1. Phentniazine
CHLORPROMAZINE:
• Anti-serolonergic
• Anti-DA
• Anti-cholinergic
• Anti-adrenergic
• H1 blockers
• Antipsychotic
Therapentic efficacy of chlorpromazine schizophrenia, 1st discovered by a French
surgeon laborit in 1947 (to relief stress in Pt. prior to surgery)
The anti-psychotic effect of chlorpromazine were demonstratrd by Delay and Deniker in
1953 at labortis investigation
M.O.A:
1. Preferential blockage of D2 (beneficial eff. To treat schizophrenia) receptors in
mesolimbic and mesocortical system than D1 receptor
2. some drugs block more selectively D4 receptors (Clorpromazine)
3. some drugs are highly selective for D2 receptors (sulpiride, Remoxipride) so, min
effect on other, so Adv. No automation side effects
4. effects take several weeks to develop probably due to
• decrease DA neuorial activity
• proliferation of DA receptors
So not taken as SOS use, as effect takes weeks to develop
PHARMACOLOGICAL ACTIONS OF CHLORPROMAZINE:
1) CNS:
i) INTELLECT AND BEHAVIOUR
a) PTS:
• No loss of intellectual functions and performance (clear sensorium)
• Alteration of deranged through process
• Emotional quieting
• Psychomotor slowing
• Antagonism of behavior eff. of amphetamine
• Decreased paranoid idea
• Decrease initiative
• Decrease aggressiveness
• Calm down hyperactive and agitated pts.
• Indifferent to environmental and pain sensation
He never tolerate interference if combine with analgesic enhance the analgesic effect
b) NORMAL (NON -PSYCHOTICS)
unpleasant feelings due to
• Sleepiness, restleseness

2. • Autonomic effects : b/c of muscarinic blockade
idea b) NORMAL (NON -PSYCHOTICS)
unpleasant feelings due to
• Sleepiness, restleseness
• Autonomic effects : b/c of muscarinic blockade
ii) EATING BEHAVIOURS:
Increase in appetite more common with clozenapine, olenzapine
iii) MOTOR FUNCTIONS:
a) AKATHESIA:
Uncontrolled motor restlessness
b) DYSTONIC Rxns:
• Tonic contraction of Ms : groups (abd, posture)
• Spastic tocticolis, Retrocollis protusion of ttongue
c) TARDIVE DYSKINESIA (LESS AITH A TYPICAL)
Disable repetitive purposeless involuntary movement of face, tongue, trunks and pelvis
Trunk and pelvis -less common
Probably because of:
• Proliferation of D2 receptors c-slriatum
• Blockade of inhib DA increase in catecholamine and or ghutamate activity
leading to excitotoxic newodegeneration
d) PARKINSONISM (EXTRAPYRAMIDEL SYNDROME)
iv) Vasomotor
v) Resp. Control
vi) Endocrine eff.
vii)sedation and sleep
iv) VASOMOTOR CENTRE:
impaired vasomotor control

3. Inpt.: decrease in B.P.
In N: no problem
v) RESP. CONTROL:
• Depressant effect
• No permanent effect in N individual
• No prominent effect in psychotic pt having N respiration
But if he suffers from resp. diseases such as Asthama them resp. depression
vi) ENDOCRINE EFFECT:
hyper prolactinemia and inflextility DA, control prolactin (check its release),if block
hyper prolactinemia manifested by Gynecomastia in infertility in male and female
vii) SEDATION AND SLEEP:
• Tranquility of mind
• Calm down
• In proper environment , sedation may progress to sleep indifference to
surroundings sleep induced by any drug is diff. from natural sleep
REM SLEEP:
Usually 4 cycles of REM/night
REM decrease
Non REM increase particularly its phase -2 increases
REM is essential for normal physiological function
viii) EEG CHANGES:
• Low frequency
• More synchronization
• Amplitude is also decreased
ix) ANTIEMETIC ACTION:

4. Because of DA recep blockade in CRTZ. Useful in drug induced vomiting and other
vomiting except motion sickness and vomiting in pregnancy
x) TEMP. REGULATION:
Dopaminergic transmission to hypothalamus is blocked. Temperature regulation is lost
person because poikelothermic
xi) DECREASE SEIZURE THRESHOLD:
Convulsive potential
High dose: cause convulsion cause seizure in patients of epilepsy
Aggrevate epilepsy
If anti-epilepsy is taken by epilepsy potent, he has to increase the dose
Potentiate cause of seizure latent epilepsy patient
xii) POTENTIATION OF OTHER CNS DEVELOPMENT:
Benzodiazapenes
Barbiturate
xiii) SK.MUSCLES:
in high doses themselves cause convulsion and spasm
xiv) ANIMALS:
• Suppression of conditioned avoidance response
• Catalepsy (decrease tone of muscle)
Apomorphin (DA aainst) by acting on limbic system produce stereo typical behaviour
2) CNS
• -ve isotropic effects more thioridazine cause death in young children
• Decrease stroke volume and decrease CO
• Decrease TPR and alpha adrenergic blockade vasodilation decrease B.P.
• Decrease B.P
• Increase H.R barorecceptor, increase QT interval

5. 3) ANS
a) ANTICHOLINERGIC
b) ADRENOCEPTORS BLOCKADE
• Orthostatic hypotension
• Less less with halo oeriod of flupenthixol and eluphenazine and other non
phenothiazines except clozapine
c) WEAK GANGLIONIC BLOCKADE:
Both symp and P/symp ganglionic blockade . Non blockade cz transmission in both is
cholinergic
4) KIDNEY:
Mild diuretic action (decreases ADH + decrease H2O and electrolyte reabsorption)
5) H1 BLOCKADE:
-plruritc effect is decreased
-sedation
6) ANTI-SHT:
Block SH2 receptors
7) LOCAL ANESTHETIC ACTIONS:
But in solutions it is very irritant (Chloropromazine)
A/E OF CHLOROMAZINE
1) CNS
• Prowsiness , sedation , lethargy
• Decrease threshold for epileptic form seizure
• Conclusion is high doses.
• Behavioral effect pseudodepression due to extra pyramidal effects
• Extra pyramidal effects are
1. Akathisea

6. 2. AC dystonic Rxns grimacing, torticollic locked jaws
3. parkinsonism like effect
4. Chorecathetoid movement tradive dyskinesia
• Impaired temp reg. due to psuedodopression can commit suicide
2) ANS:
• Atropine like effect
• Alpha- blockade orthostatic
• Hypotension
3) ENDOCRINE DISTRIBUTION:
Amenorrhea , galactorrhoeafalse +ve preg.test and increase libido } Women
Decrease libido and gynaecomashia and impotence in men
Impaired ejaculation (chloropramazine and mesoridazine)
4) METABLOIC EFFECT
Weight gain more with clozapine and olanzapine
5) CVS
Tachycardia and cardiacarrythmias orthsstatic hypotension ECG changes
Quindine like effect more with thioridazine card cond.. defects and sudden death
Myocarditis clozapine
6) BLOOD DYSCARIAS:
Chlizapine agramulocytosis and dyscrasias
7) HEPTOXICITY:
Chlorpromazine more effect. Cholostatic/jaundice obstructive
8) SKIN RXNS:
Contact dermatihs urticacial rashes in 1st few weeks excersive sensivity to U.V
tight.Photosynthesis and blue skinn pigmentation
9) OCULAR COMPLICATIONS:

7. Deposits in cornea and lens.chlorpromazine, retinal deposit and browing of vision
10) MALIGNANT NEUROLEPTIC SYNDROME:
More sever form of extraphyramidal syndrome resemble with malignant hyperthermia
11) PERI-ORAL TUMORS (RABBIT SYND.)
Most of typical drugs usually cause less motor Adv. Effects
Due to blockade of nigrostriatal pathway.
PHARMACOKINETICS OF NEUROLEPTICS.
Rapid but incomplete per oral absorption (Ist pass effect)
BA.
25-35% (Chlorpromazine, thiridazine)
65% Haloperidol.
• High lipid soluble & tissue seqwuestration.
• High protein binding 92-99%
• Large volume of distribution 77 L/kg more than total body water volum of
distribution high.
• N0 plasma volume 0.2-0.4 L/kg
• Plasma protein bound VOD.
• Lipid soluble VOD.
• Plasma distribution
METABOLISM:
Hepatic metabolism
Some drugs converted to altive metabolite.
Thioridazine Mestabolism
Some drugs converted to altive metabolite. Thioridazine Mesridazine more potent than
parent.
Ther apeutic conc---wide variation.

8. Chlorpromazine 30—300 mcg.
(Unusual wide range)
If a drug converted to activated metaboltite its t ½ es.
EXCRETION:- Clearance us hepatic liver dysfxn has effect on cleacance.
• By kidneys mostely inactive from.
• Elimination t1/2 10-30 hrs (depend solely on hepatic metabolism)
• Most drugs can be given P/O and P/A once or twice daily.
SLOW RELEASING PREPACATIONS:
• Slow relasing preparation of many drugs are available.
• Piprazine
• Butyrophenone
• Thiazenthine.
• Oily prep given I/M only not I/V depot prepacation.
• Dueation 2-4 wks of slow please prep given I/M
Lalso in B-blockers used to overcome compliance problem compliance poor as patient
don’t accept he is ill & don’t take medicine.
DOSE:
Chlorpromazin 25-300 mg
THERAPENTIC USES OF CHLORPROMAZINE.
1. Schizophrenia:
Choice depend on psychiatrist usualloy atypical antipsychotics e.g chloranzipine.
More useful in ecadication ve symptoms.
Psychotic aspect of schizoaffective disorders.
Maina & hyoprania (Olanzapine)
Pt. over confident goes on taking don’t like interference pt. lose interference.

9. Social contacts withdrawn
2. MANIC PHASE OF BIPOLAX DISORDER:
(oLANZIPINE)
Non mania excited status with Benzoic zippers.
If only hallucination thought disorders then combine with antipsychotic.
3. Gillec de-la tourette syndrome.
Haloperidor, pimozide.
Abnornal, movements invowing face neck & shoulder.
Every movement associated with unsocial words may be abrasive
4. Disturbed behaviours in Alzhermer disase & semile dementia.
Loss of memory pt. becomes irritableleading to behavioural dfistuebances.
Aggresiveness.
5. NEWOLEPTIC ANALGESIA & A NESTHESIA.
Droperidol + fantonyl cyclate Neweolept analgesia.
N2 O + Dropecidol + Fantanyl cyclate. Newrolept Anesthesia.
6. To control agitation in depressed pts.
7. Huntington’s chjorea (Haloperidol)
Opposite of parkinssonjism excess of dopamine.
8. As anti emetic (Prochlorperaine & Benzquinamide) inhibit DA recep in CTZ
9. As anti pusitic- promethazine.
10. Pre-operation sedation, Benzodiazapenes are more safer and preferred.
11. Drug induced psychotic Rxns
DA against Bromocriptine levodopa.
Amphetamine. Sympathominetic apomorphines.
12. Along with analgeric

10. Pt indifferent from surrounding & nociceptor, stimulus.
13. Intactable Hiccough
Phemothiazinbe effective.
Phremic nerve section as it is due to phrenic nerve irritation which is supplying
diaphragm.
14. Tetanus: High doses aggrevate Benzodiazipine, Phenjothazine.
15. Social maladjustment--- penfluidol.
16. Alcohol nalucinations.
DRUG INTERACTIONS:-
1.Sedative hypnojtics CNS depressants More CNS depression resp> depression.
2. x- adrenergic blockers.
3. Anti muscacinics effect augments
4. Quinidine like drugs (sp. Thioridazine cacdiodepressive action jpotentiate.)
5. Anti epileptics
Enz inducees.
Further Ist pass metab.
Enz inhibiters B.A
NEUROLEPTIC POISONING:
Can be homicidal less common suicidal less chances occure in extreme of disease.
Rarely fatal except thio & mesoridazine duer jto cacdio depressive neuro musculal,
excitability. Convulsions.
Pt. jcomatosed.
Hypothermia, miosis, deep
Tendon reflexes.
Tachycacdia

11. Thioridazine.
RX:
*Monitos vcital fxns.
* Gastric lavage with activated charcoal
*Saline catharsis (Na2SO4Mgo)
* Fluid replacement
* Pressor agents.
Diaqzepam for seizerres I/V.
PIPERIDINE DERIVATIVE:
THIORIDAZINE:
• Block D2,x-1 & 5HT-2
• More potent anti muscacinics
Extrapyramidal (packinsonian) symptoms duer jto blockade of D2 and balance is
disturbed, in this case balance is notr distubedf when cholinergicx activity es.
• Sinilac B.A (2s-30%)
• More cacdiotoxic
• Less extra pyramidal eff.
• More macked occulax eff.
Deposit in retina browning of vision.
Picture res emble that of retinitis pigmentosa pt.
Potency—related to dose.
PIPERAZINE DERAVATIVES.: More commonly used among classical drugs.
• Much more potent than chlorpromazine.
•