ANTIPSYCHOTIC

What do antipsychotics treat?  Psychotic Disorders (Psychosis) Abnormal Thinking and Perceptions Loss of Contact with Reality Delusions (false beliefs) Hallucinations

ANTIPSYCHOTIC DRUGS CLINICAL USE 1. Treatment of schizophrenia  Reduce some of the positive symptoms Hyperactivity Bizarre behavior Hallucinations and delusions  Facilitate functioning in both out and inpatient environments

ANTIPSYCHOTIC DRUGS CLINICAL USE 1. Treatment of schizophrenia  Beneficial effects may take several weeks to develop  Individual patients may respond best to specific drugs

ANTIPSYCHOTIC DRUGS CLINICAL USE 1. Treatment of schizophrenia  Negative symptoms Older drugs do not have much effect Newer atypical drugs improve some  Emotional blunting  Social withdrawal

ANTIPSYCHOTIC DRUGS CLINICAL USE 2. Other psychiatric and neurologic indications  Psychotic symptoms of other psychotic disorders  Tourette’s syndrome and other tic disorders

ANTIPSYCHOTIC DRUGS CLINICAL USE 2. Other psychiatric and neurologic indications  Toxic psychoses caused by overdosage of certain CNS stimulants  Alzheimer’s and Parkinsonism

ANTIPSYCHOTIC DRUGS CLINICAL USE 2. Nonpsychiatric indications  Antiemetic action Phenothiazines except thioridazine Antipruritics

9

Extra Pyramidal Symptoms EPS

ANTIPSYCHOTIC DRUGS 1. Reversible neurologic effects  Occurs most frequently Haloperidol Fluphenazine Trifluoperazine  Less frequent with clozapine  Less common with the newer drugs

EPS (Extra Pyramidal Symptoms)  EPS include: Acute Dystonias: happens within hours Parkinsonism: develops gradually (Days – Weeks) Tardive Dyskinesia: chronic development Tardive Dystonia: chronic development Akathisia

Parkinsonian Syndrome  Parkinsonian Syndrome Tremors Rigidity Cogwheeling Bradykinesia  May resemble Depression: Slowing in thinking Decreased initiative Masked face

Treatment of EPS BRAND NAME GENERIC NAME AkinetonBiperiden ArtaneTrihexyphenidyl SymmetrelAmantadine1

Akathisia Restless Pacing

Akathisia  Akathisia: Inability to sit still A feeling of restlessness, A need to keep moving,  Difficult to differentiate from illness-related behaviors

Akathisia  Appear Anxious: May misidentify akathisia as anxiety Anxiety can aggravate akathisia  Treatment: Lowering the dosage of the medication Anticholinergics: not always effective Propranolol: 10 to 80 mg/d Clonidine: 0.1 to 0.8 mg/d  BDZ

Tardive Dyskinesia T D

ANTIPSYCHOTIC DRUGS 2. Tardive dyskinesia  Choreoathetoid movements of the muscle of the lips and buccal cavity  Maybe irreversible  Tend to develop after years of therapy  May appear as early as 6 months

ANTIPSYCHOTIC DRUGS 2. Tardive dyskinesia  Antimuscarinic drugs that improve extrapyramidal effects increase the severity of symptoms  No effective drug for treatment  Switching to clozapine does not exacerbate the condition

Neuroleptic Malignant Syndrome NMS

NMS (Neuroleptic Malignant Syndrome)  A rare but potentially fatal complication  Main clinical findings: Hyperthermia Severe muscular rigidity Autonomic instability:  Pulse/ BP/ Breathing/ Sweating Changing levels of consciousness Unstable vital signs

NMS (Neuroleptic Malignant Syndrome)  Lab tests: Creatine Phosphokinase (CPK) Leukocytosis (increased WBC) Increased Myoglobin and Myoglobinuria  Mortality: 20 – 30 % May be higher when depot forms are used

NMS (Neuroleptic Malignant Syndrome)  Treatments Stop the antipsychotics Supportive and symptomatic TX Medications:  Dantrolene  Bromocriptine  Amantadine

Metabolic Syndrome Monitoring and Management

Equipment

ANTIPSYCHOTIC DRUGS 3. Autonomic effects  Result from blockade of peripheral muscarinic receptors and alpha adrenoceptors Strongest autonomic effects  Thioridazine Weakest  Haloperidol

ANTIPSYCHOTIC DRUGS 3. Autonomic effects  Intermediate autonomic effects Clozapine and most atypical antipyschotics

ANTIPSYCHOTIC DRUGS Autonomic effects  Atropine-like effects Dry mouth Constipation Urinary retention Visual problems Not with ziprasidone and aripiprazole

ANTIPSYCHOTIC DRUGS 3. Autonomic effects  Alpha receptor blockade Postural hypotension All atypical drugs  Failure to ejaculate Phenothiazines

ANTIPSYCHOTIC DRUGS 4. Endocrine  Dopamine D 2 receptor blockade in the pituitary Hyperprolactinemia Gynecomastia

ANTIPSYCHOTIC DRUGS 6. Sedation  More marked sedation Chlorpromazine-Clozapine- Olanzapine-Thioridazine  Less sedating among the older drugs Fluphenazine and haloperidol  Least sedating among newer drugs Aripiprazole

ANTIPSYCHOTIC DRUGS 7. Miscellaneous toxicities  Visual impairment due to retinal deposits Thioridazine  At high doses, fatal ventricular arrhythmias Thioridazine

ANTIPSYCHOTIC DRUGS TOXICITY 7. Miscellaneous toxicities  Arrhythmias Ziprasidone  Agranulocytosis, seizure at high doses Clozapine

ANTIPSYCHOTIC DRUGS TOXICITY 8. Overdosage toxicity  Usually fatal  Hypotension Fluid replacement  Seizures Diazepam or phenytoin  Cardiotoxicity is difficult to treat