Typical or "First Generation (FGA)" Antipsychotics
MOA
nTypical antipsychotics are potent D2 receptor family blockers
nVery effective in treating positive symptoms
nLess effective in treating the negative symptoms
Side effects that limit the use
nMotor side effects aka extrapyramidal symptoms (EPS) due to blockade of dopamine receptors in the nigrostriatal pathway
nNeuroendocrine side effects due to blockade of dopamine receptors in the tuberoinfundibular pathway
EPS Side Effects
nAcute EPS
–Acute Dystonia – dystonia is just painful contractions of motor muscles. You are freezing in an abnormal posture.
–Parkinson’s like symptoms: bradykinesia, rigidity, postural imbalance
–Akathisia – restlessness. Restless leg syndrome
nChronic EPS
–Tardive dyskinesia
–Tardive dystonia
Treatment of Acute EPS
nAnticholinergic drugs
–Procyclidine, orphenadrine
–Benzatropine
–Benadril
nReduction of the antipsychotic dose
nSwitch to an atypical antipsychotic
Chronic EPS: Tardive dyskinesia and dystonia
n20% of patients who have been on typical antipsychotics for long time develop tardive dyskinesia
nThere is NO clear relationship to duration, dose, or class of antipsychotic (phenthiazines vs non phenothiazines)
n“TARDIVE”: these symptoms persist even after the drugs have been stopped*
Treatment of Tardive dyskinesia and dystonia
nNo effective treatment
nPrevention by limiting the use of typical antipsychotics and early recognition of symptoms are important
nIncreasing the dose may temporarily alleviate* the symptoms, while reducing the dose may worsen them
nClozapine improves these symptoms
Neuroendocrine SE: Hyperprolactinemia
nD2 blockade in the tuberoinfundibular pathway removes dopamine inhibition of prolactin release from the anterior pituitary
n High serum concentrations of prolactin can produce galactorrhea, amenorrhea and infertility in some patients
nUse Smaller doses of typicals or switch to atypicals
Other Side Effects
nCommon to BOTH typical & atypical antipsychotics
n In addition to blocking D2 receptors, antipsychotics also block other receptors
Autonomic and Histaminergic Side Effects
nBlockade of muscarinic receptors
–dry mouth
–difficulty urinating or retention
–constipation
–blurred vision
–confusion
nBlockade of α adrenoceptors
–Orthostatic hypotension
nBlockade of H1 histamine receptors
–Sedation
Other Side Effects (cont.)
nCardiac arrythmias
nSeizures
nWeight gain*
–Once they took care of the EPS side effects, weight gain was the side effect that came up! If you treat long term, they will get weight gain!!
nIdiopathic:
–Neuroleptic malignant syndrome (NMS)
nHyperthermia, muscular contraction. (You can use dantrolene to treat this). Since it is the antipsychotics that are causing this, you might want to give bromocriptine as well!
–Hypersensitivity reactions
nYou do see these because they have similar chemical structure that they have developed these neuroleptics from
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