪ Adverse effects: drowsiness, often seen with full therapeutic doses. Blood dyscrasias, including
purpura, but these are rare. Habituation and physical dependence with long-term administration
(withdrawal from drug therapy should, therefore, be gradual).

BENZODIAZEPINES

These drugs are considered the drug of choice in the treatment of anxiety, partly because of their high
therapeutic index. The first benzodiazepines developed was Chlordiazepoxide. Others include Diazepam,
Clonazepam, Lorazepam, Oxazepam, Clorazepate, Halazepam, Prazepam, Alprazolam, the anesthetic
Midazolam, and the sedative-hypnotics Flurazepam, Triazolam and Temazepam.

Pharmacokinetics
▪ Diazepam, Flurazepam, and Clorazepate are relatively rapidly absorbed, while Oxazepam, Prazepam,
and Temazepam are more slowly absorbed. Triazolam, Midazolam, Alprazolam, and Clonazepam have
an intermediate onset of action.
▪ All benzodiazepines are soluble in lipids and cross the blood-brain barrier. Plasma levels reflect brain
levels. Benzodiazepines are highly protein bound in the plasma.
▪ Benzodiazepines are metabolized primarily by microsomal oxidation and glucuronide conjugation.
▪ Diazepam is rapidly absorbed from GIT, reaching peak serum concentration in 1 hour. There is a
secondary peak at 6 to 12 hours after an oral dose, presumably due to enterohepatic circulation. The
distribution half-life is 2.5 hours. While elimination half-life is 1.5 days.
▪ Benzodiazepines are excreted via kidney as glucuronide.

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 Pharmacokinetics of Benzodiazepines
Gastrointestinal Elimination
Drugs Duration of action
absorption rate Half-life
Midazolam Short Intermediate 2.5 hours
Triazolam Short Intermediate 3 hours
Alprazolam Intermediate Intermediate 14 hours
Lorazepam Intermediate Intermediate 15 hours
Oxazepam Intermediate Slow 10 hours
Temazepam Intermediate Slow 15 hours
Chlordiazepoxide Long Intermediate 2-4 days
Clonazepam Long Intermediate 2-3 days
Clorazepate Long Rapid 2-4 days
Diazepam Long Rapid 2-4 days
Flurazepam Long Intermediate 2-3 days
Halazepam Long Slow 2-4 days
Prazepam Long Slow 2-4 days

Pharmacological effects:

a. CNS effects
▪ Benzodiazepines potentiate the binding of GABA to receptors. The benzodiazepine receptor that
helps to potentiate the GABA binding is yet unidentified.
▪ Because they increase the seizure threshold, benzodiazepines are useful as anticonvulsants,
especially Diazepam in status epilepticus. They prevent convulsions caused by strychnine or
pentylenetetrazole.
▪ Benzodiazepines are also effective hypnotics, and Flurazepam, Temazepam, and Triazolam are
promoted as such

b. At therapeutic the benzodiazepines have minimal effects on the cardiovascular system.

Therapeutic uses
▪ Treatment of anxiety.
▪ Anesthetic premedication
▪ Use as amnestic, such as cardioversion.
▪ Use as sedative-hypnotics
▪ Management of seizures disorders
▪ Treatment of alcohol withdrawal syndromes
▪ Use as central skeletal muscle relaxants
▪ Treatment of night terrors
▪ Panic attacks (Alprazolam only; physical dependence can occur)

Adverse effects
a. Adverse effects are partially age- and dose-dependent.
▪ Ataxia, drowsiness, and sedation (additive depressant effects are seen when benzodiazepines are
combined with other drugs possessing CNS depressant activity)
▪ Paradoxically increased anxiety, including psychoses, especially with high doses
▪ Reversible confusion in the elderly
▪ Menstrual irregularities, including anovulation.
b. Overdoses, although frequently, are seldom fatal. Treatment is supportive. Owing to high plasma-
protein-binding characteristics of benzodiazepines, the benefit from dialysis is limited.
c. Withdrawal symptoms are influenza-like muscle aches and nausea. These symptoms are rare, except
in the case of Alprazolam.
d. Drugs specific effects include:
▪ Triazolam may cause rebound insomnia
▪ Lorazepam and Triazolam have a greater risk of inducing anterograde amnesia
▪ Flurazepam at higher dose (30mg) is associated with daytime residual sedation.

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BUPSPIRONE
▪ An anti-anxiety drugs that is not chemically or pharmacologically related to the benzodiazepines,
barbiturates or other sedative-anxiolytic drugs.
▪ Although the exact mechanism of action is unknown, buspirone can bind to dopamine and serotonin
receptors. It does not bind to benzodiazepine receptors and does not have muscle-relaxant,
anticonvulsant or hypnotic activity.

Pharmacokinetics
▪ Buspirone is rapidly and completely absorbed from the gastrointestinal tract.
▪ The drug undergoes an extensive first-pass effect. One hydroxylated metabolite is pharmacologically
active.
▪ A highly protein-bound
▪ It is partially excreted in the urine and has elimination half-life of 4.8 hours.

Buspirone is used for the short-term treatment of generalized anxiety. It may require 1-2 weeks for a
therapeutic effect to take place.

Untoward effects include restlessness, and dysphoria with high doses. Buspirone is remarkably free of
other adverse effects. It has little potential for abuse.