AntiPsychotics Part 1, and Vatican City’s Got Talent

Posted on February 13, 2013

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Pope Hopeful greets crowds in St Peter's Square

Pope Hopeful greets crowds in St Peter’s Square

The news has been dominated this week by two major stories. The fact that we’ve all been eating horsemeat for who knows how long hasn’t really captured my imagination. It’s not great that Findus et al. have been pushing their beef/horse lasagnes on us all this time, but I’m reconciled with the fact that I’ve probably munched down on Black Beauty’s cousin at some point. One thing that I have found quite exciting is Pope Benedict XVI’s resignation. I was christened Catholic, but wasn’t brought up in the Catholic faith. But there’s something I find highly intriguing about the Vatican. They’re not quite as secretive as North Korea, but all the ritual that goes along with the secrecy of the Papal Conclave makes electing a new Pope quite exciting. In my opinion, anyway.

These modern Popes apparently have no staying power. Maybe a bad thing for the Catholic Church, but not for Simon Cowell, who I hear is rolling in the cameras to monopolise on Pope Benedict XVI’s resignation and document a whole new electoral format. No longer will Catholics have to stand in St Peter’s square waiting for the white smoke to dance its way through the air. No no. Instead, Catholics around the world will now be able to huddle around their television sets and have their own say in picking the Pontiff. It’s all part of a global PR stunt to improve the popularity of the Catholic Church. Plans to pilot “Pope Idol” this spring promptly fell through when it became clear that several of the older Cardinals weren’t able to carry a tune, but producers were quick to replace it with the “Got Talent” format in order to showcase the varied abilities of the Papal Conclave. One hopeful is looking to capitalise on the success of the London 2012 Olympics and handspring his way into the Papal Mantum. Voting lines for “Vatican City’s Got Talent” will open after the final live performance this Sunday on ITV1.

One hopeful seeks to wow VCGT Judges with his unparalleled gymnastic ability.

One hopeful seeks to wow VCGT Judges with his unparalleled gymnastic ability.

But don’t worry; you don’t have to wait until then to be entertained! Just read on and learn all about antipsychotics!

I’m currently in week 5 of my psychiatry placement. I’ve seen two of the “three D’s” of old age psych (that’s Dementia, Delirium and Depression), psychiatry in the prison system with a glamorous trip to HMP Wandsworth and I’ve experienced drug and alcohol addiction services. Currently though I’m on general adult psychiatry, where patients have diagnoses of personality disorders, mood disorders and delusional disorders. All very exciting. The ward rounds are epic. In cinematic terms, they’re the Titanic of ward rounds. Long, slow to get going, peppered with moments of excitement and occasional anxiety, but ultimately it all feels a bit futile. Possibly a bit pessimistic of me, but I’ve sat in on a few now, and at times it feels like if patients aren’t just getting by on their medication regime, they’re regressing. One thing the ward rounds aren’t short of is antipsychotics. Most patients are on one, some patients have tried a few in search of a good fit. It’s been interesting trying to get my head around why you’d choose risperidone over chlorpromazine, for example. But today it all changed, because I had a great lecture on the pharmacology of antipsychotics. Don’t groan at the thought, I think this might be useful!

Dopamine and AntiPsychotics

You may or may not know that dopamine and the dopamine pathways in the brain are implicated in the development of schizophrenia. The idea that overactivity of dopaminergic systems plays a part in schizophrenia is supported by the fact that amphetamines, which can induce psychosis, cause dopamine release from nerve terminals. There are three dopaminergic pathways to consider when discussing antipsychotics:

  1. Mesolimbic/mesorcortical pathway: implicated in schizophrenia
  2. Nigrostriatal pathway: connects substantia nigra to the basal ganglia, implicated in Parkinson’s disease
  3. Tuberoinfundibular pathway: connects hypothalamus to pituitary and is associated with release of prolactin.

Dopaminergic Pathways in the brain, from wiki: http://en.wikipedia.org/wiki/Dopaminergic_pathways

It is helpful to consider these pathways when discussing the therapeutic effects and side effects of antipsychotic drugs, which act on the dopamine receptors within these dopaminergic pathways:

Therapeutic Effects:

Antipsychotic action, due to ability to block dopamine receptors

Adverse Effects:

Increased Prolactin

This is due to the blocking of dopamine in the tuberoinfundibular pathway. Causes:

–       Males: Hypogonadism, gynaecomastia

–       Females: Breast engorgement, inappropriate lactation, amenorrhoea

Movement Disorders (aka ExtraPyramidal Side effects, EPS)

Early- these usually occur in the first days, weeks and months of treatment

–       Parkinsonism (slowness of movement, bradykinesia etc)

–       Akathesia (motor restlessness)

–       Dystonia (often affects muscles of the neck and trunk, causing patients to hold awkward postures)

Late

–        Tardive dyskinesia- late onset abnormal movements, notably of the face eg head bobbing, tongue protruding, lip smacking. Occur usually after years/decades of treatment, and often following attempts to withdraw antipsychotic or reduce dose. Irreversible in 1/3 of cases, and difficult to treat so best to try and avoid altogether.

Interactions With Other Receptors 

The problem with antipsychotic drugs, aside from the direct unwanted effects from affecting dopamine listed above, is that they can also be antagonistic at alpha1 NorAdrenergic receptors, H1 receptors and muscarininc AcetylCholine Receptors.  The therapeutic and adverse effects of these interactions are listed in the table below.

Therapeutic Adverse
Alpha1-NA Postural hypotension
H1 Sedation
mACh Reduced EPS, esp parkinsonism Autonomic (atropine-like) effects, eg dry mouth, blurred vision, urinary retention

 Classifying AntiPsychotics

Antipsychotics are divided into 2 groups, shown below with examples of each.

Typical (or classical) antipsychotics

  • Phenothiazines:
    • Chlorpromazine (the 1st antipsychotic)
    • Piperidine
    • Piperazine
    • Fluphenazine
    • Etc
  • Thioxanthines
    • Thiothixene
    • Flupenthixol
  • Butyrophenones
    • Haloperidol
  • Substituted Benzamides
    • Sulpiride

Atypical antipsychotics

  • Clozapine
  • Olanzapine
  • Risperidone
  • Quetiapine
  • Zotepine

 

In my next post, I’ll try to compare typical and atypical antipsychotics and their therapeutic effects by looking at their receptor affinity profiles, and discuss the major side effects of some key antipsychotic players. So make sure you come back and check it out!

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