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Pharm 3 > E1: Antipsychotics: > Flashcards

E1: Antipsychotics: Flashcards

1
Q

What is the dopamine hypothesis of schizophrenia?

A
  • DA receptors may be greater in schizophrenics

- drugs that increase DA neurotransmission can induced psychosis

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2
Q

What is the serotoninc hypothesis of schizophrenia?

A

-Serotonin receptors are altered in schizophrenics and serotonin receptors mediate DA transmission

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3
Q

What are the positive symptoms of schizophrenia and what causes them?

A
  • Hallucinations, delusions, catatonic behavior, disorganized speech
  • Caused by overactive dopamine pathways in the limbic systemic
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4
Q

What are negative symptoms in schizophrenia and what causes them?

A
  • Affective behaviior, apathetic, withdrawn, antisocial

- Caused by underactive dopamine pathways in the frontal cortex

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5
Q

What are the 4 dopamine pathways in the brain?

A

1) mesolimbic: VTA to limbic system
2) Mesocortical: VTA to frontal cortex
3) Nigrostriatal: SN to Striatum
4) Tuberoinfundibular: Hypothalamus to pituitary

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6
Q

What are the “classic” antipsychotics?

A
  • “neuroleptics” that block DA D2 receptors and target the mesolimbic system
  • Alleviates the positive symptoms
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7
Q

What are the “atypical” antipsychotics?

A
  • Blocks 5-HT2A and DA receptors and targets the mesocortical and mesolimbic system
  • Alleviates both negative and positive symptoms
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8
Q

What two antipsychotics have the highest affinity for D2 receptors?

A

Haldol and Aripiprazole

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9
Q

What type of dopamine receptors predominate the mesolimbic system?

A

D2

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10
Q

What type of dopamine receptors predominate the mesocortical region?

A

D4

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11
Q

What are the general effects of antipsychotics?

A
  • delayed onset (6weeks)
  • decreased aggression, restlessness, anxiety
  • psychomotor function is slowed
  • reduce spontaneous movements
  • sedation
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12
Q

What are the common side effects of antipsychotics?

A
  • decreased seizure threshold
  • weight gain, increased prolactin secretion
  • anticholinergics: dry mouth, blurred vision
  • Alpha adrenergic: postural hypotension
  • Histamine: sedation
  • Extrapyramidal symptoms
  • Tardive dyskinesia
  • Neuroleptic malignant syndrome
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13
Q

What are extrapyramidal symptoms and what causes them?

A
  • Parkinsons like symptoms: tremor, rigidity, dyskinesias rocking, pacing, restlessness, anxiety
  • caused because DA receptor antagonists also block DA receptors in the nigrostriatal pathway, causing an imbalance in striata DA and ACh
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14
Q

How are extrapyrimidal symptoms treated?

A

-treat with anticholinergics such as Benztropine (cogentin) to restore ACh/DA balance

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15
Q

Which kind of antipsychotics tend to cause more EPS symptoms?

A

Classical antipsychotics

-degree of EPS is based on the anticholinergic activity of the drug

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16
Q

What is tardive dyskinesia?

A

Uncontrollable, jerky movements of the face and limbs, occurs late in disease following long term treatment

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17
Q

Which antipsychotics are least likely to cause TD?

A

Clozapine and Olanzapine

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18
Q

What is neuroleptic malignant syndrome?

A

A life threatening side effect

-muscle rigidity, hyperpyrexia, changes in BP and HR

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19
Q

How is neuroleptic malignant syndrome treated?

A

Dantrolene

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20
Q

What are the 4 classical antipsychotics?

A
  • Chlorpromazine
  • Prochlorperazine
  • Fluphenazine
  • Haloperidol
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21
Q

What are the atypical antipsychotics?

A
  • Clozapine
  • Olanzapine
  • Quetiapine
  • Aripiprazole
  • Risperdone
  • Ziprisadone
  • Lurasidone
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22
Q

What are the uses of Chlorpromazine?

A

Psychosis associated with mania and drugs of abuse, antiemetic (prochlorperazine), pre anesthetic

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23
Q

What are the side effects of Chlorpromazine?

A
  • Decreases seizure threshold
  • may cause retinal deposits “browning of vision”
  • sedation, postural hypotension, blurred vision
24
Q

How is Fluphenazine different from Chlorpromazine?

A

Fluphenazine is similar, it is selective for DA D2 receptors. It does have less anticholinergic activity and more EPS

25
Q

Does Haldol have anticholinergic activity? What does this mean for its side effects?

A
  • no anticholinergic activity

- high incidence of EPS

26
Q

What is the MOA of Clozapine?

A

Blocks 5-HT2A and DA D4 receptors, EPS and TD are rare

27
Q

What are the side effects of clozapine?

A
  • Hypersalivation, sedation, dizziness, postural hypotension, tachycardia, weight gain
  • decreased seizure threshold
  • rapid relapse if discontinued abruptly
28
Q

Why is Clozapine a drug of last choice?

A

Risk of agranulocytosis

29
Q

What are the side effects Olanzapine?

A
  • Hyperglycemia type II DM (Zyprexa DM)

- sedation, orthostatic hypotension, weight gain

30
Q

What are the uses of olanzapine?

A
  • Positive and negative symptoms

- Bipolar

31
Q

What is the first line drug for psychosis?

A

Risperdone

32
Q

Why is risperdone the first line drug for psychosis?

A

-no significant effect on DA neurotransmission in nigrostriatal pathway, EPS and TD are rare

33
Q

What are the uses of Ziprasidone?

A
  • Some antidepressant activity
  • Tourette’s
  • acute mania
34
Q

What are the side effects of Ziprasidone?

A
  • Prolonged QT
  • Sedation
  • Hyperprolactinemia
  • decreases seizure threshold
35
Q

What are the side effects of Quetiapine?

A
  • Very sedating, dizziness, constipation, weight gain
  • Does not elevate prolactin
  • few EPS
36
Q

What is the MOA of Aripiprazole?

A
  • Dopamine system stabilizer (if dopaminergic tone is low, DA receptors are activated. If dopaminergic tone is high, DA receptors are blocked)
  • Partial agonist for DA D2 and 5-HT1A.
  • Antagonist for 5-HT2A
37
Q

What are the side effects of Aripiprazole?

A

-Decreases esophageal motility, hyperglycemia, sedation, seizures, increased glucose

38
Q

What is the use of Lurasidone?

A

Used in the treatment of depression associated with bipolar

39
Q

What are the side effects of Lurasidone?

A
  • Some incidence of agranulocytosis and neutropenia
  • side effects similar to other atypicals
  • no antihistamine or anti muscarinic effect
40
Q

What is the treatment of bipolar disorder?

A
  • lithium
  • anticonvulsants

**patient are often treated with these drugs and antipsychotics such as olanzapine

41
Q

What causes Bipolar?

A

Lack of GABAergic activity

42
Q

How is lithium metabolized?

A

It is not metabolized, it is excreted by the kidneys in its original form
-Therefore has minimal drug interactions

43
Q

What is the MOA of lithium?

A

Supress 2nd messengers (IP3)

44
Q

Why do you need to monitor salt intake when taking lithium?

A
  • Lithium is reabsorbed by the proximal tubule in the kidney and competes with sodium for re-absorption
  • if Na+ decreases, Lithium absorption increases, leading to toxic doses and vice versa
45
Q

What are the side effects of lithium?

A
  • VERY small therapeutic window
  • DI (lithium inhibits ADH, leading to increased thirst and urine output)
  • Thyroid function reduced
  • not recommended with pregnancy
46
Q

How can you treat DI induced by lithium

A

Amiloride- blocks lithium from entering into the collecting duct

47
Q

What medications cannot be combined with lithium?

A
  • NSAIDs
  • Antidepressants (mania may increase)
  • Sodium (reduces Li concentration)
48
Q

What happens when NSAIDs and Lithium are combined?

A

Increases Li toxicity by decreasing clearance and increasing Li uptake

49
Q

What are the anticonvulsants that can be used in the treatment of bipolar?

A
  • Valproic acid
  • Gabapentin
  • Carbamzepine
  • Lamotrigine
50
Q

What is Valproic acid indicated for in bipolar?

A

Rapid cycling of manic and depressive phases

-effective in some who dont response to lithium

51
Q

What are the side effects of Valproic acid?

A
  • Surgical bleeding, GI upset, weight gain

- Teratogenic

52
Q

What is the use of Carbamazepine in bipolar disorder?

A

-Refractory bipolar, used in combo with lithium

53
Q

What are the potential side effect of Carbamazepine?

A
  • GI upset, sedation, CNS toxicity, hypersensitivity

- SJS/toxic epidermal necrosis is

54
Q

What drugs cannot be combined with Carbamazepine?

A

Carbamazepine competes for metabolism with Cimetidine, isoniazid, fluoxetine, and erythromycin so toxicity is increased

55
Q

What is the used of Lamotrigine in bipolar disorder?

A

Approved for prevention of relapse, depressive state following mania, and acute mania

Pharm 3 (20 decks)

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