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Pharm 2 Part 1 > Lecture 5: Antipsychotic Drugs and Mood Stabilizers > Flashcards

Lecture 5: Antipsychotic Drugs and Mood Stabilizers Flashcards

1
Q

What is probably the cause for the symptoms of Schizophrenia?

A

EXCESSIVE DOPAMINERGIC ACTIVITY

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2
Q

Schizophrenia

  1. What are “POSITIVE” Symptoms?
    a. What type of Hallucinations do they get?
    b. Due to INCREASED activity of what?
    c. Symptoms are controlled fairly well by what drugs?
A
  1. Abnormality/exaggeration of Normal function (Incoherent speech, agitation)
    a. Usually AUDITORY, delusions, bizarre behavior, thought disorders
    b. INCREASED DOPAMINERGIC ACTIVITY in the LIMBIC SYSTEM
    c. by Classical ANTI-PSYCHOTIC DRUGS
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3
Q

Schizophrenia

  1. “Negative” Symptoms best controlled by what drugs?
    a. Type of Behavior?
    b. Loss or decrease in function of what?
    c. Due to DECREASED activity of what?
A
  1. “Atypical” Drugs
    a. Lack of affect, lack of volition, apathy, lack of pleasure, ANTISOCIAL BEHAVIOR
    b. in general. Also, little or no speech, blunted emotions
    c. DECREASED DOPAMINERGIC ACTIVITY in FRONTAL CORTEX
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4
Q

Schizophrenia

  1. COGNITIVE IMPAIRMENT: What drugs do they respond to?
    a. Inability to do what?
    b. Type of thought and speech?
    c. Memory?
A
  1. None. No current therapy works well for this
    a. to pay attention, distraction may impair memory of recent events
    b. Disorganized thought and speech
    c. Memory Loss
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5
Q

Hypothesis of Schizophrenia

  1. Drugs that INCREASE Dopamine can produce what behavior?
  2. Most effective Antypsychotics block what receptors in the brain?
  3. PET scan shows an increase of what receptor?
  4. What other hormone may be involved?
A
  1. Psychosis
  2. Dopamine Receptors (DA D2 receptor blocking activity correlates w/antipsychotic potency)
  3. in DA receptors in treated and untreated peeps.
  4. SEROTONIN may also be involved. As drugs stimulate 5HT2a receptors ((LSD) can cause hallucinations. Drugs that BLOCK THESE are good Tx’s for Schiz’s.
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6
Q

Dopaminergic System

  1. MESOLIMBIC PATHWAY
    a. Projects from what structure to what other structure in the brian?

b. Associated with what 2 things?
c. OVERSTIMULATION APPEARS to RESULT in what?

A
  1. a. VTA to Limbic System
    b. Higher mental function and Emotions
    c. in POSITIVE SYMPTOMS of PSYCHOSIS
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7
Q

Dopaminergic System

  1. MESOCORTICAL PATHWAY
    a. Projects from what structure to what other structure?
    b. Associated with what 2 things?
    c. OVERSTIMULATION APPEARS to RESULT in what?
A
  1. a. VTA to FRONTAL CORTEX
    b. Higher Mental function and emotions
    c. NEGATIVE SYMPTOMS of PSYCHOSIS
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8
Q

Dopaminergic System

  1. NIGROSTRIATAL PATHWAY
    a. Projects from what structure to what 2 structures?
    b. Primary role is control of what 2 things?
    c. A Decrease in activity here produces symptoms seen in what disease?
    d. What are EXTRAPYRAMIDAL SYMPTOMS?
A
  1. a. Substantia Nigra to Caudate/Putamen
    b. Posture and Voluntary Movements
    c. Parkinson’s Disease
    d. PD-like symptoms induced by drugs
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9
Q

Dopaminergic System

  1. TUBEROINFUNDIBULAR PATHWAY
    a. Projects from what structure to what other structure?
    b. Involved in regulating release of what?
    c. What Inhibits this secretion?
A
  1. a. From Hypothalamus to Anterior Pituitary
    b. of Prolactin
    c. DA
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10
Q

Mechanism of Anti-psychotic drugs

  1. Classical ones help by blocking what receptor?
    a. Correlates w/what symptoms?
  2. The Newer Antipsychotics block what receptors?
    a. Effective against what symptoms?
  3. Most antipsychotic drugs also block what 3 receptors?
    a. Actions at these receptors are basically the basis for what?
A
  1. DA D2 subtype of dopamine receptor
    a. Positive symptoms
  2. 5HT2a Serotonergic Receptors
    a. Negative symptoms
  3. A-ADRENERGIC, HISTAMINE, and MUSCARINIC RECEPTORS
    a. for MANY OF THE SIDE EFFECTS
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11
Q

Pharmacological Effects

  1. 5 symptoms decrease?
  2. What happens to psychomotor function?
  3. What Activity occurs from Blockade of DA Receptors in the Chemoreceptor Trigger Zone?
A
  1. Agitation, Delusions, Fear, Hallucinations, Hostility
  2. It’s slowed.
  3. ANTIEMETIC ACTIVITY
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12
Q

Side Effects

  1. Are Antipsychotics Safe?
    a. TI level?
    b. Side effects: good or bad?
  2. Common side effects? (4)

a. Others include what kind of symptoms?
b. What do these symptoms cause?

A
  1. Yes
    a. High
    b. Bad…not pleasant
  2. Autonomic Symptoms, Restlessness, Sleepiness, Weight Gain

a. Extrapyramidal Symptoms
b. EPS: D2 antagonists block DA receptors in Limbic system and in EPS.

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13
Q

Major Side Effects of EPS: Extra pyramidal Semptoms

  1. What 2 ATYPICAL ANTIPSYCHOTICS cause EPS?
    a. Why?
A

AKATHISIA (Constant rocking), DYSTONIA (involuntary muscle spasms of the tongue…but also others); PARKINSONIAN SYMPTOMS

  1. Clozapine and Risperidone
    a. Lower affinity for D2, so bind more to 5-HT2A and/or D4 receptors
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14
Q

More Side Effects

  1. Tardive Dyskinesia: What is it?
    a. What 2 drugs are LEAST LIKELY to cause it?
  2. Endocrine Effects
    a. Most common thing seen?
    b. Increased PROLACTIN RELEASE: Why?
A
  1. Uncontrollable movements of the mouth, tongue, face, eyelids, trunk, extremities
    a. Clozapine and Olanzapine
  2. a. WEIGHT GAIN (w/DA blockade in Hypothalamus suppressing appetite…weird)
    b. DA usually Inhibits prolactin secretion…since it’s blocked, more Prolactin is released
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15
Q

More Side Effects

  1. Autonomic Effects
    a. Most Antipsychotics block what 3 receptors?
    b. Muscarinic blockage causes what?
    c. A-adrenergic blockage causes what?
    d. Blocking Histamine and Muscarinic Receptors causes what?
A
  1. a. A-adrenergic, Muscarinic and Histamine receptors
    b. Dry mouth, blurred vision, constipation, tachycardia.
    c. postural hypotension, hard to ejaculate
    d. Sedation
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16
Q

More Side Effects

  1. Seizures
    a. What do they do to the Seizure threshold?
  2. NEUROLEPTIC MALIGNANT SYNDROME
    a. Is it bad?
    b. What is it?
    c. What is it Treated with?
A
  1. a. Decrease it.
  2. a. YES. Life-threatening.
    b. Muscle rigidity, catatonia, increased BT.
    c. DANTROLENE
17
Q

Classical Antipsychotics

  1. Prototype drug?
  2. What is it used for?
A
  1. CHLORPROMAZINE

2. Schizs, mania, psychosis, hallucinations w/alcohol and drugs, nausea and vomiting, premature ejaculation.

18
Q

Classical Antipsychotics: Side Effects

  1. ANTICHOLINERGIC EFFECTS: What are they?
  2. Blockage of Alpha receptors CAUSES what 2 things?
A
  1. Blurred vision, constipation, urinary retention, decreased GI motility
  2. POSTURAL HYPOTENSION and INHIBITION of EJACULATION
19
Q

Classical Antipsychotics

  1. HALOPERIDOL
    a. What does it SELECTIVELY BLOCK?

b. Best way to take it?
c. HIGHLY LIKELY TO CAUSE WHAT?

A
  1. a. D2 RECEPTORS
    b. Oral. Also frequently injected in ACUTE PSYCHOTIC SITUATIONS
    c. EPS…no anticholinergic activity.
20
Q

ATYPICAL ANTIPSYCHOTICS

  1. CLOZAPINE
    a. What does it improve?

b. Binds to what receptors?

  1. SIDE EFFECTS
    a. what are they?
    b. What can be SEVERE and LIFE THREATENING?
A
  1. a. NEGATIVE SYMPTOMS
    b. D4 Receptors and 5-HT2a receptors more than to D2 receptors
  2. a. Sedation, lower seizure threshold, postural hypotension, weight gain.
    b. AGRANULOCYTOSIS…need to monitor blood counts weekly
21
Q

ATYPICAL ANTIPSYCHOTICS

  1. OLANZAPINE
    a. Very similar to what?
    b. What does it block? WHAT MAKES IT DIFFERENT?

c. Drugs with a higher affinity for what receptors are effective for what?

  1. Side Effects
    a. What is VERY COMMON?
    b. What else…?
A
  1. a. CLOZAPINE
    b. D2, D4, 5HT-2a Receptors
    b. DOES NOT CAUSE AGRANULOCYTOSIS

c. for 5HT2a receptors than for D2 are effective for NEGATIVE and POSITIVE Symptoms

  1. a. WEIGHT GAIN
    b. sedation, dizziness, orthostatic hypotension, increased incidence of Hyperglycemia and Type 2 Diabetes
22
Q

ATYPICAL ANTIPSYCHOTICS

  1. Quetiapine
    a. Very similar to what drug?
    b. What does it NOT cause?
    c. Few what?

d. Does not cause persistent elevations of what?
e. MOST COMMON SIDE EFFECTS?
f. VERY what?

A
  1. a. Clozapine
    b. Doesn’t cause agranulocytosis
    c. Few EPS side effects
    d. of Serum prolactin concentration
    e. Weight gain, drowsiness, dizziness, constipation, orthostatic hypotension, xerostomia, dyspepsia
    f. VERY SEDATING
23
Q

ATYPICAL ANTIPSYCHOTICS

  1. APRIPIPRAZOLE
    a. Different from other Antipsychotics. Why?
  2. What does it do with DA receptors when Dopaminergic tone is Low? When it’s High?
  3. Type of acting it does on receptors?
  4. Antagonist on what receptors?
  5. Uses?
  6. Side effects
A
  1. a. FIRST in a NEW CLASS (DOPAMINE SYSTEM STABILIZERS)
  2. Activates DA receptors; Blockes them
  3. Partial Agonist at D2 and 5HT1a
  4. 5HT2a and a1 and Histamine receptors
  5. Depression and Schiz’s. Oral. Liver. DOES NOT AFFECT PROLACTIN or QT Interval.
  6. Orthostatic hypotension; caution w/elderly as can cause Aspiration Pneumonia
24
Q

ATYPICAL ANTIPSYCHOTICS

  1. RISPERIDONE

a. FIRST LINE DRUG for what problem?
b. Effective for what symptoms?

c. What does it do to DA TRANSMISSION in BASAL GANGLIA?
2. Side Effects

a. Antagonizes what receptor?
b. Common side effects?
c. Increases release of what?

A
  1. a. for PSYCHOSIS
    b. Positive and Negative symptoms

c. ENHANCES it
2. a. a1 adrenergic receptor (postural hypotension)
b. Agitation, anxiety, insomnia, headache, weight gain LENGTHENS QT INTERVAL
c. Prolactin

25
Q

Drug Interactions of Antipsychotics

  1. Most common interactions are with what 2 types of drugs?
  2. Combination w/CNS depressants?
  3. w/Anticholinergics?
  4. w/TCAs?
  5. Carbamezapine and smoking while taking this drug will do what?
  6. Antihypertensive drugs?
A
  1. Anticholinergics and Sedative-hypnotics
  2. Increase Sedation
  3. Increase side Effects: Dry mouth, urinary retention, constipation, etc.
  4. could increase risk of seizures or cardiac conduction problems
  5. induce liver enzymes, so increased metabolism decreases antipsychotic concentration
  6. unpredictable due to a1 blockade
26
Q

Bipolar Disorder

  1. What do we think is missing?
  2. Genetic?
  3. DOC?
  4. What other drugs can be effective?
  5. Often prescribed in combination with what?
A
  1. GABAergic Activity
  2. Strong genetic component
  3. LITHIUM
  4. Anticonvulsants (VALPROIC ACID, CARBAMAZEPINE, LAMOTRIGINE)
  5. Antipsychotics like OLAZAPINE!
27
Q

Lithium

  1. How does it work?
  2. Common side effects?

Pharmacokinetics

  1. TI?
  2. Peak concentrations?
  3. How is it EXCRETED?
A
  1. Not sure. may decrease release of NE and DA or may increase release of ACh.
  2. Hypothyroidism and Polyuria
  3. SMALL THERAPEUTIC WINDOW
  4. 2-4 hrs after Tx.
  5. KIDNEY
28
Q

Lithium: Side Effects

  1. Some common side effects?
  2. RENAL EFFECTS: Major issue?
    a. TREATED with WHAT?
A
  1. nausea, diarrhea, anorexia, bloating, muscle weakness, lethargy, headache, memory impairment, confusion, TREMOR (beta blockers treat it)
  2. Nephrogenic DIABETES INSIPIDUS w/polyuria and polydipsia cuz Collecting tubule can’t conserve water as Lithium Blocks Action of ADH
    a. AMILORIDE: Blocks entry of lithium into the Collecting Duct.
29
Q

Lithium Toxicity

  1. How bad it is?
A
  1. It’s very toxic in Overdose.. treat w/Dialysis and Saline.
30
Q

Lithium: Drug Combinations/interactions

  1. Antidepressants
  2. Antypsychotics and Benzos
  3. Diuretics
  4. NSAIDs
  5. Sodium
A
  1. Can increase MANIA
  2. Helps to control Mania…usually safe..
  3. Alter lithium concentration
  4. decrease lithium clearance/increase plasma concentration
  5. Low Na intake, sweating, heavy exercise, hot weather, saunas, decrease sodium and may increase plasma lithium concentration
31
Q

Anticonvulsants w/Mood Stabilizing Properties

  1. Valproic Acid
    a. Is it as good as Lithium?
    b. most frequent side effects?
    c. Major issue with it?
A
  1. a. Yes. Equivalent or Better
    b. GI upset
    c. TERATOGENIC (don’t use during pregnancy or lactation)
32
Q

Anticonvulsants w/Mood Stabilizing Properties

  1. Carbamazepine
    a. May be helpful when?
    b. GI Side effects?
    c. CNS Toxicity?
    d. Major issue with it?
    e. May cause what Syndrome?
A
  1. a. when Pts dont respond to lithium, or combined with it.
    b. Nausea, vomiting, diarrhea, abdominal pain, constipation, anorexia
    c. drowsiness, dizziness, fatigue, clumsiness, ataxia
    d. TERATOGENIC
    e. STEVENS JOHNSON SYNDROME: have to check for the allele.
33
Q

Anticonvulsants w/Mood Stabilizing Properties

Lamotrigine

  1. Approved for prevention of what?
  2. Used to prevent what?
  3. Used to treat what?
  4. May cause what?
A
  1. Recurrence
  2. Depression that follows a Manic Phase
  3. Acute Mania
  4. Nausea, dizziness, headaches

Pharm 2 Part 1 (6 decks)

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