Clinical pharmacology: drug-induced dyskinesias (tardive dyskinesia, tardive dystonia...)

1. Drug-induced dyskinesias
Domina Petric, MD

2. Drug-induced dyskinesias
• Levodopa and dopamine agonists produce diverse
dyskinesias as a dose-related phenomenon in patients
with Parkinson´s disease.
• Dose reduction can reverse dyskinesias.
• Chorea may also develop in patients receiving phenytoin,
carbamazepine, amphetamines, lithium and oral
contraceptives.
• Dystonia may occur from administration of dopaminergic
agents, lithium, SSRIs, carbamazepine and
metoclopramide.
• Postural tremor: theophylline, caffeine, lithium, valproic
acid, thyroid hormone, tricyclic antidepressants,
isoproterenol.
Katzung, Masters, Trevor. Basic and clinical pharmacology.24.3.2018.

3. Drug-induced dyskinesias
Acute dyskinesia or dystonia
precipitated by the first few doses of
a phenothiazine can be treated with
parenteral administration of:
An antimuscarinic drug
(benztropine 2 mg iv.),
diphenhydramine 50 mg iv. or
biperiden 2-5 mg iv. or im.
Katzung, Masters, Trevor. Basic and clinical pharmacology.24.3.2018.

4. Tardive dyskinesia
• Variety of abnormal movements, common
complication of long-term neuroleptic or
metoclopramide drug treatment.
• A reduction in dose of the offending medication
commonly worsens the dyskinesia.
• An increase in dose may suppress it.
Treatment:
• depletion of dopamine (reserpine, tetrabenzine)
• dopamine receptor blockade (phenothiazines,
butyrophenones)
Katzung, Masters, Trevor. Basic and clinical pharmacology.24.3.2018.

5. Tardive dyskinesia
Paradoxically, the dopamine
receptor-blocking drugs
(antipsychotics) are the very
ones that cause the
dyskinesia and are used as
treatment of dyskinesia.
Katzung, Masters, Trevor. Basic and clinical pharmacology.24.3.2018.

6. Tardive dyskinesia
Image source:
Pinterest
Katzung, Masters, Trevor. Basic and clinical pharmacology.24.3.2018.

7. http://www.primehealthchannel.com
Katzung, Masters, Trevor. Basic and clinical pharmacology.24.3.2018.

8. Tardive dystonia
• It is usually segmental or focal.
• Generalized dystonia is less common and
occurs in younger patients.
Treatment:
• reserpine, tetrabenazine
• phenothiazines, butyrophenones
• anticholinergic drugs
• local injection of botulinum A toxin
Katzung, Masters, Trevor. Basic and clinical pharmacology.24.3.2018.

9. Rabbit syndrome
It is another neuroleptic-induced
disorder.
It is manifested by rhythmic vertical
movements about the mouth.
It may respond to anticholinergic
drugs.
Katzung, Masters, Trevor. Basic and clinical pharmacology.24.3.2018.

10. Warning!
• Tardive syndromes that develop in adults are often
irreversible and have no satisfactory treatment.
• Antipsychotic medication should be prescribed only
when necessary and should be withheld periodically to
assess the need for continued treatment and to unmask
incipient dyskinesia!
• Thioridazine (phenothiazine with a piperidine side
chain) is an effective antipsychotic agent, that causes
less likely than most other antipsychotics,
extrapyramidal reactions.
• Antimuscarinic drugs should not be prescribed
routinely in patients receiving neuroleptics:
combination may increase the likelihood of dyskinesia.
Katzung, Masters, Trevor. Basic and clinical pharmacology.24.3.2018.

11. Neuroleptic malignant syndrome
• It is a rare complication of treatment with neuroleptics.
• It is characterized by RIGIDITY, FEVER, CHANGES IN
MENTAL STATUS and AUTONOMIC DYSFUNCTION.
• Symptoms typically develop over 1-3 days and may occur
at any time during treatment.
Management of neuroleptic malignant syndrome includes:
• Withdrawal of antipsychotic drugs, lithium and
anticholinergics!
• Reduction of body temperature, rehydration!
• Dantrolene, dopamine agonists, levodopa or amantadine
may be helpful.
Mortality rate is up to 20%.
Katzung, Masters, Trevor. Basic and clinical pharmacology.24.3.2018.

12. Literature
• Katzung, Masters, Trevor.
Basic and clinical
pharmacology.
• http://www.primehealthchannel.com
• Pinterest.com
Katzung, Masters, Trevor. Basic and clinical pharmacology.24.3.2018.