Psych 1

Nigrostriatal pathway

Location: From the substancia nigra to striatum (putamen and caudate nucleus.

Characteristics: controls motor function.

Defect: Altered activity causes EPSE and movement disorders (parkisonism in the case of inhibition and chorea in case of stimulation)

Tuberoinfidibular pathway

Loc: From arcuate nucleus (infudibular nucleus) in the hypothalamus to the median eminence.

Char: Dopamine release inhibits prolactin secretion from the anterior pituitary.

Defect: Inhibition causes a decrease in dopamine level resulting in an increase in prolactin production that causes galactorrhea, sexual dysfunction, low libido.

Mesolimbic pathway

Loc: From the ventral tegment area to the nucleus accumbens and olfactory turbecle

Char: Controls motivation and reawd systems of the brain. (pleasure and positive reinforcement)

Defect: Stimulation causes positive symptoms (e.g hallucinations)

Primary tragent for antipsychotic drugs used in the treatment for schizophrenia (e.g haloperidol)

Mesocortical pathway

Loc: From the ventral tegment area to the prefrontal cortex

Char: Controls executive functions, motivation and reward systems of the brain.

Defects: Inhibition causes negative symptoms (e.g apathy, lack of energy)

Antipsychotic drugs have limited efficacy

MOA of 1st Gen antipsychotics(Typical)

Typical(FGA) work by acting on the dopaminergic transmission

MOA of 2nd Gen antipsychotics

Atypical (SGA) work by acting on the dopaminergic transmission and serotonergic receptors.

Indications of Typical antipsychotics.

• Schizophrenia spectrum disorders

• Psychotic symptoms associated with other psychiatric and medical illness

• Depression with psychotic symptoms.

• Severe agitation and violent behaviour

• Bipolar disorders-Acute mania

• Tourete’s disorder

• Dementia (low dosage)

Classification of FGA

According to potency

• Low Potency:
Chlorpromazine

Thioridazone

• Mid-Potency:
Loxapine

Molindone

• High-Potency:

Haloperidol
Fluphenazine
Trifluoperazine

Pimozide

Main side effects of FGA

• Extrapyramidal symptoms (EPS)

• Acute dystonia

• Parkinsonism

• Akathisia

• Tardive dyskinesia

• Neuroleptic malignant syndrome (NMS)

• Hyperprolactinaemia

High potency (e.g. haloperidol) → more EPS

Low potency (e.g. chlorpromazine) → more sedation/anticholinergic effects

Chlorpromazine Indications

• Schizophrenia.

• Mania and hypomania in bipolar disorder

• Severe anxiety and agitation

• Psychotic behaviour.

• Also used to control nausea and vomiting, treat intractable hiccups

• Adjunct therapy in conditions such as tetanus and acute intermittent porphyria.

• May be used for migraine-associated nausea or serotonin syndrome.

Adverse effects to Chlorpromazine use

• Drowsiness

• Orthostatic hypotension

• Dry mouth

• Blurred vision

• Constipation

• Weight gain.

• Extrapyramidal symptoms (e.g., dystonia, akathisia, parkinsonism, tardive dyskinesia)

• Rare but serious risks include cholestatic jaundice, agranulocytosis, neuroleptic malignant syndrome, and QT-interval prolongation.

Precautions and contraindications of

Chlorpromazine

• Comatose states

• Severe central nervous system depression

• Known hypersensitivity to phenothiazines.

• Caution in elderly patients with dementia, cardiovascular or hepatic impairment, and individuals on drugs that prolong the QT interval.

• Avoid alcohol and limit sun exposure due to photosensitivity Medicines.

Dosage and Administration of Chlorpromazine

• Usual maintenance range -oral: 75-300 mg

• Some patients may require up to-oral: 600-800 mg/day

• Deep IM: 25-50mg, repeated as necessary 3-4 times in 24Hrs Monitor BP for 30min after IM administration
  IM Injection is painful and may cause abscesses

Haloperidol indications

• Delusions

• Hallucinations

• Motor tics

• Schizophrenia

• Acute psychosis

• Tics of Tourette syndrome.

• Short-term control of severe behavioural problems in children

• Agitation in palliative or intensive-care settings.

• The long-acting injectable form, haloperidol decanoate, provides maintenance therapy every three to four weeks

Side effects and risks of Haloperidol

• Drowsiness

• Dizziness

• Dry mouth

• Constipation

• Extrapyramidal symptom (tremors or muscle stiffness).

• Long-term use can lead to tardive dyskinesia, a potentially irreversible movement disorder.

• Rare but serious complications include neuroleptic malignani syndrome, cardiac rhythm changes (QT prolongation), and blood dyscrasias.

• Increase prolactin levels

Contraindications and precautions of Haloperidol

• Parkinson's disease

• Severe CNS depression

• Hypersensitivity to the drug

• Dementia-related psychosis in older adults because of higher death risk.

• Caution in pts with heart rhythm disorders, electrolyte imbalance, seizure history or hepatic impairment.

• Alcohol should be avoided, as it increases sedation and hypotension.

Doses and routes of administration of Haloperidol.

PO/IM/IV

• PO: initially 1.5-5mg, 2-3times/day

• Maintenance dose: 1.5-10mg/day
  max dose: 20mg/day

• IM: Acutepsychosis/severe behavioural disturbances 2.5-5 mg at intervals of 4-8 hours max: 20mg/24H

Name FGA Injectable Preparations

• Fluphenazine Decanoate (Modecate)

• Flupenthixol decaonoate (Fluanxol)

• Zuclopentixol decanoate (Clpoixol Depot)

• Zuclopentixol acetate (Clopixol acuphase)

Zuclophentixol

Zuclopenthixol acetate- Clopixol Acuphase

• Short-acting IM formulation

• Rx of acute, difficult to control agitation/aggression

• Peak effect at 48-72hours. It does not work to immediately stop acute agitation/aggression.

• Dosage: IM 50-150mg, max: 400mg over a two week period

Zuclopenthixol decanoate- Clopixol Depot

• Long-acting IM injection

• Long-term management of schizophrenia

• Dosage: IM 200-400mg at 2-4 weekly intervals

Fluphenazine decanoate (Modecate):

• Deep IM

• Used to treat schizophrenia and other psychotic disorders

• Initially 12.5mg (test dose if naïve)

• Subsequent doses determined by individual response

• Usual range: 25-50mg IMI 2-4 weekly
  

Flupentixol (Depot Fluanxol)

• Deep IM

• Initially 10mg (test dose)

• Usual range: 20-60mg 2-4 weekly

Atypical Antipsychotics (SGA)

• Serotonin-dopamine receptor antagonist

• More effective in treating negative symptoms

• Favourable side effect profile (EPSE)

• Metabolic side effects

List the types of Atypical Antipsychotics (SGA)

• Aripiprazole

• Asenapine

• Clotiapine

• Clozapine

• Lurasidone

• Iloperdidone

• Olanzapine

• Quetiapine

• Paliperidone

• Risperidone

• Ziprasidone

Risperidone indications

• Schizophrenia

• Acute mania

• Mixed episodes in bipolar I disorder.

• Irritability in children with autism. Disruptive behaviour disorders in children 5years and older with neurodevelopmental d/o

• Short-term use for aggression linked to Alzheimer's disease

• Conduct disorders when behavioural therapy alone is insufficient

Dose and route of Risperidone administration

Dosage: PO

• Starting dose: 1-2mg OD/BID

• Usual range: 4-8mg

• Maximum: 8mg/d PO

Side effects and precautions of Risperidone use

• Drowsiness and dizziness

• Movement-related symptoms (tremor, igidity)

• Weight gain, and increased appetite.

• Elevate prolactin levels

• Serious but rare risks include Tardive dyskinesia, neuroleptic malignant syndrome, metabolic syndrome, and increased stroke risk in older adults with dementia.

• Warning against use in dementia-related psychosis due to higher mortality risk.

Olanzapine indications

• Schizophrenia

• Acute mania

• Mixed episodes of bipolar I disorder, and maintenance treatment of bipolar disorder.

• When combined vith fluoxetine, it is also prescribed for treatment-resistant depression and bipolar depression.

Side effects of Olanzapine

• Drowsiness

• Dizziness

• Weight gain

• Dry mouth

• Constipation

• Metabolic changes- elevated blood sugar, lipids

• Elevated prolactin-

• Tardivedyskinesia

• Neuroleptic malignant syndrome

• Post-iniection delirium.

• Elderly patients with dementia-related psychosis face increased mortality risk, so olanzapine is not approved for that use.

Monitoring and precautions in Olanzapine use

• Weight monitoring

• Blood glucose

• Lipid profile

• Liver function

• Caution in patients with diabetes, crdiovascular disease

• History of seizures

• Alcohol and smoking can alter drug metabolism, affecting efficacy and side-effect risk.

Dose and route of Olanzapine use

• Dosage: PO/IM

• Starting dose: 5mg/d PO

• Maintenance dose: 5-20mg/d PO

• Maximum dose: 20mg/d PO

• IM formulation available (short acting & extended-release suspension)