Antipsychotic agents group -

1.Phenothiazines -

Aliphatic - Chlorpromazine, Promazine,Thioflupromazine

Piperidines- Mesoridazine, Thioridazine

Piperazine - Acetophenazine,Perphenazine,Prochlorperazine, Fluphenazine, Trifluoperazine

2.Thioxanthenes- Chlorprothixene, Thiothixene

3. Phenylbutyl piperidine - Butylphenone - Haloperidol Diphenylbuytlpiperidine - Pimozide

4. Dihydroindolones - Molindone

5. Dibenzepine - Dibenzoxazepine - Loxapine Dibenzodiazepine - Clozapine Thiobenzodiazepine - Olanzapine Dibenzothiazepine - Quetiapine

6. Benzisoxazole - Ziprasidone, Paliperidone, Risperidone

7. Quinolinone - Aripiprazole

Antipsychotic agents group - Include-

Chlorpromazine, Promazine, Triflupromazine,Mesoridazine, Thioridazine ,Acetophenazine Perphenazine,Prochlorperazine, Fluphenazine, Trifluoperazine, Chlorprothixene, Thiothixene Haloperidol,Pimozide,Molindone,Loxapine,Clozapine ,Olanzapine,Quetiapine , Ziprasidone, Paliperidone, Risperidone, Aripiprazole

Refer Chlorpromazine

Antiemetic /antivertogo agents include

Phenothiazine-

Chlorpromazine      nausea/vomiting

Triflupromazine      nausea/vomitin

Interacting drugs - summary

Alcohol + Phenothiazine

coadmin. may result in additive CNS depression.

Alumn salts + Phenothiaz

may impair GI absorption of phenothiaz, reducing therapeutic effect

Anorexiants + Phenothiaz

coadm. may diminish pharmacologic effects of amphetamine

Anticholinergics + Phenothiaz

reduce pharmacologic effect of phenothiaz.

Barbiturates + Phenothiazine

reduce phenothiazine or haloperidol plasma levels, possibly resulting in decreased pharmacologic effect.

Barbiturate and anesthetics + Phenothiaz

preanesthesia admin. of phenothiazines may raise the frequency  of reactions

Bromocriptine + Phenothiaz

effectiveness may be inhibited by phenothiaz coadmin. inhibited

Carbamazepine + Haloperidol

carbamezepine may decrease haloperidol serum concn. decreasing its therapeutic effects

Charcoal + Phenothiaz

can prevent absorption of phenothiazine, reducing effectiveness

Epinephrine/ Non epinephrine  + Chlorpramaz

chlorpromaz decreases pressor effects of norepinephrine

Fluoxetine + Haloperidol

patient developed severe extrapyrimidal reactions during haloperidol coadmin.

Guanethidine + Phenothiaz

hypotensive effect of guanethidine is inhibited by phenothiazine, haloperidol and thioxanthene

Lithium + Phenothiaz

coadmn with phenothiaz or haloperidol may induce disorientation

Meperidine + Phenothiaz

coadmin may result in excessive sedation and hypotension

Methyldopa + Phenothiaz

may potentiate antipsychotic effects of haloperidol or combn may produce psychosis.

Metrizamide + phenothiaz

possiblity of seizure may be increased during subarchoid injection of metrizamide

Phenytoin +thioridazine/or haloperidol

 increase in phenytoin serum levels may occur

Propranolol + Phenothiaz

coadmn may result in increased plasma levels of both drugs.

Tricyclic antidep  + Phenothiaz

serum conc. may be increaesed by phenothiazine or haloperidol coadmn. 

Valproic acid + Chlorpromazine

clearance may be decreased and half-life and trough levels increased

Drug/Lab test interactions- an increase in cephalin flocculation sometimes accompanied by alterations in other liver function tests has occuredr in patients receiving fluphenazine enanthate who have had no clinical evidence of liver damage

Phenothiazine may discolor the urine to red-brown

False pregnancy tests have occurred but are less likely to occur when a test is used

Psychotic disorders.

Antipsychotic agents group -

1.Phenothiazines - Aliphatic - Chlorpromazine, Promazine,Thioflupromazine Piperidines- Mesoridazine, Thioridazine Piperazine - Acetophenazine,Perphenazine,Prochlorperazine, Fluphenazine, Trifluoperazine

2.Thioxanthenes- Chlorprothixene, Thiothixene

3. Phenylbutyl piperidine - Butylphenone - Haloperidol Diphenylbuytlpiperidine - Pimozide

4. Dihydroindolones - Molindone

5. Dibenzepine - Dibenzoxazepine - Loxapine Dibenzodiazepine - Clozapine Thiobenzodiazepine - Olanzapine Dibenzothiazepine - Quetiapine

6. Benzisoxazole - Ziprasidone, Paliperidone, Risperidone

7. Quinolinone - Aripiprazole

Antipsychotic agents group - Include-

Chlorpromazine, Promazine, Triflupromazine,Mesoridazine, Thioridazine ,Acetophenazine Perphenazine,Prochlorperazine, Fluphenazine, Trifluoperazine, Chlorprothixene, Thiothixene Haloperidol,Pimozide,Molindone,Loxapine,Clozapine ,Olanzapine,Quetiapine , Ziprasidone, Paliperidone, Risperidone, Aripiprazole

Refer Chlorpromazine

Sudden death- has occassionally been reported

Neuroleptic malignant syndrome  ( NMS ) main-
 is a rare ( 0.5 to 1% ) idosyncratic combination of extrapyrimidal symptoms , hyperthermia, and  autonomic disturbance.

 Fatalities ( 20% ) are caused  by respiratory failure.
Symptoms include- hyperpyrexia, muscle rigidity, altered mental status,evidence of autonomic instability ( irregular pulse or blood pressure ) elevated CPK, myoglubinuria ( rhabydomylysis )  acute renal failure, tachycardia, cardiac arrhythmias 

Tardive dyskinesia ( TD )-
If signs and symptoms of TD appear, consider discontinuation.
However, in some patients may require treatment despite the presence of te syndrome

Adverse behavioural effects-
Exacerbation of psychotic symptoms icluding hallucination, catoinic-like states, lethargy, restlessness hyperactivity , agitation, noctturnal confusion, bizarre dreams, depression occur

Other CNS effects-
Cerebral edema, headache, weakness, tremor, staggering gait, twitching, tension, jitteriness, fatigue, insomnia, vertigo drowsiness ( 80 % , usually lasts 1 week )

Autonomic-
Dry mouth, nasal congestion, nausea, vomiting, parasthesia, anorexia, flushed  facies, salivation, prespiration, constipation, diarrhoea, urinary retention, frequency or incontience, bladder paralysis

GI-
GI disturbances (eg.ausea, epigastric fullness, heartburn, ) are the most common reactions. They tend to be dose-related and may disaapear when dosage is reduced.
Diarrhea, (glipizide) taste alterations, (tolbutamide) cholestatic jaundice(rare, discontinue the drug if this occurs).

Dermatologic-
Allergic skin reactions, eczema, pruritus, erythema, urticaria, morbilliform or macropapular
eruptions, lichenoid reactions. These may be transcient and may disappear despite continued use of the drug. If skin reactions persist, discontinue the drug.

Hypersensitivity-
Urticarial ( 5% ) maculopapular hypersensitivity reactions, pruritus, angioneurotic edema, dry skin,

Hematologic-
Lleukopenia, thrombocytopenia, aplastic anemia, agranulocytosis,hemolytic anemia,
pancytopenia, hepatic prophyria.

Agranulocytosis -
Most cases occured between therapy weeks 4 and 10. Watch for sudden appearance of sore mouth, gums, throat or other signs of infection.
If white cell and differential show significant celluar depression, discontinue use

Cardiovascular-
Hypotension, postural hypotension, hypertension, taschycardia ( especially increase in dosage ), bradycardia, cariac arrest, circulatory collapse, lightheadedness, faintness, dizziness.
Use with caution in patients with cardiovascular disease or mitral insufficiency.
Increased pulse rates occur in most patients.
Few patients with angina pectoris have complained of increased pain while taking trifluoperazine.
Withdraw the drug from angina patients if unfavorable response is noted

Opthalmic -
Use with caution in patients with a history of glaucoma, The anticholinergic effects may precipitate angle closure in susceptive patients

Seizure disorders-
Use cautiously in patients with a hiostory of epilepsy and use only when absolutely necessary

Hepatic defects-
Jaundice usually occurs beteween the second and fourth week of treatment and is regarded as hypersensitivity reaction. It is usually , reversible. However chronic jaundice and biliary stasis have occured. If fever and flu-like symptoms occurs, peform liver function tests.If the tests are positive discontinue treatment

Endocrine- reactions identical to the syndrome of inappropiate secretion of antidiuretic hormone.  (SIADH)

Miscellaneous- disulfram-like reactins, weakness, paresthesia, tinnitus, fatigue, dizziness, vertigo,  malasise, headache ( infrequent)

Coma, hepatic dysfunction, low leucocyte counts,bone marrow depression.Therapy with thiouracil derivatives & phenylbutazone.Hypersensitivity.

Special precautions:

Concomittant conditions- use with caution in patients , exposed to exreme heat or
phosphorous insectides,  a state of alhohol withdrawal, or allergic reactions to
phenothiazine derivatives

Hematologic - if sore throat or other signs of infection occurs, or white cell differential counts indicate cellular depression, stop treatment and institute an antibiotic and other suitable therapy

Myelography- discontinue phenothiazine at least 48 hrs before myelography due to possibilty of seizures

Hyperpyrexia- a significant not expliained rise in body temperature may indicate intolerance to antipsycotics. Discontinue treatment.

Abrupt withdrawal - these drugs are not known to cause  psychic dependence and  do not  produce intolernce or addition. However, following abrupt withdrawal of high dose therapy,symptoms such as gasritis, nausea, vomiting, dizziness, headache, tachcardia, insomnia have occurred.

Suicide possibility - in depressed patients remains during treatmentand until significant
remission occurs.

Warnings-

Tardive dyskinesia- ( TD ) if signs and symptoms of tardive dyskinesia appear consider
drug discontinuation. However some patients may require treatment, despite the presence
of this syndrome.

CNS effects- these agents may impair mental or physical abilites, especially during
the first few days. Drowsiness may occur during the first few weeks, If troublesome,
lower the dose

Antiemetic effects- drugs with antiemetic effect can obscure signsof toxicity of other drugs
or mask symptoms of disease eg brain tumor, intestinal obstruction

Pulmonary - cases of bronchospasm ( some fatal ) have followed use of antipsychotic agents.
Use with caution in respiratory impairment due to acute pulmonary infections or chronic
respiratory disorders.

Pregnancy- 
Safety for use during pregnancy has not been established. Use only only when needed

Lactation-
Cholrpromazine and haloperidol have been detected in breast milk. Safety for use
in the nursing mothers not establisehed.

Children-
Not recommended for children < 12 years old.

Date of Approval      1979

Indications:

Psychotic disorders.

Dosage:

Oral- 0.5mg/kg every 4 to 6 hours as needed.

Hypyerpigmentation -

Studies of normal skin and of pimentary disorders indicate that the intensity of pigmentation as viewed clinically, depends not only on therate of melanosome production but also on the numberof melanosomes that are transferred to the keratinocytes .

Drugs causing adverse reactions- 

1. ACTH

2. Nusulfan

3. Phenothiazines

4. Hypervitaminosis A

5. Oral contraceptives

6. Gold salts

7. Chloroquine and other antimalarials

8. Cyclosphosphamide

9. Bleomycin

Constipation or Ileum

Drugs causing Adverse Reactions - ( 385 )

1. Ganglionic blockers

2. Tricyclic antidepressants

3. Phenothiazines

4. Opiates

5. Aluminium Hydroxide

6. Calcium Carbonate

7. Barium Sulfate

8. Ion exchange resins

9. Ferrous Sulphate

Retinopathy- ( 1750 )

Drugs causing adverse reactions- ( 388 )

1. Chloroquine

2. Phenothiazines

Refer Chlorpromazine

1. May cause drowsiness,use caution while driving and performing tasks requiring alertness,physical coordination and dexterity.

2. Phenthizines- Avoid prolonged exposure to sunlight.

3. May discolour the urine pink or reddish brown.

4.Allergies- tell your doctor if you have ever had any unusual or allergic reaction to phenothiazines Also tell your doctor if you are allergic to any other substances, such as foods, presevatives or dyes.

5.Pregnancy - studies in animals have shown that chlorpromazine and trifluroperazines given in many times the human dose may cause birth defects.

6.Breast feeding- phenothiazines pass into breast milk and may cause drowsiness and greater chance of unusual muscle movement in the nursing baby

7. Children - certain side effects such as muscle spasms of the face , neck, and back aremore likely to occur in children

8.Elderly- are more sensitive than younger adults to the side efects of phenothiazines

9. Other medicines - Amantadine or Antihypertensives or Bromocriptine or Dexaferoxamine or Diuretics or Levobunolol or Medicine for heart disease or Metipranolol Nabilone or Narcotic pain or Nimodipine or Other antipsychotics or Pentamidine or Pimozide or Promethazine or Trimeprazine - severe low blood pressure may occur

10. Other medical problems - Tell your doctor if you have any other medical problems especially - Alcohol abuse - certain side effects such as heat stroke may be more likely to occur Blood disease or Breast cancer or Difficult urination or Enlarged prostrate or Glaucoma or Heart or blood vessel disease or Lung disease or Parkinsons disease or Seizure disorders or Stomach ulcers - phenothiazines may the conditon worse

11. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.

12. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.

13. Outdated medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.

14. AVOID CONCURRENT USE WITH ERYTHROMYCIN

Drug/food interactiions- absorption of glipizide is delayed by about 40 minutes when taken with food,
the drug is more effective when given approxmately 30 minutes before a meal.
 The other sulfonylureas may be taken with food. 
May be taken with meals to reduce GI discomfort
 

Pregnancy- 
Safety for use during pregnancy has not been established. Use only only when needed

Lactation-
Cholrpromazine and haloperidol have been detected in breast milk. Safety for use
in the nursing mothers not establisehed.

Children-
Not recommended for children < 12 years old.