Dwi Indria Anggraini

AGENTS USED FOR ANXIETY DISORDERS

(ANXIOLYTICS)

AGENTS USED FOR DEPRESSION

(ANTIDEPRESSANTS)

AGENTS USED FOR SCHIZOPHRENIA

(ANTIPSYCHOTIC)

AGENTS USED FOR SLEEP DISORDERS

(HIPNOTIC-SEDATIVES)
 ANXIETY is a state characterized by psychological
symptoms, often accompanied by physical symptoms of
autonomic arousal (palpitations, light headedness,
perspirations, butterflies, restlessness)

Benzodiazepines and/or selective serotonin

reuptake inhibitor (SSRI) antidepressant used for
generalized anxiety disorders (GAD) and panic
disorders

Trycyclic antidepressant (TCAs) & Monoamine

Oxidase (MAO) Inhibitors for long term
management of anxiety
 SSRI have receive FDA approval for the
treatment of GAD, panic disorders, Obsessive
Compulsive Disorders (OCD), Post traumatic
stress disorders (PTSD) & Social phobia
 SSRI most be used start low, go slow
 For acute relief of anxiety or panic attacks,
benzodiazepines are useful
 All Benzodiazepins currently available & are
qualitatively similar in terms of their efficacy
& safety profiles
 Clonazepam & Alprazolam are most
commonly to treat anxiety disorders
 The benefit of Buspirone (for GAD) are virtual
absence of dependence & abuse liability
 Buspirone indicated for patients with a history
of alcohol abuse
 Prototypic agent  Diazepam (D)
 Other agents 
Clonazepam (C), Alprazolam (A), & Lorazepam (L)
 MOA:
Bind to components of GABA A Receptors 
facilitate inhibitory actions of GABA in CNS
 Indications:
- Anxiety disorders (especially A & C for panic &
phobic disorders)
- Sedation, seizures, muscle relaxants (D)
- Management of alcohol wtihdrawal
 Pharmacokinetics:
- Potency  C > A > L > D
- T½L=A<C<D
- Hepatic metabolism
 ADRS:
- Cognitive impairments
- Sedation, amnesia
- Diminished motor skill
 Warnings/Precautions:
- Additive sedative effects with other CNS
depressant depressan (ethanol)
- Toleranca & Dependence (prolonged use)
 Prototypic agent : Fluoxetine (F)
 Other agents :
Paroxetine (P), Sertraline (S), Citalopram (C)
 MOA: Inhibit reuptake of Serotonin
 Indications:
1. Depression
2. Anxiety disorders (OCD, pannic attacks,
social phobias, etc)
 Pharmacokinetics: - per oral only
- hepatic metabolism
 ADRS:
- Sedations or insomnia
- Headache, nausea, appetite & weight changes
- Sexual dysfunctions

 Warning/Precautions:
- Serotonin syndrome may accur with other
serotonergic drugs (i.e. MAO inhibitors)
- SSRI inhibit Cy-P450 liver enzymes
 MOA:
- Partial agonist AT 5 HT1A brain receptors
- Anxyiolitic action unknown
 Indications: Generalized anxiety disorders
 Pharmacokinetics:
- Per oral only
- Hepatic metabolism
 ADRS:
- Dizzines
- Headache
- Nausea
 A DECREASE IN CERTAIN NEUROTRANSMITTERS
(Serotonine norepinephrine & possibly
dopamine) have been associated with
depression
 All antidepressant are equally effective in the
general depressed population, generating a
therapeutic respons in 60-70%
 Generally, symptoms begin to impprove within
the first 2 weeks, optimal > 4 weeks
 SSRI are the most popular treatment option (Low
side effects, easy of administration)
 Venlafaxine is a dual-action antidepressant
that serotonin activity (Low dose) & Nor
epinephrine (higher dose)
 Bupropion is another second line agent,
particularly for patient who are worry of the
SSRI negative impact on sexual dysfunction
 Bupropion is contraindicated in patient with a
history of seizures or eating disorders
CLASS EXAMPLES MOA
Tricyclic AD (TCAs) -Amitriptyline Non specific blockers
-Imipramine of MAO-Uptake
Specific Serotonin -Fluoxetine Selective Blockers of
Reuptake Inhibitors -Paroxetine 5-HT Reuptake
(SSRI) -Sertraline
Serotonin Noradrenalin - Venlafaxine Selective blockers of
Reuptake Inhibitors 5-HT & NA uptake
(SNRIs)
Monoamine Oxidase -Phenelzine Non competitive, Non
Ihibitors (MAOIs) -Tranylcypromine selective,
Irrevversible blockers
of MAOA+B
Reversible Inhibitors of Moclobemide Reversibly inhibit
MAOA (RIMA) MAOA selectively
ATYPICAL Reboxetine Act by various MOA
Mirtazapine
 Traditional antipsychotic/neuroleptic block the D2
dopamnie recpetor & alleviate the positive symptoms
of schizophrenia (e.g. hallucination, delusions,
thought dysfunction)
 The positive symptoms, due to excess dopamine in
the mesolimbic pathway
 The negative symptoms, due to deficiency dopamine
in the mesocortical pathway & frontal cortex
(regulated by serotonin)
 Traditional neuroleptics have little effect on negative
symptoms or cognitive dysfungtion
 Atypical antipsychotic (newer agents) alleviate
positive & negative symptoms & improve cognitives
 Strong potency  strong afinity to D2 receptors
 Low potency  low affinity to D2 receptors
 Traditional neuroleptics are poorly tolerated due
to unfavorable side effect profiles, such as extra
pyrmidal symptoms (EPS) & tardive dyskinesia
(TD), as muskarinics (M1), histaminergic (H1) &
adrenergic (1 & 2) side effects
 Neuroleptic malignant syndrome (NMS) is a rare
but potentially fatal reaction associated with
antipsychotic therapy, with the 4 cardinal
features: Hyperthermia, Muscular Rigidity,
Autonomic Instability, Altered Consiousness
CLASS CHEMICAL CLASS EXAMPLES
TYPICAL PHENOTHIAZINES:
-Propylamine -Chlorpromazine
-Piperidine -Thioridazine
-Piperazine -Fluphenazine

NON-PHENOTHIAZINES:
-Butyrophenones -Haloperidol
-Thioxanthines -Flupentixol

ATYPICAL DIBENZODIAZEPINES -Clozapine, Olanzapine

DOPAMINE/5-HT
BLOCKERS:
-Diphenylbutyl -Pimozide
piperidines -Sulpiride
-Substituted -Risperidone
benzamides
-Benzixasoles
 ADRs on Dopaminergic pathway:
- Psychological effect due to D2 rec blockade of
mesolimbic/mesocortical
- Movement disorder due to D2 rec blockade of negostriatal pathway
- Neuroendocrine disorder due to D2 rec blockade of
tuberoinfundibular pathway

 ADRs from non selective receptor blockade:

- Anticholinergic effect
- -adrenoreceptor blockade (postural hypotension)
- H1-rec blockade (sedation)
 ADRSs due to individual drugs/immune reaction:
- Neutropenia (Olanzepine)
- Arrytmia (Pimozide)
- Skin rash (Phenothiazine)
 Insomnia is a common & non specific disorder at
40-50% peoples
 Causes of insomnia are medical ilness,
alcohol/drugs, periodic limb movement
disorders, sleep apnea, psychiatric ilness
 Without an obvious underlying cause, it is known
as primary or psycho-physiological
 Hypnotic are drug used to treat psycho-
physiological (primary) insomnia
 BARBITURATES:
- Currently not recommended, due to abuse potential &
lethal potential
- Pentobarbital, Secobarbital, Amobarbital

 NON-BARBITURATES:

- Similar mechanism with barbiturates

- Chloralhydrate is still commonly used to day, due to its

efficacy as a shortterm sedative hypnotic & low cost
 BENZODIAZEPINES:

- Widely used as sedative hypnotics

- Quick onset: Triazolam, Flurazepam, Quazepam

- Longer acting: Temazepam, Flurazepam

 NEWLY AGENTS:

- Zaleplon (Pyrazolopyridine), Zolpidem

(Imidaropyridine)
 ZOLPIDEM:
- DOC for insomnia
- Act on benzodiazepine-Omega-1-receptor,
selectively (sedation)
- Rapid onset & short duration of action
- Less potential for abuse, fatal overdose,
withdrawal reactions

 ZALEPLON:
- Short acting, faster onset than zolpidem
 DRUG ADVANTAGES DISADVANTAGES
Chlorpromazine inexpensive ADR >> (esp. autonomic)
Thioridazine Extrapyr. Synd. << Cardiotoxic
Thiothixene Decreased tardive
dyskinesia
Haloperidol Potent; p.e (+) Extrapyr. Synd severe
Clozapine May benefit: resistant Agranulocytosis
patient
Extrapyr. Synd. <<
Risperidone Broad efficacy Higher dose: extrapyr.
Extrapyr. Synd. << (low dysfunc. & hypotension
dose)
Olanzapine Neg. & pos. symptoms Weight gain (less for
Quentiapine Extrapyr. Synd. << quentiapine)
Quentiapine: short T½

Efficacy as antipsychotic are similar; SE differ significantly