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Psychopharmacology prof satya
1.
2. has about 100,000,000,000 (100 billion)
neurons
100,000 miles of blood vessels in the brain.
Neurons multiply at a rate 250,000
neurons/minute during early pregnancy.
9. PSYCHIATRIC DISORDERS
2 -3 % of UK national health spending
schizophrenia
1 in 6 persons in UK – suffer from depression
Advances in drug treatment have
revolutionized the practice of psychiatry
27. HISTORY
1952 Introduction of chlorpromazine is a
breakthrough
Reserpine lasted only a few years
1957 – 58 MAO inhibitors, antidepressants
1957 – Chlordiazepoxide
1960’s – Other benzodiazepines
1960’s – Lithium
1980”s - SSRIs
32. SCHIZOPHRENIA
Schizophrenia is a chronic,
frequently life-time,
remitting, and relapsing
psychotic disorder
the illness is usually diagnosed in late
adolescence or early adulthood .
Periodic psychotic exacerbation (relapse)
occurs throughout the course of the illness
33.
34. SCHIZOPHRENIA (Split mind)
disorder of thought and behavior
delusions
hallucinations
irrational conclusions, interpretations
patient unable to meet the ordinary
demands of life
Negative symptoms- apathy
35.
36. RISKS OF SCHIZOPHRENIA
associated with a high risk of suicide
(about 10 percent of patients die from
suicide)
significant impairment in function
(less than 10 percent of patients are fully
employed and live independently)
41. TREATMENT APPROACH
requires a multimodal approach,
including medication and
psychosocial interventions,
such as assistance with routine demands of
life
as housing,
financial sustenance,
and personal relationships
42. broad objective of treatment
to reduce the overall morbidity and mortality
of the disorder
decrease the frequency and severity
of episodes of psychotic exacerbation
and improve the functional capacity and
quality of lives of the individuals
Most patients require comprehensive and
continuous care
over the course of their lives.
43. TARGETS OF DRUG THERAPY
no cure currently exists,
pharmacological treatment is directed at
inducing and
maintaining remission
of various symptom dimensions.
positive symptoms
negative symptoms
cognitive and
neuropsychological dysfunction
44. GOAL OF THERAPY
the optimal pharmacotherapy of
schizophrenia
is one that provides
the best possible control
of the various symptoms
while minimizing side effects
from such treatment.
45. Antipsychotic Therapy:Antipsychotic Therapy:
Historical Perspective in the U.S.A.Historical Perspective in the U.S.A.
Ziprasidone
1950 1960 1970 1980 1990
2000
Reserpin
e
Chlorpromazin
e Fluphenazine
Thioridazin
e Haloperidol Clozapine
Risperidone
Olanzapine
Quetiapine
46. DRUG THERAPY OF
SCHIZOPHRENIA
antipsychotic drugs carry the risk of a wide
range of side effects,
from stiffness and restlessness
to a form of diabetes,
these drugs do little or nothing for the
cognitive impairment
New treatments for psychotic symptoms
and effective treatments for cognitive
impairment are on the horizon.
47. Ist GENERATION
ANTIPSYCHOTICS chlorpromazine (Thorazine),
trifluoperazine (Stelazine),
thioridazine (Mellaril), thio- thixene (Navane),
haloperidol (Haldol), etc.
differ from one another in potency and side
effect profile,
they have similar overall efficacy,
all cause significant EPS and tardive dyskinesia.
48. Factors in Antipsychotic SelectionFactors in Antipsychotic Selection
Short-Term and Long-TermShort-Term and Long-Term
Efficacy (general, comparative)
Safety (likelihood of dangerous side
effects)
and
Tolerability (various adverse effects)
49. LIMITATIONS OF Ist
GENERATION
EPS dysphoria and poor compliance,
worsening of negative symptoms
Worsening of cognitive function,
increased risk of tardive dyskinesia
lower doses can reduce these adverse
effects….
50. Second-Generation
Antipsychotic Agents
broader spectrum of efficacy
and lower risk of neurological adverse
effects,
greater efficacy in otherwise treatment-
refractory patients,
clozapine has the best proven track record
51. Adapted from: Jibson MD, Tandon R. J Psychiatr Res. 1998(May-Aug);32(3-4):215-228Jibson MD, Tandon R. J Psychiatr Res. 1998(May-Aug);32(3-4):215-228
Essence of AtypicalityEssence of Atypicality
Less Tardive
Dyskinesia
Less Non-
Compliance
Less
Dysphoria
Better
Cognition
Fewer EPS
Fewer
Negative
Symptoms
EPS
Advantage
60. Adapted from: Jibson MD, Tandon R. J Psychiatr Res. 1998(May-Aug);32(3-4):215-228Jibson MD, Tandon R. J Psychiatr Res. 1998(May-Aug);32(3-4):215-228
Essence of AtypicalityEssence of Atypicality
Less Tardive
Dyskinesia
Less Non-
Compliance
Less
Dysphoria
Better
Cognition
Fewer EPS
Fewer
Negative
Symptoms
EPS
Advantage
61. Optimizing Outcomes with 2ndOptimizing Outcomes with 2nd
GenerationGeneration AtypicalAtypical AntipsychoticsAntipsychotics
Maximize improvement
reduce symptoms in various domains
Minimize impairment by side-effects
No EPS
No use of anticholinergic agent
Minimize other side-effects
Monitor on ongoing basis and make
necessary adjustments
INDIVIDUALIZED DOSING IS THE KEY
62.
63. How Antipsychotic TreatmentHow Antipsychotic Treatment
ImpactsImpacts
Life of an Individual with PsychosisLife of an Individual with Psychosis
Antipsychotics
Reduce
symptoms
Causeside effects
o o
o o
Quality
of life
88. TOLERANCE AND DEPENDENCE
Tolerance develops to sedation and
hypotension.
No tolerance for antipsychotic and
extrapyramidal effects.
No dependence
103. EXTRAPYRAMIDAL DISTURBANCES
PARKINSONISM rigidity, tremor, hypokinesia,
mask like facies, shuffling gait.
ACUTE MUSCULAR DYSTONIAS – 2%
AKATHESIA – desire to move about – 20% ( Tt-
nadolol )
TARDIVE DYSKINESIA – Purposeless involuntary
movements – 10-20%( tt- vit E, BDZ,
betablockers)
RABBIT SYNDROME
104.
105.
106.
107.
108. MALIGNANT NEUROLEPTIC SYNDROME
High doses of potent agents
Marked rigidity, immobility, tremor, fever,
semi consciousness
May be fatal
TREATMENT:
Stop the neuroleptic
Symptomatically
I.V dantrolene, bromocriptine
109.
110.
111. OTHER SIDE EFFECTS
Weight gain
Rise in blood sugar and lipids
Blue pigmentation
Corneal and lens opacities
Retinal degeneration
Cardiac arrhythmia
118. INTERACTIONS
1. Potentiation of all CNS depressants
2. Block the action of Levodopa
3. Enzyme inducers can reduce blood levels of
neuroleptics
119.
120. THERAPEUTIC USES
SCHIZOPHRENIA:
Control positive symptoms better than negative
symptoms
Afford symptomatic relief
Do not remove the cause of the illness
Long term treatment is required
MANIA Antipsychotics I.M – CPZ or HALOPERIDOL
CHRONIC SCHIZOPHRENIA – atypical antipsychotics
are preferred
124. HALOPERIDOL
Extra pyramidal side effects +++
Sedation+
Hypotension +
Few autonomic effects
Less epileptogenic
No weight gain
Jaundice is rare
Preferred drug for acute schizophrenia
125.
126. TRIFLUPERAZINE AND
FLUPHENAZINE
Minimum autonomic actions
Less sedation+
Less hypotension+
Less hypersensitivity reactions
Less likely to precipitate seizures.
Marked extrapyramidal symptoms
Fluphenazine decanoate given as depot
I.M injection every 2-4 weeks
127. ATYPICAL ANTIPSYCOTICS
Second generation antipsychotics that have weak
D2 blocking and potent 5-HT2 blocking activity
Minimal EPS
Improve cognition
Clozapine, Risperidone, Olanzapine
Quetiapine, Aripiprazole, ziprasidone
128.
129. CLOZAPINE
Atypical or second generation antipsychotic
Selective D4 blocker
Anti 5HT2
Weak D2 blocking action
Produces few extrapyramidal symptoms
No increase in prolactin level
Anticholinergic +, alpha blockade+, sedation++
Suppress both positive symptoms and negative
symptoms
Useful as a reserve drug in refractory schizophrenia
130. CLOZAPINE - ADR
Agranulocytosis (0.8%) and other blood
dyscrasias (weekly monitor WBC count)
High dose induce seizures
Sedation, tachycardia, weight gain
Precipitation of diabetes
Myocarditis
131.
132.
133. RISPERIDONE
Combination of D2 +5HT2 blockade
Alpha1, alpha2, H1 blocker
Less EPS at low doses
Sedation, postural hypotension +
Increase prolactin level
Less epileptogenic than clozapine
Frequently causes agitation
CAUTION – stroke in elderly
134.
135.
136. OLANZAPINE
Blocks D2, 5HT2, alpha1, alpha2, M1, H1
like clozapine
Controls positive and negative symptoms
Broad spectum effect
covers schizo-affective disorders
Few EPS
No agranulocytosis
Little rise in prolactin
Long acting
Potent anti muscarinic – dry mouth, constipation
More epileptogenic, cause weight gain, diabetes
137.
138.
139.
140. QUETIAPINE
New, short acting atypical antipsychotic
Minimal EPS, hyperprolactinemia
Quite sedating
Postural hypotension +
Used in mania/ bipolar disorder
Interact with macrolides, anticonvulsants
141. ARIPIPRAZOLE
Partial agonist at D2, 5-HT1A
Antagonist at 5-HT2
Minimal sedation
No EPS, hyperprolactinemia, hypotension
No weight gain, diabetes
Long acting
142.
143. ZIPRASIDONE
Latest atypical antipsychotic
Same advantages of aripiprazole
In addition it has anxiolytic, antidepressant
action
CAUTION – potential to induce serious
arrhythmias
Also used in mania
144.
145. RESERPINE
Historical importance in psychiatry
low efficacy antipsychotic
Depletes – brain DA, NA, 5-HT
Cause mental depression, suicidal tendencies
146.
147. FUTURE OF SCHIZOPHRENIA
Advanced genetic screening technology,
structural and functional brain imaging,
sophisticated histological techniques
will lead to
greater understanding,
better treatments,
and eventually prevention of schizophrenia.
155. MAJOR DEPRESSION
characterized by symptoms like
1. Sad mood
2. Loss of interest and pleasure
3. Feelings of worthlessness, guilt
4. Loss of appetite, sleep
5. Suicidal thoughts and melancholia
156.
157.
158.
159.
160.
161.
162. MANIA
Elation or irritable mood
Racing thoughts
Accelerated speech
Increased activity
Reduced sleep
Violent behaviour
Progressive loss of contact with reality
169. TREATMENT OF DEPRESSION
Three phases of treatment have been
proposed:
acute,
continuation,
and maintenance treatment phases
170. ACUTE TREATMENT PHASE
clinical interview,
diagnostic assessment,
physical and neurological examination,
and clinical and laboratory studies
Lasts 6-12 weeks
171. GOALS
establishing a diagnosis,
defining a short-term and long-term
multidisciplinary treatment plan,
selecting the most appropriate medication,
titrating the dose to a therapeutic range,
monitoring of side effects, compliance,
and determining the magnitude and quality of
response
REVIEW once in 1-2 weeks
172. Maintenance Phase
prophylactic,
to maintain the response.
dosing during this phase should continue at the
same level as during the acute phase
supportive psychotherapy can help to reduce
the rate of relapse and recurrence
REVIEW every 4-12 weeks in the 1st
year
Then every 6 months to yearly review
173. CONTINUATION PHASE
Consists of monitoring for completeness of
response and side effects.
Discontinuation of medication is associated
with a high rate of relapse
treatment lasts 4 to 9 months
consolidation phase.
181. ACTIONS - In depressed
patients
little acute effects are produced
Produce sedation
Mood is gradually elevated after 2 -3 weeks of
continuous treatment
Make the patients take interest in self and
surroundings
Make them be more communicative
182.
183.
184.
185.
186. ACTIONS
Does not produce euphoria but relieves
depression
Suppress REM sleep
reduce awakenings during night
Lower seizure threshold
More sedative for patients showing anxiety
and agitation
Less sedative for withdrawn and retarded
patients
187.
188. MECHANISM OF ACTION
Inhibit active uptake of biogenic amines NA and 5-
HT potentiate them
Results in increased concentration of the amines in
the synaptic cleft enhanced nor- adrenergic,
serotonergic transmission
Uptake blockade occurs quickly but antidepressant
action develops after weeks
189.
190.
191. TOLERANCE AND DEPENDENCE
Tolerance to the anticholinergic and hypotensive
effects develops gradually
Psychological dependence is rare
Physical dependence occur when high doses
used for longer periods
Gradual withdrawal is recommended
do not carry abuse potential
192.
193. PHARMACOKINETICS
Oral absorption is good
Highly bound to plasma tissue proteins
Metabolites are excreted urine over 1-2 weeks
Plasma t ½ 16-24 hours
Once daily dosing at bed time
in the maintenance phase
Therapeutic window phenomenon has been
observed
194.
195. ADVERSE EFFECTS
Sedation, mental confusion
Postural hypotension
Anticholinergic: dry mouth, blurred vision
constipation, urinary retention, palpitation
Cardiac arrhythmias, specially in patients with
ischaemic heart disease
Increased appetite and weight gain
196.
197.
198.
199.
200. ADVERSE EFFECTS
Some patients may switch to hypomania or
mania
Sweating and fine tremors
Seizure threshold is lowered
Rashes and jaundice due to hypersensitivity
are rare
201.
202.
203. USES
1. Endogenous depression
Response takes 2-3 weeks to appear
Therapy continued upto 1 year
SSRIs – mild to moderate depression
TCAs - severe depression
2. Obsessive compulsive and phobic
states
SSRIs, clomipramine
3. Anxiety disorders
4. Neuropathic pain – imipramine
204.
205.
206.
207.
208.
209. USES
5. Attention deficit – hyperactive disorder in
children
Imipramine, nortriptyline
Less behavioural side effects than
amphetamine like drugs
6. Enuresis – imipramine 50mg at bed time
is effective in children above 5 years
7. Prophylaxis of migraine – Amitriptyline
8. Pruritus – Topical doxepin
210.
211.
212.
213. LIMITATIONS OF TCA’S
Frequent anticholinergic, cardiovascular and
neurological side effects
Relatively low safety margin
hazardous in overdose; fatalities common
Lag time of 2- 4 weeks before antidepressant
action
Significant number of patients respond
incompletely and some do not respond
214.
215.
216. MAO INHIBITORS
Inhibit monoamine oxidase
MAO –A – deaminates 5 –HT, NA, inhibited
by moclobemide
MAO- B – deaminates dopamine
Hit and run drugs
Cheese reaction
217.
218. MOCLOBEMIDE
Reversible and selective MAO-A inhibitor
Cheese reaction less likely
No side efffects of TCA’s
Safer in overdose
Preferred in elderly and heart disease
patients
Alternative to TCA’s in mild to moderate
depression
225. ADVANTAGES OF SSRIs
Little or no sedation,
Do not interfere with cognitive and
psychomotor function
Do not produce anticholinergic side effects
Devoid of alpha adrenergic blocking action –
postural hypotension does not occur
No seizure precipitating propensity
Do not inhibit cardiac conduction
Weight gain is not a problem
226.
227. ADR
Nervousness, restlessness, insomnia
Anorexia, NAUSEA
Dyskinesia
Headache and diarrhoea
Interfere with ejaculation
Impairment of platelet function
bleeding ( epistaxis)
Gastric blood loss due to NSAIDs may be
increased
228.
229.
230.
231.
232.
233. DRUG INTERACTION
The SSRIs inhibit CYP2D6 and CYP3A4
elevate plasma levels of TCAs, haloperidol,
clozapine, terfenadine, astemizole, warfarin,
Beta blockers
Tolerance
Serotonin syndrome
Discontinuation reaction
234. USES
1st
line drugs in
Mild to moderate depression
phobias,
OCDs
Panic disorders
Kleptomania and related disorders
Preferred for prophylaxis of recurrent depression
235.
236.
237.
238. FLUOXETINE
Prototype
Longest acting
More agitation and dermatological reactions
More appropriate for poorly compliant
patients
Less suitable for patients needing rapid effect
239.
240. FLUVOXAMINE
Shorter acting SSRI
No active metabolite
Used in hospitalized patients and in number
of anxiety disorders
More nausea, agitation, Discontinuation
reactions
241.
242.
243. PAROXETINE
Short acting SSRI
Does not produce active metabolite
A higher incidence of g.i. side effects,
discontinuation reaction
244. SERTRALINE
Drug interactions due to inhibition of CYP
isoenzymes are less likely to occur
Produces a longer lasting active metabolite
Efficacious in juvenile depression
247. OTHER USES OF SSRIs
Now 1st
choice drugs for OCD, Panic disorder,
social phobia, eating disorders and post
traumatic stress disorder
Many anxiety disorders, body dysmorphic
disorder, compulsive buying and kleptomania
Used to improve outlook on life and to feel
good, even in non depressed patients
post MI and other chronic somatic illnesses
256. TRAZODONE
Sedative
Cause bradycardia, less prone to cause arrhythmias
No anticholinergic side effects
No seizures
Nausea is felt, priapism, postural hypotension
Better suited for elderly depressed patients
Preferred where heavy sedation is required
257.
258. VENLAFAXINE
Novel antidepressant
SNRI
Like SSRI
Does not interact with cholinergic,
adrenergic, H1 receptors
No sedation
Faster onset
More nausea, sustained hypertension
Safer in overdose
259.
260.
261. DULOXETINE
Similar to venlafaxine
Cause agitation, rise in BP, insomnia
Also indicated in
panic attacks,
Diabetic neuropathic pain
Stress incontinence
262.
263.
264. MIRTAZAPINE
Act by blocking alpha2 autoreceptors (on NA
neurones), heteroreceptors (on 5-HT
neurones)
Cause sedation, weight gain
No anticholinergic, sexual side effects
Efficacy comparable to TCAs
265.
266. BUPROPION
Inhibit DA, NA uptake
Excitant
Available as a Sustained release formulation
for smoking cessation
No sexual side effects
Can cause agitation, insomnia, dry mouth,
nausea
267.
268. ACUTE POISONING
usually self attempted and may endanger life
Symptoms :Excitement, delirium, anticholinergic
symptoms, convulsions and coma
Respiration is depressed, BP is low, tachycardia,
ventricular arrhythmias
Treatment : Primarily supportive
Propranolol / lignocaine for cardiac arrhythmias
i.v bicarbonate for acidosis
i.v diazepam for convulsions
269. INTERACTIONS
TCAs potentiate directly acting
sympathomimetic amines rise in BP
TCAs potentiate CNS depressants including
alcohol and antihistaminics
Phenytoin, aspirin can displace TCAs from
protein binding sites and cause toxicity
SSRIs inhibit metabolism of TCAs – dangerous
toxicity can occur
Hypertensive crisis with MAO inhibitors
Arrhythmias with thioridazine, pimozide,
amiodarone
276. ANXIETY
Unpleasant emotional state associated with
Uneasiness
discomfort and
fear about future threat
Treatment is needed when anxiety is
excessive
289. ANTIANXIETY DRUGS
Control the symptoms of anxiety
Produce a restful state of mind without
interfering with normal mental or physical
functions
Closely resemble sedative – hypnotics.
Not effective in schizophrenia
Do not produce extra pyramidal side effects
Produce physical dependence
Carry abuse liability
293. BENZODIAZEPINES
One of the most widely used class of drugs
Little effect on other body systems
Relatively safe even in gross over dosage
Higher doses induce sleep and impair
performance
Potential to produce dependence in long term
use
Differences between individual BZD mainly of
pharmacokinetic
299. ADR
Sedation
Light-headedness
Psychomotor impairment
Vertigo
Confusion in elderly
Increased appetite, weight gain
Dependence on long term use
300.
301.
302.
303.
304. CHLORDIAZEPOXIDE
Ist
BZD to be used clinically
Slow oral absorption
Produce smooth long lasting effect
Preferred in chronic anxiety states
Active metabolites are produced extend the
duration of action
Dosage: 20-100mg/day
Librium 10, 25mg
305.
306. DIAZEPAM
Quickly absorbed
Produces initial phase of strong action, followed
by prolonged milder effect
Produces active metabolites
Preferred in acute panic states, anxiety
associated with organic disease
Valium 2, 5, 10mg
5 – 30mg
307.
308.
309. LORAZEPAM
Slow oral absorption
Less lipid soluble slow rate of entry to brain
Good sedative
Only BZD recommended for I.M use
Preferred for short lived anxiety states, panic ,
obsessive – compulsive neurosis, tension
syndrome, psychosomatic diseases
Dose: 1 – 6mg Larpose , Ativan
310.
311. ALPRAZOLAM
High potency anxiolytic
In addition has mood elevating action in mild
depression
Useful in anxiety associated with depression
Panic disorders with severe anxiety
Active metabolite is produced
Cause less drowsiness
Dose: 0.25-1mg TDS
312.
313.
314. BUSPIRONE
Ist
Azapirone (non BZD)
5-HT1A agonist
No sedation, No cognitive impairment, do not
interact with BZD receptor or (GABA)
No tolerance
No physical dependence
Relieves mild to moderate anxiety
Slow onset of benefit (maximum benefit delayed
upto 2 weeks)
Mild mood elevating action
320. SIDE EFFECTS
Dizziness, headache, light headedness
Does not potentiate CNS depressants
May cause rise in BP in patients on MAO
inhibitors
Caution in those operate machinery/motor
vehicles
Dose: 5-15 mg OD
321.
322. HYDROXYZINE
H1 antihistaminic
Sedative, antiemetic
has antimuscarinic and spasmolytic properties
Useful in reactive anxiety or
that associated with marked autonomic
symptoms
Also effective in pruritus and urticaria
Atarax 10, 25mg
323.
324.
325.
326. BETA BLOCKERS
Relieves sympathetic symptoms of anxiety
(Palpitation, rise in BP, shaking, tremor, GI hurrying)
Produce symptomatic relief
Do not affect psychological symptoms like worry,
tension, fear
Useful in acutely stressful situations like public
appearance , exams
Performance/situational anxiety adjuvant to BZDs
327.
328.
329.
330. TREATMENT OF ANXIETY
DISORDERS Treat when excessive and disabling
Use BZDs in smallest possible dose for short term
Individualize the dose
Longer periods gradual withdrawal
Most of the dose given at night to ensure sleep
Remaining dose divided and given in day to avoid
high peaks
Low doses of BZD are given in patients with
hypertension, peptic ulcer, ulcerative colitis,
IBW, GERD, angina pectoris for treating the
anxiety though may not be prominent
331. TREATMENT OF ANXIETY
SSRIs drug of choice for anxiety disorders
Monitor for possible ADR
Treatment effect is often slow wait 12 weeks
to assess efficacy
Specific
Buspirone nonsedating less severe forms
TCA, SSRI delayed response combined
with BZD
332.
333.
334.
335. MANIA
Elation or irritable mood
Racing thoughts
Accelerated speech
Increased activity
Reduced sleep
Violent behaviour
Progressive loss of contact with reality
336.
337.
338.
339. LITHIUM CARBONATE
Small monovalent cation
Stabilizes mood
Used in the prophylaxis of bipolar manic
depressive illness (MDI)
Standard antimanic, mood stabilizer
343. ACTIONS
On prolonged administration stabilizes mood
Does not produce sedation or euphoria
Suppress acute mania in 1 – 2 weeks
Normalizes sleep time in manic patients
Continued treatment prevents cyclic mood
changes
344.
345. ACTIONS
Inhibits the actions of ADH causes
diabetes insipidus like state
Has some insulin like action
Increases WBC count
Reduces thyroxine synthesis
346. MECHANISM OF ACTION
Exactly not known
Inhibits hydrolysis of inositol-1-phosphate
decrease supply of free inositol decrease
IP3, DAG decrease activity of hyperactive
neurones in manic state
347. PHARMACOKINETICS
Well absorbed orally
Not protein bound, not metabolized
Uniformly distributed in total body water
Eliminated by the kidneys same way as Na+
On repeated administration steady state
concentration is achieved in
5 – 7 days
Marked individual variation of elimination
348. MONITORING LITHIUM LEVEL
Monitoring Li concentration is essential for
optimum therapy Because margin of safety
is narrow
0.5 – 0.8 mEq/L – optimum for maintenance
therapy in bipolar disorder
0.8 – 1.1 mEq/L – for mania
Above 1.5 mEq/L – toxicity symptoms occur
Serum Li level measured 12 hours after the
last dose
349. ADVERSE EFFECTS
Nausea, vomiting and mild diarrhoea
Thirst and polyuria
Fine tremors, seizures (rarely)
Long term use produces renal diabetes
insipidus
Goiter reported in 4%
355. LITHIUM TOXICITY
CNS toxicity appears on higher doses –
mental confusion
giddiness, tremors
ataxia, nystagmus, motor incoordination
These symptoms seen at concentration above
2mEq/L
These progress to muscle twitchings, delirium,
convulsions, coma
356.
357.
358.
359. Treatment
Symptomatic
no specific antidote
Osmotic diuretics ( mannitol) , sodium
bicarbonate infusion promote Li excretion
Haemodialysis is indicated in serum levels
above 4 mEq/L
360.
361. INTERACTIONS
Diuretics increases lithium level
Tetracyclines, ACE inhibitors, NSAIDs cause
Li retention
Sometimes Li potentiates neuroleptic action
of haloperidol
Li enhance insulin/sulfonylurea induced
hypoglycemia
362.
363. USES
1. Acute mania – used after the episode is under
control with neuroleptics, diazepam /lorazepam
2. Prophylaxis in bipolar disorder – used after
measuring risk benefit ratio
3. Recurrent unipolar depression
4. Inappropriate ADH secretion syndrome
5. Cancer chemotherapy induced leukopenia and
agranulocytosis
364.
365.
366.
367. DISADVANTAGES OF LITHIUM
Intolerance
Risk of toxicity
50% of mania, bipolar disorder show poor
response
368.
369.
370. CARBAMAZEPINE
Equally effective as Li
Better tolerated than Li
Preferred by many as first line / adjunctive
treatment for acute mania, bipolar illness
Efficacy in long term prophylaxis is less
well established
371.
372. SODIUM VALPROATE
Act faster than Li
1st
line treatment for acute mania
Better tolerated
Useful in those not responding to Li or CBZ
Also combined with Li in resistant cases
Shows reduction in manic relapses in bipolar
disorder
373.
374. OTHER DRUGS IN MANIA
Lamotrigine – specially useful in depressed and
rapidly cycling phases of the illness
Olanzapine – carries low risk of agranulocytosis,
extra pyramidal side effects used as
adjuvant/alternative to Li in acute mania,
prophylaxis of cyclic mood swings
Risperidone
Clonidine, verapamil, nimodipine are under
investigation
375.
376.
377. TREATMENT
Psychotic illness ( Schizophrenia, mania, depressive
psychosis ) drugs as first-line treatment ,
psychotherapy adjunctive)
Depression, anxiety disorders psychotherapy 1st
line, drugs 2nd
line
Drugs and psychotherapy combination
Doctors Therapeutic relationship with patients
empathetic, supportive enhance the
pharmacological efficacy
378.
379. A despondent fellow seeks the advice of the city’s
most fashionable – and expensive – psychiatrist
cum analyst
“You have acute melancholia,” the analyst
informs him. “The circus is in town this week.
Go to it. It may give you some laughs.”
“Your advice is worthless,” mourns the despondent
one. “I’m the top clown there.”
382. “If the only tool you have is a hammer,
you tend to see every problem as a nail.”
Abraham Maslow (American
Philosopher and Psychologist, 1908-1970)
388. Writing prescriptions is easy!Writing prescriptions is easy!
Understanding people is hard…..Understanding people is hard…..
Editor's Notes
[This slide is animated]
In individuals without schizophrenia, the amount of dopamine released presynaptically results in normal activation of postsynaptic receptors (blue arrow).
In individuals with schizophrenia, excess dopamine is released from the mesolimbic pathway and postsynaptic receptors are overstimulated (red arrow). This leads to development of positive symptoms.
In the mesocortical pathway in patients with schizophrenia, too little dopamine is released and the postsynaptic receptors are understimulated (gray arrow). This hypoactivity is thought to cause negative and cognitive symptoms.