Treatment of Psychosis (Antipsychotics)

Psychosis: Loss of contact with reality. Distortion of mental capacity. Interference with the capacity to cope.

Symptoms: Hallucinations. Delusion

Dopaminergic Effect: The theorized biochemical cause of psychosis is from an overproduction of dopamine and an over-stimulation of dopamine receptors.   All the drugs listed below are going to block the dopamine receptors.

Balance of Dopamine and Acetylcholine Receptor Stimulation

Within our CNS we have Dopamine and ACh receptors and our body likes a balance between the two.  We must make these biochemical considerations whenever these meds are prescribed because they may block the dopamine receptors, causing the balance between the dopaminergic and cholinergic receptors to go out of balance.

Imbalance symptoms: If the two neurotransmitters are not in balance, these are the symptoms:

1. Parkinson-like Syndrome aka EPS that stands for extrapyramidal symptoms.  This includes rigidity, difficultly to initiate motion, etc.  They have the symptom of everything you’ve known for Parkinson disease except this time, it’s drug induced.

2. Acute Dystonic Reaction is another thing that could happen.  This is where the individual acutely contracts all the muscles around their neck and they cut off their windpipe and can’t breath.  This is less common than the EPS but still possible.

What is the solution for the above problems?  We add another drug.  Remember, just like how barbiturates cause hyperalgesia and dentists would add another drug, such as nitrous oxide to help with the pain?  In this case we would block the ACh receptors to bring it back to balance relative to the dopamine that’s being blocked by the drugs.  Anticholinergics are the name of drugs that block the ACh receptors.

3. Tardive Dyskinesia is an adverse reaction that is permanent.  They suck/smack their lips and their tongue darts like a lizard in and out and they have no idea they are doing it.  The theory about it is that the dopamine receptors have been blocked for a long time and any dopamine that comes in contact with them become supersensitized and it leads to this. To prevent this from happening, you have to take the lowest dose possible to maybe avoid it.

Side Effects

• Sedation is #1 because the drugs used to treat psychosis are major tranquilizers.
• Hypotension.  If their BP goes down, their heart speeds up, so there’s a potential for tachycardia.
• Tachycardia.
• Photosensitivity.  If they go out in sunlight they can get an exaggerated sunburn and need to wear sunscreen.
• Decreased Seizure Threshold.  This one is a nightmare.  An individual prone to seizures and now put on an antipsychotic, will be more prone to seizures.
• Anticholinergic: Dry mouth, blurry vision, dry eye, constipation, urinary retention.  How do you counteract this anticholinergic effect?  For dry eye, add visine.  For constipation, add a laxative.  Just keep adding.

Therapeutic Use:

• Psychosis
• Anti-emetic: An antiemetic is a drug that is effective against vomiting and nausea (like motion sickness).
• Intractable hiccups

Major Tranquilizer Drug List

These are easy to recognize because they all end in -ZINE or -INE

Phenothiazine class (historically the first drug class available for antipsychotic use.)

They are broken down into subclasses:

• aliphatic
• piperazine
• piperadine

At this point in your studies, you don’t need to match the drug to the drug subclass, but you need to know that phenothiazines are major tranquilizers and which drugs are phenothiazines.  However, you must still know the meaning behind the subclasses.

A. Aliphatic means low potency, high anticholinergic.  You need a lot more milligrams to get the desired effect.  In fact with aliphatics it’s not mg’s but grams.  The higher the dose, the greater the dose of adverse reactions and of course, tardive dyskinesia.  These are highly sedating, which isn’t so bad if you’re dealing with a psychotic episode.  Another interesting thing that’s happening is that it’s also highly anticholinergic so you’re not out of balance.  The chance of EPS and acute dystonic reaction are low due to this.

Example:

Chlorpromazine (Thorazine) – inj., p.o., p.r. – has low potency so there’s a higher risk of adverse effects.  We see it used nowadays for an unusual use: Intractable hiccups.  For hiccups that haven’t stopped for a day or more, it’s not (as) funny anymore and this drug has the unique ability to stop that.

So to recap aliphatic’s main points:  Low potency, high sedation, high anticholinergic, low EPS.

B. Piperazine means high potency, low anticholinergic. Low mg range but it’s also low in the anticholinergic effect so only the dopamine is being blocked.  The risk of EPS is higher with this.  How do you fix that?  Add an anticholinergic drug.  (Getting the concept here?)

Examples include:

Fluphenazine (Prolixin) – inj., p.o. – Not commonly used. It’s a long acting injection.

Prochlorperazine (Compazine) – Antinauseant – inj., p.o., p.r. – is a phenothiazine but it’s not used for psychotis, but for nausea.  The antipsychotic drugs do have some antinausea effects.

Trifluoperazine (Stelazine) – inj., p.o.

C. Piperadine means low potency and high anticholinergic.  So the dosage is high, usually in grams and it’s highly anticholinergic so it’s also blocking the dopamine and cholinergic receptors, so the chance of EPS is low.

Examples include:

Mesoridazine (Serentil) – p.o.

Thioridazine (Mellaril) – p.o.

Butyrophenone class

Haloperidol (Haldol) – inj., p.o. – Haloperidol has the chance of high EPS due to it being a low anticholinergic.

Dibenzoxazepine class

Clozapine (Clozaril) – p.o. – requires a special use procedure, no tardive dyskinesia.

This drug has been out for 20 years.  The research showed that patients who had been institutionalized for most of their life were put on this drug, and while they weren’t cured, they could be discharged and lead a functioning life.  They also had a problem with a major adverse reaction, making their white blood cell count real low and making them susceptible to infection.  The plan was to package the drug together and create their first registry.  So the patient had to be registered and when the physician was being prescribed the drug, the blood test needed to be done that went to the registry.  Before the pharmacy could fill the drug, the registry had to be given an okay.  Initially they could only be given a 7 day supply.  Then they had to do a blood test every 7 days.  It cost a fortune cause they were buying a blood test and a drug.  The guidelines have loosened up.  Once the patient looks stable for 6 months, they bump up the blood test to every 2 weeks.  If after a year it looks stabilized, they could go for 3 weeks.  The drug has gone generic and the registry must still exist.  This was the only way FDA was going to accept this.

Loxapine (Loxitane) – p.o., inj.

Atypical Antipsychotic Drugs (Benzisoxazole)

These are the atypical antipsychotics.  The advantage is that they have a high potency so they have a potentially lower risk for tardive dyskinesia, but it’s probably cause it’s been out for only a single decade.

Risperidone (Risperdal) – p.o.

Olanzapine (Zyprexa) – p.o.

Quetiapine (Seroquel) – p.o.

Ziprasidone (Geodon) –  p.o.