EXTRAPYRAMIDAL SIDE EFFECTS

EXTRAPYRAMIDAL SIDE EFFECTS


EXTRAPYRAMIDAL SIDE EFFECTS

  • Caused by antipsychotics.
    • More common with high-potency typical antipsychotics (compared to atypical antipsychotics).
  • Various movement disorders caused are collectively referred to as “extrapyramidal symptoms/extrapyramidal side effects”.
  • Mechanism:
    • Due to dopamine receptor blockade in nigrostriatal tract (neural pathway from substantia nigra to striatum).
TYPES OF MOVEMENT DISORDERS:
  • Acute dystonia.
  • Acute akathisia
  • Drug-induced parkinsonism
  • Tardive dyskinesia
  • Neuroleptic malignant syndrome
1. Acute dystonia:
  • Earliest side effect.
  • Occurs within minutes (more with injectable antipsychotic).
  • Features:
    • Characterized by sudden contraction of muscle group –
    • Symptoms like torticollis, trismus (contraction of jaw muscles), eyeballs deviation (oculogyric crisis due to extraocular muscle contraction) & laryngospasm.
  • Management:
    • Immediate administration of parenteral anticholinergicsa (benztropine, promethazine or diphenhydraminea).
    • Prevent prophylactic use of oral anticholinergics during typical antipsychotics prescription.
2. Acute akathisia:
  • Commonest side effect of antipsychotics.
  • Features:
    • Characterized by an inner sense of restlessness along with objective.
    • Observable movements (fidgeting of legs, pacing around, inability to sit or stand in one place for a long time).
  • Management:
    • Beta-blockers (propranolol DOC)
    • Anticholinergics
    • Benzodiazepines.
    • Prevented by changing to 2nd generation or low potency 1st-generation antipsychotics (lesser incidence of akathisia).
3. Drug induced parkinsonism:
  • Features:
    • Characterized by triad – Rigidity, bradykinesia & resting tremors.
  • Management:
    • Anticholinergics.
    • Changing to 2nd gen. antipsychotics or low-potency 1st gen. antipsychotics.
      • Dose reduction can be tried.
    • Prevented by prophylactic anticholinergic use.
4. Tardive dyskinesia:
  • “Tardive” refers to features developing after prolonged exposure.
  • Tardive dyskinesia develops after long-term antipsychotics treatment.
  • Features:
    • Involuntary movements of tongue (e.g. twisting, protrusion), jaw (e.g. chewing), lips (e.g. smacking, puckering), trunk or extremities.
    • Rapid, jerky movements (choreiform movements) or slow, sinusoid movements (athetoid movements).
  • Management:
    • Change to 2nd gen. antipsychotics.
5. Neuroleptic malignant syndrome: 
  • Fatal side effect of antipsychotics.
  • Features: 
  • Characterized by,
    • Muscle rigidity.
    • Elevated temperature (greater than 38°C). Increased CPK (creatine phosphokinase) levels.
  • Other symptoms: 
    • Diaphoresis, tremors, confusion, autonomic disturbances, liver enzyme elevation & leukocytosis.
  • Mechanism: 
    • D2 antagonism at various levels.
      • D2 receptors blockade in corpus striatum –> Causes muscle contraction & rigidity –> Initiating heat generation.
        • Continuing muscle damage –> Result in myoglobinuria & renal failure.
      • D2 receptors blockade in hypothalamus interferes with heat regulation.
      • D2 receptors blockade of spinal neurons causes autonomic disturbances.
    • Increased CPK indicates muscle injury.
  • Management:
    • Early recognition of symptoms & prompt withdrawal is paramount importance.
  • Treatment:
    • Skeletal muscle relaxants (dantrolene).
    • Dopamine agonists (amantadine & bromocriptine).
    • Supportive measures:
      • Adequate hydration.
      • During antipsychotics treatment is restarted – 2nd gen. antipsychotics should be used.
NOTE: ALL EXTRAPYRAMIDAL SIDE EFFECTS ARE ALSO CAUSES BY ATYPICAL ANTI-PSYCHOTICS BUT WITH LESSER INCIDENCE.

Exam Important

  • Extrapyramidal side effects are caused by antipsychotics.
  • Extrapyramidal side effects by antipsychotics are due to dopamine receptor blockade in nigrostriatal tract.
  • Extrapyramidal side effects are more common with high-potency typical antipsychotics (compared to atypical antipsychotics).
  • Types of movement disorders includes acute dystonia, acute akathisia, drug-induced parkinsonism, tardive dyskinesia & neuroleptic malignant syndrome.
  • Acute dystonia is the earliest side effect.
  • Acute dystonia is characterized by torticollis, trismus (contraction of jaw muscles).
  • Immediate administration of parenteral anticholinergicsa (benztropine, promethazine or diphenhydraminea) is used for managing acute dystonia.
  • Acute akathisia is commonest side effect of antipsychotics.
  • Acute akathisia is characterized by observable movements (fidgeting of legs)
  • DOC for acute akathisia is beta-blockers (propranolol).
  • Tardive dyskinesia develops after long-term antipsychotics treatment.
  • Neuroleptic malignant syndrome is a fatal side effect of antipsychotics.
  • Neuroleptic malignant syndrome is characterized by muscle rigidity, elevated temperature (greater than 38°C) & increased CPK (creatine phosphokinase) levels.
  • Skeletal muscle relaxants (dantrolene) is used for management of neuroleptic malignant syndrome.
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