Which of the following responds to classical neuroleptic drugs:

Positive symptom schizophrenia

Negative symptom schizophrenia

Positive symptom schizophrenia (delusions, dyscontrol, hallucinations) responds well to classical neuroleptics.

classical neuroleptics include chlorpromazine, fluphenazine, trifluorperazine, thioridazine, and haloperidol.

Negative symptoms are the "A-"s...
Apathy (loss of interest), Ambivalence, Affect (bland facial expression), and Association (loose thoughts lacking logical connections)

recall: negative symptom schizophrenia does not respond well to classical neuroleptics.   Classical neuroleptics include chlorpromazine, fluphenazine, trifluorperazine, thioridazine and haloperidol.

Instead, these negative symptoms respond well to the atypical neuroleptics: clozapine, risperidone, olanzapine, and quetiapine.

Which of the following responds to atypical neuroleptic drugs :

Positive symptom schizophrenia

Negative symptom schizophrenia

Negative symptom schizophrenia responds to the newer, atypical neuroleptics but not the classic drugs.  Positive symptom schizophrenia also responds to atypical antipsychotics (as well as the classics).

Atypical neuroleptics include the drugs risperidone, olanzapine, clozapine, and quetiapine.

trick to remember: negative symptom schizophrenia patients are removed from social interaction and tend to "whisper (risperidone) quietly (quetiapine) alone (olanzapine) in the closet (clozapine)"

Positive symptoms of schizophrenia are believed to result from excessive dopamine in the limbic system.  D2 blockers (classical AND atypical neuroleptics) are useful treatments here.

Negative symptoms of schizophrenia are explained by reduced dopamine activity in the prefrontal cortex.  5-HT inhibits dopamine activity here, and it's inhibitory influence may be responsible for negative symptom schizophrenia.  Therefore, the newer atypical neuroleptics are more useful here because they also exhert an antagonistic effect on 5-HT2 receptors, relieving the inhibition!

The dopaminergic tracts are the mesocortical, mesolimbic, tuberoinfundibular, and nigro-striatal. 

Mesocortical DA imbalance is responsible for bizarre thinking in schizo. patients.

Mesolimbic dysfunction is responsible for personality or emotional imbalances

Tuberoinfundibular tract is not very affected in schizophrenia patients, and may be more affected by the treatment with neuroleptics, leading to gynecomastia etc.

Nigro-striatal imbalance is related to motor abnormalities.

Phenotiazines are classical neuroleptics (antipsychotics).  As classical neuroleptics, they are D2 receptor antagonists.  They include chlorpromazine, trifluorperazine, fluphenazine, and thioridazine.

These drugs are useful in the treatment of positive symptom schizophrenia but not negative symptom schizophrenia.  Remember that in negative symptom schizophrenia, there is a hypothesized decrease of dopamine in the frontal cortex and the newer atypical drugs that also antagonize 5-HT2 receptors are more useful.

The butyrophenones are a type of classical neuroleptic.  The important drug of this specific class is Haloperidol.

As a classical neuroleptic, it is useful in the treatment of positive but not negative symptom schizophrenia.

The newer, atypical neuroleptics block D2 receptors, like the classic drugs.  However, they also block 5-HT2 receptors.  This second action makes them more useful in the treatment of negative symptom schizophrenia, where there is a lack of dopamine in the frontal cortex.  In this region, dopamine release is inhibited by 5-HT, so the 5-HT2 receptor antagonistic action of the atypical neuroleptics will help increase DA levels in the frontal cortex!

These drugs include Risperidone, Quetiapine, Olanzapine, Clozapine.

negative symptom schizophrenics like to whisper (risperidone) quietly (quetiapine) alone (olanzapine) in the closet (clozapine)

Classical neuroleptics block D2 receptors in the brain.  They also block alpha-1 and muscarinic receptors in the body. 
Blockade of alpha-1 receptors causes orthostatic hypotension

Blockade of muscarinics cause urine retention, constipation, dry mouth (xerostomia), tachycardia, and blurred vision.

Inhibition of dopamine in the tuberoinfundibular tract can cause gynecomastia and galactorrhea.

While the receptor blockade occurs within days, the clinical effects of neuroleptic therapy is felt after a period of 2-4 weeks of drug administration.  This is because changes in gene-regulated protein synthesis pathways take a while to occur.

Thioridazine, a classical neuroleptic, is cardiotoxic because it has a tricyclic structure.  Drugs with three rings have a higher risk of cardiotoxicity.  Do not give to patients with heart problems (ex: arrhythmias, QT defects...)

Thioridazine is converted into an active metabolite with a long half life (mesoridazine). 

other drugs with 3 rings: TCADs, carbamazepine

Thioridazine is a classical neuroleptic with a three ring structure.  Because of this structure, it is cardiotoxic.  It can also cause blindness at high doses. 

A final side-effect to note is that it it causes ejaculatory problems.

(It is relatively unassociated with EPS)

Haloperidol is a member of the butyrophenone class of classical neuroleptics.  It is used to treat Tourette Syndrome, Hypomania, and Stuttering. 

It does not have anticholinergic effects.  This correlates with a high risk for EPS!

(drugs with anticholinergic effects have a low risk of EPS)

Haloperidol is a classical neuroleptic used to treat Tourette Syndrome, Stuttering, and Hypomania. 

It has a high risk of EPS, particularly Tardive Dyskinesia.  This is exemplified by orobuccal movements, tongue protrusions, and torticollis and involve supersensitive DA receptors.

Clozapine is an atypical neuroleptic.  It is used to treat negative symptomology schizophrenia.  It is a drug of relatively low potency, so it should not be used in urgent situations.  For example, a violently aggressive schizophrenic in the ER would not be treated with clozapine.  It is not potent enough and does not act fast enough. 

Also, because it carries the potential for serious side effects (fatal agranulocytosis), it should be tried after other neuroleptics...

Clozapine is an atypical neuroleptic used to treat negative and positive symptomology schizophrenia.

Clozapine can cause seizures! (Remember: neuroleptics and SSRIs lower the seizure threshold...co-administer valproate to reduce seizure risk)

Clozapine can cause Fatal Agranulocytosis in 1% of patients... so they MUST be tested weekly.  It also causes neutropenia and may cause aplastic anemia!  yikes!

It has anticholinergic effects, which correlate with a LOW risk of EPS.  However, the anticholinergic effects mean it can produce symptoms similar to atropine-poisoning.  However, it also shows paradoxical hyper-salivation!

Cimetidine inhibits the CYP450 system, so clozapine levels will INCREASE!

remember, clozapine can produce seizures and fatal agranulocytosis! so watch out!

Risperidone is an atypical neuroleptic that has the standard side-effects of other neuroleptics (increased prolactin, postural hypotension). 

It has a low risk of EPS.

It can cause stroke in the elderly.

Try the atypical neuroleptics.  Specifically, Olanzapine is used in these patients for which a classical antipsychotic worked but was not tolerated.

Recall, olanzapine has a high affinity for antagonizing the 5-HT2c receptor and therefore causes weight gain.  It is also sedating!

Olanzapine may cause fatal Neuroleptic Malignant Syndrome (NMS)!! NMS typically occurs in the 1st week of treatment and causes high fever, altered consciousness, myoglobinemia, and elevated CK levels.  Treatment is by immediate discontinuation of the offending drug and IV dantrolene & bromocriptine.

Olanzapine is a sedating drug because it acts on M1 and H1 receptors.

Olanzapine also causes weight gain by its action on the 5-HT2c receptor. 

It may also cause priapism.

NMS is a potentially fatal condition characterized by high fever, muscle rigidity (except olanzapine), autonomic instability, elevated CK and myoglobinemia.

Immediately stop the offending drug and administer IV dantrolene and bromocriptine.  Dantrolene is a muscle relaxant that acts by blocking ryanodine receptors in skeletal muscles.  Bromocriptine is a D2 agonist.  Recall, bromocriptine is also used in the treatment of prolactinomas.

Tardive dyskinesia occurs after neuroleptic treatment (most commonly with haloperidol!).  It is characterized by orobuccal movements, lip smacking, tongue protrusions, torticollis and choreic movements.

There is no effective treatment.

Quetiapine is the drug you should use for a patient with parkinson's disease that is also psychotic. 

Quetiapine is an atypical neuroleptic.  It is therefore effective against both positive and negative symptomology schizophrenia.

This is an EPS...Recall that neuroleptics reduce dopamine effects!  This mimics parkinsonism...Discontinue the drug and the symptoms should subside.