Antipsychotics

Question 1

Atypical antipsychotics

Answer 1

Block 5-HT2 receptors in the forebrain

Often with greater potency than for DA receptors

Question 2

Pharmacokinetics of atypical antipsychotics

Answer 2

Oral absorption
Lipid soluble
Protein binding
Large Vd
Complex metabolism

Question 3

Early reactions to antipsychotics

Answer 3

Acute dystonia (1-5 days)
Parkinsonism (5-30 days)
Akathisia (5-60 days)

Late reaction – Tardive dyskinesia (months to years)

Question 4

SE of antipsychotics

Answer 4

Anticholinergic – dry mouth, blurred vision, urinary retention
Orthostatic hypotesion
Neuroendocrine effects
Allergic and idiosyncratic effecs
Cardiac effects (Thioridazine)
Decreased seizure threshold (phenothiazines)
Weight gain - Diabetes related events with atypicals

Question 5

Potential lethal hypodopaminergic side effect of antipsychotic drugs
Hyperthermia, Parkinson-like symptoms, mutism and possible death

Answer 5

Neuroleptic Malignant Syndrome

Treatment includes cooling and hydration, bromocriptine and dantrolene

Question 6

Original typical antipsychotics

Answer 6

Phenothiazines
Aiphatic – Chlorpromazine: low-medium potency, sedative, anticholinergic actions
Piperidine – Thioridazine: low potency, sedative, less extrapyramidal actions, anticholinergic
Piperazine – Fluphenazine, Prochlorperazine: high potency, less sedative, more extrapyramidal reactions, less anticholinergic

Question 7

Other Typical Antipsychotics

Answer 7

Thioxanthine derivatives - Chlorprothixene
Butyrophenone derivatives - Haloperidol
Pimozide (for Tourettes)

Question 8

How are atypical antipsychotics better than the typical antipsychotics?

Answer 8

More acceptable side effect profile
More efficacious in treating negative symptoms of schizophrenia
Lower incidence of extrapyramidal symptoms

Question 9

Blocks D4 and 5-HT2 receptors
Little effect on D2 
Muscarinic antagonist 
Improves positive symptoms 
Lowers seizure threshold 
Can cause fatal agranulocytosis

Answer 9

Clozapine

Question 10

Potent 5-HT2 antagonist
D1 and 2 antagonist, some D4
Few extra-pyramidal symptoms 
Less seizure incidence 
No agranulocytosis 
Weight gain and diabetes related adverse events

Answer 10

Olanzapine

Question 11

Combined D2 and 5-HT2 antagonist
Greater reduction in negative symptoms and less extrapyramidal symptoms
Less seizure activity and less antimuscarinic than clozapine

Answer 11

Risperidone

Question 12

Structurally related to clozapine
Similar to risperidone and olanzapine in effects on schizophrenia symptoms and SE
Shorter 1/2 life (older people with slow metabolism)
Some réponse of abuse

Answer 12

Quetiapine

Question 13

Atypical antipsychotics
5-HT2 and D2 antagonist
No weight gain

Answer 13

Ziprasidone

Question 14

Partial D2 agonist and 5-HT2 antagonist

Adjunct in depression

Answer 14

Aripiprazole

Question 15

Monovalent cation of the lightest alkali metal
No behavior effects on normals
Blocks manic behavior

Answer 15

Lithium

Question 16

How is lithium thought to treat bipolar?

Answer 16

Inhibits phosphatase that convert IP2 to IP1

Question 17

How does Li affect Na levels?

Answer 17

Increased Na excretion causes clinically significant increases in Li levels
(Thiazide diuretics, losses of fluids or electrolytes)

Question 18

What are some medications that can raise Li levels?

Answer 18

ACE inhibitors

Angiotension II receptor blockers

Question 19

SE of Lithium

Answer 19

Fatigue and muscle weakness
Tremor
GI symptoms
Slurred speech and ataxia
Impaired consciousness 
Rigidity and hyperactive deep reflexes
Coma 
Use caution in pregnant women

Question 20

Clinical uses of Lithium

Answer 20

Treat mania and prevent recurrences of bipolar disease
May be useful in preventing recurrences of unipolar depression in some patients
Schizoaffective disorder
Cluster headaches