Tag: Benzodiazepine

Benzodiazepine

Benzodiazipines

Q. 1

Diazepam poisoning is treated by:

 A Flumazenil
 B

Hemofiltration

 C Charcoal
 D

Resins

Q. 1

Diazepam poisoning is treated by:

 A Flumazenil
 B

Hemofiltration

 C Charcoal
 D

Resins

Ans. A

Explanation:

Flumazenil REF: Harrison’s 17th ed Table e 35-4

See APPENDIX-42 for list of “Antidotes”

“Specific antidote for benzodiazepine poisoning is flumazenil”


Q. 2

Benzodiazepine antagonist ?

 A

Flumazenil

 B

Naloxone

 C Furazolidone
 D

Naltrexone

Q. 2

Benzodiazepine antagonist ?

 A

Flumazenil

 B

Naloxone

 C Furazolidone
 D

Naltrexone

Ans. A

Explanation:

Flumazenil [Ref. K.D.T. 6thIe p399-400 5th/e p 362]

  • Benzodiazepine acts by enhancing presynaptic/postsynaptic inhibition through a specific BZD receptor which is an integral part of the GABA receptor-CI channel complex.
  • Flumazenil is a BZD analogue which has little intrinsic activity, but it competes with BZD agonists as well as inverse agonists for the BZD receptor and reverses their depressant or stimulant effects respectively.
  • Flumazenil is the drug of choice for benzodiazepene overdose. About other options:
  • Naltrexone                        –> Opioid antagonist
  • Butorphanol                      –> Agonist/antagonist at opioid receptors
  • Pralidoxime                      –> Cholinesterase reactivator

Q. 3

The following are the benzodiazepines of choice in elderly and those with liver disease, EXCEPT:

 A

Lorazepam

 B

Orazepam

 C

Temazepam

 D

Diazepam

Q. 3

The following are the benzodiazepines of choice in elderly and those with liver disease, EXCEPT:

 A

Lorazepam

 B

Orazepam

 C

Temazepam

 D

Diazepam

Ans. D

Explanation:

Diazepam generates active metabolites, has slow elimination and tends to accumulate with regular use.

Lorazepam, Oxazepam and Temazepam do not produce active metabolites and are relatively safer in elderly patients and in those with liver disease.

These agents should be used in preference to diazepam.

Ref: Essentials of Pharmacology By K D Tripathi, 5th Edtion, Page 364.

Quiz In Between


Q. 4

Shortest acting benzodiazepine is‑

 A

Flurazepam

 B

Alprazolam

 C

Triazolam

 D

Diazepam

Q. 4

Shortest acting benzodiazepine is‑

 A

Flurazepam

 B

Alprazolam

 C

Triazolam

 D

Diazepam

Ans. C

Explanation:

Ans. is ‘c’ i.e., Triazolam

o Midazolam (slightly shorter acting than triazolam) and triazolam are shortest acting BZDs.


Q. 5

Benzodiazepine without anticonvulsant property is‑

 A

Nitrazepam

 B

Diazepam

 C

Clonazepam

 D

Temazepam

Q. 5

Benzodiazepine without anticonvulsant property is‑

 A

Nitrazepam

 B

Diazepam

 C

Clonazepam

 D

Temazepam

Ans. D

Explanation:

Ans. is ‘d’ i.e., Temazepam

BZDs with significant anticonvulsant property are diazepam, clonazepam, nitrazepam, lorazepam and flurazepam.


Q. 6

Antagonist of Benzodiazepine is ‑

 A

Nalorphine

 B

Carbamazepine

 C

Naloxone

 D

Flumazenil

Q. 6

Antagonist of Benzodiazepine is ‑

 A

Nalorphine

 B

Carbamazepine

 C

Naloxone

 D

Flumazenil

Ans. D

Explanation:

Ans. is ‘d’ i.e., Flumazenil

o Flumazenil is a benzodiazepene analogue which competes with BZD agonists as well as inverse agonists for the BZD receptor and reverses their depressant or stimulant effects respectively.

o It also antagonizes the action of Zolpidem, Zopiclone and Zopeplon as these drugs also act on BZD site.

Quiz In Between


Q. 7

Flumazenil is –

 A

Diazepam inverse agonist

 B

Diazepam antagonist

 C

Opioid antagonist

 D

Opioid inverse agonist

Q. 7

Flumazenil is –

 A

Diazepam inverse agonist

 B

Diazepam antagonist

 C

Opioid antagonist

 D

Opioid inverse agonist

Ans. B

Explanation:

Ans. is ‘b’ i.e., Diazepam antagonist


Q. 8

A 6 yr. old child with acute onset of fever of 104° F developed febrile seizures and was treated. To avoid future recurrence of seizure attacks what should be given –

 A

Paracetamol 400 mg + Phenobarbitone daily

 B

Oral Diazepan 6 hourly

 C

Paracetamol 400 mg 6 hourly

 D

I.V. diazepam infusion over 12 hrs

Q. 8

A 6 yr. old child with acute onset of fever of 104° F developed febrile seizures and was treated. To avoid future recurrence of seizure attacks what should be given –

 A

Paracetamol 400 mg + Phenobarbitone daily

 B

Oral Diazepan 6 hourly

 C

Paracetamol 400 mg 6 hourly

 D

I.V. diazepam infusion over 12 hrs

Ans. B

Explanation:

Ans. is ‘b’ i.e., Oral Diazepan 6 hrly


Q. 9

An anxiolytic benzodiazepine which is also antidepressant :                               

September 2007

 A

Lorazepam

 B

Oxazepam

 C

Alprazolam

 D

Chlordiazepoxid

Q. 9

An anxiolytic benzodiazepine which is also antidepressant :                               

September 2007

 A

Lorazepam

 B

Oxazepam

 C

Alprazolam

 D

Chlordiazepoxid

Ans. C

Explanation:

Ans. C: Alprazolam

Alprazolam is approved for the short-term treatment of panic disorder, with or without agoraphobia. Alprazolam is very effective in the short-term symptomatic relief of moderate to severe anxiety, essential tremor, and panic attacks.

Alprazolam is indicated for the management of anxiety disorders or the short-term relief of symptoms of anxiety. Alprazolam is recommended for the short-term treatment of severe acute anxiety.

Alprazolam is sometimes prescribed for anxiety with associated depression.

The antidepressant effects of alprazolam may be due to its effects on beta-adrenergic receptors. Other benzodiazepines are not known to have antidepressant activity.

Quiz In Between


Q. 10

Benzodiazepine overdose in a patient presenting with coma, is treated by:       

March 2010

 A

Protamine

 B

Flumazenil

 C

Coumarin

 D

Midazolam

Q. 10

Benzodiazepine overdose in a patient presenting with coma, is treated by:       

March 2010

 A

Protamine

 B

Flumazenil

 C

Coumarin

 D

Midazolam

Ans. B

Explanation:

Ans. B: Flumazenil

Decontamination

– Gastric lavage is not recommended but may be considered if the presence of a lethal co-ingestant is suspected and the patient presents within 1 hour of ingestion.

–  Single-dose activated charcoal is recommended for GI decontamination in patients with protected airway who present within 4 hours of ingestion.

  • Respiratory depression may be treated with assisted ventilation.
  • Flumazenil

– Flumazenil is a competitive BZD receptor antagonist and should be used cautiously because it has potential to precipitate BZD withdrawal in chronic users, resulting in seizures.

–  Flumazenil administration is contraindicated in mixed overdoses (e.g., TCAs) because BZD reversal can precipitate seizures and cardiac arrhythmias.

– Ideal indication for flumazenil use is isolated BZD overdose, particularly if overdose is iatrogenic in nature.


Q. 11

Antidote for benzodiazepine poisoning:

FMGE 10, 13; NEET 14

 A

Naloxone

 B

Atropine

 C

Flumazenil

 D

N-acetyl-cysteine

Q. 11

Antidote for benzodiazepine poisoning:

FMGE 10, 13; NEET 14

 A

Naloxone

 B

Atropine

 C

Flumazenil

 D

N-acetyl-cysteine

Ans. C

Explanation:

Ans. Flumazenil


Q. 12

IV diazepam has which of the following effect which is not seen by other routes ‑

 A

Analgesia

 B

Sedation

 C

Hypotension

 D

Coronary dilatation

Q. 12

IV diazepam has which of the following effect which is not seen by other routes ‑

 A

Analgesia

 B

Sedation

 C

Hypotension

 D

Coronary dilatation

Ans. D

Explanation:

Ans. is ‘d’ i.e., Coronary dilatation

Mechanism of action of benzodiazepines (BZDs)

  • Benzodiazepines act preferentially on midbrain ascending reticular formation (which maintains wakefulness) and on limbic system (thought and mental function).
  • Muscle relaxation is produced by action on medulla.
  • Ataxia is due to action on cerebellum.
  • BZDs acts on GABAA receptors.
  • GABA,,, receptor has 5 subunits a / p, p, a / y.
  • GABA binding site is on p. subunit, while BZDs binding site is on a / y subunit.
  • BZDs receptor increase the conductance of Cl- channel.
  • BZDs do not themselves increase Cl- conductance, i.e. they have only GABA facilitatory but no GABA mimetic action. (Barbiturates have both GABA facilitatory and GABA mimetic actions).

Effect on CNS

  • In contrast to barbiturates, BZDs are not general depressant, but exert relatively selective anxiolytic, hypnotic, muscle relaxant and anticonvulsant effects.
  • The antianxiety action of BZDs is not dependent on their sedative property —› with chronic administration relief of anxiety is maintained, but drowsiness wanes off due to development of tolerance.
  • Stage 2 sleep is increased, while REM, Stage 3 & 4 sleep are decreased.
  • Nitrazepam is the only benzodiazepine, which increases REM sleep.
  • Clonazepan and diazepam have more marked muscle relaxant property.
  • Clonazepam, diazepam, nitrazepam and flurazepam have more prominent anticonvulsant activity than other BZDs.
  • Diazepam (but not other BZDs) has analgesic action.
  • Diazepam produces short lasting coronary dilatation on i.v. injection.
  • Diazepam decreases nocturnal gastric secretion and prevents stress ulcers.

Quiz In Between


Q. 13

Inverse agonist of benzodiazepine receptor is –

 A

Phenobarbitone

 B

Flumazenil

 C

Beta carboline

 D

Gabapentin

Q. 13

Inverse agonist of benzodiazepine receptor is –

 A

Phenobarbitone

 B

Flumazenil

 C

Beta carboline

 D

Gabapentin

Ans. C

Explanation:

Ans. is `c’ i.e., Beta carboline


Q. 14

Antidote true is all except‑

 A

Deferoxamine – Iron

 B

Flumazenil – BZDs

 C

Dimercaprol – Arsenic

 D

Naloxone – Dhatura

Q. 14

Antidote true is all except‑

 A

Deferoxamine – Iron

 B

Flumazenil – BZDs

 C

Dimercaprol – Arsenic

 D

Naloxone – Dhatura

Ans. D

Explanation:

Ans. is ‘d’ i.e., Naloxone-Dhatura


Q. 15

Midazolam causes all except:

 A

Anterograde amnesia

 B

Retrograde amnesia

 C

Causes tachyphylaxis during high dose infusions

 D

Decreased cardiovascular effects as compared to propofol

Q. 15

Midazolam causes all except:

 A

Anterograde amnesia

 B

Retrograde amnesia

 C

Causes tachyphylaxis during high dose infusions

 D

Decreased cardiovascular effects as compared to propofol

Ans. B

Explanation:

Ans. b. Retrograde amnesia

At the time of peak concentration in plasma, hypnotic doses of benzodiazepines (midazolam) can be expected to cause varying degrees of lightheadedness, lassitude, increased reaction time, motor incoordination, impairment of mental and motor functions, confusion, and anterograde amnesia.”

Midazolam:

  • It causes anterograde amnesiaQ
  • Tolerance and tachyphylaxis may occur, particularly with longer-term infusionsQ(Shafer A. Complications of sedation with midazolam in the intensive care unit and a comparison with other sedative regimens. Crit Care Med. 1998;26(5): 947-56)
  • Benzodiazepine withdrawal syndrome has also been associated with high dose/ long-term midazolam infusionsQ
  • Compared with propofol infusions, midazolam infusions have been associated with a decreased occurrence of hypotension° but a more variable time course for recovery of function after the cessation of the infusion.

Quiz In Between


Q. 16

Shortest acting Benzodiazepine ‑

 A

Diazepam

 B

Midazolam

 C

Alprazolam

 D

Chlordiazepoxide

Q. 16

Shortest acting Benzodiazepine ‑

 A

Diazepam

 B

Midazolam

 C

Alprazolam

 D

Chlordiazepoxide

Ans. B

Explanation:

Ans. is ‘b’ i.e., Midazolam

  • Ajay Yadav 4th/e p. 85] o Midazolam is the shortest acting benzodiazipine.
  • It is 3 times more potent than diazepam.
  • Midazolam is now very commonly used BZD in intraoperative period.
  • Advantages of midazolam over diazepam are :
  • Water based preparation, so injection is painless.
  • Elimination half life is 2-3 hours, so can be safely used for day care procedures.
  • Reversal with flumezanil is complete (no resedation).
  • Disadvantages are that decrease in BP and peripheral vascularresistance, respiratory depression and incidence of apnea are higher and more profound than diazepam

Q. 17

The antidote for benzodiazepine toxicity is-

 A

Flumazenil

 B

Naloxone

 C

Naltrexone

 D

Dimercaprol

Q. 17

The antidote for benzodiazepine toxicity is-

 A

Flumazenil

 B

Naloxone

 C

Naltrexone

 D

Dimercaprol

Ans. A

Explanation:

Ans. is ‘a’ i.e., Flumazenil


Q. 18

Benzodiazepine without anticonvulsant property is ‑

 A

Nitrazepam

 B

Diazepam

 C

Clonazepam

 D

Temazepam

Q. 18

Benzodiazepine without anticonvulsant property is ‑

 A

Nitrazepam

 B

Diazepam

 C

Clonazepam

 D

Temazepam

Ans. D

Explanation:

Ans. is ‘d’  i.e., Temazepam 

  • BZDs with significant anticonvulsant property are diazepam, clonazepam, nitrazepam, lorazepam and flurazepam. 

Effects of benzodiazepines

  • In contrast to barbiturates, BZDs are not general depressant, but exert relatively selective anxiolytic, hypnotic, muscle relaxant and anticonvulsant effects.
  • The antianxiety action of BZDs is not dependent on their sedative property with chronic administration relief of anxiety is maintained, but drowsiness wanes off due to development of tolerance.
  • Stage 2 sleep is increased, while REM, Stage 3 & 4 sleep are decreased.
  • Nitrazepam is the only benzodiazepine, which increases REM sleep.
  • Clonazepan and diazepam have more marked muscle relaxant property.
  • Clonazepam, diazepam, nitrazepam and flurazepam have more prominent anticonvulsant activity than other BZDs.
  • Diazepam (but not other BZDs) has analgesic action.
  • Diazepam produces short lasting coronary dilatation on     injection.
  • Diazepam decreases nocturnal gastric secretion and prevents stress ulcers.

Q. 19

Shortest acting benzodiazepine is 

 A

Flurazepam

 B

Alprazolam

 C

Triazolam

 D

Diazepam

Q. 19

Shortest acting benzodiazepine is 

 A

Flurazepam

 B

Alprazolam

 C

Triazolam

 D

Diazepam

Ans. C

Explanation:

Ans. is ‘c’ i.e., Triazolam

Quiz In Between



Benzodiazepine

BENZODIAZEPINE


CLASSIFICATION:

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

MOA:

PHARMACOKINETICS:

  • Short-acting BZDs:
  • Eg: Midazolam – IV or IM as an induction agent.
    • Rapid onset of action.
    • Quick drug clearance.
    • Causes anterograde amnesia, tachyphylaxis during high dose infusions.
    • Decreased cardiovascular effects as compared to propofol 
  • Temazepam or oxazepam – Revives insomnia. 
    • At lower doses, relieves acute symptoms of anxiety, such as panic attacks & phobias.
  • Long-acting BZDs: 
    • Slower onset of action following oral administration → Hence prolonged pharmacological action.
    • Sedation.
    • Prevents increased muscle tone of tetanus infection. 
  • Metabolized in liver by dealkylation and hydroxylation.
  • Excreted in urine as glucuronide conjugates.

ACTIONS:

  • Antianxiety
  • Sedation: 
    • Increasing dosage produce sleep & hence considerable as hypnotic
    • I.V administration used extensively to produce conscious sedation during unpleasant procedures. 
    • Eg: Diazepam & midazolam.
    • Cardiovascular stability – IV diazepam 
    • Midazolam potentiates propofol in co-induction technique.
  • Anticonvulsants: 
    • Clonazepam & diazepam – Effective in status epilepticus.
  • Muscle relaxation: 
    • Reduce muscle tone.
  •  Amnesia: 
    • IV benzodiazepines produces antegrade amnesia. 
    • Midazolam – Very intense for 20-30 minutes
    • Lorazepam – Longer amnesia – 6 hr.

DRUGS:

  • Inverse agonist of benzodiazepine receptor – Beta carboline.
  • Benzodiazepine antagonist – Flumazenil

USES:

  • As hypnotic –
    • Daytime sedation (Alprazolam)
  • As anxiolytic.
  • Antidepressant  (Alprazolam)
  • As anticonvulsants, especially emergency control of status epilepticus  
    • To avoid future recurrence of seizure attacks Oral Diazepam 6 hourly is given.
  • As centrally acting muscle relaxant.
  • For anesthetic medication and IV anesthesia 
  • Alcohol withdrawal in dependent subjects 
  • Mostly given along with analgesics (NSAIDs|). 
  • DOC in elderly & with liver disease.
    • Lorazepam, OxazepamTemazepam
  • Spasmolytics.
  • Anti-ulcer.

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.
  • BZD poisoning:
    • Benzodiazepine antagonist -Flumazenil
    • Eg: Diazepam poisoning.
  • Paradoxical stimulation, irritability, and sweating may occur with flurazepam.
  • Increase in nightmares and behavioral alterations 
  • Increased psychological effects with usage of short-acting benzodiazepines in insomnia. 
  • Disturbed REM sleep patterns.

Exam Important

  • 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 BENZODIAZEPINE

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