ANXIOLYTIC AND HYPNOTIC

DRUGS
BY
MURTALA A. AKANJI
ANXIETY DISORDERS

 A mental health disorder characterized by feelings of

worry, anxiety or fear that are strong enough to
interfere with one's daily activities.

 The main symptom of anxiety disorders is excessive

fear or worry. Anxiety disorders can also make it
hard to breathe, sleep, stay still, and concentrate.

 Specific symptoms depend on the type of anxiety

disorder you have. Common symptoms are: Panic,
fear, and uneasiness
ANXIETY DISORDERS

 Anxiety disorders are the most prevalent

class of lifetime mental disorders.
 Anxiety oftentimes co-morbidly exists with
depression.
 The high level of co-morbidity may be
because of overlapping symptoms between
depressive and anxiety disorders.
NEUROCHEMICAL BASIS OF ANXIETY
DISORDERS
 Decreased level of GABA system,

 Altered level of serotonergic and

dopaminergic systems and

 Genetic influence have all been suggested

and reported as possible pathophysiology of
anxiety.
TYPES OF ANXIETY DISORDERS

 Agoraphobia is a type of anxiety disorder in

which you fear and often avoid places or
situations that might cause you to panic and
make you feel trapped, helpless or
embarrassed.
 Anxiety disorder due to a medical
condition includes symptoms of intense
anxiety or panic that are directly caused by a
physical health problem.
TYPES OF ANXIETY DISORDERS

 Generalized anxiety disorder includes

persistent and excessive anxiety and worry
about activities or events — even ordinary,
routine issues. The worry is out of proportion
to the actual circumstance, is difficult to
control and affects how you feel physically. It
often occurs along with other anxiety
disorders or depression.
TYPES OF ANXIETY DISORDERS

 Panic disorder involves repeated episodes of

sudden feelings of intense anxiety and fear or
terror that reach a peak within minutes (panic
attacks).
 You may have feelings of impending doom,
shortness of breath, chest pain, or a rapid,
fluttering or pounding heart (heart palpitations).
 These panic attacks may lead to worrying about
them happening again or avoiding situations in
which they've occurred.
TYPES OF ANXIETY DISORDERS

 Selective mutism is a consistent failure of

children to speak in certain situations, such as
school, even when they can speak in other
situations, such as at home with close family
members.
 This can interfere with school, work and
social functioning.
TYPES OF ANXIETY DISORDERS

 Separation anxiety disorder is a childhood

disorder characterized by anxiety that's excessive
for the child's developmental level and related to
separation from parents or others who have
parental roles.
 Social anxiety disorder (social phobia) involves
high levels of anxiety, fear and avoidance of social
situations due to feelings of embarrassment, self-
consciousness and concern about being judged or
viewed negatively by others.
TYPES OF ANXIETY DISORDERS

 Specific phobias are characterized by major

anxiety when you're exposed to a specific
object or situation and a desire to avoid it.
Phobias provoke panic attacks in some people.
 Substance-induced anxiety disorder is
characterized by symptoms of intense anxiety
or panic that are a direct result of misusing
drugs, taking medications, being exposed to a
toxic substance or withdrawal from drugs.
TYPES OF ANXIETY DISORDERS

 Obsessive compulsive disorders: Excessive

thoughts (obsessions) that lead to repetitive
behaviours (compulsions).

 Obsessive-compulsive disorder is
characterized by unreasonable thoughts and
fears (obsessions) that lead to compulsive
behaviours.
SYMPTOMS OF ANXIETY DISORDERS

 Common anxiety signs and symptoms include:

 Feeling nervous, restless or tense
 Having a sense of impending danger, panic or
doom
 Having an increased heart rate
 Breathing rapidly (hyperventilation)
 Sweating
 Trembling
 Feeling weak or tired
SYMPTOMS OF ANXIETY DISORDERS

 Trouble concentrating or thinking about

anything other than the present worry
 Having trouble sleeping
 Experiencing gastrointestinal (GI) problems
 Having difficulty controlling worry
 Having the urge to avoid things that trigger
anxiety
RISK FACTORS
 Trauma. Children who endured abuse or trauma or
witnessed traumatic events are at higher risk of developing
an anxiety disorder at some point in life. Adults who
experience a traumatic event also can develop anxiety
disorders.
 Stress due to an illness. Having a health condition or serious
illness can cause significant worry about issues such as your
treatment and your future.
 Stress buildup. A big event or a buildup of smaller stressful
life situations may trigger excessive anxiety — for example, a
death in the family, work stress or ongoing worry about
finances.
RISK FACTORS
 Personality. People with certain personality types
are more prone to anxiety disorders than others
are.
 Other mental health disorders. People with
other mental health disorders, such as depression,
often also have an anxiety disorder.
 Having blood relatives with an anxiety
disorder. Anxiety disorders can run in families.

 Drugs or alcohol. Drug or alcohol use or misuse or

withdrawal can cause or worsen anxiety.
COMPLICATIONS

 Having an anxiety disorder does more than

make you worry. It can also lead to, or worsen,
other mental and physical conditions, such as:
 Depression (which often occurs with an anxiety
disorder) or other mental health disorders
 Substance misuse
 Trouble sleeping (insomnia)
 Digestive or bowel problems
 Headaches and chronic pain
COMPLICATIONS

 Social isolation

 Problems functioning at school or work

 Poor quality of life

 Suicide
PREVENTION

 Get help early. Anxiety, like many other mental health

conditions, can be harder to treat if you wait.
 Stay active. Participate in activities that you enjoy and
that make you feel good about yourself. Enjoy social
interaction and caring relationships, which can lessen
your worries.
 Avoid alcohol or drug use. Alcohol and drug use can
cause or worsen anxiety. If you're addicted to any of
these substances, quitting can make you anxious. If you
can't quit on your own, see your doctor or find a support
group to help you.
TREATMENT OF ANXIETY
DISORDERS
 Not all anxiety disorders have to be treated
when symptoms are mild, transient, and
without associated impairment in social and
occupational function.
 However, treatment is indicated when a
patient shows marked distress or suffers from
complications resulting from the disorder (eg,
secondary depression, suicidal ideation, or
alcohol abuse).
TREATMENT OF ANXIETY
DISORDERS
 Anxiety disorders can be treated mostly on
an outpatient basis.

 Indications for hospitalization include

suicidality, unresponsiveness to standard
treatments, or relevant co-morbidity, eg,
with major depression, personality disorders,
or substance abuse.
TREATMENT OF ANXIETY
DISORDERS
 There are three basic treatment options:
 Psychological therapy : lifestyle changes
(increase sleep at hours at night, moderate
work, avoid alcohol, smoking, caffeine; limit
social medial activity, read inspirational
books. It also involves Counseling.
 Pharmacotherapy,
 Or a combination of both
TREATMENT OF ANXIETY
DISORDERS
 However, life threatening side effects,
remission, treatment resistance, incidences
of withdrawal symptoms, costs, preference
of the patient and interaction with other
drugs have hugely characterized the use of
these drugs.
PHARMACOTHERAPY: ANXIOLYTICS

 Anxiolytics are psychoactive drugs which

reduce anxiety and exert a calming effect
with little or no mental function.

 Hypnotics are drugs that produce drowsiness

and encourage the onset and maintenance
of sleep.
CLASSIFICATIONS

 Benzodiazepines: This is the most important

group. It is used as both anxiolytic and
hypnotics.
 Selective serotonin reuptake inhibitors
(SSRIs) eg Citalopram, Escitalopram,
Fluoxetine, Paroxetine, Sertraline (Zoloft)
 Selective serotonin norepinephrine
reuptake (SNRIs) eg Desvenlafaxine,
venlafaxine, duloxetine
CLASSIFICATIONS

 Tricyclic antidepressants eg Amitriptyline,

Amoxapine, Desipramine, Doxepin, Imipramine,
Nortriptyline, Protriptyline, Trimipramine.
 Buspirone: This is a serotonin receptor agonist
that produces anxiolytic effect but without
appreciable sedative activity.
 Zolpidem: This hypnotic acts similar to BZPs,
although chemically distinct, but lacks
appreciable anxiolytic activity.
CLASSIFICATIONS

 Pregabalin : Pregabalin is a structural analog of

the inhibitory neurotransmitter gamma amino
butyric acid (GABA) but is thought to exert its
anxiolytic effects through calcium
modulation/inhibition. It is used to treat epilepsy
and anxiety.
 Antipsychotics: There is currently only one
antipsychotic, trifluoperazine, a first-generation
antipsychotic (FGA), which is FDA-approved for
the treatment of anxiety. 
CLASSIFICATIONS

 Antihistamines: Hydroxyzine &

diphenhydramine are the most studied
antihistamine for anxiety and the only
antihistamine which is FDA-approved for use
in anxiety).
 Beta-blockers: Effective in treating anxiety. It
acts by blocking sympathetic response rather
than on any central effects. It is used to
manage stage fright. Eg propranolol
CLASSIFICATIONS

 Barbiturates: These are now largely obsolete

or outdated. It is now replaced with BZPs.
Their use is now reduced to anesthesia.
 Non-barbiturates: They are no longer
recommended eg Chloral hydrate, alcohol.
BENZODIAZEPINES

 Short acting: Midazolam, Triazolam

 Intermediate acting: Lorazepam (i.e safest in
liver disease), Oxazepam, Temazepam,
Alprazolam.
 Long acting: Diazepam
MECHANISM OF ACTION

 The mechanism of action of benzodiazepines

in the central nervous system is by potentiation
of the inhibitory effect of γ-aminobutyric acid
(GABAA)on neuronal transmission.

 They facilitate the opening and activation of

GABA linked chloride ion thereby permitting
the influx of chloride ions in the cell membrane.
This results in repolarization of cell membrane.
MECHANISM OF ACTION

 All benzodiazepines have hypnotic,

anticonvulsant, muscle relaxant, amnesic,
and anxiolytic properties.
PHARMACOLOGICAL ACTIONS

 Reduction of anxiety and aggression

 Sedation and induction of sleep

 Muscle relaxant actions

 Anticonvulsant activity

 Anterograde amnesia:
PHARMACOLOGICAL ACTIONS

 Reduction of anxiety and aggression: BZPs

reduce anxiety and aggression.
 They do not have antidepressant activity.
 Short & ultra short acting agents produce
paradoxical aggression which is probably a
manifestation of BZPs withdrawal symptoms.
 Paradoxical effects may appear after chronic
use of benzodiazepines especially those
whose action wears off rapidly.
PHARMACOLOGICAL ACTIONS

 Sedation and induction of sleep: They

decrease time taken to get to sleep and
increase the total duration of sleep.

 Muscle relaxant actions: They reduce muscle

tone by a central action that is independent
of their sedative affect. They inhibit
polysynaptic pathways in the spinal cord.
PHARMACOLOGICAL ACTIONS

 Anticonvulsant action: All BZPs are highly

effective against GABA mediated convulsion.

 Chemical convulsants such as picrotoxin,

bicuculline, leptazole amphenazole etc cause
convulsion by antagonising GABA.

 BZPs are not effective against strychnine-induced

convulsion (glycine antagonist) in experimental
animals.
PHARMACOLOGICAL ACTIONS

 Clearly, BZPs enhance the action of GABA

but not glycine
 Anterograde amnesia: BZPs obliterate
memory of events experienced while under
their influence.
 Minor surgical procedure can be performed
without leaving unpleasant memories.
PHARMACOKINETICS

 BZPs are absorbed from oral and parenteral routes.

 BZPs have extensive plasma binding capacity (80%-
98%).
 Resulting in a small 'free fraction' which can cross
the blood-brain barrier.

 All BZPs are metabolized by the liver.

 The drugs and its metabolites are excreted in urine

as glucoronides.
INDICATIONS

 Anxiety disorders
 Skeletal muscle spasm
 Seizures/convulsion
 Sleep disorders (insomnia)
 Alcohol withdrawal
 Agitation
 As anesthetic medication
UNWANTED EFFECTS

 These are divide into 3:

 Toxic effect (overdose)
 Side effects (Therapeutic dose)
 Tolerance and dependence
Toxic effect (overdose)

 Toxic effects: Toxic effect is due to overdose.

In overdose, BZPs cause prolonged sleep
without serious depression of respiratory or
cardiovascular function.

 Flumazenil, a BZPs antagonist can be used to

manage its overdose.
Side effects (Therapeutic dose)

 These include drowsiness, confusion,

amnesia, impaired coordination, cognitive
impairment, impairment of sexual function.
Tolerance and dependence

 This may result in cases of abuse. BZPs have

tendencies to induce tolerance and
dependence following prolong use.
BENZODIAZEPINES ANTAGONISTS

 The best known compound is Flumazenil. It is

GABAA receptor antagonist. It is used to reverse the
effect of BZPs overdose. It acts quickly and
effectively when given by injection but its action
lasts for only about 2hours.
SIDE EFFECTS OF FLUMAZENIL

Common side effects include:
 pain or irritation where the medicine was injected,
 agitation or tremors (shaking),
 flushing (warmth, redness, or tingly feeling under your skin),
 dizziness,
 sweating or shivering,
 headache,
 blurred vision, or.
 ringing in your ears.