education

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