Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.
 has about 100,000,000,000 (100 billion)
neurons
 100,000 miles of blood vessels in the brain.
 Neurons multiply at a r...
MEMORY OF HUMAN BRAIN IS
13367864.5GB
PSYCHIATRIC DISORDERS
 2 -3 % of UK national health spending 
schizophrenia
 1 in 6 persons in UK – suffer from depress...
Prevalance of Psychiatric
Disorder
Dr.V. Sathyanarayanan MD
Professor of pharmacology
 Excitatory – Glutamate, aspartate
 Inhibitory – GABA, Glycine
 Others –Noradrenaline ,Dopamine, 5- HT
 Acetylcholine
...
PSYCHIATRIC DISORDERS
 Psychoses
 Neuroses
 Personality disorders
 Organic mental disorders
HISTORY
 1952  Introduction of chlorpromazine is a
breakthrough
 Reserpine  lasted only a few years
 1957 – 58 MAO in...
PSYCHOSES
 Organic – delirium, dementia
 Functional
 schizophrenia
 paranoid states
 Mood disorders – depression, Man...
SCHIZOPHRENIA
 Schizophrenia is a chronic,
 frequently life-time,
 remitting, and relapsing
 psychotic disorder
 the ...
SCHIZOPHRENIA (Split mind)
 disorder of thought and behavior
 delusions
 hallucinations
 irrational conclusions, inter...
RISKS OF SCHIZOPHRENIA
 associated with a high risk of suicide
 (about 10 percent of patients die from
suicide)
 signif...
PATHOPHYSIOLOGY
 Dopaminergic overactivity in limbic system
 Decrease in glutamate
 5- HT, NE also involved
 Complex i...
Normal
Dopamine Hypothesis
of Schizophrenia
Adapted from Stahl. J Clin Psychiatry. 2001;62:923.
Hyperdopaminergic
pathways...
NEUROCHEMICAL ABNORMALITIES
 Dopamine disregulation
 Glutamatergic hypofunction
 GABAergic hypofunction
 Nicotinic hyp...
TREATMENT APPROACH
 requires a multimodal approach,
 including medication and
 psychosocial interventions,
 such as as...
broad objective of treatment
 to reduce the overall morbidity and mortality
of the disorder
 decrease the frequency and ...
TARGETS OF DRUG THERAPY
 no cure currently exists,
 pharmacological treatment is directed at
 inducing and
 maintainin...
GOAL OF THERAPY
 the optimal pharmacotherapy of
schizophrenia
 is one that provides
 the best possible control
 of the...
Antipsychotic Therapy:Antipsychotic Therapy:
Historical Perspective in the U.S.A.Historical Perspective in the U.S.A.
Zipr...
DRUG THERAPY OF
SCHIZOPHRENIA
 antipsychotic drugs carry the risk of a wide
range of side effects,
 from stiffness and r...
Ist GENERATION
ANTIPSYCHOTICS chlorpromazine (Thorazine),
 trifluoperazine (Stelazine),
 thioridazine (Mellaril), thio-...
Factors in Antipsychotic SelectionFactors in Antipsychotic Selection
Short-Term and Long-TermShort-Term and Long-Term
 Ef...
LIMITATIONS OF Ist
GENERATION
 EPS  dysphoria and poor compliance,
 worsening of negative symptoms
 Worsening of cogni...
Second-Generation
Antipsychotic Agents
 broader spectrum of efficacy
 and lower risk of neurological adverse
effects,
 ...
Adapted from: Jibson MD, Tandon R. J Psychiatr Res. 1998(May-Aug);32(3-4):215-228Jibson MD, Tandon R. J Psychiatr Res. 199...
Comparative PharmacologyComparative Pharmacology
of Atypical Antipsychotic Drugsof Atypical Antipsychotic Drugs
Adapted fr...
Tandon R, Milner K, Jibson MD. J Clin Psychiatry. 1999;60(suppl 8):21-28Tandon R, Milner K, Jibson MD. J Clin Psychiatry. ...
Recommended Dosing ofRecommended Dosing of
First-Line AtypicalsFirst-Line Atypicals
 Risperidone 2-6 mg/day
 Olanzapine ...
Antipsychotic Treatment OptionsAntipsychotic Treatment Options
 Low-potency conventional antipsychotics
(chlorpromazine, ...
TimeTime
DoseDose
OldOld
agentagent
AtypicalAtypical
Titrate
atypical
Titrate
atypical
to
desired
dosage
to
desired
dosage...
Adapted from: Jibson MD, Tandon R. J Psychiatr Res. 1998(May-Aug);32(3-4):215-228Jibson MD, Tandon R. J Psychiatr Res. 199...
Optimizing Outcomes with 2ndOptimizing Outcomes with 2nd
GenerationGeneration AtypicalAtypical AntipsychoticsAntipsychotic...
How Antipsychotic TreatmentHow Antipsychotic Treatment
ImpactsImpacts
Life of an Individual with PsychosisLife of an Indiv...
ADJUNCTIVE MEDICATIONS
 Anticholinergics
 Mood stabilizers
 Benzodiazepines
 Betablockers
 ECT
NEW FORMULATIONS
 Injections of atypical antipsychotics
 depot antipsychotics 
 haloperidol decanoate and
 fluphenazi...
CHLORPROMAZINE – PROTOTYPE OF
ANTIPSYCHOTICS
PHARMACOLOGICAL ACTIONS - IN
A PSYCHOTIC
 Reduces irrational behavior
 Reduces agitation, aggressiveness
 Normalization...
chlorpromazine blocks – D1,
D2, D3, D4 dopamine receptors
BLOCKADE OF DOPAMINERGIC
PATHWAYS
 Mesolimbic –Antipsychotic effect
 Nigrostriatal – parkinsonian side effect
 Tuburoin...
MECHANISMS OF ACTION

TOLERANCE AND DEPENDENCE
 Tolerance develops to sedation and
hypotension.
 No tolerance for antipsychotic and
extrapyram...
PHARMACOKINETICS
 Unpredictable oral absorption, low
bioavailability
 Highly bound to plasma proteins
 Attains higher c...
ADVERSE EFFECTS
 I. DOSE RELATED SIDE EFFECTS:
 CNS – Drowsiness, mental confusion,
increased appetite , aggravation of ...
ADVERSE EFFECTS
 ANTICHOLINERGIC SIDE EFFECTS
Dry mouth, blurring of vision, constipation, urinary
retention
 ENDOCRINE
...
EXTRAPYRAMIDAL DISTURBANCES
PARKINSONISM  rigidity, tremor, hypokinesia,
mask like facies, shuffling gait.
 ACUTE MUSCUL...
MALIGNANT NEUROLEPTIC SYNDROME
 High doses of potent agents
 Marked rigidity, immobility, tremor, fever,
semi consciousn...
OTHER SIDE EFFECTS
 Weight gain
 Rise in blood sugar and lipids
 Blue pigmentation
 Corneal and lens opacities
 Retin...
HYPERSENSITIVITY REACTIONS
 Cholestatic Jaundice – 2-4%
 Skin rash, urticaria, contact dermatitis,
photosensitivity
INTERACTIONS
1. Potentiation of all CNS depressants
2. Block the action of Levodopa
3. Enzyme inducers can reduce blood le...
THERAPEUTIC USES
 SCHIZOPHRENIA:
 Control positive symptoms better than negative
symptoms
 Afford symptomatic relief
 ...
THERAPEUTIC USES
ANXIETY
 Relieve anxiety
 Useful in
 anxiety with a psychotic basis
 and not responding to other drugs
HALOPERIDOL
 Extra pyramidal side effects +++
 Sedation+
 Hypotension +
 Few autonomic effects
 Less epileptogenic
 ...
TRIFLUPERAZINE AND
FLUPHENAZINE
 Minimum autonomic actions
 Less sedation+
 Less hypotension+
 Less hypersensitivity r...
ATYPICAL ANTIPSYCOTICS
 Second generation antipsychotics that have weak
D2 blocking and potent 5-HT2 blocking activity
 ...
CLOZAPINE
 Atypical or second generation antipsychotic
 Selective D4 blocker
 Anti 5HT2
 Weak D2 blocking action
 Pro...
CLOZAPINE - ADR
 Agranulocytosis (0.8%) and other blood
dyscrasias (weekly monitor WBC count)
 High dose induce seizures...
RISPERIDONE
 Combination of D2 +5HT2 blockade
 Alpha1, alpha2, H1 blocker
 Less EPS at low doses
 Sedation, postural h...
OLANZAPINE
 Blocks D2, 5HT2, alpha1, alpha2, M1, H1
 like clozapine
 Controls positive and negative symptoms
 Broad sp...
QUETIAPINE
 New, short acting atypical antipsychotic
 Minimal EPS, hyperprolactinemia
 Quite sedating
 Postural hypote...
ARIPIPRAZOLE
 Partial agonist at D2, 5-HT1A
 Antagonist at 5-HT2
 Minimal sedation
 No EPS, hyperprolactinemia, hypote...
ZIPRASIDONE
 Latest atypical antipsychotic
 Same advantages of aripiprazole
 In addition it has anxiolytic, antidepress...
RESERPINE
 Historical importance in psychiatry
 low efficacy antipsychotic
 Depletes – brain DA, NA, 5-HT
 Cause menta...
FUTURE OF SCHIZOPHRENIA
 Advanced genetic screening technology,
 structural and functional brain imaging,
 sophisticate...
AFFECTIVE DISORDERS
 Pathological change in mood state
 Major depression
 Mania
MAJOR DEPRESSION
 characterized by symptoms like
1. Sad mood
2. Loss of interest and pleasure
3. Feelings of worthlessnes...
MANIA
 Elation or irritable mood
 Racing thoughts
 Accelerated speech
 Increased activity
 Reduced sleep
 Violent be...
BIPOLAR DISORDER
 Cycles of mood swings from mania to
depression occur over time
TREATMENT OF DEPRESSION
 Three phases of treatment have been
proposed:
 acute,
 continuation,
 and maintenance treatme...
ACUTE TREATMENT PHASE
 clinical interview,
 diagnostic assessment,
 physical and neurological examination,
 and clinic...
GOALS
 establishing a diagnosis,
 defining a short-term and long-term
 multidisciplinary treatment plan,
 selecting th...
Maintenance Phase
 prophylactic,
 to maintain the response.
 dosing during this phase should continue at the
same level...
CONTINUATION PHASE
 Consists of monitoring for completeness of
response and side effects.
 Discontinuation of medication...
ANTIDEPRESSANTS
 Drugs which can elevate mood in depressive
illness.
 Affect monoaminergic transmission
TRICYCLIC ANTIDEPRESSANTS
 IMIPRAMINE – Prototype
ACTIONS - In depressed
patients
 little acute effects are produced
 Produce sedation
 Mood is gradually elevated after ...
ACTIONS
 Does not produce euphoria but relieves
depression
 Suppress REM sleep
 reduce awakenings during night
 Lower ...
MECHANISM OF ACTION
 Inhibit active uptake of biogenic amines NA and 5-
HT  potentiate them
 Results in increased conce...
TOLERANCE AND DEPENDENCE
 Tolerance to the anticholinergic and hypotensive
effects develops gradually
 Psychological dep...
PHARMACOKINETICS
 Oral absorption is good
 Highly bound to plasma tissue proteins
 Metabolites are excreted urine over ...
ADVERSE EFFECTS
 Sedation, mental confusion
 Postural hypotension
 Anticholinergic: dry mouth, blurred vision
constipat...
ADVERSE EFFECTS
 Some patients may switch to hypomania or
mania
 Sweating and fine tremors
 Seizure threshold is lowere...
USES
 1. Endogenous depression
Response takes 2-3 weeks to appear
Therapy continued upto 1 year
SSRIs – mild to moderate ...
USES
 5. Attention deficit – hyperactive disorder in
children
Imipramine, nortriptyline
Less behavioural side effects tha...
LIMITATIONS OF TCA’S
 Frequent anticholinergic, cardiovascular and
neurological side effects
 Relatively low safety marg...
MAO INHIBITORS
 Inhibit monoamine oxidase
 MAO –A – deaminates 5 –HT, NA, inhibited
by moclobemide
 MAO- B – deaminates...
MOCLOBEMIDE
 Reversible and selective MAO-A inhibitor
 Cheese reaction less likely
 No side efffects of TCA’s
 Safer i...
SELECTIVE SEROTONIN REUPTAKE
INHIBITORS (SSRIs)
 Since 1980s
 Fluoxetine, Fluvoxamine, paroxetine,
Bupropion, venlafaxin...
ADVANTAGES OF SSRIs
 Little or no sedation,
 Do not interfere with cognitive and
psychomotor function
 Do not produce a...
ADR
 Nervousness, restlessness, insomnia
 Anorexia, NAUSEA
 Dyskinesia
 Headache and diarrhoea
 Interfere with ejacul...
DRUG INTERACTION
 The SSRIs inhibit CYP2D6 and CYP3A4
elevate plasma levels of TCAs, haloperidol,
clozapine, terfenadine...
USES
 1st
line drugs in
 Mild to moderate depression
 phobias,
 OCDs
 Panic disorders
 Kleptomania and related disor...
FLUOXETINE
 Prototype
 Longest acting
 More agitation and dermatological reactions
 More appropriate for poorly compli...
FLUVOXAMINE
 Shorter acting SSRI
 No active metabolite
 Used in hospitalized patients and in number
of anxiety disorder...
PAROXETINE
 Short acting SSRI
 Does not produce active metabolite
 A higher incidence of g.i. side effects,
discontinua...
SERTRALINE
 Drug interactions due to inhibition of CYP
isoenzymes are less likely to occur
 Produces a longer lasting ac...
CITALOPRAM
 Lower propensity to cause drug interactions
 Should be avoided in patients likely to attempt
suicide
OTHER USES OF SSRIs
 Now 1st
choice drugs for OCD, Panic disorder,
social phobia, eating disorders and post
traumatic str...
ATYPICAL ANTIDEPRESSANTS
 Trazodone
 Mianserin
 Tianeptine
 Amineptine
 Venlafaxine
 Duloxetine
 Mirtazapine
TRAZODONE
 Sedative
 Cause bradycardia, less prone to cause arrhythmias
 No anticholinergic side effects
 No seizures
...
VENLAFAXINE
 Novel antidepressant
 SNRI
 Like SSRI
 Does not interact with cholinergic,
adrenergic, H1 receptors
 No ...
DULOXETINE
 Similar to venlafaxine
 Cause agitation, rise in BP, insomnia
 Also indicated in
 panic attacks,
 Diabeti...
MIRTAZAPINE
 Act by blocking alpha2 autoreceptors (on NA
neurones), heteroreceptors (on 5-HT
neurones)
 Cause sedation, ...
BUPROPION
 Inhibit DA, NA uptake
 Excitant
 Available as a Sustained release formulation
for smoking cessation
 No sex...
ACUTE POISONING
 usually self attempted and may endanger life
 Symptoms :Excitement, delirium, anticholinergic
symptoms,...
INTERACTIONS
 TCAs potentiate directly acting
sympathomimetic amines  rise in BP
 TCAs potentiate CNS depressants inclu...
OTHER TREATMENTS FOR
DEPRESSION
ANXIETY
 Unpleasant emotional state associated with
 Uneasiness
 discomfort and
 fear about future threat
 Treatment ...
TYPES OF ANXIETY
 Cardiac neurosis
 G-I neurosis
 Social anxiety
 Obsessive – compulsive disorder ( OCD )
 Post-traum...
SLEEP MEDICATIONS
ANTIANXIETY DRUGS
 Control the symptoms of anxiety
 Produce a restful state of mind without
interfering with normal ment...
CLASSIFICATION
 Benzodiazepines – Diazepam
Chlordiazepoxide
Oxazepam
Lorazepam, Alprazolam
 Azapirones - Buspirone, Gepi...
BENZODIAZEPINES
 One of the most widely used class of drugs
 Little effect on other body systems
 Relatively safe even ...
MECHANISM OF ACTION
 Facilitates inhibitory GABAergic transmission
ADR
 Sedation
 Light-headedness
 Psychomotor impairment
 Vertigo
 Confusion in elderly
 Increased appetite, weight g...
CHLORDIAZEPOXIDE
 Ist
BZD to be used clinically
 Slow oral absorption
 Produce smooth long lasting effect
 Preferred i...
DIAZEPAM
 Quickly absorbed
 Produces initial phase of strong action, followed
by prolonged milder effect
 Produces acti...
LORAZEPAM
 Slow oral absorption
 Less lipid soluble  slow rate of entry to brain
 Good sedative
 Only BZD recommended...
ALPRAZOLAM
 High potency anxiolytic
 In addition has mood elevating action in mild
depression
 Useful in anxiety associ...
BUSPIRONE
 Ist
Azapirone (non BZD)
 5-HT1A agonist
 No sedation, No cognitive impairment, do not
interact with BZD rece...
PHARMACOKINETICS
 Rapidly absorbed
 t½ 2-3.5 hrs
 Extensive Ist pass metabolism
 BA 5%
SIDE EFFECTS
 Dizziness, headache, light headedness
 Does not potentiate CNS depressants
 May cause rise in BP in patie...
HYDROXYZINE
 H1 antihistaminic
 Sedative, antiemetic
 has antimuscarinic and spasmolytic properties
 Useful in reactiv...
BETA BLOCKERS
 Relieves sympathetic symptoms of anxiety
(Palpitation, rise in BP, shaking, tremor, GI hurrying)
 Produce...
TREATMENT OF ANXIETY
DISORDERS Treat when excessive and disabling
 Use BZDs in smallest possible dose for short term
 I...
TREATMENT OF ANXIETY
 SSRIs drug of choice for anxiety disorders
 Monitor for possible ADR
 Treatment effect is often s...
MANIA
 Elation or irritable mood
 Racing thoughts
 Accelerated speech
 Increased activity
 Reduced sleep
 Violent be...
LITHIUM CARBONATE
 Small monovalent cation
 Stabilizes mood
 Used in the prophylaxis of bipolar manic
depressive illnes...
ACUTE MANIA - TREATMENT
 Lithium – delayed onset of action
 Carbamazepine, volproic acid, divalproex
sodium ( side effec...
ACTIONS
 On prolonged administration stabilizes mood
 Does not produce sedation or euphoria
 Suppress acute mania in 1 ...
ACTIONS
 Inhibits the actions of ADH  causes
diabetes insipidus like state
 Has some insulin like action
 Increases WB...
MECHANISM OF ACTION
 Exactly not known
 Inhibits hydrolysis of inositol-1-phosphate 
decrease supply of free inositol ...
PHARMACOKINETICS
 Well absorbed orally
 Not protein bound, not metabolized
 Uniformly distributed in total body water
...
MONITORING LITHIUM LEVEL
 Monitoring Li concentration is essential for
optimum therapy  Because margin of safety
is narr...
ADVERSE EFFECTS
 Nausea, vomiting and mild diarrhoea
 Thirst and polyuria
 Fine tremors, seizures (rarely)
 Long term ...
CONTRAINDICATIONS
 Pregnancy – fetal goiter and cardiac
congenital abnormalities reported
 Sick sinus syndrome
LITHIUM TOXICITY
 CNS toxicity appears on higher doses –
 mental confusion
 giddiness, tremors
 ataxia, nystagmus, mot...
Treatment
 Symptomatic
 no specific antidote
 Osmotic diuretics ( mannitol) , sodium
bicarbonate infusion promote Li ex...
INTERACTIONS
 Diuretics increases lithium level
 Tetracyclines, ACE inhibitors, NSAIDs cause
Li retention
 Sometimes Li...
USES
 1. Acute mania – used after the episode is under
control with neuroleptics, diazepam /lorazepam
 2. Prophylaxis in...
DISADVANTAGES OF LITHIUM
 Intolerance
 Risk of toxicity
 50% of mania, bipolar disorder show poor
response
CARBAMAZEPINE
 Equally effective as Li
 Better tolerated than Li
 Preferred by many as first line / adjunctive
treatmen...
SODIUM VALPROATE
 Act faster than Li
 1st
line treatment for acute mania
 Better tolerated
 Useful in those not respon...
OTHER DRUGS IN MANIA
 Lamotrigine – specially useful in depressed and
rapidly cycling phases of the illness
 Olanzapine ...
TREATMENT
 Psychotic illness ( Schizophrenia, mania, depressive
psychosis )  drugs as first-line treatment ,
psychothera...
A despondent fellow seeks the advice of the city’s
most fashionable – and expensive – psychiatrist
cum analyst
“You have a...
“Psychology which explains everything
explains nothing, and we are still in doubt”
Marianne Moore
“If the only tool you have is a hammer,
you tend to see every problem as a nail.”
Abraham Maslow (American
Philosopher and...
LEVELS OF CONSCIOUSNESS
Writing prescriptions is easy!Writing prescriptions is easy!
Understanding people is hard…..Understanding people is hard…..
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Psychopharmacology prof satya
Upcoming SlideShare
Loading in …5
×

Psychopharmacology prof satya

1,420 views

Published on

this ppt is about basic and clinical pharmacology of psychotherapeutic drugs such as antipsychotics, antidepressants, antianxiety and antimanic drugs

Published in: Health & Medicine
  • If you’re looking for a great essay service then you should check out ⇒ www.WritePaper.info ⇐. A friend of mine asked them to write a whole dissertation for him and he said it turned out great! Afterwards I also ordered an essay from them and I was very happy with the work I got too.
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • Don'T Buy Leptitox Unless You'Ve Seen This Massive Discount & Exclusive Bonuses. 100% Money Back Guarantee. Safe & Secure. $39 Only + Free Colon Cleanse?. Free Shipping. ♥♥♥ https://url.cn/5yLnA6L
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • The 3 Secrets To Your Bulimia Recovery ♥♥♥ https://tinyurl.com/y88w4b6s
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • After years of recovery attempts this is the only one that helped me through each stage of my recovery - it is so different for everyone and the forum allowed each individual to be honest about what was going on and to get support from a lot of wonderful people. ➤➤ http://t.cn/A6Pq6OB6
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • Your program is absolutely a miracle. I am on day 15, using your method. I am completely OFF ALL MEDICATIONS. I have absolutely no negative side effects. My liver functions are normal, my blood sugar is normal, my energy is higher than it has been in years and I feel great. Your e-book has changed my life. ▲▲▲ http://ishbv.com/matt1a/pdf
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here

Psychopharmacology prof satya

  1. 1.  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.
  2. 2. MEMORY OF HUMAN BRAIN IS 13367864.5GB
  3. 3. 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
  4. 4. Prevalance of Psychiatric Disorder
  5. 5. Dr.V. Sathyanarayanan MD Professor of pharmacology
  6. 6.  Excitatory – Glutamate, aspartate  Inhibitory – GABA, Glycine  Others –Noradrenaline ,Dopamine, 5- HT  Acetylcholine  Histamine  Adenosine  Nitric oxide  Tachykinins  Opioid peptides and endocannabinoids CENTRAL NEUROTRANSMITTERS
  7. 7. PSYCHIATRIC DISORDERS  Psychoses  Neuroses  Personality disorders  Organic mental disorders
  8. 8. 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
  9. 9. PSYCHOSES  Organic – delirium, dementia  Functional  schizophrenia  paranoid states  Mood disorders – depression, Mania
  10. 10. 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
  11. 11. 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
  12. 12. 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)
  13. 13. PATHOPHYSIOLOGY  Dopaminergic overactivity in limbic system  Decrease in glutamate  5- HT, NE also involved  Complex involvement of multiple neurotransmitters.
  14. 14. Normal Dopamine Hypothesis of Schizophrenia Adapted from Stahl. J Clin Psychiatry. 2001;62:923. Hyperdopaminergic pathways Hypodopaminergic pathways Negative symptomsPositive symptoms
  15. 15. NEUROCHEMICAL ABNORMALITIES  Dopamine disregulation  Glutamatergic hypofunction  GABAergic hypofunction  Nicotinic hypofunction
  16. 16. 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
  17. 17. 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.
  18. 18. 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
  19. 19. 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.
  20. 20. 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
  21. 21. 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.
  22. 22. 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.
  23. 23. 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)
  24. 24. 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….
  25. 25. 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
  26. 26. 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
  27. 27. Comparative PharmacologyComparative Pharmacology of Atypical Antipsychotic Drugsof Atypical Antipsychotic Drugs Adapted from: Schmidt et al. Soc Neurosci Abstr. 1998;24(2):2177 5-HT5-HT2A2A αα11 αα22 DD11 DD22 DD44 HaloperidolHaloperidol RisperidoneRisperidone HH11 5-HT5-HT2A2A DD22 5-HT5-HT2C2C αα11 OlanzapineOlanzapine 5-HT5-HT2A2A MM11 HH11 5-HT5-HT2C2C DD22 αα11 ClozapineClozapine MM11 5-HT5-HT2C2C αα11HH11 5-HT5-HT2A2A DD22 5-HT5-HT1A1A QuetiapineQuetiapine MM11 αα11 HH11 5-HT5-HT2A2A DD22 5-HT5-HT1A1A 5-HT5-HT2C2C ZiprasidoneZiprasidone 5-5- HTHT1D1D 5-HT5-HT2A2A DD22 5-HT5-HT1A1A HH11 αα11 5-HT5-HT2C2C
  28. 28. Tandon R, Milner K, Jibson MD. J Clin Psychiatry. 1999;60(suppl 8):21-28Tandon R, Milner K, Jibson MD. J Clin Psychiatry. 1999;60(suppl 8):21-28 Conventional vs. Atypicals: Side-EffectConventional vs. Atypicals: Side-Effect ProfilesProfiles Key: 0 = absent; ± = minimal; + = mild; ++ = moderate; +++ =Key: 0 = absent; ± = minimal; + = mild; ++ = moderate; +++ = severesevere EPSEPS Dose-related EPSDose-related EPS TDTD Prolactin elevationProlactin elevation AgranulocytosisAgranulocytosis AnticholinergicAnticholinergic AST/ALT elevationAST/ALT elevation HypotensionHypotension SedationSedation QTc prolongationQTc prolongation Weight gainWeight gain ZIPZIP THZTHZ HALHAL CLZCLZ RISRIS OLZOLZ QTPQTP ++ ±± ±± ++ ++ ±± ±± ±± ++ ++ ++ ++++ ++++ ++++++ ++++++ + ++ + ++++++ ±± ++ ++++++ ++ ++++++ ++++++ ++++++ ±± ++ ++++++ ±± ++ ++ ++ 0 to ±0 to ± 00 00 ++++++ ++++++ ++ 00 ++++ ++ ++++++ ++++++ ++++ ++++ ++++ ±± ±± ++ ++++ ++ ++ ++ ±± ±± ++ ++++ ++++++ 00 ++++ ±± ±± ++++ ++++ ±± 0 to ±0 to ± ±± ±± ±± ±± ±± ±± ±± ±± ±± 0 to ±0 to ± 0 to ±0 to ±0 to ±0 to ±
  29. 29. Recommended Dosing ofRecommended Dosing of First-Line AtypicalsFirst-Line Atypicals  Risperidone 2-6 mg/day  Olanzapine 10-40! mg/day  Quetiapine 400-1200! mg/day  Ziprasidone 80-240! mg/day !: Above FDA recommended upper dose Daily Dose in Acute PhaseDaily Dose in Acute Phase (Refined After Clinical Experience)(Refined After Clinical Experience)
  30. 30. Antipsychotic Treatment OptionsAntipsychotic Treatment Options  Low-potency conventional antipsychotics (chlorpromazine, thioridazine)  High-potency conventional antipsychotics (haloperidol, fluphenazine, thiothixene)  Clozapine  First-line atypical antipsychotics  Risperidone  Olanzapine  Quetiapine
  31. 31. TimeTime DoseDose OldOld agentagent AtypicalAtypical Titrate atypical Titrate atypical to desired dosage to desired dosage Continue oldContinue old Slowly taper off old Slowly taper off old agent agent agentagent Switching Antipsychotics:Switching Antipsychotics: Recommended StrategyRecommended Strategy
  32. 32. 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
  33. 33. 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
  34. 34. 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
  35. 35. ADJUNCTIVE MEDICATIONS  Anticholinergics  Mood stabilizers  Benzodiazepines  Betablockers  ECT
  36. 36. NEW FORMULATIONS  Injections of atypical antipsychotics  depot antipsychotics   haloperidol decanoate and  fluphenazine decanoate
  37. 37. CHLORPROMAZINE – PROTOTYPE OF ANTIPSYCHOTICS
  38. 38. PHARMACOLOGICAL ACTIONS - IN A PSYCHOTIC  Reduces irrational behavior  Reduces agitation, aggressiveness  Normalization of disturbed thought  Relieves anxiety  Suppresses delusions, hallucinations, hyperactivity  Sedation – immediately produced  Antipsychotic effect  takes weeks to develop.
  39. 39. chlorpromazine blocks – D1, D2, D3, D4 dopamine receptors
  40. 40. BLOCKADE OF DOPAMINERGIC PATHWAYS  Mesolimbic –Antipsychotic effect  Nigrostriatal – parkinsonian side effect  Tuburoinfundibular – hormonal side effects  CTZ – Antiemetic action
  41. 41. MECHANISMS OF ACTION 
  42. 42. TOLERANCE AND DEPENDENCE  Tolerance develops to sedation and hypotension.  No tolerance for antipsychotic and extrapyramidal effects.  No dependence
  43. 43. PHARMACOKINETICS  Unpredictable oral absorption, low bioavailability  Highly bound to plasma proteins  Attains higher concentration in brain  Cumulates on chronic administration  Acute effects lasts 6-8 hours
  44. 44. ADVERSE EFFECTS  I. DOSE RELATED SIDE EFFECTS:  CNS – Drowsiness, mental confusion, increased appetite , aggravation of seizures  ALPHA ADRENERGIC BLOCKADE: Postural hypotension, palpitation, inhibition of ejaculation
  45. 45. ADVERSE EFFECTS  ANTICHOLINERGIC SIDE EFFECTS Dry mouth, blurring of vision, constipation, urinary retention  ENDOCRINE Amenorrhea, infertility, gynaecomastia, galactorrhoea occur infrequently
  46. 46. 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
  47. 47. 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
  48. 48. OTHER SIDE EFFECTS  Weight gain  Rise in blood sugar and lipids  Blue pigmentation  Corneal and lens opacities  Retinal degeneration  Cardiac arrhythmia
  49. 49. HYPERSENSITIVITY REACTIONS  Cholestatic Jaundice – 2-4%  Skin rash, urticaria, contact dermatitis, photosensitivity
  50. 50. INTERACTIONS 1. Potentiation of all CNS depressants 2. Block the action of Levodopa 3. Enzyme inducers can reduce blood levels of neuroleptics
  51. 51. 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
  52. 52. THERAPEUTIC USES ANXIETY  Relieve anxiety  Useful in  anxiety with a psychotic basis  and not responding to other drugs
  53. 53. HALOPERIDOL  Extra pyramidal side effects +++  Sedation+  Hypotension +  Few autonomic effects  Less epileptogenic  No weight gain  Jaundice is rare  Preferred drug for acute schizophrenia
  54. 54. 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
  55. 55. 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
  56. 56. 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
  57. 57. 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
  58. 58. 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
  59. 59. 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
  60. 60. QUETIAPINE  New, short acting atypical antipsychotic  Minimal EPS, hyperprolactinemia  Quite sedating  Postural hypotension +  Used in mania/ bipolar disorder  Interact with macrolides, anticonvulsants
  61. 61. ARIPIPRAZOLE  Partial agonist at D2, 5-HT1A  Antagonist at 5-HT2  Minimal sedation  No EPS, hyperprolactinemia, hypotension  No weight gain, diabetes  Long acting
  62. 62. 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
  63. 63. RESERPINE  Historical importance in psychiatry  low efficacy antipsychotic  Depletes – brain DA, NA, 5-HT  Cause mental depression, suicidal tendencies
  64. 64. 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.
  65. 65. AFFECTIVE DISORDERS  Pathological change in mood state  Major depression  Mania
  66. 66. 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
  67. 67. MANIA  Elation or irritable mood  Racing thoughts  Accelerated speech  Increased activity  Reduced sleep  Violent behaviour  Progressive loss of contact with reality
  68. 68. BIPOLAR DISORDER  Cycles of mood swings from mania to depression occur over time
  69. 69. TREATMENT OF DEPRESSION  Three phases of treatment have been proposed:  acute,  continuation,  and maintenance treatment phases
  70. 70. ACUTE TREATMENT PHASE  clinical interview,  diagnostic assessment,  physical and neurological examination,  and clinical and laboratory studies  Lasts 6-12 weeks
  71. 71. 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
  72. 72. 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
  73. 73. 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.
  74. 74. ANTIDEPRESSANTS  Drugs which can elevate mood in depressive illness.  Affect monoaminergic transmission
  75. 75. TRICYCLIC ANTIDEPRESSANTS  IMIPRAMINE – Prototype
  76. 76. 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
  77. 77. 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
  78. 78. 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
  79. 79. 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
  80. 80. 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
  81. 81. 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
  82. 82. 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
  83. 83. 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
  84. 84. 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
  85. 85. 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
  86. 86. MAO INHIBITORS  Inhibit monoamine oxidase  MAO –A – deaminates 5 –HT, NA, inhibited by moclobemide  MAO- B – deaminates dopamine  Hit and run drugs  Cheese reaction
  87. 87. 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
  88. 88. SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs)  Since 1980s  Fluoxetine, Fluvoxamine, paroxetine, Bupropion, venlafaxine, mirtazapine  Improved tolerability  Relatively safe  Faster onset of antidepressant action
  89. 89. 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
  90. 90. 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
  91. 91. 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
  92. 92. USES  1st line drugs in  Mild to moderate depression  phobias,  OCDs  Panic disorders  Kleptomania and related disorders  Preferred for prophylaxis of recurrent depression
  93. 93. FLUOXETINE  Prototype  Longest acting  More agitation and dermatological reactions  More appropriate for poorly compliant patients  Less suitable for patients needing rapid effect
  94. 94. FLUVOXAMINE  Shorter acting SSRI  No active metabolite  Used in hospitalized patients and in number of anxiety disorders  More nausea, agitation, Discontinuation reactions
  95. 95. PAROXETINE  Short acting SSRI  Does not produce active metabolite  A higher incidence of g.i. side effects, discontinuation reaction
  96. 96. SERTRALINE  Drug interactions due to inhibition of CYP isoenzymes are less likely to occur  Produces a longer lasting active metabolite  Efficacious in juvenile depression
  97. 97. CITALOPRAM  Lower propensity to cause drug interactions  Should be avoided in patients likely to attempt suicide
  98. 98. 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
  99. 99. ATYPICAL ANTIDEPRESSANTS  Trazodone  Mianserin  Tianeptine  Amineptine  Venlafaxine  Duloxetine  Mirtazapine
  100. 100. 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
  101. 101. 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
  102. 102. DULOXETINE  Similar to venlafaxine  Cause agitation, rise in BP, insomnia  Also indicated in  panic attacks,  Diabetic neuropathic pain  Stress incontinence
  103. 103. 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
  104. 104. 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
  105. 105. 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
  106. 106. 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
  107. 107. OTHER TREATMENTS FOR DEPRESSION
  108. 108. ANXIETY  Unpleasant emotional state associated with  Uneasiness  discomfort and  fear about future threat  Treatment is needed when anxiety is excessive
  109. 109. TYPES OF ANXIETY  Cardiac neurosis  G-I neurosis  Social anxiety  Obsessive – compulsive disorder ( OCD )  Post-traumatic stress disorder  Phobias  Panic disorder
  110. 110. SLEEP MEDICATIONS
  111. 111. 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
  112. 112. CLASSIFICATION  Benzodiazepines – Diazepam Chlordiazepoxide Oxazepam Lorazepam, Alprazolam  Azapirones - Buspirone, Gepirone Ispapirone  Sedative antihistaminic – Hydroxyzine  Beta blocker - Propranolol
  113. 113. 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
  114. 114. MECHANISM OF ACTION  Facilitates inhibitory GABAergic transmission
  115. 115. ADR  Sedation  Light-headedness  Psychomotor impairment  Vertigo  Confusion in elderly  Increased appetite, weight gain  Dependence on long term use
  116. 116. 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
  117. 117. 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
  118. 118. 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
  119. 119. 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
  120. 120. 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
  121. 121. PHARMACOKINETICS  Rapidly absorbed  t½ 2-3.5 hrs  Extensive Ist pass metabolism  BA 5%
  122. 122. 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
  123. 123. 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
  124. 124. 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
  125. 125. 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
  126. 126. 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
  127. 127. MANIA  Elation or irritable mood  Racing thoughts  Accelerated speech  Increased activity  Reduced sleep  Violent behaviour  Progressive loss of contact with reality
  128. 128. LITHIUM CARBONATE  Small monovalent cation  Stabilizes mood  Used in the prophylaxis of bipolar manic depressive illness (MDI)  Standard antimanic, mood stabilizer
  129. 129. ACUTE MANIA - TREATMENT  Lithium – delayed onset of action  Carbamazepine, volproic acid, divalproex sodium ( side effects – hepatic failure)  Typical antipsychotics – highly effective , ( ADR- tardive dyskinesia)  Atypical antipsychotics- clozapine ( risk of agranulocytosis), olanzapine
  130. 130. 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
  131. 131. ACTIONS  Inhibits the actions of ADH  causes diabetes insipidus like state  Has some insulin like action  Increases WBC count  Reduces thyroxine synthesis
  132. 132. 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
  133. 133. 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
  134. 134. 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
  135. 135. 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%
  136. 136. CONTRAINDICATIONS  Pregnancy – fetal goiter and cardiac congenital abnormalities reported  Sick sinus syndrome
  137. 137. 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
  138. 138. Treatment  Symptomatic  no specific antidote  Osmotic diuretics ( mannitol) , sodium bicarbonate infusion promote Li excretion  Haemodialysis is indicated in serum levels above 4 mEq/L
  139. 139. 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
  140. 140. 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
  141. 141. DISADVANTAGES OF LITHIUM  Intolerance  Risk of toxicity  50% of mania, bipolar disorder show poor response
  142. 142. 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
  143. 143. 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
  144. 144. 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
  145. 145. 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
  146. 146. 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.”
  147. 147. “Psychology which explains everything explains nothing, and we are still in doubt” Marianne Moore
  148. 148. “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)
  149. 149. LEVELS OF CONSCIOUSNESS
  150. 150. Writing prescriptions is easy!Writing prescriptions is easy! Understanding people is hard…..Understanding people is hard…..

×