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Behavioral Medicine > Schizophrenia 3: Meds & Side Effects > Flashcards

Schizophrenia 3: Meds & Side Effects Flashcards

1
Q

Blockade of 5-HT2A receptors also causes an increase in dopamine in the prefrontal cortex. This is the reason that atypical antipsychotics improve ______ (2) symptoms of psychiatric illnesses.

A
  1. mood
  2. cognitive

(Atypicals are more potent 5-HT2A antagonists→ better tolerability & less EPS (by increasing DA). The higher the relative occupancy of 5-HT2A to D2 receptors, the greater the reduction in EPS.)

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2
Q

Theoretically, blockade of dopamine D2 transmission by antipsychotic drugs is responsible for the alleviation of the _____ symptoms of schizophrenia and induction of EPS.

A

positive

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3
Q

Antipsychotics may bind to the D2 receptor with similar affinities, but dissociate at different rates. The faster a drug dissociates from the receptor, the more likely it will be displaced by_________.

A

exogenous dopamine or other drugs

(the less tightly it binds → less EPS)

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4
Q

5HT2 receptors inhibit release of dopamine. Blockade of these receptors enhances ______.

A

release of dopamine

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5
Q

Mesolimbic tract projects from the_______to the nucleus accumbens

A

midbrain ventral tegmental area

(Involved in the positive symptoms of schizophrenia. Blocking the DA receptors here → reduction in positive symptoms)

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6
Q

The mesolimbic tract is involved in the regulation of ________ and believed to be the predominant pathway regulating positive symptoms of schizophrenia.

A

emotional behaviors

(Hyperactivity → positive symptoms of schizophrenia. Blocking DA receptors → decreased positive sx)

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7
Q

Blocking D2 receptors of the mesolimbic tract may result in reduction of _____

A

positive symptoms

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8
Q

Which medication has the greatest effecacy in treating schizophrenia

A

Clozapine

(AE: agranulocytosis)

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9
Q

Mesocortical tract projects from the _____ to the (limbic) prefrontal cortex

A

ventral tegmental area

(DA deficiency in this pathway causes negative and cognitive symptoms, possibly mood symptoms)

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10
Q

Dopamine deficiency in the mesocortical tract causes which symptoms in schizophrenia (3)?

A
  1. Negative
  2. Cognitive
  3. Mood
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11
Q

In the mesocortical pathway, there may be more 5HT2A receptors than D2 receptors. 5HT antagonism of atypical antipsychotics may be more profound than the _______.

A

D2 receptor blocking activity

(Could help with negative symptoms)

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12
Q

Nigrostriatal: Projects from the ______ to the basal ganglia.

A

substantia nigra

(Involved in the control of movements. Blockade of D2-dopaminergic receptors associated with this pathway has been implicated in the induction of EPS)

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13
Q

The Niagarostriatal tract as part of the extrapyramidal system and controls _____, as well as modulates _____.

A
  • Motor movement
  • direct and indirect basal ganglia pathways
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14
Q
  • Blockade of the D2 receptors in the nigrostriatal tract causes:
  • Blockade of the 5HT2A receptors in the nigrostriatal tract causes:
A
  • movement disorders: parkinsonism & tardive dyskinesia
  • Increases dopamine in this pathway

(second generation have less EPS symptoms bc they have more serotonergic activity, less DA blockage)

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15
Q

What is the Tonic Inhibition thoery of schizophrenia (pathophysiology)?

A

GABA neurons are not inhibiting the DA neurons as they should be ⇒ hyperactivity in mesolimbic tract ⇒ positive symptoms

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16
Q

What is the Tonic Excitation theory of schizophrenia (pathophysiology)?

A
  • Typically glutamate stimulates DA neurons in the mesocortical tract
  • If this does not happen, DA nuerons in the mesocortical tract = hypoactive→ negative & cognitive symptoms
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17
Q

Glutamate is important for which area of the brain?

A

Everywhere

(we can’t use it pharmacologically yet bc it is neurotoxic)

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18
Q

Temporal onset of EPS (antipsychotic-induced movement disorders) acute and long-term

A
  • acute: dystonia, akathisia, parkinsonism
  • long-term: tarditive dyskeinsesia (months to years)
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19
Q

Dystonia reaction to antispycotics: may occur during the ________

A

first hours of treatment, with 90% occurring within the first 3 days

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20
Q

Risk factors for getting an acute dystonic reaction to antipsychotics

A

muscular men under 40 on high-potency first-gen antipsychotics

(tx: benztropine or benadryl (diphenhydramine))

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21
Q

Akathisia reaction to antipsycotics: may occur within _____

A

2 to 3 days of treatment, but more frequently has an onset after 5 days

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22
Q

Parkinsonism reaction to antipsycotics: can occur _____.

A

during the first 5 to 30 days of treatment

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23
Q

Parkinsonism symptoms do to antipsychotics include bradykinesia, rigidity, cogwheeling, tremor as well as ____ (4).

A
  1. masked facies
  2. drooling
  3. stooped posture
  4. festinating gait

(more common in elderly & w/high-potency antipsychotics)

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24
Q

Treatment: parkinsonism reaction with antipsychotics

A
  • Switch to a second-generation antipsychotic or lower dose
  • Antiparkinson drugs (caution: in the elderly)
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25
Q

Define akathisia

A

An intensely unpleasant sensation of restlessness and the need to move, especially the legs

(may cause anxiety, agitation or suicide)

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26
Q

What is the cause of extrapyramidal symptoms (chemically)?

A

Stimulating dopamine receptors on a cholinergic neurons will inhibit the release of Ach → EPS

(if you block the Ach receptors → reduces EPS)

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27
Q

Treatment of akathisia reaction to antipsychotics (3)

A
  1. beta blocker (propranolol 10-30 mg tid)
  2. benzodiazepine (lorazepam 1 mg tid)
  3. anticholinergic (benztropine 1-2 mg bid)

(careful w/anticholinergic when they already have cognitive issues)

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28
Q

Treatment with dopamine facilitator (Amantadine) for extrapyramidal symptoms (antipsychotic AE) increases CNS concentrations of DA by ______.

(primarily for pseudoparkinsonism)

A

Blocking its reuptake and increasing release from presynaptic neurons

(Restores dopamine/acetylcholine balance in the striatum)

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29
Q

Side effects when treating extrapyramidal symptoms with anticholinergics:

A
  1. constipation
  2. dry mouth
  3. blurry vision
  4. urinary retention

“Blind as a bat (mydriasis), mad as a hatter (delirium), red as a beet (flushing), hot as a hare (hyperthermia), dry as a bone (decreased secretions and dry skin), the bowel and bladder lose their tone (urinary retention and paralytic ileus), and the heart runs alone (tachycardia).”

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30
Q

Treatment with anticholinergics for extrapyramidal symptoms (antipsychotic AE) (3)

A
  • Benztropine (Cogentin)
  • Diphenhydramine (Benadryl)
  • Trihexyphenidyl (Artane)

(Dopamine and acetylcholine have a reciprocal relationship in the striatum)

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31
Q

Possible side effects of DA facilitator Amantadin (symmetrel): (3)

A
  1. Orthostatic hypotension
  2. Ankle edema
  3. GI upset
32
Q

Treatment with beta-blockers for extrapyramidal symptoms (antipsychotic AE) is _______, specifically for which symptom(s)?

A
  • Propranolol
  • Akathisia
33
Q

Treatment with alpha-agonists for extrapyramidal symptoms (antipsychotic AE) is ______, specifically for which symptom(s)? AE?

A
  • Clonidine
  • Akathisia
  • Orthostatic hypotension or sedation

(AE of DA facilitator is Orthostatic HTN also)

34
Q

acute dystonia (cramping & msk rigidity - AE to antipsychotics) treatment

A

anticholinergics

(benztropine, diphenhydramine/benadryl)

35
Q

The AIMS scale measures ______.

A

Symptoms of tardive dyskinesia

36
Q

Define tardive dyskinesia

A

Long-standing or permanent abnormal involuntary movements

(MC caused by the long-term use of typical antipsychotics, 20% will develop)

37
Q

TD presents clinically as involuntary athetoid movements of the ______or occasionally muscle groups that subserve breathing and swallowing

A

tongue, facial and neck muscles, upper and lower extremities, truncal musculature

38
Q

What is the difference between tardive dyskinesia and Parkinson’s symptoms?

A
  • Tardive dyskinesia is irregular and fast
  • Parkinson’s is slow and tremor
39
Q

Tardive dyskinesia rarely develops in patients with _____. Increased risk in those _____.

A
  • less than 3 to 6 months of antipsychotic exposure
  • over 50 y.o.
40
Q

When a patient has tardive dyskinesia you must consider risks versus benefits of ______.

A

continued antipsychotic medication when TD symptoms present

41
Q

Treatment of tardive dyskinesia

A

VMAT2 inhibitors (Deutetrabenzine or Valbenazine)

42
Q

Which 2 VMAT2 inhibitors treat TD?

A
  1. Deutetrabenzine
  2. Valbenazine
43
Q

In the tuberoinfundibular tract DA blocks the release of _______, whereas 5HT2A causes its release.

A
  • prolactin

(Increased neuronal activity in this pathway→ inhibits release; blockade of D2 receptor → hyperprolactinemia)

44
Q

Potential consequences of prolactin elevation levels?

A
45
Q

Black Box warning for antipsychotics (2)

A
  1. Mortality in dementia
  2. Suicide

(anything that treats modd may have suicide risk)

46
Q

Potential side effects for antipsychotics (9)

A
  1. Neuroleptic malignant syndrome
  2. Cardiac toxicity
  3. Sedation
  4. Postural hypotension
  5. Weight gain
  6. Hyperglycemia/diabetes/hyperlipidemia
  7. Hematologic effects
  8. Heat intolerance
  9. Bowel complications (clozapine)
47
Q

Neuroleptic Malignant Syndrome: symptoms (5)

A
  1. Muscle rigidity
  2. Fever
  3. Autonomic instability
  4. Delirium
  5. Seizures or coma (less likely)

(less common w/second gen; sx occur over hours to days, with rigidity typically occurring first)

48
Q

Neuroleptic Malignant Syndrome treatment includes stopping the antipsychotic and _____ (2).

A
  1. Supportive care
  2. Dantrolene
49
Q

Cardiac toxicity with antipsychotics include ______.

A

prolonged QT

50
Q

Which two antipsychotics have the greatest risk for cardiac toxicity (prolonged QT)?

A

Pimozide and thioridazine

(ziprasidone have FDA caution; be especially careful w/patients co-morbid for cardiac diz)

51
Q

Which are the most sedating first-generation antipsychotics? Second generation?

A
  • Chlorpromazine and thioridazine
  • Clozapine > quetiapine > olanzapine > risperidone > ziprasidone and aripiprazole
52
Q

Which first gen antipsychotics have the least sedating effects? Which second gen antipsycotics have the least sedating effects?

A
  • haloperidol and fluphenazine
  • ziprasidone and aripiprazole
53
Q

Postural hypotension (improves when pt is supine) when using antipsychotics is related to ______ blockage. MC with ______ (3) meds.

A
  • alpha-adrenergic receptor
  • chlorpromazine, thioridazine, clozapine

(May be associated with reflex tachycardia)

54
Q

Treatment of postural hypotension secondary to antipsychotic use (2)

A
  1. Teach patient to get up from recumbency slowly
  2. Switching agents to higher potency med
55
Q

All antipsychotics can increase appetite and cause weight gaine. Which second generation antipsychotics cause the most weight gain?

A
  • Most: SGA’s: clozapine and olanzapine

(Monitoring at every visit is recommended)

56
Q

Which antipsychotic causes the least amount of weight gain?

A

Ziprasidone, then quetiapine and risperidone

(monitor at every visit)

57
Q

Which medication has the highest risk for diabetes and hyperlipidemia? Least?

A
  • Olanzapine (also high risk for weight gain)
  • Ziprasidone

(routine monitoring of glucose and lipid parameters)

58
Q

Why are schizophrenic patients at a highter risk of Diabetes/Hyperglycemia/
Hyperlipidemia?

A
  • often have sedentary lifestyle

(Independent risk from antipsychotic medication)

59
Q

Hematologic effects reported with antipsychotic use: (3)

A
  • neutropenia, leukopenia and agranulocytosis (severe neutropenia)

(CBC if patient has frequent infections; routine monitoring not necessary. Except : Clozapine → 1-3 % → agranulocytosis)

60
Q

Why do schizophrenic patients have abnormal thermoregulation?

A
  • Impaired heat loss through peripheral vasodilation via abnormalities in niacin and prostaglandin E1
  • Disruption of the mesolimbic dopamine system responsible for temperature regulation and psychosis
61
Q

Anti-psychotic medication may lead to abnormal thermoregulation. How do each of the following contribute to this phenomenon: anticholinergic, anti dopaminergic, antipsychotic?

A
  1. Anticholinergic: inhibits parasympathetic pathways, leading to inhibited sweating
  2. Antidopaminergic: increase the set point of the temp regulation
  3. Antipsychotic: reduce compensatory behaviors, such as drinking more water or removing extra clothing
62
Q

Antipsychotic pharmacokinetics: when administered orally, peak plasma levels occur in _____. IM? Most are metabolised by _____.

A
  • 1-4 hours
  • 15 minutes
  • cytochrome P450 system

(Nearly all have half-lives over 24 hours)

63
Q

Antipsychotic plasma levels not used often, unless _____, or when _____.

A
  • lack of response
  • used in combination with other meds that can affect their pharmacokinetics
64
Q

Initiating treatment of acute psychosis: administer _____

A

Antipsychotic meds

(effects generally start w/in a few days of onset of treatment)

65
Q

____ (how many) discontinue their first-line antipsychotic meds. Most antipsychotic prescriptions are written for ______ (typical/atypical).

A
  • 1/3 to ¾ of all patients
  • atypicals

(5 of 9 branded antipsychotic meds will be generic in next 12-18 months, great news bc/brand name costs thousands of $$ /mo)

66
Q

Schizophrenia maintenance treatment: why is prevention of relapse is more important than risk of side effects?

A

most side effects are reversible, and the consequences of relapse may be irreversible (they lose cognitive fxn each time)

67
Q

Schizophrenia maintenance treatment: duration for first time, multiple of a danger to self or others

A
  • 1-2 years of treatment following initial episode ( high risk of relapse → possibility of social deterioration)
  • 5 years of treatment for multi-episode patients
  • Chronic, or ongoing, treatment is recommended for patients who pose a danger to themselves or others
68
Q

_______(maintenance treatment) may increase compliance in schizophrenia.

A

Long-acting depot injectables

(helpful for ppl who forget or have opposition from their family)

69
Q

Use of Antipsychotics in Bipolar Disorder

A
  • Bipolar mania, mixed or depression episodes
  • Maintenance treatment
70
Q

Second generation agents are better tolerated in ______ (2) bipolar episodes.

A
  1. mania
  2. mixed

(first gen also may be effective)

71
Q

Most efficacious antipsychotics for bipolar depression: (2)

A

Olanzapine and quetiapine

72
Q

Maintenance with antipsychotics for bipolar patients may have risks of long-term use should be weighed against the benefits. Addition of _______ to lithium or valproate reduces risk of relapse.

A

second generation antipsychotic

73
Q

Use of Cannabidiol (CBD) in Schizophrenia: While THC has psychotomimietic effects, CBD may have ____

A

opposing properties (BUT right now there is not enough evidence against or for)

(THC can provoke psychosis)

74
Q

Use of cannabidiol (CBD) in schizophrenia is not dependent on ______receptor antagonism

A

dopamine

75
Q

Use of CBD in schizophrenia may reduce _____symptoms and improve _____performance in some patients.

A
  • positive
  • cognitive

(they must get a prep w/as little THC as possible as it has psychomimetic properties)

76
Q

_________ are high potency antipsychotics.

A

Mn: “HAL TRIed to FLy high” : HALoperidol, TRIfluoperazine, and FLuphenazine

77
Q

________ are low potency antipsychotics.

A

Mn: “CHarlatans and THIeves are lowlifes” : CHlorpromazine and THIoridazine

(high and low potency antipsychotics are first-gen)

Behavioral Medicine (35 decks)

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