CNS DEPRESSANTS

Anti-Anxiety Agents
and Sedative-Hypnotics

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• A sedative drug decreases activity, moderates
excitement, and calms the recipient.

• B. A hypnotic drug produces drowsiness and

facilitates the onset and maintenance of a state of
sleep that resembles natural sleep, and from
which the patient can be easily aroused.

• C. An anxiolytic drug reduces anxiety.

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• Sedative-hypnotics are drugs which depress or
slow down the body's functions. Often these
drugs are referred to as tranquilizers and
sleeping pills or sometimes just as sedatives.

• They depress behavior, moderate excitement,

induce calmness, and may produce drowsiness
or even loss of consciousness. The sedative-
hypnotics are used clinically as antianxiety
agents, muscle relaxants, sleep inducers,
antiepileptics, and as preanesthetic medications.
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• Barbiturates and benzodiazepines are the
two major categories of sedative-hypnotics

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 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
neurotransmitter, gamma aminobutyric acid
(GABA), to activate a type of receptors known as
GABA-A receptors.

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• 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.

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BENZODIAZEPINES
ANXIOLYTICS HYPNOTICS

• DIAZEPAM • FLURAZEPAM
• ALPRAZOLAM • TEMAZEPAM
• LORAZEPAM • QUAZEPAM
• CLONAZEPAM • MIDAZOLAM
• ESTAZOLAM
• TRIAZOLAM

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 OTHER ANXIOLYTIC DRUGS
• BUSPIRONE

• HYDROXYZINE

• ZOLPIDEM

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BARBITURATES NON BARBITURATE
SEDATIVES

• PHENOBARBITAL • ANTIHISTAMINES
• PENTOBARBITAL • CHLORAL HYDRATE
• SECOBARBITAL • ETHANOL
• THIOPENTAL

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Anxiolytics and Sedative-Hypnotics
STAGES OF CNS DEPRESSION.

• With increasing dosage: 

• Calming or drowsiness {sedation}
• Sleep {pharmacological hypnosis}
• Unconsciousness
• Surgical anesthesia
• Coma
• Fatal respiratory/cardiovascular depression

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Benzodiazepines
• DIAZEPAM
• ALPRAZOLAM
• LORAZEPAM
• CLONAZEPAM

• FLURAZEPAM
• TEMAZEPAM
• QUAZEPAM
• MIDAZOLAM
• ESTAZOLAM

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Mechanism of action
• GABA RECEPTORS
• INCREASED ACTIVITY
• OPENS CHLORIDE CHANNELS
• CELL – HYPERPOLARIZED.
• ACTION POTENTIALS – DECREASED.
• BENZODIAZEPINE BINDS TO ITS RECEPTORS
• POTENTIATES GABA ACTIVITY.

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 ACTIONS
Central Nervous System
• ANXIOLYTIC
• HIGHER DOSES – HYPNOTIC, STUPOR
• ANTI – CONVULSANT
• RELAXATION OF SKELETAL MUSCLES

DOES NOT PRODUCE:

• ANALGESIA
• ANAESTHESIA

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• BZs decrease sleep latency, diminish the number
of awakenings, and increase the duration of
sleep.
• Triazolam may be a particularly good choice

• Muscle relaxation without interfering with normal

locomotor function
• Clonazepam especially is able to cause muscle
relaxation without significant sedation.

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• I.V. diazepam used for status epilepticus, but
BZs not that useful in chronic therapy of
epilepsy.

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Respiratory System
• PHARMACOLOGICAL DOSES :
---- NOT SIGNIFICANT.
• HIGH DOSES -- RESP. DEPRESSION

CVS :
• USUALLY VERY LESS
IN PREANAESTHETICS :
• BP – decreased
• HR – may be increased
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 CLINICAL USES
• ANXIETY DISORDERS.
• NOT FOR EVERYDAY STRESS
• TREATMENT PLAN
• Diazepam – long acting – for anxiety
• Alprazolam – panic disorders..

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 CLINICAL USES
• MUSCLE RELAXATION

CONDITIONS such as :
• SPASTICITY.
• CEREBRAL PALSY
• MULTIPLE SCLEROSIS

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• ANTI CONVULSANT
DIAZEPAM
• DOC – STATUS EPILEPTICUS.
• CHRONIC Rx: CLONAZEPAM

• ALCOHOL WITHDRAWAL SYMPTOMS.

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 SLEEP DISORDERS
• FLURAZEPAM : LONG ACTING
• DURATION : INCREASED
• REBOUND INSOMNIA : LESS
• HALF LIFE – LONG (85 hours)

• SE: DAY TIME SEDATION

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 SLEEP DISORDERS
• TEMAZEPAM : INTERMEDIATE ACTING
• WAKENING FREQUENCY – DECREASED.

• TRIAZOLAM: SHORT ACTING

• SLEEP – INDUCTION GOOD.
• REBOUND INSOMNIA – HIGH.

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 ADVERSE EFFECTS
• DROWSINESS, CONFUSION
• ATAXIA
• AMNESIA

• DEPENDENCE : PSYCHOLOGICAL,
PHYSICAL
WITHDRAWAL :
• ANXIETY, TENSION,CONFUSION,
INSOMNIA
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• They can cause both physical and psychological
dependence. Regular use over a long period of
time may result in tolerance, which means people
have to take larger and larger doses to get the
same effects.

• When regular users stop using large doses of

these drugs suddenly, they may develop physical
withdrawal symptoms ranging from restlessness,
insomnia and anxiety, to convulsions and death.
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 PRECAUTIONS
• LIVER FAILURE.
• Drugs that can be given in liver diseases include
Oxazepam, Timazepam, Lorazepam. These drugs are not
metabolized in liver. ( remember the first letters OTL –
Outside The Liver)
• # OTHER CNS DEPRESSANTS.
• SUICIDE SUCCESS – LESS
• UNLESS TAKEN WITH OTHER CENTRAL
DEPRESSANTS.
FOR BENZODIAZEPINE POISONING –
• DOC : FLUMAZENIL 26
Benzodiazepine antagonist
FLUMAZENIL
• GABA receptor antagonist
• Reverses the effect of benzodiazepines..
• I.V. route.
SE:
• Nausea, vomiting, agitation and dizziness.

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 BARBITURATES
MECH :
• INHIBITION OF RAS
• POLYSYNAPTIC TRANSMISSION IS
INHIBITED
• SODIUM AND POTASSIUM CHANNELS
• PROLONG : GABA ACTIVITY.

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• As a class, the various barbiturates are remarkably
similar;
• all are lipid soluble.
• Once the barbiturate reaches the bloodstream, it is
distributed throughout the body and will affect all body
tissues.
• Within the brain, barbiturates have the greatest impact
on awareness (the RAS - reticular activating system)
and respiration (medulla oblongata).
• Depending on dose, barbiturates act as either a sedative
or as a hypnotic
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 ACTIONS
CNS :
• LOW DOSE : EXCITEMENT IS REDUCED
• HIGH – HYPNOSIS- ANAESTHESIA- COMA –
DEATH

• NO ANALGESIC ACTION.

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CVS :
• LOW DOSES : MINIMUM
• POISONING : MYOCARDIAL DEPRESSION

• RESP. SYSTEM: DEPRESSION

• LIVER : INDUCES ENZYME P 450

• Barbiturates induce hepatic drug-metabolizing
enzymes and can decrease the effectiveness of
drugs metabolized by the liver, including oral
contraceptives.
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DRUGS
• PHENOBARBITAL – LONG ACTING
• PENTOBARBITAL
• SECOBARBITAL
• THIOPENTAL – ULTRA SHORT ACTING
( 20 MIN)

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USES
• ANAESTHESIA

• ANTI CONVULSANT
GRAND MAL
ECLAMPSIA
STATUS EPILEPTICUS.

• ANXIETY.

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ADVERSE EFFECTS
• CNS : HANG OVER

• METABOLISED IN LIVER
• CI : ACUTE INTERMITTENT PORPHYRIA

• DEPENDENCE:
• SEVERE: MAY CAUSE DEATH

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• Taking barbiturates with other CNS depressants,
e.g. alcohol, tranquillizers, narcotics, or
antihistamines, can be dangerous, even lethal
(ARF).

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ADVANTAGES OF BENZODIAZEPINES
Over BARBITURATES

BENZODIAZEPINES show
• TOLERANCE - LESS
• DEPENDENCE - LESS
• DRUG TOXICITY LESS
• SUICIDAL RISK LESS

• BARBITURATES – NOT FOR ANXIETY

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 OTHER ANXIOLYTICS - BUSPIRONE

• Site of action: 5-HT1A receptor subtype.

• No anticonvulsant activity.
• No interaction with benzodiazepine binding sites
• No influence on interaction of GABA with the GABA receptor.
• Not effective in management of severe anxiety/panic
disorder.
• No cross-tolerance with other sedative-hypnotic drugs
• No muscle relaxant properties.
• Minimal adverse effects
• USED FOR GAD Generalized Anxiety Disorders & IN DRUG
ABUSE PERSONS..
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ZOLPIDEM
• ACTS ON BENZODIAZEPINE RECEPTORS.
• HYPNOTIC
• NO ANTI CONVULSANT
• NO MUSCLE RELAXTION

• ONSET OF ACTION – FAST

• HALF LIFE – SHORT ( 3 HOURS)
• SE: NIGHTMARES, GI UPSET, DAYTIME
DROWSINESS

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 OTHER SEDATIVES
• ANTI HISTAMINES

CHLORAL HYDRATE
• SEDATIVE AND HYPNOTIC
• SE: GI UPSET
• TASTE CHANGES
• PREFERRED ROUTE : PER RECTAL

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ALCOHOL - ETHANOL
• RAPID ABSORPTION
• CROSSES PLACENTA
• ETHANOL CONVERTS TO ACETALDEHYDE

• MECH : STIMULATES GABA

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 CNS
• LOW DOSE : STIMULATION
• HIGH DOSES : DEPRESSION

CHR. EFFECT
• DEPRESSION, MEMORY LOSS
• RISK FOR SEIZURES
• WERNICKES – KORSAKOFFS
ENCEPHALOPATHY

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CVS :
• ACUTE : VASODILATION
• HIGH DOSES : VASOCONSTRICTION IN
HEART
• CHRONIC: MYOCARDIAL DEPRESSION
GIT :
• ACUTE : STIMULATES ACID
• HIGH : DIRECT IRRITATION
• CHRONIC: DIARRHOEA / CONSTIPATION,,
PANCREATITIS
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• LIVER :
•
CHR : CIRRHOSIS
• RESPIRATORY DEPRESSION

• CHRONIC :IMPOTENCE, TESTICULAR ATROPHY,

GYNAECOMASTIA

• PREGNANCY : FETAL ALCOHOL SYN.

• LOW IQ, MICROCEPHALY, FACIAL ABNORMAILITIES.

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 Stages of alcohol intoxication
• BAC Clinical symptoms
(g/100 ml of blood)

0.03 - 0.12 Euphoria

0.09 - 0.25 Excitement
0.18 - 0.30 Confusion
0.25 - 0.40 Stupor
0.35 - 0.50 Coma
0.45 + Death
Death from respiratory arrest

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 Rx OF WITHDRAWAL
• DISULFIRAM
• METABOLISM : ETHANOL – ACETALDEHYDE- ACETIC
ACID

• DISULFIRAM – INHIBITS ALDEHYDE

DEHYDROGENSAE.
• ACETALDEHYDE – INCREASES
• NAUSEA, HYPERVENTILATION, TACHYCARDIA,
FLUSHING.

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METHANOL
METHANOL :
• FORMS FORMALDEHYDE

• EFFECTS : BLINDNESS, SEVERE ACIDOSIS..

CNS IMPAIRMENT…

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