Benzodiazipines

CLASSIFICATION:
  • Long Acting
  1. Flurazepam 50-100 t1/2(hrs)
  2. Diazepam 30-60 t1/2(hrs)
  3. Nitrazepam 30 t1/2(hrs)
  4. Flunitrazepam 15-25 t1/2(hrs)
  • Short Acting 
  1. Temazepam 8-12 t1/2(hrs)(Benzodiazepine without anticonvulsant property )
  2. Triazolam 2-3 t1/2(hrs)
  3. Midazolam 2 t1/2(hrs)
  4. Alprazolam 
MOA:



ACTIONS:
  • Antianxiety
  • Sedation: there is a decreases responsiveness to a constant level of stimulation, with a decrease in spontaneous activity. 
  1. Increasing dosage will eventually produce sleep and the drug have gained considerable popularity as hyptonics.
  2. Intravenously, BZDs are used extensively to produce conscious sedation during unpleasant procedures . 
  3. Diazepam and midazolam have also been used as intravenous inducing agents.
  4. Cardiovascular stability is a feature of such use by IV diazepam 
  5. Midazolam potentiates propofol in the technique of co-induction.
  • Anticonvulsants:
  • Clonazepam and diazepam are effective in status epilepticus, while the former is also of use in petit mal epilepsy.
  • Muscle relaxation: benzodiazepines reduce muscle tone and this is mediated via an interneurons in the spinal cord
  • Amnesia: Intravenous benzodiazepines will reliably produce antegrade amnesia.
  1. Following midazolam this is very intense for 20-30 minutes
  2. Longer amnesia, upto 6 hr, has been reported following lorazepam. 
  3. Amnesic effects of the benzodiazepines when given intramuscularly or orally is much more variable. 
USES:
  • As hypnotic
  • As anxiolytic and for day time sedation (Alprazolam)
  • Antidepressant (Alprazolam)
  • As anticonvulsants, specially emergency control of status epilepticus
  • To avoid future recurrence of seizure attacks Oral Diazepam 6 hourly is given
  • As centrally acting muscle relaxant 
  • For preanaesthetic medication and IV anaesthesia 
  • Alcohol withdrawal in dependent subjects 
  • Along with analgecis, NSAIDs. 
  • Benzodiazepines of choice in elderly and those with liver disease Lorazepam, Orazepam & Temazepam
  • Spasmolytics, anti-ulcer and many other drugs
PHARMACOKINETICS:
  • Short acting BZDs such as midazolam may be given intravenously or intramuscularly as an induction agent
  1. Onset of action is rapid but the drug is quickly cleared from the body under most clinical circumstances. 
  2. Other relatively short-acting BZDs, such as temazepam or oxazepam, are used to revive insomnia. 
  3. At lower doses, may also be used to provide demand relief of acute symptoms of anxiety, such as panic attacks and phobias.
  4. Midazolam causes Anterograde amnesia, tachyphylaxis during high dose infusions & Decreased cardiovascular effects as compared to propofol
  • Long acting BZDs, 
  1. Slower onset of action following oral administration and subsequently, a prolonged pharmacological action.
  2. Sedation and sleep may ensure sleep
  3. Because of their persistent pharmacological action the long-acting BZDs may be used in some form of epilepsy and will find a use in preventing the increased muscle tone of tetanus infection. 
  • Benzodiazepines are metabolized in liver by dealkylaytion and hydroxylation to many metabolites, some of which are active.
  • Inverse agonist of benzodiazepine receptor is Beta carboline
  • Benzodiazepine antagonist Flumazenil
  • The biological half-life of these drugs may be much longer than the plasma t1/2 of the administered compound. 
  • Benzodiazepines and their phase I metabolites are excreted in urine as glucoronide conjugates.
ADVERSE EFFECT:
  • Dizziness, lassitude, vertigo, disorientation, amnesia, increased reaction time with motor incoordination, impairment of mental coordination occur. 
  • Weakness, blurring of vision, dry mouth and urinary incontinence 
  • Diazepam poisoning is treated by Flumazenil
  • Paradoxical stimulation, irritability and sweating may occur with flurazepam.
  • Increase in nightmares and behavioural alterations 
  • There are a no. of psychological effects that may accompany the use of short acting benzodiazepines in insomnia. 
  • Normal pattern of sleep, no. of episodes of REM sleep are frequently disturbed. 
  • Defect in overall production of REM sleep can lead to persistent tiredness or hangover effect. 
  • With repeated medication, some tolerance to these effects develops, to the extent that proportion of REM returns to normal.
Exam Question
  • Diazepam poisoning is treated by Flumazenil
  • Benzodiazepine antagonist Flumazenil
  • Benzodiazepines of choice in elderly and those with liver disease Lorazepam, Orazepam & Temazepam
  • Shortest acting benzodiazepine is Triazolam
  • Benzodiazepine without anticonvulsant property is Temazepam
  • To avoid future recurrence of seizure attacks Oral Diazepam 6 hourly is given
  • Alprazolam is an anxiolytic benzodiazepine with antidepressant action
  • IV diazepam shows Coronary dilatation
  • Inverse agonist of benzodiazepine receptor is Beta carboline
  • Midazolam causes Anterograde amnesia, tachyphylaxis during high dose infusions & Decreased cardiovascular effects as compared to propofol

Don't Forget to Solve all the previous Year Question asked on Benzodiazipines