Pharmacokinetics

Question 1

Which of the following drugs has its plasma levels reduced even after regular administration of the same dose for a month?

Select one:
1. Lithium
2. Clozapine
3. Chlormethiazole
4. Valproate
5. Carbamazepine

Answer 1

Carbamazepine

Carbamazepine exhibits autoinduction: it induces the expression of the hepatic microsomal enzyme system CYP3A4, which metabolizes carbamazepine itself.

Question 2

Which of the following is best choice to treat alcohol withdrawal in a man with severe liver damage?

Select one:
1. Naltrexone
2. Carbamazepine
3. Chlordiazepoxide
4. Lorazepam
5. Diazepam

Answer 2

Lorazepam

Irrespective of the indications, the choice of the benzodiazepine should be contingent upon the circumstances: e.g. shorter-acting benzodiazepines such as lorazepam and oxazepam may be more appropriate in the presence of liver damage.

Question 3

Which one among the following statements is least likely to be correct with respect to the tissue distribution of drugs?

Select one:
1. Drugs with high affinity for tissues such as fat have high volume of distribution
2. The drug distribution in plasma to various tissues depends on plasma protein binding
3. The drug distribution in plasma to various tissues depends on tissue permeability
4. Distribution is uniform across the body tissues
5. Tissue distribution leads to a fall in plasma concentration

Answer 3

Distribution is uniform across the body tissues

Drugs are not evenly distributed in the body. There are three main compartments through which a drug may be distributed. (1) The vascular compartment (2) The extra cellular compartment (3) The intracellular
compartment. Drugs that are large molecules and those which bind tightly to plasma proteins remain in the
vascular compartment; drugs with low lipid solubility are distributed in the vascular plus the extracellular
compartment whilst lipid soluble drugs are distributed through the three compartments. Drugs such as
Phenytoin, diazepam, chlorpromazine and amitriptyline are all highly bound to plasma proteins. They are
very lipophilic and once absorbed pass readily into peripheral fat stores; from which they are gradually
released long after the last dose has been administered.

Question 4

Steady-state plasma concentration is usually achieved after

Select one:
1. 1-2 half-lives
2. 2-3 half-lives
3. 10-20 half lives
4. 4-5 half-lives
5. 9-10 half-lives

Answer 4

4-5 half-lives

Steady state concentration is achieved after repeated doses, which lead to an equilibrium between absorption and elimination. It is usually achieved after 4-5 half-lives. When the drug is given at shorter
intervals than the half-life, this leads to lesser fluctuations in plasma concentration. Attempts to reduce plasma fluctuations include using slow release (called MR for modified release or XL for extended release) preparations, e.g., lithium, venlafaxine or to allow long intervals between administration, e.g., depot
antipsychotics.

Question 5

Which of the following is not altered much when considering pharmacokinetics in the elderly?

Select one:
1. Total body fat
2. Renal clearance
3. Plasma protein binding
4. GI absorption
5. Gastric pH

Answer 5

GI absorption

Following changes are noted- Increase in total body fat, gastric pH is increased as acidity drops, reduced renal clearance, decrease in plasma protein binding and decreased number of brain acetylcholine
postsynaptic receptors. However, GI absorption and hepatic metabolism are not altered.

Question 5

Which of the following psychotropic will be affected most by contact with moist air?

Select one:
1. Olanzapine
2. Gabapentin
3. Carbamazepine
4. Topiramate
5. Sodium valproate

Answer 5

Sodium Valproate

Deliquescent salts such as valproate absorb moisture from the air

Question 5

A patient works and drives to work at 6:30 AM and wants night sedation. Based on half life, which of the following is the best? (June 2008)

Select one:
1. Lorazepam
2. Zopiclone
3. Zolpidem
4. Temazepam
5. Diazepam

Answer 5

Zolpidem

Zolpidem is rapidly absorbed through the gastrointestinal tract, reaching peak concentration from 30 minutes to 2 hours after administration. It is metabolized in the liver to several inactive metabolites and has
an elimination half-life of approximately 2.5 hours. Hence, a ‘hangover’ effect is rare.

Question 6

Valproate levels are decreased by

Select one:
1. Lithium
2. Cimetidine
3. Erythromycin
4. Carbamazepine
5. Fluoxetine

Answer 6

Carbamazepine

Valproate can increase the plasma levels of some drugs like TCAs (particularly clomipramine), lamotrigine and phenobarbitone by competitive inhibition of their metabolism. The level of valproate itself is decreased by carbamazepine.

Question 7

A clear therapeutic window is noted for which of the following?

Select one:
1. Nortriptyline
2. Amitriptyline
3. Carbamazepine
4. Fluoxetine
5. Clozapine

Answer 7

Nortriptyline

Although blood levels are available for many antidepressants; those for imipramine, desipramine, and nortriptyline have been best established. Imipramine and desipramine appear to have a curvilinear dose-response curve with an optimal range of 150 to 300 ng/mL. Nortriptyline appears to have a therapeutic window in the range of 50 to 150 ng/mL, usually reached by doses ranging from 50-100mg/day.

Question 8

Which of the following is least likely to be a pharmacokinetic property of the tricyclic antidepressants?

Select one:
1. Extensive hepatic breakdown
2. Their activity may delay their own absorption
3. Lipid solubility
4. Metabolism being reduced by smoking
5. Extensive protein binding in the plasma

Answer 8

Metabolism being reduced by smoking

Tricyclics are rapidly and almost completely absorbed from the gut and are widely distributed in the tissues of the body. They readily cross lipid barriers such as blood-brain barrier and placenta. They are extensively bound to plasma proteins. E.g. Imipramine 80-95%. Smoking and barbiturates facilitate metabolism and neuroleptics inhibit metabolism. Due to anticholinergic effects, they may reduce their own absorption (delayed gastric emptying esp. amitriptyline).

Question 9

Drug B is a prodrug whose metabolite is an active hypnotic agent. If drug A induces the metabolism of drug B, which of the following is true?

Select one:
1. Effects of drug B are more pronounced
2. No change occurs in drug effect
3. Effect of drug A will increase
4. Hypnotic effect is lost
5. Level of drug B’s metabolite falls in blood

Answer 9

Effects of drug B are more pronounced

Prodrug’s metabolism is increased. It will undergo more metabolism increasing the level of the active metabolite; drug B’s effect will be more pronounced.

Question 10

Which of the following atypical agents have the shortest half life?

Select one:
1. Quetiapine
2. Aripiprazole
3. Olanzapine
4. Clozapine
5. Risperidone

Answer 10

Quetiapine

Half life of quetiapine is around 6 hours, requiring multiple daily dosings.

Question 11

A 30-year-old is on combined oral contraceptive pill. The risk of becoming pregnant is increased by all except

Select one:
1. Venlafaxine
2. Topiramate
3. St John’s wort
4. Carbamazepine
5. Phenytoin

Answer 11

Venlafaxine

Low potency oral contraceptives may be rendered ineffective by enzyme-inducing medications such as carbamazepine, phenytoin, St John’s Wort and topiramate.

Question 12

Which one among the following is preferable to be used in the elderly than other tricyclic antidepressants?

Select one:
1. Imipramine
2. Dothiepin
3. Trimipramine
4. Amitryptyline
5. Lofepramine

Answer 12

Lofepramine

Both Lofepramine and Nortriptyline are less sedative, less anticholinergic. Lofepramine is the least cardiotoxic of the ones listed here and so preferred in the elderly.

Question 13

Which of the following drugs have a half-life of 3 days?

Select one:
1. Quetiapine
2. Reboxetine
3. Aripiprazole
4. Carbamazepine
5. Fluoxetine

Answer 13

Aripiprazole

Aripiprazole has a half-life of 75 to 96 hours.

Question 14

Which of the following drugs has a higher therapeutic index than the others listed?

Select one:
1. Lithium
2. Phenytoin
3. Type 1 antiarrythmics
4. Paracetamol
5. Tricyclics

Answer 14

Paracetamol

Drugs available over the counter usually have a better therapeutic index (else they won’t be sold without a prescription). This does not mean that they are absolutely safe.

Question 15

Which one among the following statements is true with respect to the interaction of fluoxetine with other
drugs?

Select one:
1. Fluoxetine reduces the effects of propranalol
2. Fluoxetine reduces the plasma concentration of carbamazepine
3. Fluoxetine reduces the concentration of Haloperidol
4. Fluoxetine enhances the effects of oral anticoagulants
5. Fluoxetine reduces the plasma concentration of Phenytoin

Answer 15

Fluoxetine enhances the effects of oral anticoagulants

Fluoxetine increases concentration of haloperidol, carbamazepine and phenytoin. Fluoxetine enhances the effects of oral anticoagulants and propranolol.

Question 16

Which of the following medications has the least protein-binding?

Select one:
1. venlafaxine
2. paroxetine
3. valproate
4. clomipramine
5. fluoxetine

Answer 16

Venlafaxine

Venlafaxine has lower levels of protein binding (25%-30%) than other SSRIs (80%-100%). As a result, the free fraction of venlafaxine is much greater than SSRIs at the same total plasma drug level.

Question 17

Which of the following is true concerning tricyclic metabolism?

Select one:
1. Elderly clear more than adults
2. Children clear more tricyclics than adults
3. None of the drugs need plasma monitoring
4. Metabolism is not affected by CYP enzyme polymorphisms
5. They do not interact with chlorpromazine

Answer 17

Children clear more tricyclics than adults

Tricyclic antidepressants are not effective in prepubertal children but may have marginal efficacy in adolescents with depression. Due to more extensive metabolism, young people require higher mg/kg doses than adults.

Question 18

Which of the following drugs has the least propensity to cause a withdrawal effect?

Select one:
1. Temazepam
2. Zolpidem
3. Buspirone
4. Zopiclone
5. Zaleplon

Answer 18

Buspirone

No evidence of a withdrawal syndrome and no interaction with alcohol have been reported with Buspirone.

Question 19

Regarding the pharmacokinetics of Lithium which one of the following statements in not true?

Select one:
1. It passes freely through the glomerular membrane independent of serum concentration.
2. Lithium has a wide therapeutic range
3. It is not bound to serum proteins
4. Lithium renal clearance is reduced when sodium is depleted.
4. The half-life of Lithium lies between 10 and 24 hours

Answer 19

Lithium has a wide therapeutic range

Lithium has a narrow therapeutic range, i.e., when compared with other drugs, there is a narrow gap between the minimum blood level (0.4 m mol/L) required for therapeutic efficacy and the maximum level (1.5 m mol/L) beyond which toxicity may ensue.

Question 20

A fatal combination with respect to potentially severe serotonin syndrome is

Select one:
1. Moclobemide and paroxetine
2. Paroxetine and methylphenidate
3. MDMA and moclobemide
4. Pethidine and tranylcypromine
5. Phenelzine and Amitriptyline

Answer 20

Pethidine and tranylcypromine

MAOIs potentiate the actions of general anaesthetics, sedatives, including alcohol, antihistamines, centrally acting analgesics (particularly pethidine due to an enhanced release of 5-HT) and anticholinergic drugs.

Question 20

Which of the following can be given as a loading dose in acute mania?

1. Select one:
2. Lithium
3. Clozapine
4. Valproate
5. Olanzapine
6. Clonazepam

Answer 20

Valproate

Both lithium and valproate take at least seven days to produce antimanic effects. But loading doses of (usually 20mg/kg/day) for valproate can increase the speed of action.

Question 21

In a patient with severe liver disease, antipsychotic of choice will be

Select one:
1. Amisulpride
2. Clozapine
3. Quetiapine
4. Risperidone
5. Olanzapine

Answer 21

Amisulpride

Amisulpride is predominantly renally excreted, so dosage reduction should not be necessary as long as renal function is normal, but there are no clinical studies in people with hepatic impairment and little clinical experience.(Maudsley Pres. Guidelines 9th)

Question 22

The area under the curve after a single dose allows determination of the

Select one:
1. Plasma half-life (t-1/2)
2. Metabolism
3. Elimination
4. Distribution
5. Bioavailability of the drug

Answer 22

Bioavailability of the drug

The area under the curve (AUC) is proportional to the amount of drug in plasma and allows determination of fraction of dose absorbed (i.e. Bioavailability of the drug). Low Bioavailability usually means high first pass metabolism. T-1/2 is the time taken for the plasma concentration to fall by a half. It only applies for drugs with first order kinetics.

Question 23

Enzyme autoinhibition is most likely to be seen with which of the following antidepressants?

Select one:
1. Sertraline
2. Duloxetine
3. Fluoxetine
4. Paroxetine
5. Citalopram

Answer 23

Paroxetine

Three of the five commonly available SSRI antidepressants (fluoxetine, paroxetine and sertraline) show autoinhibition of CYP2D6 though paroxetine is the one that is most affected.

Question 24

A drug X, when given at a dose of 300 units, is cleared from the body at a rate of 30 units per hour. When the dose is increased to 600 units, it is still cleared at a rate of 30 units per hour. Which of the following is true? The drug follows

Select one:
1. first order kinetics
2. zero order at lower doses and first order at higher doses
3. first order at lower doses and zero order at higher doses
4. no specific kinetics
5. zero order kinetics

Answer 24

Zero order kinetics

When the system facilitating first order clearance of drugs gets saturated, drugs follow zero-order kinetics. Here a constant amount, not a fraction, of the drug is cleared per unit time. This means that irrespective of the amount of drug in plasma or dose of drug administered, only a fixed unit of the drug is cleared by the body. As such, increasing dose might result in serious toxicity in this case.

Question 25

Which of the following undergoes metabolism predominantly by first order kinetics?

Select one:
1. Phenytoin
2. Depot antipsychotics
3. Venlafaxine XL
4. Alcohol
5. Thioridazine

Answer 25

Thioridazine

Elimination of a constant quantity per time unit of the drug quantity present in the organism is called zero order kinetics. 95% of the drugs in use at therapeutic concentrations are eliminated by first-order elimination kinetics. A few substances are eliminated by zero-order elimination kinetics because their elimination process is saturated, especially at higher doses. Examples are Ethanol, Phenytoin, high dose Salicylates, high dose Fluoxetine, high dose Omeprazole. Because in a saturated process the elimination rate is no
longer proportional to the drug concentration but decreasing at higher concentrations, zero-order kinetics are also called ‘non-linear kinetics’ in clinical pharmacology. The absorption rate constant is slower than the elimination rate constant and, therefore, the depot antipsychotics exhibit ‘flip-flop’ kinetics where the time to steady-state is a function of the absorption rate, and the concentration at steady-state is a function of the elimination rate.

Question 25

Most orally administered psychotropic drugs undergo hepatic metabolism followed by renal clearance. Which of the following statement about clearance is true?

Select one:
1. Clearance can occur only via urine
2. It helps calculating half life of a drug in the body
3. It is fixed for each individual with minor variations among drugs
4. It is the amount of drug eliminated from the body in a given time
5. It always depends on the dose consumed

Answer 25

It helps calculating half life of a drug in the body

Clearance is defined as the volume of blood cleared of a particular drug in unit time. It is specific for each drug and does not depend on drug concentration in plasma (because if concentration increases, elimination will also increase under first order kinetics). It represents the relationship between the rate of drug elimination (t1/2) and plasma level. For drugs with first order kinetics, clearance is constant irrespective of dose consumed because the rate of elimination is directly proportional to plasma level. Total body clearance
depends on renal and non-renal clearance such as sweat, bile etc. Renal elimination without significant liver breakdown is seen in lithium, amisulpride, surprise, gabapentin, acamprosate and amantadine.

Question 25

The ratio between minimum plasma level causing toxic effect to minimum plasma level causing therapeutic effect is called

Select one:
1. Toxic dose
2. Therapeutic index
3. Volume of distribution
4. Affinity
5. Potency

Answer 25

Therapeutic index

Therapeutic index: It is the ratio of minimum plasma concentration causing toxic effects to that causing a therapeutic effect. This can vary according to the toxic symptom specified for a given drug.

Question 26

Which of the following enzymes are responsible for oxidative metabolism of most psychotropic drugs?

Select one:
1. Cytochrome P450 family
2. Glycoprotein P
3. Aryl Sulfatase
4. Monoamine Oxidase
5. G Protein

Answer 26

Cytochrome P450 family

The cytochrome P450 (CYP450) enzyme superfamily is the primary phase I enzyme system involved in the oxidative metabolism of drugs and other chemicals. These enzymes also are responsible for all or part of the metabolism and synthesis of a number of endogenous compounds, such as steroid hormones and prostaglandins.

Question 27

A psychotropic drug is observed to undergo phase 2 metabolism directly without undergoing phase 1
reactions. Which one of the following fits with the above description best?

Select one:
1. Lithium
2. Fluoxetine
3. Chlordiazepoxide
4. Diazepam
5. Lorazepam

Answer 27

Lorazepam

lorazepam, temazepam and oxazepam undergo direct phase 2 reactions.

Question 28

A new molecule investigated for anxiety disorder failed at initial stages of animal testing as it failed to reach the brain crossing the blood-brain barrier. Which of the following factors decide the degree of blood-brain barrier permeability?

Select one:
1. Frequency of administration of drug
2. Time of drug administration
3. Half life of drug
4. Lipid water partition coefficient
5. Nitrogen content of the drug

Answer 28

Lipid water partition coefficient

The ability of a drug to pass blood brain barrier depends on its molecular size, lipid solubility and ionic status. Unionized molecules that are freely available and less protein bound are transported across the barrier easily. In general higher the lipid-water partition coefficient, greater the ability to cross the barrier.

Question 28

Under which of the following conditions interactions with drugs that alter protein binding becomes important?

Select one:
1. Obesity
2. Children
3. Lung disease
4. High altitude living
5. Renal disease

Answer 28

Renal disease

Protein binding interactions become relevant in the presence of a renal disease where proteinuria can
occur.

Question 28

The enhancement of drug effects following the repeated administration of the same dose of a drug is called

Select one:
1. Tolerance
2. Neuroadaptation
3. Habituation
4. Sensitisation
5. Cross Tolerance

Answer 28

Sensitisation

Tolerance refers to the diminished response to the administration of a drug after repeated exposure. It may be behavioural tolerance through learning to cope with the effects, increased metabolism, reduced receptor sensitivity or number, activation of a homeostatic mechanism. Cross-tolerance refers to shared tolerance among drugs with similar chemical structure. Cross-tolerance forms the basis for a number of drug interactions (E.g. alcohol with barbiturates). Sensitisation refers to the enhancement of drug effects following the repeated administration of the same dose of the drug. Drug sensitization occurs in drug addiction and is the physiological opposite of drug tolerance.

Question 28

Which of the following hypnotic drugs acts for the longest duration?

Select one:
1. Temazepam
2. Triazolam
3. Zolpidem
4. Zaleplon
5. Nitrazepam

Answer 28

Nitrazepam

Nitrazepam is a long acting benzodiazepine with an elimination half-life of 15-38 (mean elimination half-life 26 hours).

Question 29

Urinary acidification can help eliminate which of the following medications on overdose?

Select one:
1. Amphetamines
2. Salicylates
3. Paracetamol
4. Tricyclics
5. Barbiturates

Answer 29

Amphetamines

Acidification may help in the elimination of amphetamines and phencyclidine, but often complications of such a procedure override any benefits.

Question 29

A drug follows first order kinetics and has a t1/2 of 4 hours. In a healthy male how long will it take for this drug to reach steady state assuming no loading dose is given, and the drug is administered at equal
intervals regularly?

Select one:
1. 10 hours
2. 2 hours
3. 4 hours
4. 20 hours
5. 1 hour

Answer 29

20 hours

It is estimated that it takes 4-5 t ½ for a drug to reach the steady plasma level.

Question 29

Which of the following is incorrect with respect to the pharmacokinetic properties of diazepam?

Select one:
1. The peak concentration is achieved within 30-90 minutes after single dose
2. The protein binding ratio is 30-40%
3. Bioavailability is almost complete with
4. The oral dose Desmethyldiazepam is the active phase 1 metabolite.
5. The rate of absorption is rapid.

Answer 29

The protein binding ratio is 30-40%

The protein-binding ratio of diazepam is 95%.

Question 29

What is the volume of distribution of drug A if the plasma concentration immediately after IV administration of 10mg is 0.01mg/mL?

Select one:
1. 100mL
2. 1000mL
3. 1 mL
4. 10mL
5. 0.1mL

Answer 29

1000mL

(Volume of distribution) Vd =Q/Cp, where Vd-volume of distribution, Q-quantity of drug and Cp-plasma concentration at time of administration (‘zero time’).

Question 29

The active metabolite of imipramine is
Select one:

1. Lofepramine
2. mcPP
3. Desipramine
4. Nortriptyline
5. Amitriptyline

Answer 29

Desipramine

The active metabolite of amitriptyline is nortriptyline and imipramine is desipramine.

Question 30

Which of the following should be considered when switching from one brand of medication to another
brand?

Select one:
1. Rate of absorption
2. Bioequivalence
3. Bioavailability
4. Volume of distribution
5. Clearance

Answer 30

Bioequivalence

Bioequivalence is important feature to be considered when changing from one brand to other brand of the same compound e.g. camcolit vs. priadel for lithium carbonate or Clozaril vs. zaponex for clozapine. It is a measure of comparability of plasma levels of two different formulations of the same active compound when given at same dose and same route of administration.

Question 30

Which one of the following is a potent hepatic enzyme inducer?

Select one:
1. Gabapentin
2. Carbamazepine
3. Lamotrigine
4. Valproate
5. Lithium

Answer 30

Carbamazepine

Liver enzyme induction can increase the rate of metabolism of many drugs resulting in lower plasma levels and so lessened efficacy. Phenytoin, phenobarbitone, Primidone and carbamazepine are potent enzyme inducers that tend to lower the plasma levels of each other and other drugs. Carbamazepine especially is a potent hepatic enzyme (cytochrome P450) inducer that induces its own metabolism as well as other drugs and is metabolised by CYP3A4.

Question 31

Some drugs such as fluoxetine move from first order to zero order kinetics in supratherapeutic doses. What happens to their t1/2 in such cases?

Select one:
1. t1/2 doubles
2. t1/2 becomes independent of dose
3. t1/2 becomes dependent on dose
4. t1/2 quadruples
5. t1/2 halves

Answer 31

t1/2 becomes dependent on dose

In very high supratherapeutic doses, saturation of enzymes can happen for drugs such as fluoxetine,
wherein first order elimination switches to become zero order. In zero-order kinetic state, a constant
amount, rather than a constant fraction, of the drug is cleared per unit time. This means that irrespective of the amount of drug in plasma or dose of drug administered, only a fixed unit of drug is cleared by the body. Here the concept of half-life does not hold true as ‘half life’ depends on the dose administered (i.e the time taken to eliminated 50% of dose, becomes dose dependent, and the concept of t1/2 loses its validity).

Question 32

The SSRI with longest total half-life is

Select one:
1. Citalopram
2. Fluoxetine
3. Duloxetine
4. Sertraline
5. Paroxetine

Answer 32

Fluoxetine

The only serotonin reuptake inhibitor with an active metabolite is fluoxetine, whose metabolite norfluoxetine has a half-life of 7 to 15 days. Thus, it may take several months to achieve steady state with this agent. This is considerably longer than citalopram (half-life 1.5 days) or sertraline and paroxetine (half-lives 24 hours).

Question 33

A patient suddenly withdraws from a medication. How many half-lives does it take for the medication to be completely excreted?

Select one:
1. 5
2. 3
3. 2
4. 8
5. 10

Answer 33

5

From a clinical standpoint, it is common to assume that a drug is effectively eliminated after 4-5 half-lives, assuming first order kinetics.

Question 34

SSRI most selective for serotonin reuptake is

Select one:
1. Citalopram
2. Paroxetine
3. Sertraline
4. Duloxetine
5. Fluoxetine

Answer 34

Citalopram

Of the available SSRIs, citalopram and escitalopram are the most selective for serotonin receptor blockade; citalopram is made up of both cis and R enantiomers. Escitalopram is 100 times more potent than the R-enantiomer.

Question 35

There is poor oral absorption of most psychotropics in which of the following parts of the gastrointestinal system?

Select one:
1. Ileum
2. Stomach
3. Jejunum
4. Colon
5. Rectum

Answer 35

Stomach

Absorption by oral administration occurs primarily in the small bowel, though absorption of many slow or sustained release drugs occurs in the large bowel. There is poor absorption in the acidic stomach but conversely good absorption in the alkaline jejunum, ileum, colon and rectum.

Question 36

Which of the following types of drug molecules is most efficiently absorbed?

Select one:
1. Small, water soluble electrically neutral molecules
2. Small, water soluble electrically charged molecules
3. Large, water soluble electrically neutral molecules
4. Small, lipid soluble electrically neutral molecules
5. Large, lipid soluble electrically neutral molecules

Answer 36

Small, lipid soluble electrically neutral
molecules

To achieve a therapeutic effect most drugs need to cross at least one lipid membrane. This will depend on the size and shape of the molecule, lipid solubility and ionic charge. The blood-brain barrier only allows lipid-soluble molecules in the brain.

Question 37

Which of the following drugs is excreted completely via renal route?

Select one:
1. Olanzapine
2. Lithium
3. Quetiapine
4. Amisulpride
5. Carbamazepine

Answer 37

Lithium

Lithium is completely renally handled for its clearance. Though largely renal, amisulpride has some hepatic involvement.

Question 38

How many minimum weeks of interval should be given between fluoxetine and phenelzine when switching from the SSRI to the MAOI?

Select one:
1. 5 weeks
2. 1 week
3. 12 weeks
4. 3 weeks
5. 2 weeks

Answer 38

5 weeks

When the switch involves an MAOI, sufficient time must be given for medication clearance. Fluoxetine
requires a much longer period-6 weeks-whereas sertraline and paroxetine require about two weeks when switching to an MAOI.

Question 39

Which of the following acts on presynaptic receptors as the main mechanism of action?

Select one:
1. Donepezil
2. Diazepam
3. Phenelzine
4. Propronalol
5. Clonidine

Answer 39

Clonidine

Clonidine, lofexidine act at alpha2 presynaptic receptor.

Question 40

Which of the following is an enzyme inducer?

Select one:
1. Caffeine
2. Smoking
3. Grapefruit juice
4. Paroxetine
5. Valproate

Answer 40

Smoking

Smoking induces CYP1A2 via PAH.Caffeine is an inhibitor. Paroxetine, to some extent fluoxetine,
neuroleptics, amitriptyline and clomipramine inhibit.

Question 41

Advantages of buspirone over benzodiazepines when used for anxiety includes all of the following except

Select one:
1. Buspirone cause no dependence
2. Buspirone can be given once daily
3. Buspirone can be withdrawn more easily
4. Buspirone has no street value
5. Buspirone causes no tolerance usually

Answer 41

Buspirone can be given once daily

The advantage of buspirone is its lack of withdrawal and tolerance effects. Its main clinical disadvantage lies in the delay in onset of its therapeutic effect (up to 2 weeks in some cases) and its limited efficacy in attenuating anxiety in those patients who had previously responded to benzodiazepines. It is usually given twice or thrice daily.

Question 42

The drug of choice for alcohol detoxification in a patient with liver disease is

Select one:
1. Chlordiazepoxide
2. Diazepam
3. Carbamazepine
4. Chlormethiazole
5. Oxazepam

Answer 42

Oxazepam

Oxazepam has a lesser propensity to accumulate and cause adverse reactions in the elderly or people with hepatic impairment. As it does not require hepatic oxidation, an is entirely metabolized via glucuronidation, it is a safer choice if benzodiazepines are required in those with liver failure.

Question 43

Which of the following medications must be used with caution when fluvoxamine is prescribed?

Select one:
1. Theophylline
2. Naproxen
3. Amlodipine
4. Salbutamol
5. Paracetamol

Answer 43

Theophylline

Fluvoxamine decreases the clearance of cytochrome CYP1A2 substrates such as theophylline, leading to
toxic levels when co-administered.

Question 44

Which of the following drugs is excreted unchanged in urine?

Select one:
1. Quetiapine
2. Gabapentin
3. Valproate
4. Diazepam
5. Morphine

Answer 44

Gabapentin

Gabapentin doses must be reduced for patients with renal insufficiency as it is solely excreted by kidneys.

Question 45

The metabolism of which one among the following follow first order kinetics?

Select one:
1. Alcohol
2. Oral Antipsychotic
3. Depot antipsychotic
4. Absorption of controlled release drugs
5. Phenytoin

Answer 45

Oral Antipsychotic

Most drugs show first order kinetics where the rate of absorption or elimination is directly proportional to the amount of drug remaining. The concentration of a drug in the plasma will normally follow first order kinetics, decreasing in an exponential manner related to plasma concentration. However, drugs like ethanol and Phenytoin are metabolised by zero order kinetics, their concentration decreasing in a linear fashion i.e., at a constant rate irrespective of plasma concentration. With zero-order kinetics, a fixed amount of drug is absorbed each time independent of drug concentrations and hence a small increase in drug ingestion results in a large increase in plasma concentration. Absorption of controlled release drugs and depot.

Question 46

A 44-year-old man is on warfarin for thromboprophylaxis. He returns from a holiday to mainland Europe where he obtained a preparation for treating his depression. The GP is concerned about his INR and organizes an urgent blood test. What is the likely drug taken?

Select one:
1. St John’s Wort
2. Duloxetine
3. Carbamazepine
4. Citalopram
5. Venlafaxine

Answer 46

St John’s Wort

St John’s Wort, an over-the-counter herbal preparation with antidepressant properties, poses a high-risk interaction with oral anticoagulants by reducing the anticoagulant effect of coumarins such as warfarin.

Question 47

Zaleplon has a half-life of approximately

Select one:
1. 12-24 hours
2. More than 24 hours
3. 1-3 Hours
4. 1 hour
5. 3-6 Hours

Answer 47

1 hour

Zopiclone- 3-6 hours Zolpidem- 1-3 hours Zaleplon- approximately 1 hour.

Question 48

Hepatic metabolism may involve various chemical reactions. Which one of the following is not a common chemical activity seen in hepatic metabolism?

Select one:
1. oxidation
2. reduction
3. dealkylation
4. hydroxylation
5. polymerisation

Answer 48

Polymerisation

Hepatic metabolism may involve non-synthetic reactions that involve oxidation, reduction, hydroxylation, dealkylation, demethylation, acetylation; methylation may produce active compounds (Phase 1). The metabolism also involves synthetic reactions such as conjugation usually with glucuronic acid and sulphation that produce inactive water-soluble compounds (Phase 2).

Question 49

Which one among the following statements is incorrect about the oral route of administration?

Select one:
1. Preparations that are soluble in gastrointestinal fluids are absorbed better
2. Oral route drugs are subject to renal first pass metabolism
3. Lipid solubility aids absorption
4. Oral route leads to variable plasma concentration because the absorption may be
erratic
5. Acid-resistant drugs are better absorbed

Answer 49

Oral route drugs are subject to renal first pass metabolism

Drugs taken orally are subject to metabolism by the liver (First-Pass Effect). A drug taken orally is absorbed from the gut into the enterohepatic circulation, where the liver inactivates some of the drug before even it reaches the systemic circulation, which is known as the first pass effect. It can be avoided if the drug is injected intravenously whereby the drug directly enters the systemic circulation.

Question 50

Which one among the following drugs can decrease lithium excretion and precipitate toxicity?

Select one:
1. Diazepam
2. Valproate
3. Propranolol
4. Haloperidol
5. NSAIDs

Answer 50

NSAIDS

Thiazide diuretics, Furosemide, NSAIDs, Haloperidol, carbamazepine, SSRIs and ACE inhibitors can
decrease its clearance, increase serum lithium levels and can precipitate lithium toxicity. Though
haloperidol is associated with increased neurotoxicity in combination with lithium, it does not have any direct effect on lithium levels.

Question 51

Bioavailability is least likely to be influenced by

Select one:
1. Metabolism
2. Absorption
3. Distribution
4. Excretion
5. Gender

Answer 51

Gender

Bioavailability is the fraction of an ingested dose of a drug that gains access to the systemic circulation. It may be low because the drug is metabolised in the gut wall or liver before reaching the systemic circulation.

Question 52

What is least likely to be correct concerning the pharmacology of clozapine?

Select one:
1. High affinity towards D4 receptors
2. Slow release from D2 receptors
3. Has antimuscarinic properties
4. Acts on D1 receptors
5. Blocks 5HT2A receptors

Answer 52

Slow release from D2 receptors

the rates of antipsychotic dissociation from the human-cloned D2 receptor. For instance, radioactive haloperidol, chlorpromazine, and raclopride all dissociate very slowly over a 30-minute time span, while radioactive quetiapine, clozapine, remoxipride, and amisulpride dissociate rapidly, in less than 60 seconds. These data also match clinical brain-imaging findings that show haloperidol remaining constantly bound to D2 in humans undergoing two positron emission tomography (PET) scans 24 hours apart. Conversely, the occupation of D2 by clozapine or quetiapine has mostly disappeared after 24 hours.

Question 53

Which of the following drugs has a metabolite that has the longest half-life?

Select one:
1. Fluoxetine
2. Duloxetine
3. Venlafaxine
4. Paroxetine
5. Citalopram

Answer 53

Fluoxetine

There are substantial differences in term of their half-life between fluoxetine and others SSRIs. The half-life of fluoxetine and its active metabolite norfluoxetine is respectively 2 to 4 days and 7 to 15 days, more extended than other SSRIs (approximately one day).

Question 54

A newly developed antipsychotic is said to be highly permeable across lipid membranes and so achieve
very high bioavailability when given orally. Which of the following properties of the drug enable this?

Select one:
1. All of the above
2. Low concentration gradient across membranes
3. Low protein binding
4. Exists in highly ionised form predominantly
5. Balanced hydrophilic and lipophilic properties

Answer 54

Balanced hydrophilic and lipophilic properties

If highly hydrophilic; the drug cannot cross the lipid cell membrane. On the other hand, if highly lipophilic, the drug is not soluble enough to cross the water layer adjacent to the cell. Balanced hydrophilic and lipophilic property is essential for high permeability.

Question 55

A drug X is used to treat acute behavioural disturbances. It can be given orally or intravenously. 15mg of the oral drug is needed for an acutely disturbed man of weight 70kgs while 10mg is sufficient if given intravenously. What is the bioavailability of IV administration of 10mg?

Select one:
1. 10.5mg
2. 10mg
3. 5mg
4. 1.5mg
5. 15mg

Answer 55

10mg

When a drug is administered intravenously the availability of the drug is 100%.

Question 56

Which of the following factors can improve absorption of orally administered drugs?

Select one:
1. High hydrophilic capacity of drug
2. Fast intestinal motility
3. None of the above
4. Presence of food in the GI tract
5. Presence of P glycoprotein

Answer 56

None of the above

This is mainly due to lack of absorption from the intestine related to presence of inhibitory factors like food, or gastric acid or due to changes in intestinal motility e.g. having diarrhoea or vomiting can affect drug absorption. Inherent properties of certain drugs can also affect their absorption e.g. highly hydrophilic drugs cannot cross the lipid cell membrane, while highly lipophilic drugs will struggle to cross the water layer in extracellular space Inhibition of P-glycoprotein (e.g. by grapefruit juice) can increase absorption of certain medications.