This document discusses benzodiazepines (BDZs), including their discovery, mechanism of action, effects, and examples like diazepam and midazolam. It notes that BDZs bind to GABA receptors in the brain to have sedative, anxiolytic, hypnotic, amnestic, and anticonvulsant effects. Their onset and duration of action depends on lipid solubility. While generally safe, they can cause respiratory depression, especially in high doses or with pre-existing lung conditions. Their effects are reversed by the antagonist flumazenil. Midazolam is water-soluble and shorter-acting than diazepam. It is metabolized in the liver

1. DR.N.K.AGRAWAL
PROF. JNMC

2.  SEDATIVE: Ally Anxiety –decreases activity,
reduces excitement, calm the individual
 HYPNOTICS: produces drowsiness and induces
sleep

4.  Discovery began in 1955 by Leo-H. Sternbach
 1st
BDZ  Chlodiazepoxide
 Pharmacological action revealed by Randal & his
colleagues few years later.
 Properties  Inducing calming
 Without ataxia or marked
anticonvulsant properties

5. Mode of action 
BDZ having similar pharmacological activity,
therapeutic use, potency and solubility.
Receptors present in the gray matter

6.  BDZs bind the same set of receptors in the CNS as
barbiturates but bind to different site of receptors.
 BDZs binding to the GABAa receptor increases the
frequency of opening of the associated chloride ion
channel
 For eg:BDZs-receptor binding facilitates binding of
GABA to its receptor.
 FLUMAZENIL(an imidazobenzodiazepine) is a specific
BDZs-receptor antagonist that effectively reverses
most of the CNS effect of BDZs

8. There are number of other drugs bind to GABA-BDZ
receptor complex, notably barbiturates (including
thiopentone) which bind to a separate site, and
some non-benzodiazepine sedative such as
zopiclone and zolpidem which act at the
benzodiazepine site.

9. CNS :BDZ dose related depression of the CNS.
Amnesia
Anticonvulsant effect
Hypnotic effect
Induction of Anesthesia

10. AMNESIA: BDZ produce anterograde but not retrograde
Useful  Used as sedation for endoscopy or for surgical
procedure under local anaesthesia
Note :  It is not produce by Oral or I/M
ANTICONVLSANT:
All BDZ have an anticonvulsant action but not all used for
these purpose due to BDZ1 & BDZ2 receptors differes

11. HYPNOTIC EFFECT:
 Main long term clinical uses of BDZ is as a night time
hypnotics.
 It decreases REM sleep
 Significant is not fully understood
 There is a period of rebound wake full ness
 Tolerance & dependence after long term use

12. INDUCTION OF ANAESTHESIA :
 Diazepam, midazolam and flunitrazepam have
been used as induction agents
 Claimed advantage is that BDZ having greater
cardiovascular stability and compared with
Thiopentone
 Counter balanced by unreliability of effect and
slow recovery

13. CVS:
 Systemic vascular resistance decrease with
peripheral vasodilatation
 Decreased cardiac output
 Postural hypotension

14. RESPIRATORY SYSTEM:
 Therapeutic doses, Oral administration of BDZ does
not cause respiratory depression.
 Intravenous injection as the consciousness lost, so is
sensitive to CO2  decreased tidal volume 
compensated by increased respiratory rate (RR)
 In patient with chronic obstructive airway disease, the
respiratory depressant effect of BDZ > normal subject.

15. PHARMACOKINETIC:
CNS AND BLOODBRAIN BARRIER:
 Onset and duration of action at psychosedative drug BDZ
depend on capacity to BBB, rate directly proportion to
intrensic lipid solubility at physiological pH
 All benzodiazepine are highly liphophilic
e.g. diazepam midazolam – Acts quickly
 Lesser liphophilic e.g. lorazepam chlorodizepoxide

16. DRUGS EQUIVALEN
T DOSE(mg)
VOLUME OF
DISTRIBUTIO
N
(litres/kg)
PROTEIN
BINDING(%
)
CLEARANC
E
(ml/kg/min)
MIDAZOLAM 0.15-0.3 1.0-1.5 96-98 6-8
DIAZEPAM 0.3-0.5 1.0-1.5 96-98 0.2-0.5
LORAZEPA
M
0.05 0.8-1.3 96-98 0.7-1.0

17.  Elimination half life :Midazolam is 1-4hrs
Diazepam-21-37 hrs
Lorazepam-10-20 hrs

18. DIAZEPAM:
 Colourless crystalline base
 Insoluble in water
 M.W. 285
 Injectable preparation
 Contains 5 mg/ml in aqueous vehicle
 Consist of mainly propylene glycol, Ethyl
alcohol, Sodium Benzoate in Benzoic acid.
 pH 6.4 – 6.9
 Diazepam is lipid emulsion made up from
soya bean similar to the fat emulsion used
for parentral nutrition.

19. MIDAZOLAM:
 Nitrogen in the imidazole ring
 Water soluble
 Shorter duration at action than other
 Prepared as a water soluble salt with
hydrochloric, & maleic lactic acid.
 Available in stable aqueous solution as hydrochloride salt
 Half life is 10 minutes
 Must not mixed with acidic solution.

20. PHARMACOKINETIC OF MIDAZOLAM:
 Properties relevant to the fat of relevant diazepam
 Increase fraction of free drug
 Similar volume of distribution with similar onset time
 Quicker & earlier recovery
 10 times faster than diazepam
 Bio ability 44 % after administration of 15 mg & reduce
with volume of distribution.
 Greater dose in women (0.8 to 1.51 / kg)

21. METABOLISM OF MIDAZOLAM:
 Eliminated by hepatic biotransformation
 70% eliminated in urine
 Half life 2 to 2.4

23.  FLUMAZENIL: It is a BDZs analogue which
has little intrinsic activity,but competes with
BZD agonists as well as inverse agonists for
the BZD receptor and reverses their
deppresant or stimulant effects respectively

24.  TO REVERSE BZD ANAESTHESIA:
Patients anaesthetized/sedated witha BDZ
wakeup,get oriented and regain motor control
within 1min of an i.v injection of 0.3-1mg of
flumazenil.
 BDZ OVERDOSE:
Majority of patients of BDZ overdose require
only supportive measures like patent
airway,maintenance of BP,cardiac and renal
function etc

25.  In addition, FLUMAZENIL 0.2mg/min may be
injected i.v till the patient regains consciousness.
 Practically all patients intoxicated with BDZ alone
respond within 5 mn.

26.  FLUMAZENIL is a safe and well tolerated.
 Agitation,discomfort,tearfulness,anxiety,coldness
are the occasional side effects...

27.  Use short acting midazolam
 Dose is 0.15 to 0.3 mg/kg
 Can be used IV/IM
 Some have tried oral and nasal rout
 Antidote is flumanzenile