1. Pharmacology
PHARMA BOARD

3. Anxiety
 Fear, apprehension and worry
 Accompanied by physical sensations such
as anxiety, nausea, chest pain and/or
shortness of breath

4. Neurotransmitters
 Excitatory NTs
 Key words: sodium, calcium, depolarization
 Inhibitory NTs
 Key: chloride, GABA, hyperpolarization

5. Excitatory neurotransmitters
 opens Na or Ca channels/ influx
depolarization (more positive) nerve
impulse
 e.g. Norepinephrine, Dopamine,
Acetylcholine, Glutamate, Aspartate

6. Inhibitory neurotransmitters
 opens Cl channels hyperpolarization
(more negative)  no nerve impulse
 e.g. glycine, gamma-aminobutyric acid
(GABA)

7.  1. Panic disorder- recurrent unexpected
panic attacks that can occur with
agoraphobia in which patients fear places
in which escape might be difficult.
 2. Specific phobia- intense fear of
particular objects or situations (e.g. snakes,
heights);most common psychiatric disorder

8.  3. Social phobia-intense fear of being
scrutinized in social or public situations
(e.g., giving a speech, speaking in class).
 4. Generalized anxiety disorder- intense
pervasive worry over virtually every aspect
of life

9.  5. Post-traumatic stress disorder-
persistent reexperience of a trauma, efforts
to avoid recollecting the trauma, and
hyperarousal
 6. Obsessive-compulsive disorder-
recurrent obsessions and compulsions that
cause significant distress and occupy a
significant portion of one’s life

10. Sedatives-Hypnotics
 Benzodiazepines
 Increase the frequency of GABA-mediated
chloride ion channel opening
 Barbiturates
 Increase the duration of GABA-mediated
chloride ion channel opening

11. Classes of Anxiolytic and Hypnotic
drug
Benzodiazepines
 5-HT1A-receptor agonists
 β-adrenoceptor antagonists

12. Benzodiazepines
 Act by binding to a specific regulatory site
on the GABA A-receptor
 enhances the inhibitory effect of GABA.
 Subtypes of the GABA A-receptor exist in
different regions of the brain
 differ in their sensitivity to benzodiazepines.
 Anxiolytic benzodiazepines are agonists at
this regulatory site.

13. Receptor Empty
Intra cellular
GABA
GABA
Receptor
-
CL
+++++++
- - - - -
NaChannel
NaChannel

14. Intra cellular
GABA
GABA
Receptor
-
CL
+ + + +
- - - -
NaChannel
NaChannel
- - - -

15. Use of The Drugs
Clinical indications for the use of the
anxiolytics, sedatives and hypnotics
 1. Prevention of anxiety
 2. Formation of sedative state
 3. Induction of sleep

16. ACTIONS
 Reduction of anxiety
 Sedative – hypnotics
 Anticonvulsant
 Muscle relaxant

17. The BENZODIAZEPINES
The benzodiazepines are the most frequently used
anxiolytic drugs.
These agents prevent anxiety states without
causing much sedation, with less physical
dependence than other agents.

18. The BENZODIAZEPINES
 Long Acting
 Intermediate Acting
 Short Acting

19. Long Acting (1-3 days)
 Charlie Chaplein Died From Q-fever

20. Long Acting (1-3 days)
 Charlie - Chlorazepate
 Chaplein - Chlordiazepoxide
 Died - Diazepam
 From - Flurazepam
 Q-fever - Quazepam

21. Intermediate
 L A T E

22. Intermediate
 L - Lorazepam
 A - Alprazolam
 T - Temazepam
 E - Estazolam

23. Short Acting
 O- Oxazepam
 T- Triamzolam

24.  Uses:
 Anxiety- alprazolam, diazepam
 Seizures- diazepam, clonazepam,
lorazepam
 Insomnia- flurazepam, midazolam
 Pre-operative sedation- midazolam

25. The BENZODIAZEPINES
Special uses
Diazepam
(Valium)
Status epilepticus
Chlordiazepoxide
(Librium)
Alcohol
withdrawal
Alprazolam
(Xanax)
Panic attack

26. The BENZODIAZEPINES
These agents are indicated for the treatment of
1. anxiety disorders
2. alcohol withdrawal
3. hyperexcitability, and agitation
4. pre-operative relief of anxiety and tension
and in induction of balanced anesthesia.

27. The BENZODIAZEPINES
Pharmacodynamics: The adverse effects
 CNS effects= drowsiness,
depression, lethargy, blurred vision
 GIT= dry mouth, constipation, nausea,
vomiting
. sedation,

28.  CVS= Hypotension or hypertension,
arrhythmias, palpitations, and
respiratory difficulties.
 Hematologic= blood dyscrasias and
anemia
 GU= urinary retention, hesitancy, loss of
libido and sexual functions changes.

29. The BENZODIAZEPINES
 Instruct to avoid consuming
ALCOHOL while taking the drug.

30. The BENZODIAZEPINES
 Have available FLUMAZENIL as an
antidote for benzodiazepine
overdose.

31. 5-HT1A Agonists as Anxiolytic
Drugs
 Buspirone
 potent (though non-selective) agonist at 5HT1A-
receptors.
 Lacks anti-seizure and muscle relaxant properties as
benzodiazepines
 Headache, minimal tolerance and withdrawal
 Anxiolytic effects take days or weeks to develop.
 Ipsapirone and Gepirone are similar.
 Side effects include dizziness, nausea, headache, but
not sedation or loss of coordination

32. The BARBITURATES
 These are also anxiolytics and
hypnotics with a greater likelihood of
producing sedation, with increase risk
of addiction and dependence.

33. Barbiturates
Non-selective CNS depressants
Sedation and unconsciousness
Bind to the GABA receptor and
enhances activity
potent inducers of hepatic drug-
metabolising enzymes
Tolerance and dependence
occur.

34. Barbiturates
Non-selective CNS depressants
Sedation and unconsciousness
Bind to the GABA receptor and
enhances activity
potent inducers of hepatic drug-
metabolising enzymes
Tolerance and dependence
occur.

35. MODE OF ACTION
 Interferes with Na and K transport
 Potentiates GABA action on Cl

36. ACTIONS
 Depression of CNS
 Respiratory depression
 Enzyme induction

37. CLASSIFICATION
 ULTRA – SHORT
 Thiopental
 Thiamylal
 Methohexital
 Duration: 30min

38.  SHORT ACTING
 Hexobarbital
 Pentobarbital
 Secobarbital
 Duration: 2hrs

39.  INTERMEDIATE ACTING
 Amobarbital
 Butabarbital
 Duration: 3 – 5hra

40.  LONG ACTING
 Barbital
 Phenobarbital
 Duration: > 6hrs

41. The BARBITURATES
Pharmacodynamics: The Adverse effects
 CNS= CNS depression, somnolence, vertigo,
lethargy, ataxia, paradoxical excitement, anxiety
and hallucinations.
 GIT= nausea, vomiting, constipation/diarrhea
and epigastric pain

42.  CVS= bradycardia, Hypotension and
syncope.
 Respi= serious hypoventilation, respiratory
depression and laryngospasms
 Others= hypersensitivity and Stevens-
Johnson syndrome.

43. Other Notes
 Benzodiazepines have no analgesic
properties
 Fatality of alcohol and benzodiazepines
 Hypnotics does not induce REM so less
restful than normal sleep
 Longer acting drugs are easier to dose so
effective in alcohol withdrawal

44. Sedative-Hypnotics: Barbiturates
Drug Interactions
 Additive effects:
 ETOH, antihistamines, benzodiazepines,
narcotics, tranquilizers
 Inhibited metabolism:
 MAOIs will prolong effects of barbiturates
 Increased metabolism:
 Reduces anticoagulant response, leading to
possible clot formation

45. Benzodiazepines vs. Barbiturates
Criteria BZ Barb.
Relative Safety High Low
Maximal CNS depression Low High
Respiratory Depression Low High
Suicide Potential Low High
Abuse Potential Low High
Antagonist Available? Yes No

46. Ion channel that contains the
GABA receptor:
A. sodium
B. calcium
C. chloride
D.potassium

47. Anxiolytic drug acting through
serotonin receptors:
A.diazepam (Valium)
B. buspirone (BuSpar)
C. triazolam (Halcion)
D. phenobarbital

48. A comatose patient is brought to the emergency
department with severe respiratory
depression caused by diazepam overdosage.
Reasonable intervention at this point include:
A. administer naloxone (Narcan) to block the
drug's effect at the receptor
B. provide supportive therapy until the drug
effect wears off.
C. administer flumazenil
D. B & C

49. Short-acting benzodiazepine
A. diazepam (Valium)
B. flurazepam (Dalmane)
C. triazolam (Halcion)
D. buspirone (BuSpar)

50. Most useful in reversing symptoms
of benzodiazepine overdosage:
A. amphetamine
B. buspirone (BuSpar)
C.flumazenil (Romazicon)
D. naltrexone (ReVia)