Tuesday 9 November 2010

MRCP revision battle 44.1: Antipsychotic medication

Today is a psychiatry and overdose fest...

MRCP revision battle 44.1: Antipsychotic medication
MRCP revision battle 44.2: SSRIs
MRCP revision battle 44.3: Serotonin syndrome
MRCP revision battle 44.4: Baby blues, post natal depression and psychosis
MRCP revision battle 44.5: Quinine toxicity/overdose
MRCP revision battle 44.6: Theophylline overdose
MRCP revision battle 44.7: Ethylene glycol poisoning

MRCP revision battle 44.1: Antipsychotic medication

Antipsychotic medications are used in the treatment of schizophrenia, severe anxiety, mania and occasionally for their sedative properties.

Antipsychotic medications have an immediate sedative action but their antipsychotic action may tak up to 3 weeks to become effective.

Atypical antipsychotics

Atypical antipsychotics are the newer drugs.  They produce a highly selective blockade of the mesolimbic D2 receptors and serotonin 5HT2A receptors.

Examples include amisulperide, olanzapine, quetiapine, risperidone and clozapine.

Side effects include:
  • weight gain
  • nausea, dyspesoa
  • hyperglucaemia and impaired glucose tolerance
  • increased risk DVT
  • increased risk stroke (especially olanzapine and risperidone)
  • clozapine only:
    • 1% agranulocytosis/neutropenia - therefore weekly blood tests for 1st 6 months then fortnightly afterwards
    • 3% seizures

All antipsychotics have roughly the same effectiveness except clozapine, which is better.  However, in light of its worse side effect profile clozapine is only recommended if 2 others have already failed.

Typical antipsychotics

Typical antipsychotics are the older drugs,
Examples include haloperidol, chorpromazine, phenothiazine and sulperide.

Side effects of the typical antipsychotics include:
  • extrapyramidal side effects
  • anticholingergic effects
  • antihistaminergic effects
  • photosensitivity (especially phenothiazine)
  • prolonged QT
  • lower seizure threshold
  • hyperprolactinaemia.

Now on to SSRIs...

MRCP revision battle 44.2: SSRIs

Selective Serotonin Reuptake Inhibitors (SSRIs) do exactly what their name implies: selectively inhibit serotonin reuptake.

Examples include citalopram, escitalopram, fluoxetine, paroxetine and sertraline.

They are widely used for depression, anxiety, post-traumatic stress disorder and panic disorder.
Fluoxetine, paroxetine and sertraline can be used in OCD.

There are many side effects, the commonest of which is GI disturbance.

Other possible side effects to be aware of include:
  • interaction with platelet function --> increase risk of GI bleed
  • hyponatraemia
  • urinary retention

Given the increased risk of bleeding SSRIs should be avoided if on heparin/warfarin - use mirtazepine instead.

The safest SSRI post MI is sertraline.

If combined with MAOIs/moclobemide there is a serious risk of toxicity and serotonin syndrome - do not start MAOIs until 5 weeks after stopping fluoxetine, 2 weeks after stopping sertraline or 1 week after stopping any other SSRI.  Conversely you must wait 2 weeks after stopping MAOIs before starting an SSRI.

Triptans and SSRIs must also not be combined due to increased risk of serotonin syndrome.

When SSRIs are stopped they should be reduced over 4 weeks to decrease withdraw.  Paroxetine is worst on stopping.

Now on to the next battle to explore serotonin syndrome....

MRCP revision battle 44.3: Serotonin syndrome

Serotonin syndrome is characterised by the triad of:

  • autonomic hyperactivity
    • hypertension
    • hyperthermia
    • tachycardia
    • mydriasis
  • neuromuscular abnormality
    • hyperreflexia
    • clonus
    • tremor
    • hypertonicity
  • mental state changes

Drugs associated with serotonin syndrome include:
  • lithium
  • carbamazepine
  • triptans
  • illegal drugs
    • LSD
    • cocaine
    • MDMA
  • antidepressants
    • MAOIs
    • SSRIs
    • St Johns Wort

  • remove cause
  • supportive treatment
  • cyproheptadine - a 5HT antagonist
  • chlorpromazine for hyperthermia and agitation

 Now for some postnatal depression...

MRCP revision battle 44.4: Baby blues, post natal depression and psychosis

Every now and then the MRCP exam will throw a slightly curve-ball question about a woman who has recently given birth being depressed.  The key facts to know ready to deal with this are:

  1. 'baby blues'
    • affects 60-70% of mothers 
    • tends to last for 3 to 7 days
    • characterised by being weepy and irritable
  2. post natal depression
    • affects 10% of mothers
    • begins 1 to 3 months after childbirth
  3. postpartum psychosis
    • affects 0.2% of mothers
    • riskiest period is 2 to 3 weeks post partum
    • there is a 20% risk of reccurence with subsequent births

 Next - on to an overdose

MRCP revision battle 44.5: Quinine toxicity/overdose

Quinine is used in the prevention of falciparum malaria and the treatment of nocturnal leg cramps.

It is very toxic in overdose and can be toxic in some individuals at therapeutic doses.
Quinidine, a stereoisomer of quinine and a class Ia antiarrythmic, can be toxic in a single dose.

Signs/symptoms include:
  • tinnitus
  • hearing loss
  • abdominal pain
  • blurred vision
  • hypotension (due to alpha blockade)
  • long QT

There is a risk of irreversible blindness.

Treatment is recurrent doses of activated charcoal and supportive management

Now for another overdose requiring activated charcoal...

MRCP revision battle 44.6: Theophylline overdose

Theophylline/aminophylline has a narrow therapeutic window so overdoses may occur accidentally.

Signs and symptoms of toxicity include:
  • vomiting
  • tachycardia
  • arrythmias
  • seizures
  • confusion

Treatment is with repeated doses of activated charcoal.  Haemoperfusion and haemodialysis may also be considered.

And to finish off the day, and the hattrick of overdoses - an antifreeze overdose

MRCP revision battle 44.7: Ethylene glycol poisoning

Ethylene glycol = antifreeze.

The stages of ethylene glycol poisoning are:
  1. alcohol drunk-like state
  2. metabolic acidosis with high anion gap
  3. acute renal failure

Treatment is fomepizole, an inhibitor of alcohol dehydrogenase.
The old-fashioned treatment failing this is to give lots of ethanol which competes with the ethylene glycol for liver metabolism and prevents glyclic acid being produced.

Haemodialysis is a final option.