The document discusses various types of anti-psychotic drugs, including their classification, mechanisms of action, pharmacokinetics, clinical indications, and adverse effects. It focuses on drugs that block dopamine receptors in the brain to treat schizophrenia and other psychoses by modifying dopaminergic activity. The drugs discussed include both typical and atypical antipsychotics, as well as mood stabilizers like lithium that are used to treat bipolar disorder.

1. ANTI-PSYCHOTIC DRUGS
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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

8. CLASSIFICATION OF ANTIPSYCHOTIC DRUGS
2. ATYPICAL ANTIPSYCHOTICS
• CLOZAPINE LOXAPINE
• OLANZAPINE
QUETIAPINE
• RISPERIDONE
MOLINDONE
• ZIPRASIDONE
• SERTINDOLE
ARIPIPRAZOLE

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

11. DOPAMINERGIC SYSTEM
• MESOLIMBIC-MESOCORTICAL :
substancia nigra………>limbic system
BEHAVIOR
2. NIGROSTRIATAL : substancia
nigra,,,……...>caudate & putamen
VOLUNTARY MOVEMENTS
3.TUBEROINFUNDIBULAR: arcuate
nuclei & periventricular neurons,,,>
hypothalamus & post pituitary;
INHIBITS PROLACTIN SECRETION

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

13. DOPAMINE RECEPTORS
• D1: CHROMOSOME 5; ↑ cAMP…>
activation of adenyl cyclase
• D5 : CHROMOSOME 4; ↑ cAMP
• D2: CHROMOSOMES 11: ↓ cAMP…>
blocks Ca ++ channels…> opens K +
channels
• D3: CHROMOSOME 11: ↓ cAMP
• D4: ↓ cAMP

14. DIFFERENCES AMONG
ANTIPSYCHOTIC DRUGS
CHLORPROMAZINE: a1=5HT2 >D2 >D1
HALOPERIDOL: D2>D1=D4>a1>5HT2
CLOZAPINE : D4=a1>5HT>D2=D1

15. DIFFERENCES AMONG
ANTIPSYCHOTIC DRUGS
OLANZAPINE: 5HT2A >D4 >D2 >a1 >D1
ARIPIPRAZOLE: D2 = 5HT 2A > D4 > a1
=H1 > > D1
QUETIAPINE: H1 >a1 > M1,3 > D2 > 5
HT2a

16. ANTIPSYCHOTIC AGENTS
• PSYCHOLOGICAL EFFECTS
> sleepiness, restlessness, impaired
performance & judgment
• NEUROPHYSIOLOGIC EFFECTS
> hypersyncrony focal /unilateral
• ENDOCRINE EFFECTS
> amenorrhea, galactorrhea, increase libido,
false( +) pregnancy tests
• ↓ libido in males, gynecomastia

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

28. LITHIUM ADVERSE EFFECTS
1. CNS EFFECTS; dizziness, mild ataxia
2. NEUROMUSCULAR EFECTS: fine tremors
3. CV EFFECTS: ventricular arrythmias
4. GIT EFFECTS: nausea, vomiting,
diarrhea
5. GUT EFFECTS: polyuria
6. ENDOCRINE EFFECTS: hypothyroidism
7. ALLERGIC REACTION: pruritus, rash
8. OVERDOSE TOXICITY: vomiting,
drowsiness, decrease consciousness
seizures
Rx: dialysis

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

33. ANTIDEPRESSANTS
C. SELECTIVE SEROTONIN REUPTAKE
INHIBITORS (SSRI)
• FLUOXETINE FLUVOXAMINE
• PAROXETINE ESCITALOPRAM
• SERTRALINE CITALOPRAM
D. MONOAMINE OXIDASE
INHIBITORS (MAOI)
• PHENELZINE, TRANYLCYPROMINE
• MOCLOBEMIDE

34. ANTIDEPRESSANTS PHARMADYNAMICS
A. ACTION OF ANTIDEPRESSANTS ON
BIOGENIC AMINE
NEUROTRANSMITTERS
 TRICYCLICS: BLOCK AMINE REUPTAKE
PUMPS
 MAOI: BLOCK DEGRADATIVE PATHWAY
FOR THE AMINE NEUROTRANSMITTERS
 TRAZODON, NEFAZODONE &
MIRTAZAPINE: SERETONIN RECEPTORS
ANTAGONIST

35. B.RECEPTOR & POSTRECEPTOR
EFFECTS
• SSRI: ↓ in norepinephrine cAMP &
in beta -adrenoreceptor binding
• MAOI: mixed action with
norepinephrine & serotonin
• ↑ serotonergic transmission
mediated through diverse
mechanisms

36. Drug Sedati Muscar NE 5HT reuptake
ve inicrBl reuptake block
ock Block
Amitryptyline +++ +++ ++ +++
Imipramine ++ + + ++
Amoxapine ++ + ++ +
Bupropion - - - -
Trazodone +++ - - ++
Mirtazepine +++ - - -
Venlafaxine - - +++ ++
Fluoxetine - + - +++

37. PHARMACOKINETICS
• A. TRICYCLICS
Incompletely reabsorbed
First pass metabolism
Large Vd
Metabolized
HETEROCYCLICS
Variable bioavailabilitiy
High protein binding
Variable and large Vd
Active metabolites

38. PHARMACOKINETICS
• SSRI : FLUOXETINE
• Well absorbed
• PPC: 4 – 8 hrs
• Inhibits drug metabolizing enzymes
• MAOI
• Readily absorbed

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

40. ADVERSE EFFECTS
• TRICYCLICS
Sedation: Sleepiness
Synpathomimetic; tremors,
insomnia
Antimuscarinic; blurred vision.
constipation
confusion,
urinary
incontinence

41. TRICYCLICS
Psychiatric: psychoses
aggravated
CVS: orthostatic
hypotension
Neurologic: Seizures
Metabolic-Endocrine: weight
gain, sexual
disturbance

42. ADVERSE EFFECTS
MAO INHIBITORS
headache, drowsiness, dry mouth,
weight gain, postural hypotension,
sexual distn
AMOXAPIN
 Tricyclic & antipsychotic effects
MAPROTILINE
Tricyclic Effects

43. ADVERSE EFFECTS
TRAZODONE & NEFAZODONE:
drowsiness, dizziness, insomnia,
nausea, agitation
BUPROPION
dizziness, dry mouth, tremor
FLUOXETINE
Anxiety, insomnia, tremors, decr
libido, GIT effects

44. Foods that interact with MAOI
• High in tyramine content:
BEER.
BROAD BEANS, LAVA BEANS
CHEESE.
CHICKEN LIVER
 SAUSAGES
 SNAILS WINE, RED WINE
YEAST

45. Drugs that Interact with MAOI
A.INDIRECTLY ACTING
SYMPATHOMIMETICS: amphetamines,
ephedrine, metaraminol,
phenylpropanolamine
B. OTHER ADRENORECEPTOR AGENTS &
RELATED AGENTS: levodopa, methyldopa,
guanethidine, reserpine
C. OPIOID ANALGESICS &
DERIVATIVES: morphine, codeine,
meperidine, dextromethorpham
D.MISCELLANEOUS DRUGS: buspirone,
fluoxetine, LSD