Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Therapeutics > Exam 4 lecture 2 > Flashcards

Exam 4 lecture 2 Flashcards

1
Q

What is the concentration at which drug occupies 50% of receptors? What is 1 order above that limit? One order below?

A

1 order above- Kd=90%
1 order below- Kd=10%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What percent occupancy do we need dopamine receptors for antipsychotic efficacy?

A

60-70%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How can we measure dopamine receptor occupancy and serotonin receptor occupancy?

A

PET

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Receptor occupancy and antipsychotic effect of risperidone?

A

Risperidone has doses either 3 or 6 mg/day. in 3 mg, 3 of 4 pts free of EPS and 3 of 4 pts have good receptor occupancy, for 6 mg/day, all patients are abpve threshold but 3 of 4 will have EPS.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the drug induced movement disorders

A

Extrapyramidal symptoms (30-50%)
Tardive dyskinesia
Neuroleptic malignant syndrome (NMS)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What percent of people have EPS? What are the symptoms? When does it occur?

A

Occurs in 30-50% of people
occurs early, days/weeks, reversible

symptoms-
Dystonia- increased muscle tone
Pseudoparkinsonism- muscle rigidity
Tremor
Akathisia- restelssness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Drug therapy to treat EPS?

A

-Benztropine (Cogentin), trihexyphenidyl (Artane), or akineton (Biperiden) –anticholinergic agents

– Diphenhydramine (Benadryl) – Antihistamine

– Amantadine (Symmetrel) – Dopamine releasing agent

– Propranolol – used for akathisia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Rationale for using anticholinergics to treat EPS

A

Neuron gets excitatory input from Ach. Gets inhibitory signaling from dopamine.
If we block receptors using D2 antagonists all dopamine signaling is gone and we have a relative excess in Ach signaling. Use anticholinergic.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What percent of people will have Tardive dyskinesia? When does it occur? Reversible? Symptoms? Monitoring? MOA?

A

20-40%, occurs late, months to a year. They are irreversible.

symptoms- mouth- Rhythmic involuntary movements
Choreiform- irregular purposslessness
Athetoid- worm like
Axial hyperkinesias- To and Fro movemnts

Monitoring- AIMS (abnormal involuntary movement scale). Check every 6 months

Unknown MOA- thought to be neuroadaptive response following chronic antagonists

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Treatment of tardive dyskinesia

A

Prevention! Use the least risky agent at the
lowest dose possible and monitor
1. Reduce dose of current agent
2. Change to a different drug; possibly a newer agent
3. Eliminate anticholinergic drugs
4. VMAT inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the newer drug therapies for TD

A

VMAT2 inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are some VMAT inhibitors for tardive dyskinesia and huntingtons (which do they treat)

A

Tetrabenzine (xenazine)- huntingtons chorea
valbenzine (ingrezza)- TD
Deutetrabenazine- both

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

VMAT2 MOA? Use?

A

Vesicular monoamine transporter 2
Prevents dopamine from being packaged in synaptic vesicles (If dopamine is not going into vesicles, it is being metabolized, so they deplete dopamine)

Used as add on treatment to treat tardive dyskinesia associated with antischizophrenia medication.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is NMS? symptoms? treatment?

A

EPS symptoms with fever.
impaired cognition- agitation, delirium, coma
muscle rigidity

treatment
restore dopamine balance - discontinue drug
- DA agonist, diazepam or dantrolene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the therapeutic uses of antipsychotic drugs

A

Treatment of psychosis
Anxiety treatment (Overkill)
mood disorders (mania and depression)
Tourettes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How long does it take to treat psychosis with antipsychotics?
How do antipsychotics treat mood disorders?
How to treat tourettes with antipsychotics

A

Treatment of psychosis- 2-3 weeks for effectiveness, 6 weeks to 6 months for maximal effectiveness

Mood disorders
mania- secondary to lithium, used in combination
depression- accompanied by agitation and delusions

Tourettes
treat with pimozide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are some miscellaneous uses of antipsychotics? What drugs do we use?

A

huntingtons chorea
-tetrabenazine, deutetrabenazine

intractable hiccups
-chlorpromazine

Alcohol withdrawals (hallucinations)
- haloperidol

Nausea and vomiting
-metoclopramide, promethazine

Potentiation of opiates and sedatives
-droperidol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are some pharmacologic effects of antipsychotics

A

Behavioral effects- Unpleasant in normal subjects or reversal of s/s of psychosis in affected individuals

Neuroleptic syndrome- Suppress emotion, initiative and interests. may resemble negative symptoms

Block conditioned avoidance response in animal studies

reduce spontaneous activity, aggressive and impulsive behavior

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Know this for exam

What are the types of adverse pharmacologic effects of antipsychotics

A
  1. Autonomic
  2. CNS
  3. Endocrine
  4. other
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Know this for exam

What are the mechanisms of autonomic adverse pharmacologic effects of antispychotics? WHat are the different manifestations of these mechanisms?

A

Autonomic has muscarinic cholinoceptor blockade MOA and alpha adrenoceptor blockade MOA

Muscarinic cholinoceptor blockade is manifested by loss of accomodation, dry mouth, difficulty urinating, constipation

alpha adrenoceptor blockade is manifested by orthostatic hypotension, impotence, failure to ejaculate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the different mechanisms of CNS advrese pharmacologic adverse effects of antipsychotics? What are the manifestations of these mechanisms

A

Dopamine receptor blockade- manifestations include parkinsosns syndrome, akathisia, dystonias

Supersensitivity of dopamine receptors- manifested by tardive dyskinesia

muscarinic blockade- manifested by toxic-confusional state

Histamine (H1) receptor blockade- sedation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the different mechanisms of endocrine adverse pharmacological effects of antipsychotics? How are they manifested?

A

Dopamine receptor blockade resulting in hyperprolactinemia. Manifested by Amenorrhea-galactorrhea, infertility, impotence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How does weight gain happen in antipsychotics

A

H1 and 5ht2C blockade

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

precautions and contraindications of antipsychotics

A

cardiovascular
parkinsosn disease
Epilepsy (clozapine will lower seizure threshold)
Diabetes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are drugs that have a high 5-HT2a/D ratio

A

Haloperidol, fluphenazine, chlorpromazine, thiothixene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What does a drug having a high 5 HT 2a/D ratio mean?

A

Drugs will tend to have a higher risk of EP symptoms
(Good at D2 blockers. but not good 5HT2a blockers)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

If a drug has high propensity to cause hypotensive effects, what receptors does it block?

A

alpha
(chlorpromazine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Which receptors are responsibe for sedation?

A

Histamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are typical 1st gen antipsychotics characterized by?

A

More movement problems, increased EPS and tardive dyskinesia due to strong D2 block

30
Q

Be able to recognize key structural features of phenothiazine antipsychotics

A

Chlorpromazine is three hexane groups. The 2 wide ones have double bonds, the middle one has S on top and N on bottom

31
Q

What are some aliphatic phenothiazines and their uses

A

Chlorpromazine- no longer 1st line
promethazine- used for H1 antagonist properties

32
Q

What are some piperidine phenothiazines and their uses

A

Thioridazine- sedation, hypotension, anticholinergic
Fluphenazil- EPS
prochlorperazine- antiemetic
perphenazine- CATIE studies compared perphenazine to newer agents in combo with anticholinergics. FOund perphenazine + anticholinergics were just as effective as newer agonists

33
Q

Name antipsychotics and their side effects

A

Thioxanthines- modest EPS
butyrophenones (haloperidol)- EPS

34
Q

What are some miscellaneous antispychotic? What are their uses?

A

Molindone- may cause moderate EPS
Pimozide is used in tourettes disease tics

35
Q

Name antipsychotic drugs and their key points

A

Chlorpromazine- 1st antipsychotic, antihistamine side effets

promethazine- ANtihistamine, antiemetic

Thioridazine- Many SE, anticholinergic, sedation, sexual dysfunction, cardiovascular

Fluphenazine- EPS

Prochlorperazine- antiemetic

Perphenazine- CATIE studies- combination with anticholinergics

Thiothixene- modest EPS

Haloperidol- EPS

Molindone- Moderate EPS

Pimozide- tourettes disease, suppress motor and vocal tics

36
Q

What are atypical (second generation) antipsychotics characterized by compared to typical antipsychotics

A

Reduced EPS
Efficacy for negative symptoms
Similar or enhanced 5HT2a receptor antagonism vs D2
More metabolic problems
linked to diabetes (greater risk in pts <50)
(in olanzapine and clozapine)
(less evidence in quetapine and risperidone)

37
Q

why do typical antipsychotics lead to movement disorders

A

They block D2 receptors (post synaptic dopamine receptors).

38
Q

MOA of atypical antispsychotics

A

D2 and 5HT 2A receptor antagonist that blocks presynaptic 5HT2A receptor. Leads to increase in synthesis and release of dopamine that competes for D2 receptors, restoring normal movement.

39
Q

What is the 1st antipsychotic? side effects? When to use?

A

Clozapine

side effects- agranulocytosis (this is why it is 2nd or 3rd line therapy, even though it is very effective)
anticholinergic, antihistamine disorders (reduce D2 potency and reduce movement disorders)

40
Q

Name the atypical antipsychotics and their key points

A

Clozapine- 1st atypical antipsychotic, agranulocytosis, risk of diabetes, superior efficacy

Olazapine- weight gain, risk of diabetes

Quetiapine- Metabolite with antidepressant activity, hypotension, sedation

Risepridone- 5HT2a/D2 receptor antagonist

Ziprasidone- 5HT2a/D2, a1 affinity, prolongs QT interval

lurasidone- 5HT2a/D2, reudced metabolic effects, rapid titration

Aripiprazole- High 5HT2a/D2 affinity, partial agonist activity

41
Q

What are some antipsychotic drugs under investigation

A

Dual M1/M4 muscarinic agonist combined with peripheral muscarinic antagonist

5HT receptor ligands (14 receptors, 5HT3)

42
Q

How do partial agonists affect dopaminergic activity

A

Partial agonists like aripiprazole bring dopaminergic activity down if we have high dopaminergic activity

Partial agonists like aripiprazole bring dopaminergic activity up if we have low dopaminergic activity

43
Q

What are D2/D3 receptor partial agonist drugs? Side effects?

A

Brexipiprazole- less akathisia vs aripiprazole

cariprazine- D2/D3 partial agonist with greater affinity for D3. Akathisia is high

Lumateperone- partial D2 agonist presynaptic receptor/antagonists

44
Q

What are some key features that define psychotic disorders? Define them?

A

Delusions- fixed and false beliefs that are not amenable to change even with conflicting evidence

Hallucinations- Perception-like-experiences that occur without an external stimulus (usually auditory, visual, tactile or olfatory)

Disorganized thinking and speech- switching from one topic to another, unrelated answers to questions

Negative symptoms

45
Q

Disease onset of schizophrenia

A

Men- late teens, early 20s
Women- late 20s, early 30s

46
Q

schizophrenia Link to substance use and effects on antipsychotics

A

Smoking is associated with induction of 1A2 (due to hydrocarbons not nicotine) which decreases the serum concentration of 1A2 substarte antipsychotics

Marijuana, cocaine and amphetamines can hasten the onset of schizophrenia, exacerbate symptoms, and reduce time to relapse

Substance use treatment can be successfully achieved along with mental health treatment in patients with schizophrenia, should be undertaken at the same time.

47
Q

Where in the brain do we get EPS symptoms?
What structure in brain causes excess dopamine hallucinations in schizophrenia? Where in brain are cognitive issues caused in schizophrenia?

A

Substantia nigra causes EPS
Mesolimbic pathway- excess dopamine causes hallucinations
Prefrontal cortex- cognitive issues

48
Q

What are things to consider when doing antipsychotic drug therapy

A

Doses per day
Side effects
previous drug therapy
Cost of drug
COncomitant drug therapy
Monitoring? (labs, weight, ECG)

49
Q

Is oral antipsychotic drug therapy 1st line or IM depot therapy?

A

Oral is 1st line unless patient presents reasons to consider IM drug therapy

50
Q

compare efficacy for typical (older) vs atypical (newer) agents

A

Efficacy for positive symptoms is similar to atypical antipsychotics

51
Q

Most commonly used typical antipsychotic? side effects? Efficacy?

A

Haloperidol. Routine or PRN

More EPS with higher potency typicals

Are very effective for treating the positive symptoms, but are likley to worsen negative and cognitive symptoms

52
Q

What antipsychotics are assiciated with akathisia more than others

A

Partial agonists (stabilize dopamine transmission)

53
Q

what boxed warnings do all partial agonists have?

A

Suicidal thoughts/behaviors

54
Q

What are partial agonist drugs? enzyme substrates and side effects?

A

Aripiprazole- 2D6 and 3A4 substrate, moderate akathisia, low weight gain

Brexipiprazole- 2D6 and 3A4 substrate, moderate akathisia, low-moderate weight gain

Cariprazine- 3A4 substrate, moderate akathisia, low moderate weight gain

55
Q

Which drugs are “the pines”?

A

Asenapine
Clozapine
Olanzapine
Quetiapine

associated with significantly less EPS/ Higher weight gain than others

56
Q

Asenapine dosage form, substrate and side effects

A

Sublingual and patch formulations
1A2 substrate
QTc prolongation

57
Q

Clozapine boxed warning, substrate, side effects

A

1A2 substrate

Boxed warning- neutropenia, orthostasis, bradycardia, syncope, seizures, myocarditis, cardiomyopathy

side effects- sedation, weight gain, constipation, hypersalivation, dry mouth, GI hypomotility

QTc prolongation

58
Q

Olanzapine Substrate, side effects, warning

A

1A2 substrate
Significant weight gain and sedation
High risk metabolic syndrome
DRESS warning

59
Q

Quetiapine substrate, side effects? Boxed warning?

A

3A4 substrate
QTc prolongation
Weight gain and sedation
Boxed warning for suicidal ideation

60
Q

How to use asenapine? warning? What to do if given with strong 1A2 inhibitor?

A

Apply 1 patch Q24hrs, rotate patch to minimize application site rxns

Warnings for QTc prolongation

Reduce dose of patch if gven with strong 1A2 inhibitor

61
Q

Monitoring clozapine

A

Monitoring timelines weekly x 6 months, then every 4 weeks

62
Q

Why is olanzapine given with samidorphan? What is samidorphan?

A

Samidorphan reduces weight gain risk

Samidorphan is an opioid antagonist with preferential activity at mu opioid receptor

63
Q

What drugs are referred to as the “dones”

A

Iloperidone
Lurasidone
Ziprasidone
Risperidone
Paliperidone

64
Q

Iloperidone substrate? Side effets?

A

2D6 substrate
Higher risk for orthostasis and syncope
QTc prolongation

65
Q

Lurasidone substrate? side effects?

A

3A4 substrate
higher risk for akathisia
warning for suicidal thoughts (adjunct for bipolar depression)
Take with food to increase bioavailability?

66
Q

Ziprasidoe substrate? warning and contraindication

A

Contraindication- QTc prolongation
DRESS earning
Take with food to increase absorption and bioavailability
3A4 substrate (1/3) and aldehyde oxidase (2/3) Less worry for p450 interactions)

67
Q

Risperidone substrate? Side effects?

A

2D6 substrate (minor 3A4)
EPS, hyperprolactinemia, weight gain, sedation, orthostasis

68
Q

Paliperidone side effects? How is it eliminated?

A

EPS, hyperprolactinemia, weight gain, sedation, orthostasis
QTc prolongation
Renally eliminated. Dose adjustment in renal impairement

69
Q

Lumateperone side effects? substrate?

A

Low risk for EPS or akathisia
Low risk for weight gain or metabolic side effects

70
Q

Pimavanserin use? MOA? Substarate?

A

Treatment of hallucinations or delusions in patient with parkinsons disease

MOA- inverse agonist and antagonist at serotonin (5HT)2A

3A4 substrate

Therapeutics (38 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions