SECOND GEN / ATYPICAL ANTIPSYCHOTICS and ADR

SECOND GEN / ATYPICAL ANTIPSYCHOTICS

• Addressed 5-HT Theory

• Mechanism of Action: Blocks D4 and 5 HT2A receptors > D2 receptors

• Advantage: Low EPS effects

Tx of (+) Sx

1st Gen = 2nd Gen

Tx of (-) Sx

2nd Gen > 1st Gen

D4 Receptors

less likely associated with extrapyramidal syndrome (EPS)

Clozapine

o Prototype 2nd gen antipsychotic

o ↓ Risk of suicidality

o No EPS

o Never given as 1st line because of SAM (seizures, agranulocytosis, myocarditis) effects

o Highest risk of seizure

o Requires WBC monitoring every week for the 1st 6 months of therapy and every 3 weeks thereafter

Olanzapine

S/E: Weight gain

Quetiapine

used to induce sedation

Risperidone

o First line

o Does not have muscarinic effects

o Equal effect on D4 and 5-HT blockade

o S/E: Hyperprolactinemia

Paliperidone

S/E: QT Prolongation

Weight neutral antipsychotic drugs (AMA)

Aripiprazole, Molindone, Amisulpride

2nd gen: atypical

Dopamine receptor blockade, weight gain (↓ DA level = ↑ ACh effects)

EXTRAPYRAMIDAL SYNDROME (EPS)

• Movement disorders due to cholinergic stimulation

• 1st line tx: centrally acting anticholinergics - ✓ Benztropine ✓ Biperiden ✓ Trihexyphenidyl

AKATHISIA

• Uncontrolled restlessness

• Most difficult to treat

• Only EPS that is not treated with anticholinergics

• Mgt: BZD, β-blockers (Propranolol)

DYSTONIA

• Aka Retrocollis / Torticollis / Twisting of Neck

• 1st EPS seen

• Easier to treat but can be fatal

• Management: o IV Diphenhydramine

▪ 1st gen antihistamine

▪ Antimuscarinic effects

o CNS Anticholinergics (BBT)

PSEUDOPARKINSONISM

• Parkinson-like syndrome

• Due to severe depletion of Dopamine

• SSX: (TRAP): ✓ Tremors ✓ Rigidity ✓ Akinesia – limited movement ✓ Postural instability / imbalance

• Mgt: CNS Anticholinergics

TARDIVE DYSKINESIA

• Potentially irreversible

• Toxic effect of 1st gen antipsychotics

• Due to hypersensitivity of D2 receptors

• Tic-like motion; repetitive involuntary movement

Tardive dyskinesia : management

o Best: Discontinue the drug

o Reduce dose

o Switch to Clozapine or Quetiapine

o Tx with Diazepam

HYPERPROLACTINEMIA

• Increased prolactin in the blood

• Dopamine – prolactin inhibiting hormone

• Patient manifests galactorrhea along with the ff: ✓ Amenorrhea ✓ Gynecomastia ✓ Impotence

Malignant Hyperthermia

• Succinylcholine – Depolarizing NMB

• Inhalational anesthetics

Malignant Hyperthermia: management

o Dantrolene (Ca antagonist, muscle relaxant)

o Bromocriptine (D2 agonist)

Seizure

all anti-psychotics can lower seizure threshold, highest with Clozapine

Weight Gain

common to 2nd generation antipsychotics EXCEPT AMA

Increased Risk of DM

↑↑ with Olanzapine

Agranulocytosis

o Low basophil, neutrophil, eosinophil count

o Neutropenia Effect: bacterial infection

Myocarditis

Clozapine (Idiosyncratic)

QT Prolongation

Ziprasidone, Sertindole, Thioridazine, Quetiapine