Psychopharmacology (MRCP) Flashcards
Aripiprazole is
A. A partial agonist at the dopamine receptor
B. A full agonist at the dopamine receptor
C. A dopamine receptor antagonist
D. An inverse agonist
E. A reuptake inhibitor at the dopamine receptor
A. When a neurotransmitter has a stimulating effect on receptors, this leads to agonistic
actions. Drugs which stimulate receptors similar to these neurotransmitters are therefore called
agonists. Drugs which block the action of the neurotransmitter on the receptors are antagonists.
They act only in the presence of the neurotransmitter and do not have any intrinsic activity on
their own. Inverse agonists have the opposite action of an agonist. For example, instead of
opening an agonist operated channel, they close the channel after binding to the receptor. Inverse
agonists thus have intrinsic activity (can act even in the absence of neurotransmitter molecules in
the vicinity) and so can also be blocked by the antagonist. Partial agonists act as net agonists in
the absence of the neurotransmitter, but act as a net antagonist in the presence of the
neurotransmitter. Aripiprazole is a partial agonist at the dopamine (D2) receptor
Lofexidine is an A. Alpha 2 autoreceptor agonist B. Alpha 1 postsynaptic agonist C. Alpha 2 autoreceptor antagonist D. Alpha 2 heteroceptor agonist E. Noradrenaline reuptake inhibitor
A. Lofexidine is an alpha 2 agonist which acts at the autoreceptor. When the presynaptic
autoreceptors are stimulated, they generally stop the release of the particular neurotransmitter.
Thus they act as a brake. Lofexidine stimulates the alpha 2 autoreceptors, thus stopping the
release of noradrenaline into the synapse. The antagonists of autoreceptors increase the release
of the neurotransmitter. In the case of serotonin, 5HT1B are autoreceptors. Some alpha 2
receptors are found on serotonergic neurones and control the release of 5HT; these alpha 2
receptors are called heteroreceptors.
Which of the following is NOT a reuptake inhibitor? A. Cocaine B. Sertraline C. Clomipramine D. Bupropion E. Buspirone
E. Buspirone is a partial agonist at 5-HT1A autoreceptors and can infl uence the fi ring of
serotonergic (5-HT) neurones. Neurotransmitters in the synaptic cleft are actively transported
back into the presynaptic neurone by a reuptake pump. Most antidepressants block this pump,
thus increasing the availability of the monoamine neurotransmitters. Cocaine is a dopamine
reuptake inhibitor. Bupropion inhibits reuptake of both dopamine and noradrenaline.
Which of the following combinations is NOT paired correctly? A. Alprazolam: benzodiazepines B. Zopiclone: hypnotics C. Haloperidol: butyrophenones D. Phenytoin: anticonvulsant E. Acamprosate: opiates
E. Phenytoin is an anticonvulsant. Alprazolam is a benzodiazepine and it is not used as a
mood stabilizer; valproate, lithium, lamotrigine, and carbamazepine can be considered as mood
stabilizers. Haloperidol is a butyrophenone and not a phenothiazine. Acamprosate is used to treat
alcohol dependence. It is not an opiate. It has a structure similar to GABA and it is thought to act
via glutamate receptor mechanism. Zopiclone is not a benzodiazepine. It is a hypnotic classed
with other ‘Z drugs’; Z drugs are non-benzodiazepines which act on the GABA complex but at a
slightly different site than benzodiazepines
Paralytic ileus is most likely to be associated with which one of the following antipsychotics? A. Olanzapine B. Haloperidol C. Clozapine D. Amisulpride E. Thioridazine
C. Clozapine causes anticholinergic effects by blocking muscarinic (M3) receptors. This can
cause side-effects such as dry mouth, constipation, loss of accommodation, and urinary retention.
Constipation is a side-effect in around 15% of patients taking clozapine, and, in most, simple
advice about diet and fl uid intake is suffi cient. More signifi cant ileus is an uncommon but
potentially more serious side-effect. It may particularly be associated with bowel surgery. It could
potentially be fatal. Though isolated reports of similar problems with olanzapine and risperidone
have been recorded, these are not well-established associations.
Which route is most liable for fi rst-pass metabolism? A. Sublingual B. Intramuscular C. Subcutaneous D. Oral E. Inhalational
D. Orally administered drugs reach the liver via the portal circulation. If hepatic metabolism
is extensive, a large amount of drug will be removed during this fi rst passage through the liver.
Thus, even if a drug is extensively absorbed, fi rst-pass removal will reduce its systemic availability.
So, drugs administered parenterally may need lower dosage compared to the same compound
taken orally. Apart from the liver, fi rst pass metabolism also takes place in gut mucosa, muscle
tissue, and lung parenchyma, albeit to a smaller extent.
Which of the following statements regarding treatment adherence is FALSE?
A. Non-adherence occurs in up to 10% of people with schizophrenia.
B. Non-adherence increases relapse rate in schizophrenia.
C. Non-adherence is associated with poor insight.
D. Adherence is affected by the route of administration.
E. Adverse effect is a major factor contributing to non-adherence.
A. Non-adherence occurs in up to 40–60% of patients with schizophrenia at any time.
Adherence is a multidimensional and dynamic concept and it is not useful to consider adherence vs
non-adherence as the only categories in the spectrum. Non-adherence is not exclusive to
psychosis; it has also been recorded in other psychiatric disorders including depression. In fact,
adherence is a problem even in non-psychiatric but long-term illnesses such as diabetes and
hypertension. Side-effects are major factors in causing non-adherence. Depot preparations have
better adherence rates, largely due to direct supervision and non-reversibility.
If a young male is administered 400 mg of lithium once daily, the average
time taken for lithium to reach a steady state in plasma is
A. 1 day
B. 2 days
C. 10 days
D. 4 days
E. 8 days
D. The time taken for a drug to reach the steady state is the function of its half-life. If the
drug is given regularly within its half-life, it will reach a steady state in the plasma in about four to
fi ve half-lives. In this case, Lithium has a half-life of nearly 24 hours. So if we give lithium once
daily for 4 days, it would have reached a steady state, and a blood taken on the 4th or 5th
morning 12 hours after the last dose will give the trough lithium level, which will be an estimate
of the plasma level of lithium
A 45-year-old man with schizoaffective disorder is on lithium, sertraline,
lorazepam, and olanzapine. He develops low sodium levels and complains of
extreme lethargy. The most likely offending agent is
A. Sertraline
B. Lithium
C. Olanzapine
D. Benzodiazepines
E. None of the above
A. Hyponatraemia has a well-known association with the use of antidepressants, especially
SSRIs. Elderly people and those medically frail are worst affected. Hyponatraemia can also
confuse the picture of depression by inducing lethargy and fatigue. The propensity to cause
hyponatraemia seems to be a class effect of antidepressants – so replacing an SSRI with another
SSRI will not eliminate the risk completely. Carbamazepine is also associated with SIADH and
hyponatraemia. Lithium causes nephrogenic diabetes insipidus and sodium levels are either
normal or marginally high as a result. Antipsychotics are also reported to be associated with
hyponatraemia, although SSRIs are more likely to be associated with this phenomenon.
Which of the following predisposes to a nocebo effect?
A. The expectation of adverse effects at the start of a treatment
B. Aversive conditioning
C. Premorbid neuroticism
D. Coexistent emotional disturbances
E. All of the above
E. Placebos can also have adverse effects. Some patients will not tolerate placebos despite the
fact that they are inert, and suffer from adverse effects (called the nocebo phenomenon). Nocebo
effects with medication include all complaints mistakenly attributed to the medication, such as
symptoms of the illness itself, symptoms of stress and the emotional response thereto, symptoms
that refl ect the patient’s normal physiology, and symptoms that refl ect normal variations in health.
Predisposing factors for a nocebo response include expectations of adverse effects at the onset of
treatment, conditioning, wherein the patient learns from prior experiences to associate medication
taking with certain somatic symptoms, predisposition due to gender (women complain more),
neuroticism, hypochondriasis, a tendency to somatize, coexistent emotional disturbances, and
situational and contextual factors that alter expectations or result in aversive conditioning.
Flumazenil can reverse the effects of an overdose of which of the following drugs? A. Opioids B. Ecstasy (MDMA) C. Nitrazepam D. Valproate E. Clozapine
C. Flumazenil is an antagonist of benzodiazepine receptors at the GABAA complex. It is used
to reverse sedative effects of benzodiazepines used in anaesthesia and in management of
benzodiazepine overdose. As a result of this effect, it can precipitate benzodiazepine withdrawal
seizures and can also precipitate anxiety in patients with anxiety/ panic disorder. It is not used to
treat benzodiazepine withdrawal symptoms. It is not useful for any other drug toxicity or abuse
as mentioned in the question. Naloxone is used in opioid overdose
Regarding depot preparations, which of the following statements is FALSE?
A. Depot medications are useful in cases of non-compliance
B. They undergo less fi rst-pass metabolism than oral preparations
C. There is less reversibility of side-effects
D. Injection site reactions are a side-effect
E. All antipsychotic depot preparations are oil based
E. Depot antipsychotic drugs have the following advantages: they decrease the risk of
problems associated with medication non-compliance and undergo signifi cantly less fi rst-pass
metabolism. The disadvantages include the fact that, once injected, the drug cannot be removed
and hence adverse effects or adverse drug interactions are less reversible. An associated
complication is injection site reaction. Depot risperidone is an aqueous suspension of risperidone
in a glycolic acid–lactate copolymer matrix. The copolymer is slowly hydrolysed, resulting in the
gradual release of risperidone. As depot risperidone is water based, it causes fewer reactions
than the other oil-based preparations
Which one of the following is NOT a CYP3A4 inducer? A. St. John’s wort B. Rifampicin C. Barbiturates D. Carbamazepine E. Fluoxetine
E. Fluoxetine is an inhibitor of CYP450 enzymes. CYP1A2 is inhibited by fl uvoxamine and
duloxetine, and induced by phenytoin. CYP2D6 is inhibited by fl uoxetine, paroxetine, sertraline,
and duloxetine. CYP3A4 is inhibited by fl uoxetine, nefazodone, and sertraline and is induced by
carbamazepine, phenobarbital, and phenytoin. CYP2C9/10/19 is inhibited by fl uvoxamine,
fl uoxetine, moclobemide, sertraline, and minimally by venlafaxine. St John’s wort induces CYP3A4.
CYP3A4 metabolizes carbamazepine, oral contraceptives, atypical antipsychotics, Z hypnotics,
benzodiazepines, and calcium channel blockers.
Which of the following statements about fi rst-order kinetics is false?
A. A fraction of the drug is eliminated per unit time
B. Half-life of a drug is directly proportional to the volume of distribution of the drug
C. Digoxin has a high volume of distribution
D. Half-life of a drug is directly proportional to the clearance
E. None of the above
D. In fi rst order kinetics, a constant fraction of the drug in the body is eliminated per unit
time. The rate of elimination is proportional to the amount of drug in the body. The majority of
psychiatric drugs are eliminated in this way. Volume of distribution is the amount of drug in the
body divided by the concentration in the blood. So a drug that is highly lipid soluble and
redistributes into fat has a high volume of distribution (Vd). These drugs stay out of the blood
most of the time and, as a result, will have a long half-life. The lesser the clearance of the drug, the
longer the half-life; so half-life is inversely proportional to the clearance. Digoxin is highly lipid
soluble and has a long half-life.
Which of the following is a butyrophenone? A. Risperidone B. Quetiapine C. Haloperidol D. Chlorpromazine E. Clozapine
C. Risperidone is a benzisoxazole; quetiapine is a dibenzothiazepine; clozapine and is a
dibenzodiazepines; olanzapine is a thienobenzodiazepine; sulpiride and amisulpiride are
substituted benzamides; chlorpromazine is a phenothazine; and haloperidol is a butyrophenone
Which of the following medications is NOT associated with zero-order kinetics? A. Phenytoin B. Salicylates C. Theophylline D. Alcohol E. Haloperidol
E. Zero-order kinetics occurs when the body metabolizes a constant amount of the drug.
The metabolic pathway is rapidly saturated, leading to a limit being set for drug elimination. So
only a constant amount of drug is eliminated irrespective of plasma levels, for example our body
can metabolize around 1 unit of alcohol per hour; if you have taken 4 units, it will take 4 hours
for the alcohol to get out of your system. So the time taken is directly proportional to the
amount consumed, unlike in fi rst-order kinetics where it takes four to fi ve half-lives for the drug
to get out of the system, irrespective of the dose consumed. The most important difference to
remember is that a constant fraction (percentage) is eliminated in fi rst-order kinetics while a
constant amount is eliminated in zero-order kinetics.
In which of the following situations is a measurement of plasma
concentration of a drug the least valuable?
A. The drug has a wide therapeutic index
B. The drug has a therapeutic window
C. Unexplained toxicity at therapeutic dose
D. Failure to respond to treatment
E. Suspected interaction with a co-administered drug
A. Measurement of plasma level is not routinely done for most of the available psychotropic
medications. But it is useful, and often indicated, when there is a therapeutic window, suspected
drug interactions, unusual toxic reaction at therapeutic doses, and non-response to treatment in
spite of administering adequate dose. Therapeutic window is a range of plasma concentration
within which a drug produces the therapeutic response. If the level of drug is outside the defi ned
‘window’, the therapeutic response is inadequate. Therapeutic index is a ratio of median toxic
dose to median effective dose of a drug. Failure to respond to treatment may be due to noncompliance,
which can be detected in some cases by measuring the plasma levels
The most probable diagnosis in a clozapine-treated patient who has
persistent tachycardia, fatigue, fever, and eosinophilia is:
A. Pulmonary embolism
B. Paralytic ileus
C. Agranulocytosis
D. Myocarditis
E. Atypical NMS
D. Myocarditis is a fatal complication of clozapine use. It can occur very subtly with
observable signs developing well after cardiac failure sets in. This is an idiosyncratic, eosinophilic
infl ammation of the myocardium. Persistent tachycardia, fever (fl u like), chest pain, palpitations,
dependent oedema, and signs of heart failure must prompt a detailed investigation, including
cardiac enzymes (elevated), ECG (ST elevation), ESR (elevated), WBC (eosinophilia), and
echocardiogram. With a good monitoring system in place for agranulocytosis, myocarditis is
becoming a leading cause of clozapine-related fatalities.
Which of the following patients is at a higher risk of developing lithium induced
hypothyroidism?
A. 21-year-old man with bipolar disorder
B. 33-year-old man with schizoaffective disorder
C. 45-year-old woman with depression
D. 14-year-old boy with learning diffi culties and aggression
E. All of the above are at same risk levels
C. It is well established that the risk of hypothyroidism related to lithium use varies widely
across the population. Middle-aged women, who probably have a higher risk of having
asymptomatic antithyroid antibodies before initiation of lithium, are at the maximum risk of
clinical hypothyroidism (up to 20% prevalence). Importantly, this hypothyroidism does not
correlate with the dose of lithium prescribed
Which one of the following regarding mirtazapine is true? It is
A. A central alpha 2 autoreceptor antagonist
B. A serotonin noradrenalin reuptake inhibitor
C. A selective serotonin reuptake inhibitor
D. A tricyclic antidepressant
E. A dopamine noradrenaline reuptake inhibitor
A. Mirtazapine is called a noradrenergic and specifi c serotonergic antidepressant (NaSSA).
The therapeutic action of mirtazapine is due to central alpha 2 antagonist action, thus cutting the
brakes for the release of norepinephrine (alpha 2 inhibitory autoreceptors) and serotonin (alpha 2
heteroreceptors constantly inhibit serotonin release too). Mirtazapine also acts as an antagonist at
5HT2A, 5HT2C, and 5HT3 receptors, which may contribute to the favourable side-effect profi le
compared to SSRIs. Mianserin acts in a similar way. Mirtazapine does not block the reuptake pump.
Which one of the following regarding buspirone is true? It is:
A. A tricyclic antidepressant
B. A selective serotonin reuptake inhibitor
C. A dopamine antagonist
D. A partial 5HT agonist
E. A partial adrenaline agonist
D. Buspirone is a partial agonist at 5HT1A. It is used in generalized anxiety disorder and as an
augmenting agent to treat resistant depression. It does not have an action on the GABA receptors;
hence it is free from interaction with alcohol and benzodiazepines. It does not lead to dependence or
withdrawal symptoms with long-term use. It has a delayed onset of action similar to antidepressants.
Which of the following drugs stabilizes dopamine release through its action on dopamine receptors? A. Aripiprazole B. Quetiapine C. Haloperidol D. Olanzapine E. Chlorpromazine
A. Aripiprazole has been dubbed a dopamine system stabilizer due to its partial agonist
action. It acts as an agonist where dopamine is depleted and acts as an antagonist where there is
an excess of dopamine, making the availability of dopamine ‘just right’ for normal function
Which one of the following is NOT a cholinesterase inhibitor? A. Rivastigmine B. Donepezil C. Gallantamine D. Organophosphates E. Memantine
E. Memantine acts by partially blocking NMDA receptors, thereby preventing cell death
related to calcium-mediated excitotoxicity. Donepezil is a non-competitive, reversible acetyl
cholinesterase inhibitor (AChI). Rivastigmine is a non-competitive inhibitor for both butyryl
cholinesterase and acetyl cholinesterase. Gallantamine is a competitive, reversible inhibitor which
modulates nicotinic receptors. Tacrine is a non-competitive, non-selective, reversible inhibitor which
acts both centrally and peripherally. It is no longer used because of high hepatotoxicity.
Organophosphates are often used in pesticides and have acetyl cholinesterase-inhibiting properties.
Which of the following drugs is NOT metabolized by CYP3A4? A. Clozapine B. Quetiapine C. Ziprasidone D. Sertindole E. Risperidone
E. Among the antipsychotics, typical antipsychotics are mostly metabolized through
CYP2D6. Risperidone is metabolized by CYP2D6. Clozapine and olanzapine are primarily
metabolized through CYP1A2, and to a lesser extent, through the CYP 3A4 enzyme system.
Olanzapine is also metabolized through the CYP3A4 enzyme system. The other antipsychotics
listed in Question 24 are metabolized through the CYP3A4 system
