slides are useful for ug/pg students with clear description

1. DR.MAHI YERUVA
PG STUDENT.
DEPT OF PHARMACOLOGY
GOVT MEDICAL COLLEGE

2. ANXIETY
 Unpleasant state of tension,
apprehension or uneasiness that
seems to arise from an unknown
source.
 Usually associated with somatic
symptoms tachycardia, sweating,
tremor, palpitation, hyper apnea, etc

3. EMOTIONAL SYMPTOMS OF ANXIETY
Irrational and excessive fear and worry
Irritability
Restlessness
Trouble concentrating
Feeling tense

4. PHYSICAL SYMPTOMS OF ANXIETY
Sweating
Tachycardia
Shortness of breath
Stomach upset
Frequent urination or diarrhea
Sleep disturbances (Insomnia)
Fatigue

6. ANXIETY DISORDERS
oPanic Disorder
oGeneralized Anxiety Disorder
oPhobic Disorders
oStress Disorders
oObsessive-Compulsive Disorder

8. ANTI ANXIETY DRUGS
o Mostly mild CNS depressants
o Control the symptoms of anxiety,
produce a restful state of mind without
interfering with normal mental or
physical functions.

9. CLASSIFICATION
1. Benzodiazepines: Diazepam ,Chlordiazepoxide
Oxazepam, Lorazepam, Alprazolam, Flurazepam
2) Azapirones :Buspirone ,Gepirone, Ipsapirone
3) Sedative Antihistaminic: Hydroxyzine
4) Beta blockers :Propranolol
5) Others: SSRIs, TCA, MAO- inhibitors,
SNRI (venlafaxine)
Antiepileptics-gabapentin,vigabratin.
 Meprobamate , Clonidine,

10. BENZODIAZEPINES
•Have the suffix “zolam” or “zepam”
 Lorazepam
 Oxazepam
 Temazepam
 Diazepam
 Flurazepam
 Alprazolam
 Estazolam
 Triazolam*

11. CLASSIFICATIONS OF
BENZODIAZEPINES
are classified according to duration of action into:
1.Short acting (3-8 hours): triazolam, Midazolam,
Oxazepam
2.Intermediate (10-20 hours):
Alprazolam, Lorazepam, Estazolam, Temazepam
3. Long acting: ( 1-3 days):
Diazepam, Chlordiazepoxide, Flurazepam,
Quazepam, Clorazepate

12. BENZODIAZEPINES
MOA
Benzodiazepines act by binding to GABA-A
receptors in the brain
GABA (γ-aminobutyric acid): GABA
Enhance GABA action on brain  chloride
channels opening   chloride influx to the cell
 hyper- polarization  more difficult to
depolarizes  reduction of neural excitability.

16. PHARMACOKINETICS
Are lipid soluble
Well absorbed orally
Chlordiazepoxide- diazepam (IV only NOT IM)
Widely distributed.
Cross placental barrier (fetal depression)
Excreted in milk (neonatal depression)
Metabolized in the liver to active metabolites (long
duration of action- cumulative effect).

17. PHARMACOLOGICAL ACTIONS
Anxiolytic action
Depression of cognitive and psychomotor
function
Sedative & hypnotic actions
Anterograde amnesia
Some have anticonvulsant effect e.g.
clonazepam, diazepam
 Therapeutic doses have minimal depressant
effects on , cardiovascular system & respiratory
system

18. THERAPEUTIC USES OF
BENZODIAZEPINES
1. Anxiety disorders:
Short term relief of severe anxiety
General anxiety disorder
Obsessive compulsive disorder
Panic disorder with depression Alprazolam
(antidepressant effect)
Benzodiazepines are fast acting: onset within thirty
minutes to an hour.
2. Sleep disorders (Insomnia):
Triazolam, Lorazepam, Flurazepam

19. THERAPEUTIC USES OF
BENZODIAZEPINES
3. Treatment of epilepsy Diazepam –
Lorazepam
4. In anesthesia


Pre-anesthetic medication (diazepam).
Induction of anesthesia (Midazolam, IV)

20. ADR
 Sedation
 Light headedness
 Cognitive impairment
 Vertigo
 Confusion
 Appetite & Wt gain
 Alt in sexual function
 Dependence

21. BENZODIAZEPINES DRUG
INTERACTIONS
• DRUG CLASSES
CNS depressants
Alcohol & antihistamine
Cytochrome P450 inhibitor
Cimetidine & erythromycin
CYT P450 inducers Phenytoin & rifampicin
EXAMPLES
effect of benzodiazepines
t ½ of benzodiazepines
t 1/2 of benzodiazepines

22. BENZODIAZEPINES
PRECAUTIONS
 Pregnant women or breast-feeding.
 Dose reduction is recommended in
Liver disease
Old people

23. Advantages of BZD
 High therapeutic index
 Do not affect respiration or cardiovascular
function
 No microsomal induction
 Low abuse liability
 Specific BZD antagonist Flumazenilis
available

24. CHLORDIAZEPOXIDE
 First BZD used as an antianxiety agent
 Produce smooth long lasting effect
 Preferred in chronic anxiety states
 T1/2 :5-15 hours
 Dose : 20-100 mg
 Tablets brand name :-librium (10mg & 25mg)
 Equilibrium -10mg tab)

25. OXAZEPAM
 Hepatic metabolism is less significant
 It is preferred in the elderly and those with liver
disease
 No active metabolite.
 Short duration of action
 Used in short lasting anxiety state
 Daily dose -30-60mg tid
 Tablet brand – SEREPAX 15,30mg tab.

26. LORAZEPAM
 Oral & IM administration
 No active mtb
 Short acting  preferred in elderly
 Used in short lasting anxiety ,Panic, OCD,
tension syndrome
 Dose: 1 - 6mg/day

27. ALPRAZOLAM
Anxiolytic + antidepressant
High potency anxiolytic
Useful in anxiety associated with
depression
 Plasma t1/2-12 hours
Less drowsiness
Dose : 0.25-0.5mg BD or TDS
active mtb
Tablet brand:- ALPRAX & RESTYL

28. AZAPIRONES
 Buspirone , Gepirone, Ipsapirone
MOA:
Selective agonistic action on 5HT-1A
receptor
Weak D2 blocking action – no
antipsychotic or extrapyramidal S/E
Site of action:
Dorsal raphe seretoninergic neurones

29. Azapirones
Advantages:
 No sedation
 No tolerance or physical
dependence
 No abuse liability
 Less psychomotor
impairment
 Does not potentiate the
effect of other CNS drugs
Disadvantages
 Slow onset of action
 not suitable for acute
anxiety
 Requires thrice daily
admin

30. PK
 given orally, rapidly absorbed
 Extensive first pass metabolism
 Excreted through urine and faeces
ADR
 Dizziness ,headache, Nausea
 Tachycardia , Pupillary Constriction
 RISE IN BP WITH MAO INHIBITORS.
DOSE: 5-10mg OD-TDS
TABLET BRAND:- BUSPIN.

31. SSRI in Anxiety
 Preferred in chronic anxiety states
 Started in low dose
 Slow onset of action
 Started along with BZD
HYDROXYZINE :- ANTIHISTAMINIC DRUG
RELIVES ANXIETY AT HIGHER DOSES 400mg/day
USED IN PRURITIS AND UTRICARIA
MEBROMATE:- CENTRAL MUSCLE RELAXANT
NOT USED NOW AS IT IS HIGHLY SEDATIVE.

32. Beta blockers
o Propranolol :reduce the symptoms of
anxiety
o They do not affect the psychological
symptoms (worry ,tension, anxiety)
o Used for performance/situational anxiety
o Dose: 20-40mg 2hr before the
performance

33. Different type of anxiety
 Generalized Anxiety Disorder: persistent excessive,
unrealistic worry associated with somatic symptoms.
 Acute phase – Benzodiazepines are preferred
 Rapid onset of action
 Eg: lorazepam, Oxazepam
 Not ideal for long term treatment due to abuse
liability & development of tolerance
 For long term use : Buspirone ,SSRIs .

34. OBSESSIVE-COMPULSIVE
DISORDER
• everyday functioning
  Treatment
o TCA (clomipramine) poorly tolerated
o SSRI
• Fluoxetine (5–60 mg/d),
• fluvoxamine (25–300 mg/d),
• sertraline (50–150 mg/d)
o Buspirone
o BZD
 Obsessive thoughts and compulsive behaviors that impair

35. Panic Disorder:
Recurrent and unpredictable panic
attacks, with intense discomfort and fear
of impending doom or death.
Treatment
• SSRIs low doses
• Eg: 5–10 mg fluoxetine, 25–50 mg sertraline,
10 mg paroxetine

36. Phobic Disorders
 Persistent fear of objects or situations, exposure
to which results in an immediate anxiety
reaction. The patient avoids the phobic
stimulus, and this avoidance usually impairs
occupational or social functioning.
Treatment
Beta blockers : Propranolol 20–40 mg orally
2 h before the event (performance anxiety)
o SSRIs
o MAO inhibitors

37. Stress Disorders
 Anxiety following exposure to extreme traumatic
events. The reaction may occur shortly after the
trauma (acute stress disorder) or be delayed and
subject to recurrence (PTSD) . In both syndromes,
individuals experience associated symptoms of
detachment and loss of emotional responsivity.
 Treatment:-
o Benzodiazepines and supportive/expressive
psychotherapy
o SSRI
o MAO inhibitors

38. Future prospects
 Cholecystokinin (CCK) antagonists
 Alpiderm: partial agonist on BZD
receptor
 Corticotropin-releasing factor
(CRF) antagonists
 Neuroactive steroids

39. LIVE FREE
FROM ANXIETY