1.3.1 Psychopharmacology General Concepts

Question 1

Which one of the following is the first antidepressant to be introduced?
MAO inhibitors
SNRIs
SSRIs
Tetracyclics
Tricyclics

Answer 1

Iproniazid is a monoamine oxidase inhibitor. This was the first antidepressant developed in 1952. Iproniazid was being used in treating tuberculosis discovery of mood lifting properties. But hypertensive reactions precluded large scale use. Imipramine manufactured as chlorpromazine derivative came to market soon.

Question 2

Which of the following can be called as a major tranquilliser?
Chlordiazepoxide
Chlorpromazine
Propofol
Risperidone
Secobarbital

Answer 2

Chlorpromazine.
Antipsychotics came to be known as major tranquilizers, while barbiturates and benzodiazepines were called minor tranquilizers. 1950-52, Presurgical antihistamine chlorpromazine was shown to have antipsychotic effects independently by Delay and Deniker’s team, and Charpentier from France

Question 3

Zimeldine caused demyelination disorder on introduction, leading to its withdrawal. Which of the following class does it belong to?
Antipsychotics
Benzodiazepines
MAO inhibitors
SSRIs
Tricyclics

Answer 3

Zimeldine.
Carlssen synthesized purpose made SSRI Zimeldine – but withdrawn due to incidence of hypersensitivity syndrome and demyelinating disease that followed its use.

Question 4

True or false

Aripiprazole = Benzisothiazole

Answer 4

False

Aripiprazole = arylpiperidylindole (quinolone).

Question 5

True or false

Droperidol: butyrophenones

Answer 5

True.

Droperidol & haloperidol are classified as butyrophenones.

Question 6

True or false

Flupentixol: dihydroindole

Answer 6

False.

Flupentixol = Thioxanthenes

Question 7

True or false

Risperidone: dibenzoxapine

Answer 7

False.

Risperidone = Benzisoxazole derivative

Question 8

True or false

Thioridazine: diphenyl butyl piperidine

Answer 8

False.

Thioridazine = Piperidine derivatives-

Question 9

Chose a secondary amine from the below list:
Amitriptyline
Amoxapine
Clomipramine
Dothiepin
Imipramine

Answer 9

Amoxapine.
Secondary amines = desipramine, amoxapine, nortriptyline and protriptyline also duloxetine)
[more potent mg to mg basis; less sedating; more noradrenergic, less antihistaminic or anticholinergic than tertiary].

Question 10

Which of the following chemical class of drugs used as antidepressants can increase seizure risk heavily?
Aminoketone
Cyclopyrrolone
Hydrazine derivatives
SSRIs
Triazolopyridine

Answer 10

Aminoketone (Bupropion) is contraindicated in seizure disorder.

Question 11

What is an “active placebo”?

Answer 11

An ‘active placebo’ has some activity inherently, but not against the treated condition.

Question 12

What is a “nocebo”?

Answer 12

A drug administered as placebo produces prominent side-effects.

Question 13

What is the “placebo sag”?

Answer 13

Placebo sag is a term used to refer to decrease in placebo effect with repeated or chronic administration of placebo drugs.

Question 14

True/False:

A group of ‘placebo reactors’ with stereotyped personality can be identified.

Answer 14

False.

There are no homogenous placebo reactors in the population.

Question 15

True/False:

Degree of placebo response is similar irrespective of the treatment studied.

Answer 15

False.

Placebos work better for severe than mild pain, but mildly depressed patients respond well than severely depressed ones.

Question 16

True/False:

No placebo response is seen in personality disorders.

Answer 16

False

Question 17

True/False:

Opioids may have a role to play in placebo response.

Answer 17

True.
Endogenous opioids (e.g. endorphins) play a significant role in mediating placebo-induced analgesia. Dopamine reward system is being increasingly implicated in placebo effects in psychotropic. .

Question 18

True/False:

Placebo response to depression is gradual but persistent

Answer 18

False.

Placebo response to depression starts abruptly, occurs early in treatment and is less likely to persist.

Question 19

Before approval of a drug molecule, mutagenicity, carcinogenicity and organ system toxicity are studied at which phase of clinical trials?
Phase 1
Phase 2
Phase 3
Postmarketing surveillance
Preclinical animal phase

Answer 19

Preclinical Animal Studies: The pathway a drug must undergo before approval and marketing starts with animal studies where the molecule is demonstrated to have specific actions. These extensive preclinical animal studies must be carried out at least on two different animal species. Mutagenicity, carcinogenicity and organ system toxicity are studies at this phase.

Question 20

Which of the following ethnic differences in pharmacogenetics create natural alcohol deterrence?

High alcohol dehydrogenase
High aldehyde dehydrogenase
High CYP 3A4
Lack of aldehyde dehydrogenase
Low cholinesterase

Answer 20

Lack of aldehyde dehydrogenase

Nearly 40% Asians and around 60% South American Native Indians lack Aldehyde dehydrogenase enzyme in sufficient amounts to metabolise alcohol – this serves as a natural deterrent in these communities

Question 21

Ethnic differences in psychiatric drug effects are noted in which of the following pharmacological actions?

Alcohol metabolism
All of the above
Blood levels of haloperidol
Hydroxylation of tricyclics
Prolactin response to antipsychotics

Answer 21

All

Maximal haloperidol concentration in plasma after rapid tranquilisation is significantly high for Asians than Caucasians.

Nearly 40% Asians and around 60% South American Native Indians lack Aldehyde dehydrogenase enzyme in sufficient amounts to metabolise alcohol.

Caucasians appear to have lower plasma levels of tricyclic antidepressants and attain plasma peaks later when compared with Asians (of Far Eastern ancestry as well as those from the Indian subcontinent).
These differences have been attributed to a greater incidence of slow hydroxylation among Asians when compared with Caucasians.

On administration of antipsychotics, Asian subjects were reported to produce greater serum prolactin levels than Caucasian subjects.

Question 22

Who discovered the tranquilising properties of chlorpromazine?

Answer 22

Dale

Chlorpromazine was synthesized on December 11, 1951 by Paul Charpentier, in the laboratories of Rhône-Poulenc, a French pharmaceutical company, and released for clinical investigation in May 1952 as a possible potentiator of general anesthesia.

Clinical investigations with CPZ began at Saint-Anne’s hospital – at Pierre Deniker’s service in Jean Delay’s department in 1952.

Question 23

Who discovered psychotropic use of lithium?

Answer 23

Cade

Believing that mania might be caused by intoxication by normal body products, Cade’s experiments led him to focus on lithium urate. He observed that guinea pigs became very lethargic on the compound, and he subsequently conducted a clinical trial of lithium with ten manic patients.

Question 24

Placebo effect is NOT mediated via

classical conditioning
expectancy
Natural remission
Nocebo response
operant conditioning

Answer 24

Nocebo

A placebo makes patients feel better for reasons unrelated to the specific healing properties of the treatment.

A nocebo makes patients feel worse (or does other harm) in the same way.

Question 25

Which of the following psychotropic agents has the same pharmacokinetic properties in Asians and White Europeans? ``` Alprazolam Chlorpromazine Diazepam Haloperidol Lithium ```

Answer 25

Lithium is completely excreted renally; its excretion does not differ between Asians and Europeans.

Question 26

Duloxetine and milnacipran are classified as: ``` Adrenergic type 2 antagonists Monoamine oxidase inhibitors Selective serotonin reuptake inhibitors Serotonergic and noradrenergic reuptake inhibitors Tricyclic antidepressants ```

Answer 26

Serotonergic and noradrenergic reuptake inhibitors Same as Venlafaxine

Question 27

Which one among the following is a butyrophenone derivative? ``` Chlorpromazine Flupenthixol Haloperidol Thioridazine Zuclopenthixol ```

Answer 27

Haloperidol First-generation agents are usually classified into three groups: 1) phenothiazines (chlorpromazine, Thioridazine), 2) butyrophenones (e.g., haloperidol), 3) and several other minor chemicals (e.g., thiothixene, molindone, and loxapine), based on their structure.

Question 28

Which one among the following is a benzisoxazole derivative? ``` Amisulpride Clozapine Risperidone Sulpiride Ziprasidone ```

Answer 28

Risperidone = benzisoxazole derivative sulpride and amisulpride = substituted benzamides. Ziprasidone = a Benzisothiazole Clozapine = a Dibenzodiazepine.

Question 29

Which of the following is a substituted benzamide used as an antipsychotic? ``` Amisulpride Benzhedrine Olanzapine Paliperidone Risperidone ```

Answer 29

Amisulpride = substituted benzamide.

Question 30

Acamprosate is a ``` Alpha-1 agonist Long acting opiod agonist Opioid receptor antagonist Synthetic taurine analogue Type of benzodiazepine ```

Answer 30

Acamprosate = synthetic taurine analogue It appears to act centrally on glutamate and GABA neurotransmitter systems, although the mechanism has not been fully established.

Question 31

The risk factor predicting poor response to lithium prophylaxis in bipolar illness is: ``` Dominant personality High age of illness onset High number of previous hospitalizations High social status Social support ```

Answer 31

Predictors of poor response to lithium in bipolar prophylaxis include: ``` High number of prev hospitalization, stress, high expressed emotion, and high number of life events, episodic patterns of depression- mania interval, continuous cycling, and unemployment and neurotic personality. ```

Question 32

Which drug is useful for the treatment of OCD? ``` Duloxetine Phenelzine Sertraline Trazadone Venlafaxine ```

Answer 32

SSRIs remain as the first line treatments of OCD. Sertraline is SSRI drug, which is also useful for the treatment of OCD in children. (Refer - POTS study).

Question 33

The minimum effective dose of Aripiprazole in treating a psychotic episode is ``` 10mg 15mg 20mg 25mg 5mg ```

Answer 33

10mg Aripiprazole was shown to be superior to placebo at doses of 15 mg/day, 20 mg/day, and 30 mg/day in at least two clinical trials for each dose and at 10 mg/day in another trial. Two studies that evaluated the efficacy of aripiprazole at lower doses (2 and 5mg/day) in schizophrenia, failed to demonstrate the superiority of aripiprazole versus placebo. The available trial evidences indicate that Aripiprazole 10 mg/day is the minimum effective dose for the treatment of patients with schizophrenia experiencing acute relapse. Aripiprazole 5 mg/day produced improvements in some outcome measures but not in the primary efficacy measure, suggesting that it may lack efficacy for treating acute psychosis. CNS Spectr. 2006;11(9):691-702