Pharmacology Test 4

Front 1

"Positive" Symptoms
Schizophrenia

Back 1

• Thought disturbances
• Delusions, hallucinations
• Motor hyperactivity
• Paranoia
• Sometimes aggressive behavior

Front 2

"Negative" Symptoms
Schizophrenia

Back 2

• Social withdrawal
• Loss of drive
• Diminished affect
• Paucity of speech

Front 3

“Cognitive Symptoms”
Schizophrenia

Back 3

• Poor executive functioning
• Inability to sustain attention
• Problems with working memory

Front 4

"dopamine hypothesis" of schizophrenia

Back 4

schizophrenia is promoted by a relative excess of dopaminergic tone to brain limbic (emotional) centers. This excess tone then gradually distorts higher (cognitive) brain centers to disrupt the capacity for assessing objective reality

Front 5

Circumstantial evidence for the dopamine hypothesis

Back 5

1. Drugs that facilitate or mimic dopamine transmission (i.e., amphetamine, L-DOPA) exacerbate symptoms in schizophrenic patients or precipitate symptoms during remission.

2. High chronic doses of some indirect dopamine agonists (i.e., amphetamine) can induce symptoms identical to those of an acute paranoid schizophrenic reaction.

3. Many antipsychotic drugs block post-synaptic D2 receptors in the central nervous system.

Front 6

Problems with the dopamine hypothesis:

Back 6

1. Although disruption of dopaminergic transmission by neuroleptics can occur within hours, 2-3 weeks of treatment are required before schizophrenic symptoms are relieved.

2. Other systems (GABA, glutamate, 5HT, norepinephrine, histamine, neuropeptides) have been implicated in schizophrenia.

Front 7

“Dysregulation” and schizophrenia

Back 7

• Many transmitters involved in schizophrenia
• Disease is likely a failure in regulation, rather than absolute increase/decrease in brain activity.

Front 8

Reserpine
Mechanism
Side effects:

Back 8

Inhibits VMAT-2 and reuptake of dopamine and serotonin, and NE.
• Side Effects: decreased blood pressure, drowsiness, mental depression, motor impairment
No longer used.

Front 9

First Generation Agents
or
Typical antipsychotics

Back 9

Chlorpromazine (Thorazine)
Haloperidol (Haldol)

Front 10

General Properties of First Generation Agents or Typical antipsychotics

Back 10

• All lack liability for depression of respiration and chemical dependence.
• These agents are more effective against "positive" vs. "negative" symptoms.
• Latency to benefits may be weeks-months.
• Noncompliance is common.

Front 11

Mechanism of action of First Generation Agents or Typical antipsychotics

Back 11

antagonist at D2 receptors

note that other receptors (α1, muscarinic, H1) blocked as well

Front 12

Overview of side effects for First Generation Agents or Typical antipsychotics

Back 12

1. Extrapyramidal Symptoms – slow movement, rigidity and tremor, akathisia (uncontrollable motor restlessness), dystonias. (tardive dyskinesia most limiting)

2. Neuroleptic malignant syndrome - The incidence is ≈1%

3. Hyperprolactinemia

4. Weight gain

5. Anticholinergic effects: dry mouth, blurred vision, confusion, constipation, urinary retention

6. Sedation

7. Cardiovascular effects: hypotension, reflex tachycardia

Front 13

What characterizes tardive dyskinesia?

Back 13

involuntary movements of the face, mouth, and tongue, and sometimes the upper limbs, trunk and neck. It can be irreversible.

Front 14

Why does tardive dyskinesia lead to compliance issues?

Back 14

It wakes these patients up to reality and they don’t like people staring at them for the unusual neck and tongue movements.

Front 15

What should be done to help prevent tardive dyskinesia from developing in patients on typical antipsychotics?

Back 15

Drug holidays.

Tardive dyskinesia can be permanent.

Front 16

What type of state is Neuroleptic malignant syndrome?

Back 16

Hyperthermic state

Front 17

What are some signs/symptoms of Neuroleptic malignant syndrome?

Back 17

Variable rapidity of onset
severe muscular rigidity
diaphoresis
delirium
fluctuating blood pressure
tachycardia
extrapyramidal symptoms

Front 18

Cause of Neuroleptic malignant syndrome?

Back 18

Blockade of dopamine receptors or abrupt withdrawal of a dopamine agonist