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Pharm 3 > E1: Antipsychotics: > Flashcards

E1: Antipsychotics: Flashcards

(55 cards)

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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  • Affective behaviior, apathetic, withdrawn, antisocial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?

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

How is Fluphenazine different from Chlorpromazine?

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A

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

25
Does Haldol have anticholinergic activity? What does this mean for its side effects?
- no anticholinergic activity | - high incidence of EPS
26
What is the MOA of Clozapine?
Blocks 5-HT2A and DA D4 receptors, EPS and TD are rare
27
What are the side effects of clozapine?
- Hypersalivation, sedation, dizziness, postural hypotension, tachycardia, weight gain - decreased seizure threshold - rapid relapse if discontinued abruptly
28
Why is Clozapine a drug of last choice?
Risk of agranulocytosis
29
What are the side effects Olanzapine?
- Hyperglycemia type II DM (Zyprexa DM) | - sedation, orthostatic hypotension, weight gain
30
What are the uses of olanzapine?
- Positive and negative symptoms | - Bipolar
31
What is the first line drug for psychosis?
Risperdone
32
Why is risperdone the first line drug for psychosis?
-no significant effect on DA neurotransmission in nigrostriatal pathway, EPS and TD are rare
33
What are the uses of Ziprasidone?
- Some antidepressant activity - Tourette’s - acute mania
34
What are the side effects of Ziprasidone?
- Prolonged QT - Sedation - Hyperprolactinemia - decreases seizure threshold
35
What are the side effects of Quetiapine?
- Very sedating, dizziness, constipation, weight gain - Does not elevate prolactin - few EPS
36
What is the MOA of Aripiprazole?
- 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
What are the side effects of Aripiprazole?
-Decreases esophageal motility, hyperglycemia, sedation, seizures, increased glucose
38
What is the use of Lurasidone?
Used in the treatment of depression associated with bipolar
39
What are the side effects of Lurasidone?
- Some incidence of agranulocytosis and neutropenia - side effects similar to other atypicals - no antihistamine or anti muscarinic effect
40
What is the treatment of bipolar disorder?
- lithium - anticonvulsants **patient are often treated with these drugs and antipsychotics such as olanzapine
41
What causes Bipolar?
Lack of GABAergic activity
42
How is lithium metabolized?
It is not metabolized, it is excreted by the kidneys in its original form -Therefore has minimal drug interactions
43
What is the MOA of lithium?
Supress 2nd messengers (IP3)
44
Why do you need to monitor salt intake when taking lithium?
- 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
What are the side effects of lithium?
- VERY small therapeutic window - DI (lithium inhibits ADH, leading to increased thirst and urine output) - Thyroid function reduced - not recommended with pregnancy
46
How can you treat DI induced by lithium
Amiloride- blocks lithium from entering into the collecting duct
47
What medications cannot be combined with lithium?
- NSAIDs - Antidepressants (mania may increase) - Sodium (reduces Li concentration)
48
What happens when NSAIDs and Lithium are combined?
Increases Li toxicity by decreasing clearance and increasing Li uptake
49
What are the anticonvulsants that can be used in the treatment of bipolar?
- Valproic acid - Gabapentin - Carbamzepine - Lamotrigine
50
What is Valproic acid indicated for in bipolar?
Rapid cycling of manic and depressive phases | -effective in some who dont response to lithium
51
What are the side effects of Valproic acid?
- Surgical bleeding, GI upset, weight gain | - Teratogenic
52
What is the use of Carbamazepine in bipolar disorder?
-Refractory bipolar, used in combo with lithium
53
What are the potential side effect of Carbamazepine?
- GI upset, sedation, CNS toxicity, hypersensitivity | - SJS/toxic epidermal necrosis is
54
What drugs cannot be combined with Carbamazepine?
Carbamazepine competes for metabolism with Cimetidine, isoniazid, fluoxetine, and erythromycin so toxicity is increased
55
What is the used of Lamotrigine in bipolar disorder?
Approved for prevention of relapse, depressive state following mania, and acute mania

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