2. ANTI – PSYCHOTIC DRUGS
• NEUROLEPTIC DRUGS
• ANTI-SCHIZOPHRENIC DRUGS
• MAJOR TRANQUILIZERS
• DOPAMINE RECEPTOR
ANTAGONISTS
3. TYPES OF PSYCHOSIS
• SCHIZOPHRENIA
• AFFECTIVE DISORDERS
(DEPRESSION/MANIA)
• ORGANIC PSYCHOSES
(CAUSED BY HEAD INJURY,
ALCOHOLISM, OTHERS)
4. THE NATURE OF SCHIZOPHRENIA
• Begins at an early age
• Strong hereditary factor
POSITIVE SYMPTOMS
Delusions / Hallucinations
Thought disorder
NEGATIVE SYMPTOMS
Withdrawal from social contacts
Flattening of emotional responses
5. THE DOPAMINE HYPOTHESIS
• SCHIZOPRENIA: WITH EXCESSIVE
DOPAMINIERGIC ACTIVITY
1. ANTIPSYCHOTIC DRUGS BLOCK
POSTSYNAPTIC D2 RECEPTORS IN CNS
2. DRUGS THAT INCREASE DOPA
AGGRAVATE SCHIZOPHRENIA
6. THE DOPAMINE HYPOTHESIS
3. DOPAMINE RECEPTOR DENSITY ↑ in
schizophrenia
4. POSITRON EMISSION TOMOGRAPHY
(PETS) ↑ DRD
5. HOMAVANILLIC ACID (HAV) change in
amount
7. CLASSIFICATION OF ANTIPSYCHOTIC DRUGS
1. TYPICAL ANTIPSYCHOTICS
a. Phenothiazine derivatives
• Aliphatic Derivative: CHLORPROMAZINE
• Piperidine Derivative: THIORIDAZINE
• Piperazine Derivative: FLUPENAZINE,
PERPHENAZINE, TRIFLUOPERAZINE
b. Thioxanthene Derivative: THIOTHIXENE
c. Butyrophenone: HALOPERIDOL
9. PHARMACOKINETICS
• READILY BUT INCOMPLETELY
ABSORBED
• FIRST PASS METABOLISM
• HIGHLY LIPID SOLUBLE
• LARGE V d > 7 L / kg
• PROTIEN BOUND
• COMPLETELY METABOLIZED
• LITTLE EXCRETED UNCHANGED
• T ½ is 10 -24 hours
10. MECHANISM OF ACTION
• DOPAMINE RECEPTOR-BLOCKING
ACTIVITY IN THE BRAIN
• SEROTONIN RECEPTOR-BLOCKING
ACTIVITY IN THE BRAIN
• BLOCK CHOLINERGIC,
ADRENERGIC & HISTAMINERGIC
RECEPTORS
12. DOPAMINERGIC SYSTEM
4.MEDULLARY-PERIVENTRICULAR :
motor nuclei of the vagus
EATING BEHAVIOR
5. INCERTOHYPOTHALAMUS : from
the medial zona incerta to the
hypothalamus and the amygdala
REGULATE THE ANTICIPATORY
MOTIVATIONAL PHASE OF
COPULATORY BEHAVIOR IN RATS
17. ANTIPSYCHOTIC AGENTS
• CARDIOVASCULAR EFFECTS
orthostatic hypotension
high resting pulse rate
↑ PR, ↓ stroke volume, ↓ mean
arterial pressure,
↓ peripheral resistance
NAUSEA & VOMITING
Block the chemoreceptor trigger zone
18. CLINICAL INDICATIONS
A. PSYCHIATRY INDICATIONS
• SCHIZOPHREMIA
• SCHIZOAFFECTIVE DISORDERS
• MANIC EPISODES IN BIPOLAR
DISORDERS
• GILLES DE TOURETTE SYNDROME
• SENILE DEMENTIA
B. NONPSYCHIATRIC INDICATIONS
>ANTI-EMETIC EFFECT (prochlorperazine)
>ANTI-PRURITIC EFFECTIphenothiazines)
>PREOPERATIVE
ANESTHESIA.promethazine
>NEUROLEPTIC ANESTHESIA..droperidol
19. SIDE EFFECTTS OF NEUROLEPTIC
DRUGS
A. NEUROLOGIC EFFECTS
1. ACUTE DYSTONIA : Spasm of muscles
tongue, face, neck, back, may mimic
seizures
• During the first 1 -5 days of Rx
• Mechanism unknown
• Rx: antiparkinson’s agents
2. AKATHISIA : Motor restlessness
• 5 -60 days
• Mechanism unknown; Rx with
diphenhydramine
20. 3. PARKINSONISM
bradykinesia, rigidity, tremor, mask facies,
shuffling gait seen in 5-30 days
Mechanism is antagonism of Dopamine
Rx: Antiparkinson’s Agents
4. NEUROLEPTIC MALIGNANT SYNDROME:
catatonia, stupor, fever, unstable BP,
myoglobulinemia after weeks of treatment
Mechanism: Antagonism of Dopamine
Rx: Stop neuroleptic immediately; Dandrolene;
Bromocriptine, Antiparks not effective
21. 5. PERIODIC TREMOR (RABBIT SYNDROME)
Perioral tremors
after months or years of treatment
Mechanism : unknown
Rx Antiparkinson’s Drugs
6. TARDIVE DYSKINESIA
oral-facial dyskinesia, choreoathetosis, dystonia
After months or years of Rx
Worse on withdrawal
Mechanism: excess function of dopamine
Rx: prevention crucial Rx unsatisfactory
22. ADVERSE EFFECTS
II. BEHAVIORAL EFFECTS:
• Pseudo-depression; toxic confusional state
III. AUTONOMIC NERVOUS SUSTEM EFFECTS :
• urinary retention,dry mouth, loss of
accommodation, constipation (MUSCARINIC
CHOLINERGIC BLOCKADE)
• orthostatic hypotension, impotence, failure to
ejaculate ( ALPHA ADRENORECEPTOR
BLOCKADE)
23. ADVERSE EFFECTS
IV. METABOLIC & ENDOCRINE EFFECTS
Weight gain, hyperglycemia, hyper -
prolactenemia, amenorrhea-galactorrhea
syndrome, infertility, impotence in males
V. TOXIC OR ALLERGIC REACTIONS
Agranulocytosis (clozapine) , cholestatic
jaundice, skin eruptions
VI. CARDIAC TOXICITY
Ventricular arrythmias (thioridazine)
VII. OCULAR COMPLICATIONS: “ browning
of vision”
24. ANTIMANIC AGENTS
• MOOD STABILIZING AGENT
• BIPOLAR DISORDERS (MANIC-
DEPRESSIVE)
• DISORDER WITH PREPONDERANCE OF
CATHECHOLAMINE RELATED ACTIVITY
• LITHIUM CARBONATE
• CARBAMAZEPINE, VALPROIC ACID
25. LITHIUM P’KINETICS
ABSORPTION : virtually complete
within 6 -8 hrs; peak plasma levels in 30 min
to 2 hrs
DISTRIBUTION: in total body water; slow
entry into intracellular compartment. No
protein binding
METABOLISM: None
EXCRETION: virtually entirely in urine; plasma
half life is about 20 hours
26. LITHIUM ‘ DYNAMICS
• EFFECTS ON ELECTROLYTES & IONS
TRANSPORT:
Substitute for sodium
• EFFECTS ON NEUROTRANSMITTER
enhance effects of serotonin?
Decrease norepinephrine & dopamine
turnover
Block dopamine receptor
supersensitivity
Augment synthesis of acetylcholine?
27. LITHIUM PHARMACODYNAMICS
• EFFECTS ON SECOND MESSENGER
effect on IP3/ DAG
EFFECTS ON PHOSPHOINOSITOL
TURNOVER…..> EARLY RELATIVE
REDUCTION OF MYOINOSITOL IN HUMAN
BRAIN
29. LITHIUM CONTRAINDICATION
A. MARKED DEHYDRATION OR
SODIUM DEPLETION
B.SIGNIFICANT RENAL OR CARDIAC
DISEASES
C. PREGNANCY(W)
D. RENAL CONCENTRATION
ABILITY(W)
• Nephrogenic diabetes insipidus with
polyuria
30. DRUG INTERACTIONS
A. THIAZIDE DIURETICS: ↓ RENAL
CLEARANCE OF LITHIUM
B. NSAID: ↓ LITHIUM CLEARANCE
C. ANTIPYSCHOTIC AGENTS:
↑ NEUROTOXICITY
31. DEPRESSION
I.REACTIVE OR SECONDARY DEPRESSION
Core Depression Syndrome: depression, anxiety,
tension, bodily complaints, guilt (> 60%)
II.ENDOGENOUS DEPRESSION
Core Depression Syndrome plus ABNORMAL VS
rhythm of sleep, motor activity, livido,
decrease appetite ( 25%)
III. DEPRESSION ASSOCIATED WITH BIPOLAR
AFFECTIVE DISORDER
(10-15%)
32. ANTIDEPRESSANTS
I.TRICYCLIC ANTIDEPRESSANTS
IMIPRAMINE. AMITRYPTYLINE, DOXAPIN,
NORTRIPTYLLINE ,DESIPRAMINE.
CLOMIPRAMINE , PROTIPTYLINE,
TRIMIPRAMINE
B. HETEROCYCLIC, SECOND & THIRD
DEGENERATIONS
1. SECOND GENERATIONS
AMOXAPINE, MAPROTILINE
TRAZODON, BUPROPION
2. THIRD GENERATIONS
MIRTAZAPINE, VENLAFAZINE
NEFAXODONE
39. CLINICAL INDICATIONS
A. DEPRESSION
B. PANIC DISORDER
C. OBSESSIVE COMPULISVE
D. ENURESIS
E. CHRONIC PAIN
F. OTHERS: Eating Disorder(Bulemia)
Cataplexy asstd with Narcolepsy,
School Phobia, Attention Deficit
Syndrome