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Benzodiazepine (BZD)


  1. Lipid soluble; excellent absorption
  2. High first pass metabolism:
    a. Lorazepam  
    b. Oxaxepam         
    c. Temazepam
  • Metabolized outside liver
  1. BZDs neither induce/inhibit microsomal enzymes (vs phenobarbitone)
  2. Prazepam, Clorazepate - PRODRUGS.
  3. Vd-high
  4. Midazolam & Triazolam undergoes Redistribution


  1. Midazolam
    1. DOC-endoscopies/colonoscopies
    2. Inducing agent as an alternative to ketamine
    3. Sedation in ICU
    4. Status epilepticus
  2. Triazolam
    1. Shortest antianxiety drug
    2. S/e-day time anxiety (withdrawal reaction) 
  3. Alprazolam (DOC)
    1. Gen. Anxiety Disorder
    2. Acute panic
    3. Agoraphobia (fear of open spaces)

*Long term management of anxiety related disorders is now a days being done by SSRIs

  1. Lorazepam


  1. Status epilepticus
  2. Preanethetic medication
  1. Clonazepam (Most potent), Clobazepam, Clorazepate.
    1. Anticonvulsant BDZs
    2. Tolerance develops after 6 months
    3. ‘Add on’ antiepileptics 
  2. Oxazepam
    1. Hypnotic in elderly              
    2. Hypnotic in liver disease              
    3. Zolpidem is safest
  3. Clordizepoxide
    1. Chronic anxiety            
    2. ​DOC- Alcohol Withdrawal
  4. Diazepam (DOC)
    1. Central spasticity        
    2. Picrotoxin poisoning                    
    3. Strychinine poisoning
    4. Febrile seizures            
    5. Convulsions in tetanus patients          
    6. Delirium tremens  
  5. Nitrazepam
    1. Physiological hypnotic
    2. Does not interfere with REM Sleep
  6. Flunitrazepam
    1. ‘DATE RAPE’ drug 

Side effects

  1. MC-sedation
    1. Tolerance develops
  2. Anterograde amnesia
    1. Maximum with lorazepam
  3. Psychomotor retardation
  4. Falling down chances are more
  5. Accidents more common
  6. Tolerance
  7. Addiction
  8. Dependence
  9. ‘REM rebound’
    1. Nightmares

Advantages Of Bzd’s Over Barbiturates

  1. Have a high therapeutic index.
  2. Hypnotic doses do not affect respiration or cardiovascular functions
  3. BZDs have practically no action on other body systems
  4. Cause less distortion of sleep architecture. Rebound insomnia is less marked
  5. Microsomal enzyme induction absent
  6. They have lower abuse liability: tolerance is mild, psychological and physical dependence and withdrawal syndrome is less marked.
  7. A specific BZD antagonist Flumazenil is available which can be used in case of poisoning/overdose.
  1. Atypical Non-Bzd’S
  • Bind selectively to a sub-group of GABAA receptors, acting like benzodiazepines to enhance membrane hyperpolarization.
  • Rapid onset of sleep with minimal rebound insomnia or withdrawal symptoms.

Toxicity: Dizziness

  • fatigue
  • endocrine changes
  • Interactions: Fluvoxamine inhibits metabolism.

Sleep And Treatment Of Insomnia

EEG waves have been divided into:



High amplitude, 8-14 c.p.s. (cycles per second)


Low amplitude, 15-35 c.ps.


Low amplitude, 4-7 cps.


High amplitude, 05-3 c.p.s.,

K complex

Deep negative wave followed by positive wave and few spindles

  1. NREM

Stage 0 (awake)

From lying down to falling and occasional nocturnal awakenings; constitute 1-2% sleep time. Eyes movement are irregular or slowly rolling

EEG shows alpha activity when eyes are closed and beta  activity when eyes are open.


Stage 1 (dozing)

Eye movements are reduced but there may be thrust of rolling. Neck muscles relax. Occupies 3-6 % of sleep time.

Alpha activity is interspersed with theta waves

Stage 2 (unequivocal sleep)

Little eye movement; subject are easily arousable. This comprises 40-50 % of sleep.

Theta waves interspersed spindles, K complexes can be evoked, on sensory stimulation

Stage 3 (deep sleep transition)

Eye movements are few; subjects are not easily arousable; comprises 5-8% of sleep time

EEG shows theta, delta, and spindle activity, K complexes can be evoked with strong stimuli only.

Stage 4 (cerebral sleep)

Eyes are practically fixed; subjects are difficult to arouse. Night terror may occur at this time. It comprises l0-20 % of sleep time

Delta activity predominates in EEG, K complexes cannot be evoked


* During stage 2, 3 and 4 heart rate, BP and respiration are steady and muscles are relaxed.

* Stages 3 and 4 together are called slow wave sleep (SWS)

  1. REM

REM (Paradoxical sleep)


There are marked irregular and darting eye movements; dreams and nightmares occur, which may be recalled if the subject is aroused Heart rate and BP fluctuate; respiration is irregular. Muscles are fully relaxed, but irregular body movements occur occasionally Erection occurs in males. 10-30% of sleep time is spent in REM.


EEG has waves of all frequency, K complexes cannot be elicited



Effects Of Sedative-Hypnotics On Sleep Pattern

More rapid onset of sleep and prolongation of stage 2 are presumably clinically useful effects.


Hypnotic dose shortens sleep latency and increases sleep duration. The sleep is arousable, but the subject may feel confused and unsteady if waken early. Night awakenings are reduced.

REM and stage 3, 4 sleep are decreased; REM-NREM sleep cycle is disrupted. The effects on sleep become progressively less marked if the drug is taken every night consecutively. A rebound increase in REM sleep and nightmares is often noted when the drug is discontinued after a few days of use and it takes several days for normal pattern to be restored.

Hangover (dizziness, distortions of mood, irritability and lethargy) may occur in the morning after a nightly dose.

Higher dose of a barbiturate induces a predominance of slow, high voltage EEG activity. Progressive burst suppression occurs if dose increased.


The latency of sleep onset is decreased (time to fall asleep);  the duration of stage 2 NREM (non-rapid eye movement) sleep is increased;  the duration of REM sleep is decreased; the duration of stage 4 NREM slow-wave sleep is decreased. There is little evidence of REM rebound


All decrease the latency to persistent sleep.

Zolpidem decreases REM sleep but has minimal effect on slow-wave sleep. Zaleplon decreases the latency of sleep onset with little effect on total sleep time, NREM, or REM sleep. Eszopiclone increases total sleep time; mainly via increases in stage 2 NREM sleep, and at low doses has little effect on sleep patterns. At the highest recommended dose, eszopiclone decreases REM sleep. No REM rebound seen

  1. Buspirone
    1. 5-HT1A partial agonist
    2. Highly Protein bound
    3. Cumulative
    4. Takes 1-2 weeks to achieve steady state
      1. Not effective in acute phase
      2. Selective antianxiety drug (No sedation)  


  1. Paresthesia
  2. GI upset
  3. Meiosis
    1. Efficacy is lower than BZDs
    2. Antismoking Activity
    3. Used when substance abuse is associated with anxiety


  1. Melatonin agonist
  2. Melatonin is a physiological entity acts on two main receptors: MT1 and MT2.
  3. MT1 is present on suprachiasmatic nucleus of hypothalamus and involved in maintaining circadian rhythm and MT2 receptor is involved in sleep initiation.
  4. Ramelteon and agomelatine are two drugs which are agonist of both of these two receptors and useful for the treatment of shift workers, jet lag patients and old age patient where circadian rhythm is disturbed. And also useful for the treatment of insomnia.
  5. Metabolized by CYP450 enzyme.
  6. Free from benzodiazipine like side effects.
  7. Rare side effects are increase prolactin and decrease testosterone.


10. Meprobamate

  1. Ramelteon
    1. Anxiety with insomnia
    2. BZDs are DOC now a days


  • No intrinsic activity (no effect on Normal individual)
  • Competitive antagonist to BZD’S, Atypical Non BZD’S
  • USES:
  1. Reversal of BZD’S anesthesia
  2. Overdose
  • S/E:  Safe and well tolerated. Agitation, discomfort, tearfulness, anxiety, coldness and withdrawal seizures are the occasional side effects.


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