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CONTENTS;
1. GENERAL INTRODUCTION
..
5. ANTIEPILEPTICS
6. ANTIDEPRESSANTS
7. ANTIPSYCHOTICS
.........
..
8. MOOD STABILIZERS
..
10.
DRUG THERAPY OF INSOMNIA
..
11.
PHARMACOTHERAPY OF SUBSTANCE ABUSE
DISORDERS
12.
APPLICATION OF ANTIANXIETY AGENTS,
ANTICONVULSANTS, ANTIHISTAMINICS IN
PSYCHIATRY
13.
PSYCHIATRIC DRUG THERAPY IN SPECIAL
SITUATIONS .
14.
MEDICAL CONDITIONS ASSOCIATED WITH
PSYCHIATRIC DISORDERS.
.
15.
PSYCHATRIC EMERGENCIES
BIBLIOGRAPHY
Common Neurotransmitters
________________________________________________________________
_____________
Amino Acids
Peptides
Amino Acids :
1.
2.
3.
4.
5.
6.
3
GABA
Glycine
Taurine
Glutamate
Aspartate
Homocystine
Biogenic Amines
Others
Neuro-
Biogenic Amines :
1. Acetylcholine
2. Monoamines
Neuro-Peptides :
1.
2.
3.
4.
5.
Substance P
Vasopressin
Encephalin, Endorphin
Neurotensin
Oxytocin
Others :
1. ATP, AMP
2. NO, CO
3. PG, NH
Monoamines can be further subdivided into
i)Serotonin, ii) Catecholamine,
Agmatine v) PEA
iii)
Histamine
iv)
Neurotransmitters
________________________________________________________________
__________________
Inhibitory
Excitatory
GABA
Glutamate
Serotonin
4
Epinephrine
Glycine
Norepinephrine
Taurine
Phenylethylamine
Dopamine
Histamine
Agmatine
Acid
Aspartic
Dopamine
Glycine
GABA
Dopamine
Glycine
Serotonin
Glutamate
Epinephrine
Aspartate
Norepinephrine
Taurine
Histamine
Agmatine
Neurotransmitter
criteria :
Phenylethylamine
:
Chemical
agent
fulfilling
following
****************
basal forebrain area responsible for mediating antipsychotic effect of anti-psychotic drugs.
3. Tubero-infundibular tract The cell bodies are in the
arcuate nucleus and periventricular area of hypothalamus
and project to the infundibulum and anterior pituitary.
Importance :
- Dopamine acts as prolactin release inhibitor factor.
Hence Dopamine receptor antagonists have S/E of
hyperprolactinaemia.
- Highest concentration of Dopamine occurs in brain.
Phenylalamine and Tyrosine are the precursors of DA.
The rate limiting step in synthesis is Tyrosine to DOPA
by Tyrosine hydroxylase
The action of Dopamine is terminated either by
reuptake mechanism, where Dopamine is taken up into
the pre-synaptic neuron via pre-synaptic dopamine
transporter (DAT) or by metabolism. The dopamine
transporter is the target of action of cocaine
methamphetamine. It is also the target of neurotoxins
like MPP, the metabolite of MPTP which ultimately
causes neuronal death, condition mimicking Parkinsons
disease. Metabolism of Dopamine occurs primarily by
MAO-B, and less importantly by COMT. The end product
of dopamine metabolism is Homovarillic Acid (HVA),
concentration of which can be assessed from CSF, urine
or serum.
There are 5 subtypes of Dopamine receptors D to D
which are broadly grouped into two, D and D are
grouped in one, D, D and D in the other. D receptor
found predominantly in caudate nucleus and putamen.
The typical antipsychotic drugs used in Schizophrenia
have antagonistic action at D receptor. Bupropion
blocks the dopamine transporter while dopamine
containing storage vessicles are depleted irreversibly by
reserpine, reversibly by Tetrabenzine. D selective
antagonists are useful in de-addiction. Dopamine is the
neurotransmitter involved in the pathophysiology of
8
Blockade of central
confusion and delirium.
cause
11
Psychopathlog
ical
implications
Endogenous Opioids
Act on ,, May have role in
- receptors;
addiction.
Encephalins
regulates
- Endorphins
stress, pain and
- Dynorphins
mood.
Corticotropin
Releasing
(CRF)
Function
Modulates
Factor response
to
internal
and
external stress.
Substance P
Primary
afferent
sensory
neurons, nigrostriatal
pathway
involved in pain
perceptions.
Neurotensin
Association
with Dopamine
in some nerve
terminals.
Cholecystokinin
Triggers anxiety
and
panic
attacks.
CRF antagonists
may have a role
in treatment of
depression.
May have a role
in Huntingtons
disease,
Alzheimers and
mood disorders.
Pathophysiology
of
Schizophrenia.
Pathophysiology
of Schizohrenia
eating disorders
movement
8
9
10
11
12
13
12
disorders.
Somatostatin
GH
inhibiting Huntingtons
factor.
disease,
Alzheimers
dementia.
Vasopressin, Oxytocin Regulation
of Behavioural.
mood
and
social
behaviour.
Neuropeptide Y
Stimulates
Eating
appetite.
disorders.
GABA
Anxiolytics,
Anxiety,
Anti-epileptics
Epilepsy.
act via GABAergic pathway.
Glycine
Independent
Decrease
in
inhibitory
negative
neurotransmitt symptoms
of
er
and Schizophrenia.
adjunctive role
for
glutamate
activity.
Glutamate
Responsible for Excess
NMDA
excitotoxicity
activity
kills
and
neurons may be
Schizophrenia.
responsible for
May have a role Parkinsons
in learning and Disease.
memory.
Nucleotides
Action opposite Adenosine
to
caffeine analog may be
terminates
useful
as
seizures.
sedatives, anticonvulsants.
Neurotrophic factors
Neuronal
Not
yet
growth,
established.
development
and survival.
****************
Hypnotics and Sedatives
Sedatives Agents which depress CNS activity producing a
calming effect or drowsiness.
Hypnotics- Agents which facilitates the onset and
maintenance of sleep.
Classification;
13
Benzodiazepines:
*Ultra short acting- (t
*Short acting - (t
*Intermediate acting - (t
*Long acting -(t
6-24hr ) eg.Temazepam
>24hr ) eg.Diazepam
Barbiturates:
* Ultra short acting Thiopentone sodium, Methohexitone
*Short acting Pentobarbitone, Butobarbitone
*Long acting - Phenobarbitone
Newer Non Benzodiazepines or Z- compounds:
*Zolpidem,Zaleplon,Zopiclone
Melatonin Congener:
*Ramelteon
Others
*Buspirone, Chloral hydrate, Paraldehyde
Mechanism of action.
BENZODIAZEPINES act selectively on benzodiazepine
receptor, an integral part of GABA A receptor-chloride channel
complex; binding site between two 1 and 2 subunits
enhances presynaptic and postsynaptic inhibition by;
Enhancing response to GABA
Facilitating opening of GABA activated chloride channels
BARBITURATES- act on or subunit of GABA A receptors in
CNS , at sites different from that of Benzodiazepines and
increase the duration of opening of the chloride channels
14
Benzodiazepines;
Pharmacokinetics : All are absorbed orally .
Have huge lipid water distribution coefficient in nonIonized form.
Rate of oral abs, differ according to lipophilicity; most
barbiturates & newer hypnotics are absorbed rapidly into
the blood .
Extensive distribution; crosses BBB,placental barrier, and
secreted in milk.
Plasma protein binding varies markedly (e.g 99% for
Diazepam while 10% for Flurazepam
Metabolized in the liver, many produce active metabolites;
eg.Flurazepam, Diazepam, Chlordiazepoxide, Alprazolam
Ultra-rapid elimination seen with Triazolam, Midazolam
life 2-40 hrs; long life as with Diazepam, Flurazepam,
Lorazepam, Clonazepam
Metabolites are excreted in urine as glucuronide
conjugates
Actions;
Reduction of anxiety and aggression
Sedation and induction of sleep
15
Sedation
Sedation is a function of GABA receptors containing 1
subunit
Calming effect at relatively low doses
Depressant effects on psychomotor & cognitive functions
Euphoria
Impaired judgement, loss of self control
Dose dependant anterograde amnesia
Other Actions
ANAESTHESIA- i.v. anaesthesia, induction of anaesthesia;
diazepam, midazolam, lorazepam
MUSCLE RELAXATION- inhibitory effect on polysynaptic
reflexes & internuncial neurons; meprobamate, diazepam
ANTI-CONVULSANT- clonazepam, diazepam,lorazepam,
nitrazepam
RESPIRATORY & CARDIOVASCULAR SYSTEM- dose related
depression of medullary resp. centre and or vasomotor
centre causing respiratory depression or circulatory
collapse
16
Adverse Effects;
Dizziness, headache, vertigo , ataxia,
Amnesia, delayed reaction time, impaired psychomotor
skills
Weakness, blurring of vision, dry mouth, urinary
incontinence
Paradoxical actions eg. Irritation, anger
Tolerance, cross tolerance
Drug Interactions;
Synergistic with alcohol, other CNS depressants
CYP 3A4 inhibitors eg. Ketoconazole, Erythromycin,
Cimetidine, INH, OCP retard benzodiazepine metabolism
Uses;
Anxiety states- generalised anxiety disorder, panic
disorders, agarophobia
Sleep disorders- newer non-benzodiazepine hypnotics are
better
Seizure disorders- Diazepam, Clonazepam
I.v. anaesthesia- Midazolam, Diazepam
Preanaesthetic medication
In short surgical procedures eg. Bronchoscopy,diagnostic
procedures
To control symptoms of ethanol or other hypnotic sedative
withdrawal
Barbiturates;
CLASSIFICATION
LONG ACTING- Phenobarbitone
SHORT ACTING- Butobarbitone, Pentobarbitone
ULTRA-SHORT ACTING- Thiopentone, Methohexitone
Barbiturates are substituted derivatives of barbituric acid;
general CNS depressants; cause dose-dependant
anxiolysis, amnesia, hypnosis, anaesthesia, coma,
respiratory depression
Pharmacokinetics;
life 4-60 hrs
Orally absorbed, widely distributed
Onset of action dependant on lipid solubility
17
ADVERSE EFFECTS;
Hangover, tolerance, dependance, idiosyncracy,
precipitation of porphyria in susceptible patients
Newer Hypnotics;
SPECIAL FEATURES;
Rapid onset of hypnosis
Minimum incidence of hangover, amnesic or psychomotor
depressant action
Sleep pattern is minimally affected; withdrawal effect is
not seen on discontinuation
Anti-convulsant, anti-anxiety or muscle relaxation effects
are not evident sp.with Zolpidem
Short duration of effect
No tolerance or dependance noted
DRUGS- Eszopiclone, Zaleplon, Zolpidem
USES- Insomnia specially with prolonged sleep latency
Ramelteon
Melatonin receptor agonist
Activates MT1 and MT2 melatonin receptors in
suprachiasmatic nuclei of CNS
Rapid onset of sleep; minimal rebound insomnia or
withdrawal symptoms
Orally active ; active metabolite
Adverse effects- dizziness, fatigue, decreases
testosterone, increases prolactin
18
Barbiturates;
19
Drugs
IndIcations
Dose
Comments
Phenobarbitone
Generalsed
tonic clonic
seizure,Partial
seizure;Sedativ
e Hypnotic
Thiopentone
25mg/ml in
Ultra short
Induction
Duration 5-8
solution+
1.5mg/ml
Na2CO3
acting
Intravenous
Anaesthetic
dose 2.5%
solution
3-5mg/kg
min
Highly alkaline,
pH 10-11
Methohexital
10mg/ml in
solution+
1.5mg/ml
Na2CO3
Ultra short
acting
Intravenous
Anaesthetic
Induction
dose
4-7 mg/kg
Duration of
induction
4-7 min; pH
10-11
Benzodiazepines;
20
Drug
Indications
Dose
Comments
Diazepam
As Hypnotic
Oral, IM,
sedative,Anticonvul IV,Rectal 0.1sant i.v. anaesthetic 0.2mg/kg;max60
mg/day 5-10mg
tab/day;2.5-5mg
suppository;0.30.5mg/kg for
induction
Several
active
metabolites,
Sedation,Mi
nimal drug
interactions
Lorazepam
As Sedative
,hypnotic
Slower
onset, more
potent,profo
und
amnesia
Midazolam
As i.v anaesthetic
for induction &
maintenance;anti
hallucinatory,antico
nvulsant;
IV , IM;
Premedication
0.07-0.08mg/kg
IM;induction
0.150.3mg/kg;infusio
n0.020.1mg/kg/hr
Rapid onset
of action;
duration 6-8
min; liable
to
abuse,rapid
metabolism
Alprazolam
Anxiety disorders
Oral
Intermediat
e
acting,withd
rawal
effect,residu
al effect
present
Clonazepa
m
Seizure disorders,
Acute Mania
Oral
Tolerance
may
develop
Chlordiazep Insomnia,anxiety
Oral,IM,IV
oxide
disorders,anaesthet 0.30.5mg/kg/day;
c premedication,
10-25mg tab BD
alcohol withdrawal
Long acting,
produce
active
metabolites
Flurazepam Insomnia
Oral; 15-30
mg /day
Long acting
Nitrazepam
Insomnia
Oral;0 0.51mg/kg/day
OD/BD
Long acting
Temazepam Insomnia
Oral; 7.5-15
mg /day
Intermediat
e acting
Triazolam
Oral;0.125-0.25
mg/day
Rapid
metabolism
Insomnia
Newer Benzodiazepines
21
Zolpidem
Insomnia
Zaleplon
Insomnia
Oral; 5-20 mg at
bed tme
Shortest acting
Eszopiclon
e
Insomnia
Oral; 1-3 mg at
bed time
Mesocortical
pathway
Nigrostriatal
pathway
Actions
Reward,
learned
behaviour
Motivation,
reward,
emotion,
impulse
control
Key regulator
of movement
Dysfunctions
Addiction,
psychosis,
schizophrenia,
learning
deficits
Psychosis
schizophrenia
Hypokinesia,
rigidity,
dyskinesia
24
Highest in
CNS
kidney,
retina CVS
Actions Activates
c-AMP PKA
pathway
and
interacts
with
A
receptors,
NMDA
receptors,
NaKATP
ase
calnexin,
caveolin
Predominan Limbic
tly
areas of
expressed
brain
in brain
Retina
Brain
(most
abundan
t), partly
in brain
Occurs post
synaptically
, regulates
K
channels, L
type and N
type
Ca
channels,
Arachidonic
DA tr.
disease,
restless
legs
syndrome,
MAO
3-methoxy-4OH-
acid (DOPAC)a
In clinical practise levodopa is always administered in
combination with peripherally acting inhibitor of aromatic Lamino acid decarboxylase eg. carbidopa or benserazide.
If levodopa is administered alone, the drug is largely
decarboxylated by enzymes in the intestinal mucosa and
peripheral sites, such that < 1% of levodopa can ultimately
cross the blood brain barrer.
25 mg of carbidopa and 100 mg of levodopa combination
given 3 times or more daily.
Levodopa produces dramatic improvement in early phase of
disease but with time its buffering capacity is lost with onset of
motor complications, wearing off phenomenon disabiling
dyskinesias and on off phenomenon.
Adverse Effects of Levodopa :
Nausea, motor complications, hallucinations, confusion
specially in elderly occur. (clozapine and quetiapine appear to
be effective)
Activation of vascular DA receptors may produce orthostatic
hypotension.
Wearing off phenomenon each dose of levodopa being
effective only for a period of 1-2 hours; with re-appearance of
symptoms increase the dose and frequency can benefit to
some extent but will result in
a) dyskinesia excessive and abnormal involuntary movements
specially when plasma concentration of levodopa is high,
b) on-off phenomenon,
c) abrupt withdrawal of levodopa or other dopaminergic
medications may precipitate leading to neuroleptic malignant
syndrome of confusion, rigidity and hyperthermia and may be
potentially lethal.
28
nausea,
orthostatic
29
nausea,
orthostatic
to
their
corresponding
32
33
ANTI EPILEPTICS
Early diagnosis and treatment of seizure disorders with a single
appropriate agent offers the best prospect of achieving
prolonged seizure free periods with the lowest risk of toxicity.
Monotherapy is instituted with a single agent until seizures are
controlled or toxic signs occur. When therapy with a single drug
is ineffective, a second drug maybe added to the therapeutic
regimen. Once initiated antiepileptic drugs are typically
continued for at least 2 years.
Phenobarbitone :
Barbiturate have anti-seizure activity at doses less than that
of hypnotic.
Oldest, cheapest anti-convulsant with minimum toxicity.
Acts by inhibiting synaptic transmission via GABA-A receptor.
Other barbiturates used as anti-seizure drug Mephobarbital,
Metharbital and Primidone.
34
Phenytoin :
Non-sedative structural relative of Phenobarbitone.
Effective in partial, tonic-clonic seizure but not in absence
seizure.
Prodrug Fosphenytoin is water soluble can be administered
intravenously.
MOA- blocks high frequency firing of neurons via voltage
gated Na channels, decrease in Glutamate release at synapsis.
Oral absorption of Phenytoin is dependent on the dosage
form and particle size.
Highly plasma protein bound 90% t =12-36 hours.
Rate of elimination is non-linear; metabolism follows first
order kinetics.
90% Phenytoin metabolised by hepatic CYP2C 9/10, partly by
CYP2C19.
Use Generalised tonic clonic seizures, partial seizure
trigeminal or other neuralgias.
35
Carbamazepine :
36
eruptions,
eosinophilia,
37
Valproic Acid :
Simple branched chain carboxylic acid effective in inhibiting
a variety of seizures.
Fully ionised at body pH the active form of the drug is
valproate ion.
MOA Inhibits high frequency repetitive firing of neurons by
affecting Na currents (MOA in partial seizure). Blockade of
NMDA receptor mediated neuronal stimulation. Facilitates the
enzyme glutanic acid decarboxylase (GAD) responsible for
GABA synthesis. In high concentration inhibits GABA
transminase thereby preventing breakdown of GABA. May also
influence inhibition on GABA transporter GAT-1. Slight reduction
in Ttype Ca current is also seen.
Use Absence seizure, generalised tonic clonic seizure,
myoclonic seizure, partial seizure.
Other uses Bipolar disorder, migraine prophylaxis.
Well absorbed orally, BA 80%.
Peak plasma concentration in 2 hours.
90% plasma protein bound.
Available in both tablet and symptomatic formulation.
t 9-18 hours; elimination is slow, 95% hepatic metabolism.
Adverse effects GI effects : most common anorexia, nausea,
vomiting.
38
Ethosuximide :
Succinimide with selective action in absence seizure.
MOA reduces low threshold T-type Ca current in thalamic
neurons. Does not inhibit sustained repetitive firing or does not
have any effect on GABA concentration.
Oral absorption complete peak action in 3 hours.
Not significantly plasma proten bound.
75% of drug metabolised by hepatic microsomal enzymes.
t is about 40-50 hours.
Adverse effects GI effects : nausea, vomiting and anorexia.
CNS effects drowsiness, lethargy, headache, dizziness,
Parkinson like symptoms, photophobia restleness, agitation.
Hypersensitivity Urticaria, skin reactions, Steven Johnson
syndrome.
39
Haematological
effects
thrombocytopenia, pancytopenia.
Eosinophilia,
leucopenia,
Gabapentin
Consists of a GABA molecule covalently bound to a lipophilic
cyclohexane ning.
High lipid solubility.
May promote non vesicular release of GABA.
Abs after oral admins, excreted unchanged, mainly in urine.
life 4-6 hours.
Effective for partial seizure, migraine, chronic pain, bipolar
disorder.
S/E well tolerated, somnolence, dizziness, ataxia, fatigue
usuall resolve in 2 weeks of onset.
Lamotrigine
May have actions in addition to regulating recovery from
inactivation of Na channels possibly involves inhibition of
glutamate release.
Completely abs. from GIT.
Metabolised by glucuronidation.
life 15-30 hours.
Concurrent use of volproate increase of lamotrigine
concentration, carbamazepine increase in toxicity of
carbamazepine.
40
Topiramate
Decrease voltage gated Na current in cerebellar granule
cells.
Broad spectrum anti-seizure activity.
Rapidly absorbed after oral adminstration.
41
42
43
CHAPTER 3: ANTIDEPRESSANTS
Antidepressants
Depression and anxiety disorders involve variations in mood,
behaviour cognition and somatic function and are amenable to
pharmacological treatment. Depressive episodes are
characterised by sadness, pessimism, lack of concentration,
insomnia, mental slowing, feeling of guilt and worthlessness.
Antidepressants used are as follows :1. Selective Serotonin Reuptake Inhibitors (SSRIs) Sertraline,
Fluoxetine, Fluvoxamine, Citalopram, Escitalopram, Paroxetine.
2. Selective Serotonin and Norepinephrine Reuptake Inhibitors
(SNRIs) Venlataxine, Duloxetine, Desvenlafaxine.
3. Atypical Antidepressants (5HT receptor Antagonists)
Duloxetine, Mirtazapine, Mianserin, Bupropion, Nefazodone,
Trazodone.
4. Tricyclic Antidepressants
Amitriptyline
Amoxapine
Clomipramine
Nortriphyline
Imipramine
Doxepine
Protriptyline
Maprotiline
44
45
46
47
Trazodon
e
Weakly blocks of
5HT uptake weak
5HT antagonistic
activity
adrenergic
blocking action
Sedation,
bradycardia,
postural
hypotension,
priapism
Major
depres
sion
Mirtazapi
ne
Blocks auto
and hetero
receptors,
increases both NA
and 5HT release
concurrent block
of 5HT, 5HT
receptors
additional H
receptor blockade
Sedation, increase
in appetite, weight
gain, rarely
agranulocytosis
Do
Mianserin Blocks
presynaptic
receptors,
Sedation,
anxiolysis, seizure,
liver dysfunction,
Depres
sion
with
48
increase in NA
antagonistic
action on 5HT,
5HT and H
receptors
blood dyscrasia
anxiet
y
Bupropio
n
Inhibitor of NA
and Dopamine
Non-sedative
antidepressant
prolonged
elimination t, 11
hours
Agitation,
insomnia, dry
mouth, seizures in
high dose
Smoki
ng,
cessati
on
Tianeptin
Increase in 5HT
uptake but has
anti-depressant
and antianxiolytic effect
Insomnia/drowsine
ss, dry mouth,
body ache, tremor
Depres
sion
with
anxiet
y
Aminepti
n
Increase in 5HT
uptake but has
anti-depressant
activity
Anticholinergic S/E Do
eg. tachycardia,
dry mouth, CVS S/E
eg. postural
hypotension,
arrhythmias
51
53
Plasma Pr
Binding
Metabolit
e Active
Peak
Plasma
Fluoxetine
Norfluoxeti
ne
Paraxetine
Sertraline
Citalopram
Escitalopra
m
Fluvoxamin
e
4-6 days
7-9 days
94%
Metabolit
e
+
Level
21 hours
26 hours
35 hours
27-32
hours
15 hours
99%
95%
94%
56%
NA
+
NA
+
2-8 hours
6-8 hours
4-6 hours
5 hours
77%
NA
2-8 hours
6-8 hours
Inhibition
of NE
reuptake
Fluoxetin
e
+++
Paroxetin
e
++++
Sertraline +++
Citalopra ++++
+
+
55
Inhibition Others
of
Dopamine
reuptake
Binds to
5HT
receptor
Significant
anticholinergic
action
+
+
Slight H,
Escitalopr +++
am
GABA,
Benzodiaza
m action at
receptors
Do
Uses :
A. First-line therapy for
a) Depression SSRIs are the drugs of first choice. They
are specially considered in
-
b) Anxiety disorders
-
Panic Disorder.
c) Eating Disorder
-
Bulimia Nervosa.
Anorexia Nervosa.
Obesity.
56
Premature ejaculation.
Paraphilias.
Autism.
Adverse effects :
1. GI adverse effects nausea, diarrhoea, cramping, heart
burn, flatulence, dyspepsia. Sertraline and Fluvoxamine
are specially responsible. GI effects gradually reduce in 24 weeks of therapy.
2. Weight gain Initially there is appetite and weight loss,
peaking at 20 weeks, coming to baseline gradually. rd
patients on SSRI gain weight, which resistant to diet and
exercise regimen. Paroxetine is specially responsible.
3. CNS symptoms Headache, anxiety, insomnia, agitation,
probably due to activation of diffuse serotonergic
pathways.
Sleep effects eg. vivid dreams, nightmares, restless legs,
nocturnal myoclonus, insomnia, hypersomnia. Chronic use
leads to emotional blunting, increased yawning. Rarely
seizures and EPS associated with dystonia, tremor, rigidity.
4. Anticholinergic effects Dry mouth, constipation and
sedation are seen due to Paroxetine.
5. Hematologic SSRIs can cause functional impairment of
platelet aggregation manifested as easy bruising or
prolonged bleeding.
6. Endocrinal SSRIs can decrease prolactin levels and can
cause mammoplasia and galactrohoea in either sex.
Breast changes are reversible.
7. Serotonin syndrome Co-administration of SSRI and
MAOIs or lithium or Tryptopham can increase plasma
serotonin level resulting in diarrhoea, agitation,
57
58
59
61
65
67
68
DRUG
RECEPTOR AFFINITY
Tertiary
Tricyclics
++
+
1. Amitripty
line
2. Clomipra ++
mine
3. Imiprami +
ne
4. Trimipra ++
mine
5. Doxepin
Secondary
Tricyclics
1. Desipra
mine
2. Nortripty
line
3. Protriptyl
ine
Tetracyclic
Agents
1. Amoxapi
ne
2. Maprotili
ne
69
UPTAKE
INHIBITION
5H 5H NE
Dopam
T
T
ine
+/- ++ +
Dose
mg
150300
H M
+
+
5H
T
++ +/+
100250
150300
++ 0
++ ++
+
+/- ++ +
+
+
+
+
+
+
+
++ 0
+/- 0
++ +/-
+/- +
+/- +
++
+
++
+
150300
150300
50150
1560
150400
+/-
++
++ 0
+
+
+/-
++
+
++
150225
+
+
+/- 0
+
++
++ +
+
++
Newer
0
Antidepressan
ts
1. Bupropio
n
2. Mirtazapi 0
ne
3. Nefazodo +
ne
4. Sertralin 0
e
5. Venlafaxi 0
ne
+/-
+
+
+
0
++ +
0/+
++ 0
+
++ +
2. Sedation
3. Seizures
Maximum
Imipramine,
Amitriptyline,
Clomipramine,
Desipramine
Amitriptyline,
Clomipramine,
Trimipramine
Maprotiline and
other Tricyclics
4. Conduction
Abnormalities
Trimipramine,
Protriptyline,
Amitriptyline,
Clomipramine
5. Anticholinergic Amitriptyline,
effects
Clomipramine,
Trimipramine
Drug interactions of TCAs :
70
Minimum
Nortriptyline,
Amoxapine,
Doxepin,
Maprotiline
Protriptyline,
Amoxapine,
Desipramine
Desipramine,
Nortriptyline,
Protriptyline
Doxepin,
Amoxapine
Desipramine,
Maprotiline
71
II.
III.
74
****************
75
CHAPTER 4: ANTIPSYCHOTICS
1. First Generation / Typical Antipsychotics :
Chlorpromazine
Haloperidol
Triflupromazine
Trifluperidol
Thioridazine
Pimozide
Trifluoperazine
Loxapine
Fluphenazine
2. Second Generation / Atypical Antipsychotics :
Clozapine
Risperidone
Quetiapine
Olarzapine
Antipiprazole
Ziprasonidone
Amisulpride
Zotepine
Pharmacokinetics :
Well absorbed from GIT, absorption may be affected if
antacids / anticholinergics are co-administered.
Low potency antipsychotics like chlorpromazine, thioridazone
have a wide dosing range while highly potent antipsychotics
like risperidone, olanzapine have a narrow dose range and
needs titration of dose monitoring.
Highly lipid soluble.
Highly protein mainly to albumin.
Metabolised primarily in liver by CYP P and undergoes
glucuronidation before being excreted in urine.
76
DOC
1.
Diabetes
Aripiprazole
2.
Hyperlipidaemi
a
Aripiprazole
78
Drugs to be
avoided
Clozapine,
Olanzapine
Clozapine,
Olanzapine
3.
Orthostatic
Hypotension
Aripiprazole
4.
Weight
gain/Obese
Glaucoma
Aripiprazole, Molindone
5.
6.
Prostate
Hypertrophy
7.
QTc
prolongation
Parkinsonism
8.
9.
Aripiprazole,
Risperidone, Quetiapine
Do
Olanzapine
Low dose Clozapine,
Quetiapine
Aripiprazole,
Risperidone, Quetiapine
Dryness of
eyes or
dryness of
mouth
10. Hypomania/mo Quetiapine, Olanzapine
od
Clozapine,
Quetiapine,
Risperidone
Clozapine,
Olanzapine
Clozapine,
Thioridazine
Clozapine,
Olanzapine,
Thionidazine
Thioridazine,
Ziprasonidone
Haloperidol
Clozapine,
Thioridazine
Adverse
Effects
Chlorpromazin EPS, sedation,
e
hypotension
Triflupromazin EPS, sedation,
e
hypotension
Thioridazine
Sedation,
hypotension
Trifluoperazine EPS, sedation,
hypotension
Fluphenazine
EPS, A-E, mild
sedation,
hypotension
Haloperidol
EPS, A-E Do
80
Dose
mg/day
100-800
50-200
100-400
2-20
1-10
2-20
Trifluperidol
Flupenthixol
Pimozide
Loxapine
EPS, A-E Do
EPS, Do
EPS, Do
EPS,
hypotension
1-8
3-15
2-6
20-50
Dosag
e
1 Clozapine
12.5
.
mg, 25
mg, 50
mg,
100
mg,
200
mg
tab,
25200
mg/da
y OD
2 Risperidon Schizophre 2-6
.
e
nia, Acute mg/da
Mania,
y
Schizoaffe
ctive
disorder
81
Indicatio
n
Refractory
Schizophre
nia
Adverse
Effects
Sedation,
weight gain,
hyperlipidaemia
, diabetes,
agranulocytosis
, orthostatic
hypotension,
hyper-salivation
Special
Remarks
Relative
selectively
to D
receptor
additional
5HT and
-receptor
block WBC
count
monitoring
to be done
Hyperprolactina
emia, increased
risk of stroke in
elderly,
orthostatic
hypotension
Combined
D and
5HT
blockade
also , ,
H
receptor
3
.
2.5
mg., 5
mg,
7.5
mg, 10
mg, 15
mg, 20
mg
tablets
. 5-20
mg/da
y OD.
Injecti
on
availa
ble
4 Quetiapine Acute
50.
mania,
100
bipolar
mg/da
depression y
, negative 400symtoms
800
of
mg/da
schizophre y
nia
5 Aripiprazol Schizophre 10 mg,
.
e
nia,
30 mg,
Mania,Bipo 5 mg
lar
tablet,
disorders, 5-10
adolescent mg/da
82
Olanzapin
e
Positive
and
Negative
Schizophre
nia, Acute
Mania,
Bipolar
Disorder,
Agitation
Dry mouth,
constipation,
increase in
prolactin,
hyprglycaemia,
weight gain,
epileptogenic,
postural
hypotension
block BP
increase
when
given
along with
SSRI
Blocks D,
5HT, ,
,
muscarinic
and H
receptors
also D, D
and D.
Most
commonly
used and
most
expensive
Sedation,
weight gain,
postural
hypotension,
hyperglycaemia
Blocks
5HT,
5HT, D,
, , HR
Insomnia may
occur, nausea,
dyspepsia,
constipation.
Other S/E are
minimum
Partial
agonist at
D,5HT
but
antagonist
at
s with
schizophre
nia
6 Ziprasoni Schizophre
.
done
nia, mania,
agitation
in
psychotic
patients,
bipolar
manic
patients
5HTR,long
acting (t
3 days)
60-80 Postural
Blocks D,
mg BD hypotension,
5HT,
120- mild sedation,
, H,
160
weight gain,
5HT,
mg,
hyperglycaemia agonistic
BD /
, nausea,
at 5HT.
day.
vomiting,
Blocks NE
Injecti increase in QTc reuptake,
on
cardiac
additional
availa arrhythmias
antidepres
ble.
sant and
anxiolytic
property
Antipsychotic Depot Preparations :1. Flupentixol decanoate 20-100 mg I. M. every 2-4 weeks
2. Fluphenazine decanoate 12.5 mg 100 mg I. M. every 24 weeks
3. Haloperidol decanoate 25-250 mg I. M. every 4 weeks
4. Olanzapine Pamoate 150-300 mg I. M. every 2 weeks /
40-50 mg very 4 weeks
5. Risperidone Consta 25-75 mg I. M. every 2 weeks
6. Zuclopenthixol decanoate 200-400 mg I. M. every 2-4
weeks
As adherence to oral medication is often difficult in many
psychotic patients including schizophrenia, injectable once or
twice a month is of convenience in maintenance therapy
****************
83
Lithium Carbonate
Sodium Valproate
Carbamazepine
Lamotrigine
Atypical Antipsychotics Olanzapine, Risperidone,
Quetiapine, Aripiprazole.
Dosage
Side Effects
Valproate
Carbamaze
pine
Therapuetic
Level
50-125 g/ml
6-10 g/ml
15-60
mg/kg/day
200-1600
mg/day
Lamotrigine NA
50-200
mg/day
Gabapentin
NA
900-3600
mg/day
Oxcarbazepi NA
ne
600-2400
mg/day
sedation, tremor,
ataxia, increase in
liver enzymes,
pancretitis, rash,
alopecia,thrombocyto
penia
sedation, dizziness,
ataxia, increase in
liver enzymes, SIADH,
arrhythmia,
thrombocytopenia
somnolence,
ataxia,nausea,
vomiting, rash, acne,
vaginitis, UTI
somnolence,
dizziness,
ataxia,dyspepsia,
leucopenia
increase in liver
enzymes,
hyponatremia
Formulations :
1. Lithium Carbonate Capsule 150/300/600 mg; CR tab 300
mg; SR tab 450 mg
2. Lithium Citrate Syrup 8 meq/ ml (480 ml bottle)
3. Valproic Acid Capsule 250 mg; syrup 250 mg/5 ml (480
ml bottle)
4. Valproate Sodium Injection 100 mg/ml (5 ml/vial)
5. Carbamazepine Tab 200 mg; chewable tab 100/200 mg;
suspension 100 mg/5 ml (450 ml bottle)
6. Lamotrigine Tab 25/100/150/200 mg, chewable tab
2/5/25 mg
87
****************
CHAPTER 6: ANTI-ANXIETY
Benzodiazepines are the most frequently prescribed
anxiolytic agents.
88
Therapy of
Insomnia :
Insomnia is defined as difficulty in initiating and or maintaining
sleep. Insomnia may be primary or secondary due to
depression, anxiety, mania, disease states or substance abuse.
Drugs used in insomnia are
1. Benzodiazepines Flurazepam, Triazolam, Nitrazepam,
Diazepam, Alprazolam, Temazepam
2. Non-Benzodiazepines - / 2 compounds Zolpidem,
Zaleplon, Zopiclone.
3. Melatonin Agonist Remelteon.
4. Sedative Antihistaminics.
Patient can be advised about sleep hygiene along with
pharmacotherapy.
Non-pharmacological approaches :
1. Sleep Hygiene - Go to bed only when sleepy, avoid naps.
Avoid caffeine, nicotine, alcohol, heavy or spicy food four
hours before bedtime. Avoid exercise at least four hours
91
92
Pharmacotherapy of
Substance Use Disorders :
Drug dependence syndromes due to illicit drug use are often
seen with
93
94
Withdrawa
l
Symptoms
Pharmacotherapy
Craving,
tremor,
irritation,
sleep
disturbance
s
tachycardia,
hypertensio
n,
visual/audit
Diazepam/Chlorazepple/P
henobarbitual in acute
withdrawal.
Detoxification
disulfiram,
naltrexone/acamprosate.
Clonidine transdermal
patch
2. Benzodiaz
epines
Diazepam
Alprazola
m
3. Barbiturat
e
4. Opioids,
heroin,
morphine,
codeine
95
Chronic
use over
months
to years
leads to
increase
in dose
due to
tolerance
Do,
Withdraw
al
symptom
s can be
severe or
fatal
Anxiety,
insomnia
,
yawning,
craving
ory/tactile
hallucinatio
ns
Anxiety,
agitation,
restlessness
, dizziness,
vomiting
and fatigue.
Insomnia
and
nightmare
Insomnia,
agitation
etc. as
benzodiaze
pine, but
may lead to
seizures
delirium or
coma
Restlessnes
s, irritability,
nausea,
muscle
cramps,
sweating,
tremor,
rhinorrhoea,
fever,
piloerection
(goose
skin),
increase in
pulse, B. P.,
respiration,
vomiting,
diarrhoea
CNS Stimulants :
1 Amphetam Normally
. ine
used in
Dextroamp ADHD,
hetamine
abused
Methamph as
etamine
euphoria
nt
2 Cocaine
Dose
. (free base depende
alkaloid nt.
crack)
Increase
in
arousal,
heart
rate, B.
P.,
feeling of
well
being
and
increase
in
confiden
ce,
euphoria.
Involunta
ry motor
activity,
paranoia,
promiscu
ous
sexual
activity
3 Cannabis
Euphoria,
.
anxiety,
96
Dysphoria,
fatigue
depression,
sleepiness,
craving,
bradycardia
(withdrawal
crash)
Desipramine,
Imipramine, Bupropion,
Venlafaxine may be used
Insomnia,
irritability,
Lorazepam, 1 mg four
hourly, haloperidol two
impaired
judgeme
nt,
increase
in
appetite,
dry
mouth
4 Hallucinog Visual
. ens LSD, illusions
Muscaline
and
hallucina
tions
tremor,
doses of 2-5 mg orally
nausea,
restlessness
, cramps
Perceptual
Benzodiazepine,
changes
Diazepam
10-20
leading
to orally
frank panic
attacks (bad
trip)
mg
Drug testing for illicit drug use :1. Urine drug screens typically evaluated for cannabinoids,
cocaine, opioids, amphetamine and phencyclidine.
Primarily detect drugs taken within 7 days of the test.
2. Salivary tests for drug screening detect drugs taken
recently within past few hours till previous three days.
3. Serum blood screens are most sensitive assays and detect
most drugs that have been used in last 90 days.
Some drug-dosage regimens used in Alcoholism
Drug
Diazepam
Chlordiazepoxi
de
Clonidine
97
Dosage
Alcoholism
10-20 mg/4-6 hours for 3
days. Then decrease by
25% per day
25-50 mg/4-6 hours for 2
days. Then decrease by
25% per day
0.1-0.2 mg/4-6 hours for Typical oral dose
2 days. Then decrease 0.4-0.6 mg day in 2by 25% per day
4 divided doses.
Transdermal patch
lasts
one
week;
delivers
0.1-0.3
mg/day
Naltrexone
Acamprosate
(Taurine
analogue)
Drug
Phencyclidine
(Angel Dust)
98
50 mg/day multiplied by
3-6 months, leads to
decrease
in
binge
drinking
Upto 3000 mg/day in
divided doses, reduction
in relapse drinking and
alcohol craving
Withdrawal
Symptoms
Behavioural
changes
mimicking
paranoid
schizophrenia.
Bizarre
violent
behaviour,
increase
in
muscle
tension,
tachycardia,
hypertension, drooling,
nystagmus
Treatment
Seclusion,
Benzodiazepam and
Antipsychotic Urine
acidification
with
NHCl
hastens
excretion
Pharmacotherapy of
Dementia :Elderly patients suffering from mild, moderate or severe
dementia may be suffering from Alzheimers disease, multiinfarct dementia, dementia due to underlying disease or
medical condition like hypothyroidism, congestive cardiac
failure or vitamin deficiency. Pseudo-dementia occurs
secondary to major depression.
Alzheimers Disease :
Symptoms - Anterograde memory loss
- Repetition of questions
- Misplacement of items
- Missed appointments
- Forgetfulness in daily chores of life
End stage characterised by dependence increased progression
of disease to akinetic mute state. Death occurs due to
99
2.
Donezepil
3.
Rivastigmine
4.
Galantamine
100
Mechanism
Dose
of Action
Noncompetitive
inhibition
of
NMDA
glutamate
receptor
Reversible
10 mg OD
antagonist of oral
cholinesterase
Adverse
Effects
Headache,
dizziness
GI distress,
muscle
cramps,
bradycardi
a,
abnormal
dreams,
fatigue
Reversible
3-6 mg BD GI
upset;
antagonist of oral;
9.5 well
cholinesterase mg/day
tolerated
;
more transderma
centrally
l patch
active
Reversible
8-12
mg
antagonist of BD
oral;
5.
Tacrine
cholinesterase 16-24 mg
, effects are SR, OD
sustained for
at least 12
months
Old drug
20mg four Hepatotoxi
times daily c
101
Anticonvulsants in
psychiatry :History :
In 1950 phenytoin was found to be effective in mania as
because it was found that kindling phenomenon of limbic area
seizures probably had a role in development of psychosis or
psychiatric symptoms. Gradually it was found that drugs like
Carbamazepine, Valproic Acid was effective as mood stabilizers
due to the preferential anticonvulsant action at the temporal
lobe or limbic system.
Uses in Psychiatry
Sl.
No.
1.
102
Drug
Valproate
Clinical Indications in
Psychiatry
Bipolar disorder,
aggression, agitation,
impulsivity, acute mania,
Special
Remarks
Rapid
discontinuatio
n, increase in
seizure disorders
2.
Carbamaze
pine
3.
Lamotrigine
Sl
.
N
o.
103
Drug
risk of relapse
in pregnancy
Dose should
gradually be
increased
over 6
months.
Decrease in
25% of dose
in every 3
days
Generally well
tolerated
Special
Remarks
No
D/I,
renal
excretion
Lower
hypnotic,
resistant to
other
drugs, anticonvulsant
3. Gabapenti Panic
100
n
attack,
social
anxiety
disorder,
reduction
in alcohol
craving,
adjunct to
mood
stabilizer,
post
herpetic
neuralgia,
neuropathi
c pain
4. Levetirace Acute
250
tam
mania,
anxiolytic,
add on with
antidepress
ants
5. Topiramat Primary
25
e
alcoholism,
Post
traumatic
stress
disorder,
borderline
personality
disorder,
binge
104
4001200
6-21
5002000
---
2001000
3-5
doses
should be
used
in
hepatic
dysfunction
No
drug
interaction
s,
renal
excretion
Nonhepatic
hydrolysis
and renal
excretion
Induces of
CYP3A4
Drug
Interaction
s
eating
disorder,
neuropathi
c
pain,
migraine
6. Zonisamid Acute
25e
mania,
100
drug
induced
weight gain
100600
15-40 Sulfonamid
e
may
cause
hypersensit
ivity
reactions,
blood
dyscrasia
Conclusion :
Other anti-convulsants like oxcarbamazepine, ethosuximide
may have a role in bipolar disorders and other psychiatric
disorders but their use as monotherapy has not been justified.
So, they have an adjunctive role in most psychiatric disorders.
105
Antihistaminics
in Psychiatry :Indications of use in psychiatry
Neuroleptic induced Parkinsonism.
Neuroleptic induced acute dystomia.
As hypnotic.
As anxiolytic.
Anorexia nervosa.
H receptor antagonists commonly used in psychiatry
Sl.
Drug
No
.
1. Diphenhyra
mine
Rou
te
2.
Hydroxyzine
Oral
3.
Promethazin
e
Cyproheptadi
ne
Oral
4.
106
Oral
Oral
Dose
25-50
QDS
Dosage
Form
mg Capsules,
tablet
25mg,
50mg,
liquid 12.5
mg/ml
Common
Indication
Neurolepti
c induced
Parkinsonis
m,
neuroleptic
induced
dystonia
50-100 mg Tablet
Sedative,
TDS/QDS
10/25/50/1 anxiolytic,
I.M.
00
mg, pruritus.
Syrup
10 Do
mg/5
ml,
25-50
mg/ml
50-100 mg 15.2/25/50 Sedative
TDS/QDS
mg tablets anxiolytic
4-20
4
mg Anorexia
mg/day
tablet
nervosa,
syrup
drug
2mg/5ml
induced
orgasmic
disorders
Pharmacotherapy in
special situations :Pregnancy None of the psychotropic drugs are completely
safe during pregnancy or lactation. The risk and benefit ratio
needs to be weighed on individual situations. The US PDA rates
drugs used in psychiatry into five categories according to its
safety in use during pregnancy.
Categ
Definition
ory
A
No fetal risks in
controlled
human
studies
B
No fetal risks in
animal studies but
no
controlled
human studies
C
Adverse
fetal
effects in animals
but no human data
107
Examples
Iron
Clozapine
Lamotrigine
Gabapentin, SSRI,
SGA
available
Human fetal
seen
risk TCA,
Benzodiazepine,
lithium
Proved fetal risk in Valproic
acid,
humans
thalidomide
Drug
therapy
during
Pregnancy
and
Paediatric / Young Adolescent Age Group :Sufficient data regarding effect of psychotropic drugs in
children or adolescents on brain function, behaviour or future
physical health in adulthood has not yet been established. So,
FDA approval of use of standard psychiatric drugs in children or
adolescent age group is not existent.
Use of D-amphetamine and methylphenidate in attention deficit
or hyperactivity disorder in children have been studied. It was
found to affect body growth eg. 1-3 cm in height throughout the
period of development.
Methylphenidate 18-54
mg/day,
transdermal patch OD
Dextroampheta 2.5 mg BD/day 40
mine
mg BD/QDS/day
Desipramine
10-25 mg QDS
Bupropion
3-6 mg/kg/day
Anorexia, insomnia,
dysphoria, tics
Sleep disturbance
---
Anorexia,
risk
of
seizures
1.2 mg/kg/day 1.8 Decrease in body
mg/kg/day
weight, increase in
heart rate, B. P.
300-400 mg/day
Headaches, mild GI
symptoms
Atomoxetine
Modafinil
Antipsychotics in children
Second
Generation
Antipsychoti
cs eg.
Aripiprazole
Risperidone
First
Generation
Antipsychoti
cs in
low
dose eg.
Haloperidol
Pimozide
Indicated
in Akathesia, Dystonia.
childhood
Weight gain
schizophrenia
- 2-10 mg/day
- 1-2 mg/day
Indicated in tics of
Tourettes disorder,
Autism,
violent
behaviour
- 0.5-3 mg/day
- 2-10 mg/day
Antidepressants in children
110
Drugs
Indications
Comments
SSRIs
Childhood
Fluoxetine depression
5 mg/day 3
mg/day
gradually increase
Adverse effects
in 1-2 weeks
are similar to
Fluvoxami Childhood OCD
those in adults
ne
Sertraline
TCA0.3-1.0 mg/kg/day
Imipramin in Enuresis
e
Mood stabilizers in children and adolescents
Drugs
Indications
Lithium
Mania,
Bipolar
Dose
150-300 disorder,
co-morbid
mg/day
substance
abuse
explosive,
violent
behaviour
Valproate
Aggressive behaviour
Dose
15-60 in adolescents
mg/kg/day
Carbamazepine
Bipolar mood disorder
Dose
10-50
mg/kg/day
in
divided doses
Comments
Children
have
increase in renal
clearance
and
better
tolerance
compared to adults
Children less than 2
years increase in
risk
of
hepatotoxicity
Anticonvulsants
show increase in
risk
of
hepatotoxicity
in
children
Drugs
Zolpide
m
Alprazol
am
Indications
Pavor nocturnes/sleep
walking
Panic
Disorder,
Generalised
anxiety
disorder,
avoidant
personality
Buspiron Childhood
e
disorders
Comments
Somnambulism,
Amnesia
If used in daytime
may
increase
activity
or
aggravate
behaviour
disorders
anxiety
---
drug
administration
may
lead
to
drug
113
Anti-psychotics : Lower doses should be used as blood levels are 1.5-2 times
higher in elderly compared to adults.
Quetiapine even at higher doses carries low risk of EPS;
hence preferred.
Anticholinergic effects of Clozapine are poorly tolerated by
elderly.
Aripiprazole, Risperidone, Olanzapine are other alternatives
to Quetiapine.
There is increased risk of mortality in elderly with dementia
treated with second generation anti-psychotics. Hence use of
anti-psychotics in presence of dementia should be avoided.
In agitated patients with dementia Valproate 500-800 mg/day
or Oxazepam, Benzodiazepine of simple metabolism and low
abuse potential may be tried.
Benzodiazepines,
disturbances in elderly.
Barbiturates
ADHD,
Memory
114
Depression,
Adrenocortical Insufficiency
Psychosis, Delirium, Fatigue.
Insomnia,
Lethargy,
Mania,
Depression,
Mood
disturbances,
Delusions,
Irritability,
Inattentiveness,
115
Anxiety,
Apprehension,
Fear
of
Psychiatric Emergencies
Sl.
Clinical
No.
Condition
1. Delirium Tremens
2.
116
Alcohol Withdrawal
Emergency Management
Chlordiazepoxide 25-50 mg QDS x
2 days parenterally then 15-100 mg
oral
Haloperidol may be added for
psychotic symptoms
Maintenance
of
fluid
and
electrolytes and monitoring of vital
signs
Benzodiazepines eg. Diazepam 210 mg
Thiamine 100 mg I.M.
3.
4.
5.
6.
7.
8.
9.
117
Benzodiazepine
Intoxication
Anticholinergic
Intoxication
Supportive measures
Flumazenil 7.5-45 mg/day
Discontinue the drug
Physostigmine 0.5-2 mg for
severe agitation
Hallucinogen
Benzodiazepines, Diazepam, 2-20
Induced Psychotic mg orally, reassurance
Disorder
Lithium Toxicity
Lavage with wide bare tube
osmotic diuresis; ICU treatment if
required
Neuroleptic
Discontinue antipsychotic
Malignant
I. V. dandtrolene sodium 1
Syndrome
mg/kg/day x 8 days
Bromocriptine 2.5 mg orally
Hydration and proper cooling
Monitoring of blood CPK level
Acute Onset Panic Propranolol 10-30 mg
Disorder
Alprazolam 0.25-2 mg
ECG to exclude mitral valve
prolapse
Stupor / Catatonic Supportive measures A, B, C etc.
Syndrome
specially airway
50 ml of 50% Dextrose or 2 ml/kg
body weight for children (for
hypoglycaemia)
Naloxone 0.4 mg I. V. (morphine
poisoning)
Physostigmine 1-2 mg I. V. (anticholinergic poisoning)
Thiamine 100 mg I. V. (Wernickes
encephalopathy)
Hydrocortisone 100 mg I. V.
(adrenal crisis)
I. Thyroxin 200-500 mg I. V.
(myxoedema coma)
Flumanzil
0.2
mg
I.
V.
(benzodiazepine toxicity)
10.
11.
12.
13.
14.
Akathisia
(agitation,
restlessness,
dysphoria)
Delirium
Antipsychotic
after
proper
evaluation
Acute
Dystoria Decrease dose of antipsychotic
(acute involuntary Diphenhydramine or Benztropine
spasm of muscles I. M.
of
neck,
jaw,
tongue, face, eyes,
even trunk)
Hyperventilation
Correction of alkalosis
(clouded
Patient counselling
consciousness,
Tranquilizers
blurred
vision,
anxiety, tremor)
Excited or Violent Diazepam 5-10 mg or Lorazepam
Behaviour
1-2 mg parenterally
Haloperidol 2-10 mg parenterally
in psychosis
Restraint / ECT only as last resort
Antipsychotic Depot Preparations :7. Flupentixol decanoate 20-100 mg I. M. every 2-4 weeks
8. Fluphenazine decanoate 12.5 mg 100 mg I. M. every 24 weeks
9. Haloperidol decanoate 25-250 mg I. M. every 4 weeks
10.
Olanzapine Pamoate 150-300 mg I. M. every 2
weeks / 40-50 mg very 4 weeks
11.
Risperidone Consta 25-75 mg I. M. every 2 weeks
12.
Zuclopenthixol decanoate 200-400 mg I. M. every
2-4 weeks
118
V.
VI.
1. Phenothiazine - Fluphenazine
- Perphenazine
2. Thioxanthenes Thiothixene
3. Butyrophenones - Haloperidol
- Droperidol
4.
Diphenylbutylpiperidine Pimozide
5.
Second Generation Antipsychotics Risperidone,
Aripiprazole
6.
Non-psychotropic drugs Metaclopramide,
Prochlorperazine
Drugs used in the treatment of EPS :1. Anticholinergics Benztropine, Biperiden, Procyclidine,
Tripexyphenidyl
2. Antihistaminics Diphenhydramine
3. Amantadine
4. -blocks-Propranolol
5. receptor antagonist Clonidine
6. Benzodiazepine Clonazepam, Lorazepam, Buspirone
7. Vitamin E
Sl.
Drug
Daily Dosage
No.
1. Benzotropine 0.5-2
mg
TDS
orally
1-2 mg I. M./I.V.
2. Biperiden
2-6 mg TDS orally
2 mg I.M./I.V.
3. Trihexiphenid 2-5 mg TDS orally
yl
4. Diphenhydra 25 mg QDS orally
mine
25 mg I.M./I.V.
5. Propranolol
20-40 mg TDS
6. Clonidine
0.1 mg TDS orally
7. Clonazepam 1 mg BD orally
8. Lorazepam
1 mg TDS orally
9. Buspirone
20-40 mg QDS
orally
120
10. Vitamin E
1200-1600
I.U./day
BIBLIOGRAPHY;
1.Biological Therapies. In: Benjamin James Sadock, Virginia
Alcott Sadock, editors, Kaplan & Sadocks Synopsis of
Psychiatry. 10th ed. New Delhi: Walters Kluver(India) Pvt Ltd;
2013. p.992-1113
2. Neuropharmacology.In: Brunton L, Chabner B, Knollman B
,editors,Goodman & Gilmans The Pharmacological Basis of
Therapeutics 12th ed.New York: McGraw-Hill: Medical Publishing
Division;2011.p.363-649
3.Neuophysiology and Neurochemistry. In: Benjamin James
Sadock, Virginia Alcott Sadock, editors, Kaplan & Sadocks
Synopsis of Psychiatry. 10th ed. New Delhi: Walters Kluver(India)
Pvt Ltd; 2013. p. 94-110
4.Alan F. Schatzberg, Jonathan O. Cole, Charles DeBattista. In:
Manual of Clinical Psychopharmacology.7th ed.USA:American
Psychiatric Publishing ; 2007. p37-630
5.Treatment of Movement Disorders. In: S Jacobson, R. Pies, I
Katz, editors,Clinical Manual of Geriatric Psychopharmacology.
7th ed.USA:American Psychiatric Publishing;2007.p477- 599
6. Katzung B G,Masters SB,Trevor AJ, editors,In. Basic
and Clinical Pharmacology 12th ed.New Delhi:Tata McGraw Hil
Publishing Divisionl; 2012.p.371-568
7. Drugs Used in Mental Illness.In:K D Tripathi
edited,Essentials of Medical Pharmacology 6th ed.New Delhi:
Jaypee Brothers Medical Publishers (P)Ltd;2008.p.435-454
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