Pharmacology-Antipsychotics

Question 1

Schizophrenia as a disease of thirds

Answer 1

1/3 need antispychotics their entire lives, 1/3 have psychosis once every few years, 1/3 only have a few episodes their entire lives

Question 2

The first drug developed to sedate schizophrenics that led to decreased institutionalization.

Answer 2

Chlorpromazine

Question 3

Two categories of antipsychotics

Answer 3

Typical: blocks D2 receptors and causes extrapyramidal side effects, mostly used in institutions. Atypical: weak D2 antagonist, 5HT2a antagonist, fewer extrapyramidal side effects, but weight gain & type II diabetes is common.

Question 4

What correlation has been shown in management of psychosis with typical antipsychotics?

Answer 4

The higher D2 receptor affinity, the better control of schizophrenia

Question 5

What drugs may cause dopamine-induced schizophrenia?

Answer 5

Drugs that increase dopamine activity: L-dopa, bromocriptine, ropinirole and amphetamines

Question 6

Injury to what region of the brain can result in psychotic-like behavior?

Answer 6

Mesolimbic system (contains DA receptors)

Question 7

What are the three dopamine pathways?

Answer 7

Substantia nigra -> Striatum. Hypothalamus. Ventral Tegmental Area.

Question 8

How does chlorpromazine help control schizophrenia while minimizing extra-pyramidal side effects? What other drugs could you prescribe that would have a similar effect?

Answer 8

It also has anti-cholinergic properties that inhibit the muscarinic receptors on the external globus pallidus. This decreases Parkinson-like side effects from the drug. Antimuscarinic drugs like benztropine or trihexyphenidyl would also do this.

Question 9

Why block D2 receptors in patients with schizophrenia?

Answer 9

There may be more D2 receptors expressed in their brains.

Question 10

Why do patients rarely need more than one dose of an antipsychotic per day?

Answer 10

They are lipid soluble, so the get into all the tissues. Also, they have a long half life.

Question 11

What are non-neurological side effects seen in patients given antipsychotic drugs?

Answer 11

Orthostatic hypotension (D2 and alpha-1 blockade). Gynecomastia, amenorrhea (D2 block in ant. pituitary causes hyperprolactinemia). Antimuscarinic side effects. Lots of infections (leukopenia). Weight gain & type II diabetes.

Question 12

What are neurological side effects seen in patients given antipsychotic drugs?

Answer 12

Parkinsonian syndrome. Acute dystonia. Akathisias (restless). Tardive dyskinesia (facial tics develop as a sign of D2 receptor proliferation, especially on the presynaptic nerve terminal, causing increased DA release when those receptors are inhibited, causing overactivity). Seizures (GABA depletion). Sedation (H1 block). Altered sexual function (D2 block in nucleus accumbens eliminates pleasure and alpha-1 blocks orgasm/ejaculation function).

Question 13

Risperidone class, mechanism, side effect.

Answer 13

Atypical antipsychotic. Weak D2 block (less extrapyramidal effects), strong 5HT2A serotonin receptor block. Its main side effect is weight gain.

Question 14

What street drug is a 5HT2A agonist?

Answer 14

LSD. Note the increased incidence of hallucinations.

Question 15

Clozapine class, mechanism, side effect.

Answer 15

Atypical antipsychotic. Strong 5HT2A and D4 blocker. Weak D2 blocker. Free of extrapyramidal side effects. Seizures and agranulocytosis are what make it a last resort drug.

Question 16

What antipsychotic drug do you need to do blood tests on regularly?

Answer 16

Clozapine due to agranulocytosis.

Question 17

Olanzapine class, mechanism, side effect.

Answer 17

Atypical antipsychotic. Strong 5HT2A and D4 blocker. Weak D2 blocker. Few extrapyramidal side effects. No agranulocytosis or tardive dyskinesia.

Question 18

What antipsychotics improve cognitive function?

Answer 18

Clozapine and olanzapine.

Question 19

Quetiapine class, mechanism, side effects.

Answer 19

Atypical antipsychotic. Weak D2 block (less extrapyramidal effects), H1, alpha-1, strong 5HT2A serotonin receptor block. Some extrapyramidal side effects. Less likely to cause weight gain.

Question 20

Aripiprazole class, mechanism, side effects.

Answer 20

Dopamine system stabilizer. Partial D2, 5HT1a partial agonist (helps block excess neurotransmitter). 5HT2A antagonist. Less weight gain. Few side effects

Question 21

NMDA receptors and psychosis

Answer 21

A normally functioning NMDA receptor sends feedback inhibition to the glutaminergic neuron. A defective NMDA receptor does not send inhibitory feedback and glutamate is continually released.