Transcript Slide 1

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BNZ-1 r.: sedation, hypnotic, antianxiety
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BNZ-2 r.: anxiolysis, muscle relaxation, sedation,
anticonvulsant, psychomotor impairment
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BNZ-3 r.: tolerance, withdrawal
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Diazepam (tab 2&5&10& inj10mg/2ml)
Lorazepam (1&2)
Clonazepam (1&2)
Alprazolam (0.5&1)
Oxazepam (10)
Chlordiazepoxide (5&10)
Flurazepam (tab30& cap15)
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The absorption, the attainment of peak
concentrations, and the onset of action are
quickest for diazepam (Valium), lorazepam
(Ativan), alprazolam (Xanax).
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Several benzodiazepines are effective following
intravenous (IV) injection, whereas only
lorazepam and midazolam (Versed) have rapid
and reliable absorption following intramuscular
(IM) administration.
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Diazepam, chlordiazepoxide, clonazepam,
flurazepam have plasma half-lives of 30 to more
than 100 hours and, therefore, are the longestacting benzodiazepines.
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The half-lives of lorazepam, oxazepam are
between 8 and 30 hours. Alprazolam has a halflife of 10 to 15 hours.
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The advantages of long half-life drugs over short
half-life drugs include less-frequent dosing, less
variation in plasma concentration, and lesssevere withdrawal phenomena.
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The disadvantages include drug accumulation,
increased risk of daytime psychomotor
impairment, and increased daytime sedation.
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The advantages of the short half-life drugs over
the long half-life drugs include no drug
accumulation and less daytime sedation.
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The disadvantages include more-frequent dosing
and earlier and more-severe withdrawal
syndromes. Rebound insomnia and antrograde
amnesia are thought to be more of a problem
with the short half-life drugs than with the long
half-life drugs.
medication
Dose
equivalent
diazepam
5
lorazepam
1
clonazepam
0.25
alprazolam
0.5
chlordiazepoxide
25
flurazepam
15
oxazepam
15
zolpidem
10
Insomnia
 Anxiety Disorders: GAD, panic dis., social phobia
 BMD1
 Other Indications: akathisia, alcohol withdrawal,
agitation, catatonia.
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Because insomnia can be a symptom of a
physical or psychiatric disorder, hypnotics should
not be used for more than 7 to 10 consecutive
days without a thorough investigation of the
cause of the insomnia.
Benzodiazepines are highly effective for the relief
of anxiety associated with generalized anxiety
disorder.
 Most persons should be treated for a
predetermined, specific, and relatively brief
period.
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Alprazolam and clonazepam, both high-potency
benzodiazepines, are commonly used medications for
panic disorder, with or without agoraphobia.
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SSRIs are still often preferred,because they target
common comorbid conditions, such as depression or
obsessive-compulsive disorder (OCD).
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Benzodiazepines and SSRIs can be initiated together to
treat acute panic symptoms; use of the benzodiazepine
can be tapered after 3 to 4 weeks once the
therapeutic benefits of the SSRI have emerged.
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Clonazepam is an effective treatment for social
phobia.
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In addition, several other benzodiazepines (e.g.,
diazepam) have been used as adjunctive
medications for treatment of social phobia.
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Benzodiazepines are used adjunctively for
treatment of adjustment disorder with anxiety,
OCD, and posttraumatic stress disorder.
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The most common adverse effect of
benzodiazepines is drowsiness.
The most serious adverse effects of
benzodiazepines occur when other sedative
substances, such as alcohol, are taken
concurrently. These combinations can result in
marked drowsiness, disinhibition, or even respiratory
depression.
Ataxia, dizziness, mild cognitive deficits, antrograde
amnesia, rashes, paradoxical increase in
aggression .
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The symptoms of benzodiazepine intoxication
include confusion, slurred speech, ataxia,
drowsiness, dyspnea, and hyporeflexia.
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Persons with hepatic disease and elderly persons
are particularly likely to have adverse effects and
toxicity from the benzodiazepines, especially when
the drugs are administered repeatedly or in high
dosages.
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Benzodiazepines can produce clinically significant
impairment of respiration in persons with COPD and
sleep apnea.
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Alprazolam can exert a direct appetite stimulant
effect and may cause weight gain.
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Benzodiazepines should be used with caution by
persons with a history of substance abuse,
cognitive disorders, renal disease, hepatic disease,
porphyria, CNS depression, or myasthenia gravis.
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Some data indicate that benzodiazepines are
teratogenic; therefore, their use during pregnancy
is not advised(group D/X).
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The drugs are secreted in breast milk in sufficient
concentrations to affect the newborn.
Benzodiazepines can cause dyspnea,
bradycardia, and drowsiness in nursing babies
(group L3-moderately safe).
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The appearance of a withdrawal syndrome,
depends on the length of time the person has
been taking a benzodiazepine, the dosage the
person has been taking, the rate at which the drug
is tapered, and the half-life of the compound.
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Benzodiazepine withdrawal syndrome consists of
anxiety, nervousness, diaphoresis, restlessness,
irritability, fatigue, light-headedness, tremor,
insomnia, and nausea. Delirium and seizures may
occur.
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The most common and potentially serious
benzodiazepine receptor agonist interaction
results in excessive sedation and respiratory
depression occurring when benzodiazepines, &
zolpidem, are administered concomitantly with
other CNS depressants, such as alcohol,
barbiturates, tricyclic and tetracyclic drugs,
dopamine receptor antagonists (DRAs), opioids,
and antihistamines.
Cimetidine , disulfiram , isoniazid, and oral
contraceptives increase the plasma
concentrations of diazepam, chlordiazepoxide
and flurazepam.
 The plasma concentrations of alprazolam are
increased to potentially toxic concentrations by
fluvoxamine .
 The benzodiazepines can increase the plasma
concentrations of phenytoin and digoxin .
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Benzodiazepine use should be started at a low
dosage, and the person should be instructed
regarding the drug's sedative properties and abuse
potential.
An estimated length of therapy should be decided
at the beginning of treatment, and the need for
continued therapy should be reevaluated at least
monthly because of the problems associated with
long-term use.
medication
Usual adult dose
diazepam
2.5 to 40 mg/d
clonazepam
0.5 to 4
alprazolam
0.5 to 6
lorazepam
0.5 to 6
oxazepam
15 to 120
chlordiazepoxide
10 to 100
flurazepam
15 to 30
zolpidem
5 to 10
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Zolpidem (tab 5&10)
Specific for BNZ-1 receptor
Zolpidem reaches peak plasma concentrations in
1.6 hours and has a half-life of 2.6 hours.
For insomnia
Lower rate of tolerance, abuse and dependence
Safe in pregnancy(group B)
In rare cases, zolpidem can cause hallucinations
and behavioral changes.
Any Question?