1. ANTI ANXIETY DRUGS.
(Sedative) Hypnotics, Psychoanalgesia)
ANXIETY. Unpleasant emotional state associated with uneasiness & fearful concern
about future and behavioral changes in response to environmental events that are non
Rewarding (when it is expected).
Punishing
Frustrating.
Secondary
Diseases:
MI
PU (Peptic Ulcer)
IHD (Ischemic heart Diseases)
Situational Anxiety:
Illness.
Tragedy.
Medical or surgical procedure.
Other stressful events.
Manifestations of Anxiety.
Psychological
Behavioural
Psysocilogical.
a) Verbal complaints of being anxious (Anxiety)
b) B) Somatic & Autonomic ffects:
• vigilance.
• Restlessness.
• Agitation.
• Motor tension.
• Tachycardia.
• Sweating
• Emotional upset like weeping etc.
• G-I upset (Abdominal pain, diasehea etc.)
c). Interference with N0 productiove activity &^ stressful tasks like:
* driving
*Public speaking.
* Playing instrument
*Sitting in exams.
* Surgery.
* Sports.
CONDITIONS RELATED TO ANXIETY
Phobic anxity
Panjic disorder.
Generalized anxiety disorder.
Excersive & unreasonable anxiety about N0 life circumstance.
Post- transmatic stress disorders

2. ANXIOLYTIC SEDATIVE & HYNOTIC)
1) Benzodiazepines:
Diazepam.
2. 5-HT1A recap Agonists.
Buspirone.
Ipsapirone.
Gepirone
Tendospiron.
3. Barbituates.
(Obsoleted Now)
4. B-Recep. Antagonists.
Propranolol.
5. X2 recep Agonists.
Clonidine.
From 6-10 gp No need to remember gp name.
6) imidazopydine.
Zolpidem.
7. Pyrazolopyrimidine. Zaleplon.
8. Cyclopynelone.
Zopidone
Eszopiclone.
9. Melatonin recap. Against: Rameltcon.
10. MISC:-
Cacbamates:-
Meprobamate
Pipecidinediones:-
Glutethincide
Methylprylon.
ALCOHOLS (CJLORAL DERIVATIVES)
Chloral hydrate.
Trichloralethonal.
Etheclorvynol.
Cyclic Ethers:-
Parcaldehyde.
Sedative anti-histamines:_
Diphenhydramine
Pyrilamine
Doxylamine.
Promethazine
Hydroxyzine.
Other Drugs:-
Ethynamate
Clomethiazole.
TCA
Etomidate (I/V anaesthetic, in dose is used for sedation.

3. Antipsychotics.
Anti- Narcoleptic Drugs: Modafinil.
Inhibitory NYS in CNS.
Gaba
Glycine
Tausine.
DISTRIBUTION OF GABA.
Transmitter at about 30% of synapses in CNS.
Cerebellum, cerebral coirtex, hypothalainus.
All newrons sentitive to Gaba.
GABA RECEPTORS:
Effects Gabaq-A
Post synptic inhibition,
CT conductance.
Gaba.
Pre synatic
Inhibition Ca+2 conductance, IC conductance.
Agonists.
Gaba + +
Balofen - +
Muscimol. + _
Antagonists
Bicnculline Competitive
Picrotoxin Non-competitive
Direct channel block.
Phacloten - +
Potentiation.
Benzodiazzepines + -
Bacebitucates + -
Macrommolecular/supra. Competent.
Contains Gaba A + benzodia zepeines binding site + ion channel CT channel
Binding of Gaba-A & drug to their respective binding sites.
Openinbg if ion channel occurs
Carring cl influx
Hyperpolacization
So, stablise the cell.
OTHER DRUGS INTERACTING WITH GABA RECEPTORS.
Alcohol.

4. I/V anaesthetyics Alphyoxolone etomidate.
Propfol.
Inhalation anesthetics Halothance
Antiepilptics
Gabapenter.
Vigabation.
Antihalmintics.
Ivenmetion cause pacalyisi of worm
CNS Stimulants
Biccusculine.
BENZODIAZEPINES
CHEMISTRY:-
A seven members ring fused jto an aromatic ring with 4 main substitution sites (R1---R4)
A= Benzene
B= Diazepine ring (7 membered)
C=5 aryl substituent
(4 substrate sites R1—R4)
A substitution in 7th position a Halogen or Nitro group is required for sedative hypnotic
activity.
Triazolam & alprazolam include a triazolam & at 1,2 position
Several BDZ are synthesized by diff substitution.
GABA- a RECEPTORS.
Pentaminc structure assembled from 8 submits selected from sultiple polypeptide clones
i.e B V S which have multiple submits.
Eg 6diff & 4B 3V
Gaba receptor displays heterogeneity in diff areas of CNS consisting of diff combination
of these essentiasl sub units In most areas Gaba A receptor is made up to 2 & 2B and one
V sub-unit.
CC
Muscule relaxainton.
X5 Subunit:
Memory impairment.
BDZ- Recep interaction:
1. Agonist
BDZS, zolpidem, zaleplon, zopiclone, E szopiclone.
2. Antagainst:-
Funmezenil, antagonize all above but not bacbituraters, meprobanate, and
ethanol.
3. Inverse against:
4. B- carbolines can procduce anxiety & seizures.
5. They can also blockl the effect of BDZ’s ]
Basal activities recap has some activity always, not zzero activity any time.
When recap. Has 2 conformations like BDZ recap.
BDZ bind configueation shift. To the configureation to which BDZ can bind.
BDZ against
A configueration efficacy
B-cacboline, Inverse against efficacy.
Basal activity is ed basdal activity is responsible for day to day control of
anxiety when B-A ed person become anxiogenic Inverse aginst:

5. Block effect of against antagonist effect
Opposite to
No clinical anxixoylic
No sigrificance effect of BDZ.
MOA 7 DISTRIBUTION OF RECEPTORS.
BDZ potentiate Gaba ergic inhibition at all the levels of nerural axis.
They are no Gabaergic not Gaba memetic
Including:
• Sp. Cord
• Hypothalamus.
• Hippocartnpus
• Subst. Nigra
• Cerbral cortex
• Cerebellac cortex.
SPECIFICITY.
1. Structural related to structural.
2. Biology, every recap has its own tissue distribution.
Gaba bind b/w x & B- submunit
BDZ bind b/w B&X subunit.
1. .
Both REM & NREM. Sleep imp for N0 physiological behaviors Dissemblance in any
one of them cause refreshment. PHARMACOLOGICAL EFFECT OF BDZ.
a) CNS:
2. Sedfation calming effect of anxious, resteress, against pt.
3. Reduction of anxiety & aggervsion.
4. Depression of psychormotol & congnitive fxns mental. Memory, leaving, recall.
5. Diminish the punjishment suppressed behaviours in animals this disinhibited
behavoin equates with anxioulytic action on human).
6. Behavioueral disinhibijtory eff lead to impaired judgement loss of self control &
some enphorient eff. Due to anxiety relief not enphoric effect.
7. Anterograde Amnesia (Dose dependent)
8. with small dose less events undec with laege dose more drug effect for some hrs.
Retrogrfade Amensia by drugs:
Hyoscine (Anti muscacinic)
Induction of sleep from sedation hyprosis
• Sleep latency (Pt goes to bed wait for hrs and tirs bt not sleep)
• Duration NREM stfage-2 sleep
• Sleep is not refreshing
• Duration of total sleep
• Intermitten awakening
• Dueration of REM sleep
• Duration of BREM stage-4
Show wave. Sleep (Metab rate & adr. Steroid sec. are at lowerst & growth hormone at
highest) No prominent eff on metabolic fxns & secretions but after prolonged.
9. Anaesthersia- Diaz loraz, midaz & in combination with othert agents.
(midazepam, Diazepam, Lorzepam)

6. Reduction of muscle tone & co-ordination- independent of se4dation. Fine movement
lost Muscle tone Hypotonia. In pregnancy
I/V ose is not practiced CZ resp support sudden apnea death should be present.
For jendoscopy small period anaesthetics ishort procedures.
10. Central muscle relaxant eff (BDZ) & meprobamate use of BDZ
*epilepsy
For RX of dnig induced convulsion list line linedrugs.
• spasticity disorderts.
• Inhibit poly synaptic reflexes
• Depren internucial transmission
• High dose depress tramission in sk muscle.
11. Anti convulsant eff. (leptfazole induced)
RX of convulsionh:
Diazepan, chlorazepam.
Statis Absence
Epi lepticus seizures.
12. Anti depressant eff (Alprazolam)
13. Tolerance & cross tolerance
Ph.K component
Memtabolism
Dyna plaer4ance due to recap denyelination.
Defect in drug recap coupling.
Psycholgivcal dependace 6-8 wks use
Physical dependence but not sever.
Rebound eff withdrawal eff.
14. Dependance: (more than 2-6 wks). Opiod just 1-2 days use cause dependence.
WIDE SPREAD SAFETY MARGIN.
B) CVS;
Depressed.
N0 no prominent phenonmen effect.
If hypovolemica then prominent eff in ferson.
b) RESP. SYSTEM
Normal person not prominent eff.
Pt suffering from COPD bdz leads to resp deprevsion death can occure.
PHARMACOKINTICS OF BDZS.
ABSOCPTION: oral injectable, I/M
Highly lipid soluble abscbed from site of absorption
Chlorfazepate undergo activations in stomach by hydrolysis.
DISTRIBUTION.
Groos top CNS cross BBB central effect. Aq humor
Blood aq
Blood mille
Blood testis.
Can be secreted in milk 16.6- 6.9
Basic drugs are secrtelted in milk (non polac in blood) lipid shouble goes in milk
become polar these and remain these.

7. BIO TRANSFUNATION.
Dealkylation (Active)
Hydroxylation Glu crnidation Active (inactivation)
Occucin CYP 3 A4 in liver
So. Metabolism of most BDZ is affected by enz inducers & enz interibitos hepatic
dysfxn & eldecly pt.
No active metabolite with Lorazepam oxazepam & estazolam.
FNZ inducers: ducation ½ liver dystxn
EXCRENTION:
Glucronideslinaetive by kidneys.
No roles of kidney.
CC
CCCC
They are of SD____lcrs. Chances of long overs
Tolerance.
Addictive pot
Mental & physical impairment.
BDZ ANTAGONISTYS:
FLUMAZEIL:
• Imidazo BDZ.
• Ist discovered in 1981.
• Competitive antagonist of against and inv agonists b/C it will bind recap in
constitutive states.
• At high doses partial agonistic activity.
• Do not block eff of other sed hypnotics opiods, ethanol & gene anesthetic b/C
only bind BDZ recap.
Pharmaeokinetics.
T1/2 0.7-1.3 hrs rapid hepatic collearance.
Dosage 1-1omg.
I/V
USES:
BDZ & mixed CNS deprersion.
Nevrological deficit in hepatic encephyalo pathy.
Diagnosis of addiction.
cc
5HT1A AGONISTS AS ANXIOLYTICS:
1. BUSPIRONE:
5mg TDS
Act as partial against at 5ht recap.
They are abundant in septohippo-campal region & receive projection. From
midbrain raphae SHT neurons.
They will the 5HT autoinhyibitory recap eff. Release of mediators so, they act
indirectly.
5HTT1A recap are authionhibitory.
Aslo bind doparmine recap.
Chronic use adaptive reduction in cortical SHT recap activity.

8. So the eff onset is delayed so cannot used for acute conditions.
Not eff in panic disorders & acute anxicty states.
Also inhibit NA act of locus ceruleus neurons interfere e arousal reactions.
ADV: No sedation>
No motor incoordination no withdrwal symptoms.
No anticonvulsant eff.
No memory impairment.
Addicitive potential.
Tolerance potential.
A/E Nausea, Dizziners, Headache, Restlessness.
KINETICS.
Well absorbed pec orally.
Metabolism in liver by dealkylations & hydroxylation.
Active metabolitie.
Major is 1 (2 pyrimdyl) piprazine which also has antagonistic action on x-recep.
2) ISAPIRONE.
Has high selectively for 4HT1A recap.
Also 5HT transmission iridirectly.
NATI ENXIETY
3) SUMOTRIPAN.
4) GEPIRONE. All have similar action.
5) TAMDPSPIRONE
All of them:-
 Less psychomotor impairment so
 Do not effect driving skill
 No sedation & hypnosis
 No above liability
 No motor in coordination
 No rebound anxiety
 No withdrawal effects
 No binding with GABA OR BDZ binding Sites
 No anti conwlsents
 No muscle relaxant effects
 No euphoriant potential
 Do not potential effect of other
 Sedatives, hypnotics, alcohol & Tricycles
 Elderly pts are not more sensitive
.
CI:
MAO-I therapy (BP)
Vses:
Generalized anxity atates

9. Drug Innteraction:
• Refampicin ½ Buspirone
• Ketoconazole inhibit ayp 3A4 & 1+ ½
MELATONIN RELEPTOR AGONIST
Remelteon:-
MDA:
• Agonist at Melatorin receptors MT1 & MT2
• Melatonin involved in maintaining circadian rhythm of sleep/wake cycles
• Has MT1 & MT2
DISTRIBUTION:
Supra chiasmatics nuclei
KINETICS:
 Well – absocbed per orally extensive, 1st pars effect by cyp-I A2 – active
metabolite with long T1/2
Action:
 Reduce sleep latency
 T sleep duration
 No rebound insomnia or withdrawl effect – ( particularly with short acting
drugs)
A/E:
 DIZZINESS
 Fatigue
 Somnolence
 Prolactines level is
 Testostecon lavel
Uses:
Sleep disorder especially those with sleep latency & difficulty in falling sleep
Interaction:
Flurocamine which inhibits hepatic cyp 1A2
BARBITURATES:
a) long Acting:
Phenopasbitone
Mephobasbitone
b) Intermediate Acting:
Butobasbitone Now obsolete
Hexobasbitone
Cyclobasbitone

10. Allobasbitone
Amylo basbitone
c) Short Acting: (2-hrs)
Secobasbitone
Pentobasbitone
d) ULTRASHORT ACTING:
Thiopentone
Thiol basbitone
Thiamylol
Methohexitone
CHEMISTRY:
Basbituric acid derivative
GABA A---- Post synoptic
GABA B---- Pre- synoptic
M.O.A:
