Psychopharmacology Discussion Thread

[Admin]

Hi Friends,

I will be posting important questions from Psychopharmacology section here .

Everyone is encouraged to participate by either posting questions/answering questions/posting doubts related to Psychopharmacology.


*****Discussion is the Most Effective Way of Learning *****


Regards
Admin

[Admin]

Clinical Vignettes: Drug Interactions with Antipsychotic Agents.

1. Patient on Quetiapine diagnosed with AIDS, started on Protease Inhibitor (HAART).
(a) What is the consequence of this interaction?
(b) What is the underlying mechanism responsible for this consequence?
(c) What will you do next?

2. Patient on Clozapine, Fluvoxamine added.
(a) What is the consequence of this interaction?
(b) What is the underlying mechanism responsible for this consequence?
(c) What will you do next?

3. Patient on Ziprasidone, started on Erythromycin
(a) What is the consequence of this interaction?
(b) What will you do next?
(c) What is the underlying mechanism responsible for this consequence?

4. Patient on Olanazapine starts smoking heavily
(a) What is the consequence of this interaction?
(b) What is the underlying mechanism responsible for this consequence?
(c) What will you do next?

5. Patient on Quetiapine, Carbamazepine added.
(a) What is the consequence of this interaction?
(b) What is the underlying mechanism responsible for this consequence?
(c) What will you do next?

[Admin]

6. Which of the following is NOT the treatment of choice for Typical antipsychotics induced severe hypotension:

(a) Metaraminol
(b) Norepinephrine
(c) Epinephrine
(d) All of the above
(e) None of the above

[Admin]

7. Which of the following statement is FALSE:

(a) Long term Thorazine use can cause reversible blue gray discoloration of skin areas exposed to sunlight
(b) Thorazine can cause benign pigmentation of eye
(c) Irreversible retinal pigmentation is associated with Thioridazine >1000mg/day
(d) Do not use emetics in suspected case of typical antipsychotic overdose
(e) Molindone is the most epileptogenic of all all typical antipsychotics
(f) All are correct
(g) All are wrong

[Admin]

8. Which of the following is FALSE regarding Antipsychotics:

(a) Cigarette smoking can reduce the plasma concentration of antipsychotic agents
(b) ACE inhibitors added to antipsychotics can result in postural intolerance
(c) Caffeinated beverages can possibly diminish the antipsychotic effects by forming a precipitate
(d) Disulfiram can decrease the antipsychotic concentration
(e) Antipsychotics can decrease the warfarin levels

[Admin]

9. Which of the following is FALSE regarding "Transition of Antipsychotics":

(a) Transition from Clozapine to Olanzapine is safe in terms of cholinergc rebound.
(b) Transition from Olanzapine to Risperidone is safe in terms of cholinergc rebound.
(c) Transition from Clozapine to Ziprasidone is not safe in terms of cholinergc rebound
(d) All are correct
(e) All are wrong

[Admin]

10. Which of the following Atypical Antipsychotic have LEAST RISK for EPS (Extra Pyramidal Symptoms)

(a) Olanzapine
(b) Risperidone
(c) Clozapine
(d) Quetiapine
(e) Aripiprazole

[Admin]

11. Based on ADA/APA recommendations, which of the following parameter is MOST FREQUENTLY monitored in patients on Atypical Antipsychotics.

(a) Personal/Family History
(b) Weight (BMI)
(c) Waist Circumference
(d) Blood Pressure
(e) Fasting Plasma Glucose
(f) Fasting Lipid Profile

[Admin]

12. Which of the following medication is least likely to cause Tardive Dyskinesia?

(a) Risperidone
(b) Ziprasidone
(c) Paliperidone
(d) Clozapine
(e) Quetiapine

[Admin]

13. Which of the following statement is FALSE regarding Sedative-Hypnotics?

(a) Zolpidem absorption can be delayed by 1 hr if taken immediately after heavy meal
(b) Doses above 2 mg of Flumazenil do not reliably produce additional effect in the treatment of benzodiazepine overdose
(c) Benzodiazepines can cause paradoxical increase in aggression in pt with preexisting brain damage
(d) Co-administration of Zolpidem and SSRIs can extend the duration of hallucinations in susceptible patients.
(e) Use of Tegretol (Carbamazepine) during benzodiazepine withdrawal permit better tolerated withdrawal than does gradual taper alone

[Admin]

14. Choose the correct Pregnancy Category Sequence of Following Medications:

(a) Zolpidem (Category B); Zaleplon (Category B); Ramelteon (Category B); Benzodiazepines (Category D)
(a) Zolpidem (Category A); Zaleplon (Category B); Ramelteon (Category C); Benzodiazepines (Category B)
(a) Zolpidem (Category B); Zaleplon (Category C); Ramelteon (Category C); Benzodiazepines (Category D)
(a) Zolpidem (Category B); Zaleplon (Category A); Ramelteon (Category B); Benzodiazepines (Category B)

[Admin]

Q15. Choose the correct statement regarding Sedatives-Anxiolytics-Hypnotics

(a) In PTSD pt with prominent insomnia and no comorbid depression: try trazadone first as hypnotic
(b) During the treatment of Social Anxiety: No need to start low and go slow
(c) Ramelteon can increase prolactin level in women by >30%
(d) All are correct
(e) All are wrong

[Admin]

Q16. Which of the following SSRI is least likely to complicate treatment due to drug interactions?

(a) Fluoxetine
(b) Fluvoxamine
(c) Paroxetine
(d) Citalopram

[Admin]

Q.17: Match the following drug interactions with responsible CYP450 enzyme:

(1) Fluvoxamine + Theophylline =Raises Theophyline
(2) Fluvoxamine + Cisapride = Raised QT Interval
(3) Nefazodone + Alprazolam = Raises Alprazolam
(4) TCAs + SSRIs =Raises TCAs
(5) Fluozetine + Triazolam = Raises Triazolam
(6) Carbamazepine Autoinduction
(7) Imipramine + Smoking= Decreases Imipramine level

(a) CYP450 1A2
(b) CYP450 2D6
(c) CYP450 3A4

[Admin]

Q18. Which of the following Statement is FALSE regarding Fluoxetine?

(a) Fluoxetine use during pregnancy is not associated with decrease in global IQ in children
(b) Only Fluoxetine is FDA approved for use as an antidepressant in children
(c) Most common adverse effect associated with long term use is sexual dysfunction
(d) Pt on Fluoxetine gain weight initially followed by weight loss.
(e) Fluoxetine can change the duration of menstrual period by more than 4 days

[Admin]

Q19. Which Antidepressant is MOST LIKELY to cause:

(1) Agranulocytosis= _ _ _ _ _ _ _ _ _ _

(2) Seizure= _ _ _ _ _ _ _ _ _ _

(3) High Cholesterol= _ _ _ _ _ _ _ _ _ _

(4) Hypertension= _ _ _ _ _ _ _ _ _ _

[Admin]

Answer Q19:

[P450]

Answers for q's 1-5:

1. Patient on Quetiapine diagnosed with AIDS, started on Protease Inhibitor (HAART).
(a) What is the consequence of this interaction?
(b) What is the underlying mechanism responsible for this consequence?
(c) What will you do next?

PI's are generally potent 3A4 inhibitors. Quetiapine is a major substrate of 3A4 and would therefor have an increase in serum concentration when these two medications are combined, likely leading to increase in adverse events. I would switch quetiapine to another medication that either is not metabolized by 3A4 or has multiple metabolic pathways (metabolized by more than one cyp enzyme) given that PI's are an integral component to anti-retroviral therapy (as far as I know).

2. Patient on Clozapine, Fluvoxamine added.
(a) What is the consequence of this interaction?
(b) What is the underlying mechanism responsible for this consequence?
(c) What will you do next?

Clozapine is mainly metabolized by 1A2, although minor metabolic pathways include 2D6 and 3A4. Fluvoxamine is a potent inhibitor of 1A2 and also of 3A4, leading to increase in serum clozapine concentration. The consequence of this interaction is, of course, increase in adverse reactions, although fluvoamine has been used to give lower doses of clozapine while still achieving therapeutic serum levels of clozapine. In this case, I would check the serum level of clozapine, and if within the therapeutic range, I would let it ride, unless of course I was suspecting an adverse reaction. In which case, I would still order a serum concentration and then discontinue vs decrease dose of fluvoxamine.

3. Patient on Ziprasidone, started on Erythromycin
(a) What is the consequence of this interaction?
(b) What will you do next?
(c) What is the underlying mechanism responsible for this consequence?

Ziprasidone is metabolized by 3A4 and also cytosol aldehyde oxidase. Erythromycin is a potent inhibitor of 3A4 and therefor has the potential to increase serum ziprasidone's concentration. The consequence of this interaction is again an adverse reaction. I would change erythromycin to another antibiotic which does not inhibit 3A4. Of note, amongst the macrolides, clarithromycin is also a 3A4 inhibitor.

4. Patient on Olanazapine starts smoking heavily
(a) What is the consequence of this interaction?
(b) What is the underlying mechanism responsible for this consequence?
(c) What will you do next?

This is an excellent question! Olanzapine is, like clozapine, primarily metabolized by 1A2. Smoking, or more specifically, inhalation of poly-aromatic hydrocarbons (also produced by smoking cannabis), induces 1A2. The result may be the decrease in serum concentration of olanzapine. I would probably increase the dose of olanzapine and may check the serum levels as well prior to doing that. Of course the other option is to treat the nicotine addiction.


5. Patient on Quetiapine, Carbamazepine added.
(a) What is the consequence of this interaction?
(b) What is the underlying mechanism responsible for this consequence?
(c) What will you do next?

Carbamazepine is generally referred to as a 'pan-inducer' meaning it induces all cyp enzymes (with the possible exception of 2D6). It has been found to have a potent effect on 3A4 induction and would there decrease quetiapine serum concentration as this is 3A4 metabolized. The two possible options are to change to a medication which has a different metabolic pathway (preferred IMO) vs increasing dose of quetiapine.

[Admin]

Answers for q's 1-5:

1. Patient on Quetiapine diagnosed with AIDS, started on Protease Inhibitor (HAART).
(a) What is the consequence of this interaction?
(b) What is the underlying mechanism responsible for this consequence?
(c) What will you do next?

PI's are generally potent 3A4 inhibitors. Quetiapine is a major substrate of 3A4 and would therefor have an increase in serum concentration when these two medications are combined, likely leading to increase in adverse events. I would switch quetiapine to another medication that either is not metabolized by 3A4 or has multiple metabolic pathways (metabolized by more than one cyp enzyme) given that PI's are an integral component to anti-retroviral therapy (as far as I know).

2. Patient on Clozapine, Fluvoxamine added.
(a) What is the consequence of this interaction?
(b) What is the underlying mechanism responsible for this consequence?
(c) What will you do next?

Clozapine is mainly metabolized by 1A2, although minor metabolic pathways include 2D6 and 3A4. Fluvoxamine is a potent inhibitor of 1A2 and also of 3A4, leading to increase in serum clozapine concentration. The consequence of this interaction is, of course, increase in adverse reactions, although fluvoamine has been used to give lower doses of clozapine while still achieving therapeutic serum levels of clozapine. In this case, I would check the serum level of clozapine, and if within the therapeutic range, I would let it ride, unless of course I was suspecting an adverse reaction. In which case, I would still order a serum concentration and then discontinue vs decrease dose of fluvoxamine.

3. Patient on Ziprasidone, started on Erythromycin
(a) What is the consequence of this interaction?
(b) What will you do next?
(c) What is the underlying mechanism responsible for this consequence?

Ziprasidone is metabolized by 3A4 and also cytosol aldehyde oxidase. Erythromycin is a potent inhibitor of 3A4 and therefor has the potential to increase serum ziprasidone's concentration. The consequence of this interaction is again an adverse reaction. I would change erythromycin to another antibiotic which does not inhibit 3A4. Of note, amongst the macrolides, clarithromycin is also a 3A4 inhibitor.

4. Patient on Olanazapine starts smoking heavily
(a) What is the consequence of this interaction?
(b) What is the underlying mechanism responsible for this consequence?
(c) What will you do next?

This is an excellent question! Olanzapine is, like clozapine, primarily metabolized by 1A2. Smoking, or more specifically, inhalation of poly-aromatic hydrocarbons (also produced by smoking cannabis), induces 1A2. The result may be the decrease in serum concentration of olanzapine. I would probably increase the dose of olanzapine and may check the serum levels as well prior to doing that. Of course the other option is to treat the nicotine addiction.


5. Patient on Quetiapine, Carbamazepine added.
(a) What is the consequence of this interaction?
(b) What is the underlying mechanism responsible for this consequence?
(c) What will you do next?

Carbamazepine is generally referred to as a 'pan-inducer' meaning it induces all cyp enzymes (with the possible exception of 2D6). It has been found to have a potent effect on 3A4 induction and would there decrease quetiapine serum concentration as this is 3A4 metabolized. The two possible options are to change to a medication which has a different metabolic pathway (preferred IMO) vs increasing dose of quetiapine.

Excellent answers with accurate explanation.

[Admin]

Summary:

Clozapine + Fluvoxamine ---> Fluvoxamine is inhibitor of CYP450 1A2 (which metabolizes Clozapine) ---> raises Clozapine level -----> increased risk of seizure ---> reduce Clozapine dosage or choose other antidepressant

Patient on Olanazapine starts smoking heavily ---> Smoking induces CYP 450 1A2 --> Olanazapine level goes down --> patient relapses ---> instruct patient to stop smoking or use higher dose of Olanazapine in smokers

Patient on Quetiapine diagnosed with AIDS, started on Protease Inhibitor (HAART) ---> Protease inhibitors are inhibitors of CYP450 3A4 (which metabolizes Quetiapine) ----> reduce the dosage of Quetiapine

Patient on Ziprasidone, started on Erythromycin ---> Erythromycin is inhibitors of CYP450 3A4 (which metabolizes Ziprasidone) ----> reduce the dosage of Ziprasidone

Patient on Quetiapine, Carbamazepine added---> Carbamazepine is inducer of CYP450 3A4 (which metabolizes Quetiapine) ---->patient relapses ---> increase the dosage of Quetiapine

[Admin]

Q 1-5 & Q19 are answered.

14 more questions left.

Everyone is encouraged to participate.


Regards
Admin

[adisuper]

6. Which of the following is NOT the treatment of choice for Typical antipsychotics induced severe hypotension:

(a) Metaraminol
(b) Norepinephrine
(c) Epinephrine
(d) All of the above
(e) None of the above

c) epinephrine is CI in typical antipsychotic induced hypotension as it will cause unopposed stimulation of beta receptors thus worsening the hypotension

[adisuper]

7. Which of the following statement is FALSE:

(a) Long term Thorazine use can cause reversible blue gray discoloration of skin areas exposed to sunlight
(b) Thorazine can cause benign pigmentation of eye
(c) Irreversible retinal pigmentation is associated with Thioridazine >1000mg/day
(d) Do not use emetics in suspected case of typical antipsychotic overdose
(e) Molindone is the most epileptogenic of all all typical antipsychotics
(f) All are correct
(g) All are wrong

e) low potency antipsychotics such as chlorpromazine are most epileptogenic....molindone is a mid-potency typical anti-psychotic hence above statement should be false

[adisuper]

8. Which of the following is FALSE regarding Antipsychotics:

(a) Cigarette smoking can reduce the plasma concentration of antipsychotic agents
(b) ACE inhibitors added to antipsychotics can result in postural intolerance
(c) Caffeinated beverages can possibly diminish the antipsychotic effects by forming a precipitate
(d) Disulfiram can decrease the antipsychotic concentration
(e) Antipsychotics can decrease the warfarin levels


e) as phenothiazines enhances the action of oral anticoagulants but chlorpromazine decreases their effect hence i m not sure

[Admin]

6. Which of the following is NOT the treatment of choice for Typical antipsychotics induced severe hypotension:

(a) Metaraminol
(b) Norepinephrine
(c) Epinephrine
(d) All of the above
(e) None of the above

c) epinephrine is CI in typical antipsychotic induced hypotension as it will cause unopposed stimulation of beta receptors thus worsening the hypotension

You are right Adisuper.
Ans: (C) Epinephrine

Do not use epinephrine. Reason: because hypotension is produced by alpha adrenergic blockage property of DRAs, & these drugs also block the alpha adrenergic stimulating property of epinephrine, leaving beta adrenergic stimulating property untouched. As a result epinephrine will cause paradoxical worsening of hypotension and hence epinephrine is contraindicated in antipsychotic induced hypotension.

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