Schizophrenia and Antipsychotic Drugs Flashcards
What is schizophrenia?
Highly disabling psychiatric illness.
Affects 1% of population.
Abnormal thinking and perception.
Emerges in adolescence/young adult life - family history.
Pathologies in the brain of those with Schizophrenia?
Enlarged ventricles and cortical atrophy.
What are the positive signs?
Excess of the norm
1) Delusions - inaccurate belief of self
2) Illusions - misinterpret sensory stimuli
3) Hallucinations - sensing things that are not there - auditory>visual ‘hearing voices’
4) Thought disorder - wild train of thought with irrational conclusions.
5) Abnormal behaviour - aggressive/stereotyped
6) Defects in selective attention
What are the negative signs?
Suppression of the norm.
1) Social withdrawal
2) Flattened emotions
3) Lack of drive and motivation
4) Alogia - disorganised speech
What are the associated symptoms?
Deficits in cognitive function
Anxiety and depression may co-exist.
What are the causes of schizophrenia?
Genetic risk -1% of pop, 50% if affected twin. >1000 genes associated - but if just 1 - not significant.
Environmental risk
- maternal infection/malnutrition (14-22 weeks of gestation - same time as ridges in thumb print forms).
- cannabis exposure
- urban living
- stress during adolescence
underlying NT dysfunction - DA. 5HT and glutamate.
Explain the dopamine hypothesis of schizophrenia.
Evidence that DA hyperactivity underlies the positive symptoms.
- amphetamine (releases DA) induces stereotyped psychotic like symptoms.
- L-DOPA induces psychosis in PD patients.
- genetic association with the DA system - DRD2, DRD, BDNF, COMT.
- increased # of D2 receptors in schizophrenic brains (because drugs block D2 receptors - chronic upregulation?)
- affinity of receptors correlates with clinical potency of drugs.
Explain the general classes of antipsychotic drugs.
Typicals or atypicals.
Target receptors in line with the DA hyperactivity theory
Plasma t1/2 si approx 15-30 hrs therefore 1-2 days - oral or im every 2-4 weeks.
What are the Typical Antipsychotic drugs?
Chloropromazine, Haloperidol.
Antagonists at D2>A>D1=5HT=mACH>H1
Theraputic effects due to D2 blockade.
Lag in clinical effect - acute blockade not sufficent? Changes in DA neurones firing.
At start - increase in firing (compensation) then declines over next 3 weeks!
Side effects of typical antipsychotics.
Due to their ‘rich’ pharmacology.
- Sedation (H1), hypotension (A), constipation, dry mouth, blurred vision (mACh)
- Due to D2R blockade…
…mesolimbic pathway (VTA to NA), excess DA…positive symptoms therefore blockade provides relief.
…tuberoinfundibular pathway - normally, DA inhibits prolactin release therefore D2R blockade = increase prolactin release = gynaecomastia (breast development in males)
…nigrostriatal pathway - extra pyramidal side effects.
What are the ACUTE extra pyramidal side effects of typical antipsychotics?
Dystonia - involuntary movements (protruding tongue)
Parkinson like syndrome - akinesia, rigidity, tremor. In 20% of patients within a few weeks…reversible upon drug withdrawal, related to block of DA transmission within nigrostriatal pathway.
What are the CHRONIC extra pyramidal side effects of typical antipsychotics.
Abnormal involuntary movements
- oro-bucco-facial-lingual dsykinesia
- choreiform movements of extremites
- abnormal of gait and trunk posture.
- mycoclonic jerks
- grunting vocalisms
in 20-40% patients within 6 moths of chronic treatment
may be druing drug treatment or after withdrawal.
due to DA overactivity - compensatory D2 upregulation.
What are the atypical antipsychotic drugs?
Clozapone.
5HT2>D4>D2=D1=alpha=mACh-H1.
Block of D4 and or D2 = combat the symptoms.
D4 in limbic, not nigrostriatal - therefore decrease extra pyramidal side effects.
Some effects against negative symptoms due to 5H2T2 blockade.
Side effects - sedation, hypotension, antichoinergic effects as per typicals
BUT weight gain (food craving - 5HT2 antagonism), insulin resistance and can trigger diabetes.
What is leucopenia/agranulocytosis.
Reverisble, potentially fatal loss of neutrophils/basophils/eosinophils.
Side effect of atypical use.
