MCQ Quiz: Pharmacology of Antidepressants

A deep understanding of the pharmacology of antidepressants is fundamental for any pharmacy student aiming to excel in clinical practice. This quiz is designed to test your knowledge of the mechanisms of action, pharmacodynamics, and pharmacokinetic principles that govern how these essential medications work. We will explore how different drug classes, from SSRIs and SNRIs to TCAs and MAOIs, interact with neurochemical pathways to exert their therapeutic effects. Understanding these pharmacological nuances is key to optimizing patient outcomes, managing side effects, and preventing drug interactions. Let’s begin!

1. The primary mechanism of action for Selective Serotonin Reuptake Inhibitors (SSRIs) is the blockade of which transporter?

• A. Norepinephrine Transporter (NET)
• B. Dopamine Transporter (DAT)
• C. Serotonin Transporter (SERT)
• D. GABA Transporter (GAT)

Answer: C. Serotonin Transporter (SERT)

2. Tricyclic antidepressants (TCAs) like amitriptyline produce significant sedative effects due to their antagonist activity at which receptor?

• A. Dopamine D2 receptor
• B. Serotonin 5-HT2A receptor
• C. Beta-1 adrenergic receptor
• D. Histamine H1 receptor

Answer: D. Histamine H1 receptor

3. Irreversible Monoamine Oxidase Inhibitors (MAOIs) like phenelzine increase synaptic neurotransmitter levels by:

• A. Blocking the reuptake of monoamines.
• B. Preventing the enzymatic degradation of monoamines in the presynaptic neuron.
• C. Acting as a direct agonist at postsynaptic receptors.
• D. Increasing the synthesis of monoamines.

Answer: B. Preventing the enzymatic degradation of monoamines in the presynaptic neuron.

4. Bupropion’s antidepressant effect is attributed to the inhibition of the reuptake of which two neurotransmitters?

• A. Serotonin and norepinephrine
• B. Serotonin and dopamine
• C. Norepinephrine and dopamine
• D. GABA and glutamate

Answer: C. Norepinephrine and dopamine

5. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) like venlafaxine and duloxetine block which transporters?

• A. SERT and DAT
• B. NET and DAT
• C. SERT and NET
• D. SERT only

Answer: C. SERT and NET

6. The therapeutic effect of antidepressants is delayed by several weeks, despite immediate changes in synaptic neurotransmitter levels. What pharmacological concept best explains this delay?

• A. The time required to reach peak plasma concentration.
• B. The need for downstream adaptive changes, such as receptor downregulation and changes in gene expression.
• C. The saturation of plasma protein binding sites.
• D. The time it takes for the drug to cross the blood-brain barrier.

Answer: B. The need for downstream adaptive changes, such as receptor downregulation and changes in gene expression.

7. Mirtazapine enhances both serotonergic and noradrenergic neurotransmission through which unique pharmacological mechanism?

• A. Inhibition of SERT and NET
• B. Inhibition of MAO-A
• C. Antagonism of presynaptic alpha-2 adrenergic autoreceptors
• D. Partial agonism at the 5-HT1A receptor

Answer: C. Antagonism of presynaptic alpha-2 adrenergic autoreceptors

8. A tyramine-induced hypertensive crisis is a major risk with MAOIs. This occurs because the inhibition of MAO-A in the gut and liver leads to:

• A. Decreased absorption of tyramine.
• B. An increase in systemic tyramine, which acts as an indirect sympathomimetic, causing massive norepinephrine release.
• C. A direct agonistic effect of the MAOI on adrenergic receptors.
• D. Inhibition of tyramine metabolism in the brain.

Answer: B. An increase in systemic tyramine, which acts as an indirect sympathomimetic, causing massive norepinephrine release.

9. The anticholinergic side effects of TCAs, such as dry mouth, constipation, and blurred vision, result from the blockade of which receptors?

• A. Nicotinic receptors
• B. Muscarinic acetylcholine receptors
• C. Alpha-1 adrenergic receptors
• D. Dopamine D1 receptors

Answer: B. Muscarinic acetylcholine receptors

10. What is the pharmacodynamic rationale for augmenting an SSRI with bupropion?

• A. To add a different mechanism of serotonin reuptake inhibition.
• B. To add dopaminergic and noradrenergic activity, which may help with symptoms like low energy and anhedonia.
• C. To inhibit the metabolism of the SSRI.
• D. To add significant antihistaminic effects for sedation.

Answer: B. To add dopaminergic and noradrenergic activity, which may help with symptoms like low energy and anhedonia.

11. Trazodone’s primary mechanism of action at therapeutic doses for depression involves:

• A. Potent inhibition of serotonin reuptake.
• B. Irreversible inhibition of MAO-B.
• C. Antagonism of serotonin 5-HT2A receptors and weak serotonin reuptake inhibition.
• D. Blockade of norepinephrine and dopamine transporters.

Answer: C. Antagonism of serotonin 5-HT2A receptors and weak serotonin reuptake inhibition.

12. The orthostatic hypotension seen with some TCAs is a result of their antagonist activity at which receptor?

• A. Beta-2 adrenergic receptors
• B. Alpha-1 adrenergic receptors
• C. Serotonin 5-HT3 receptors
• D. Muscarinic M2 receptors

Answer: B. Alpha-1 adrenergic receptors

13. SSRIs can cause sexual dysfunction as a side effect. This is believed to be mediated primarily by increased serotonin stimulation of which receptor subtype?

• A. 5-HT1A
• B. 5-HT2A
• C. 5-HT1D
• D. 5-HT3

Answer: B. 5-HT2A

14. From a pharmacokinetic perspective, which SSRI has the longest half-life, making it more “forgiving” of missed doses but requiring a longer washout period?

• A. Paroxetine
• B. Sertraline
• C. Fluvoxamine
• D. Fluoxetine

Answer: D. Fluoxetine

15. Vilazodone (Viibryd) possesses a dual pharmacological action. In addition to SERT inhibition, it acts as a:

• A. Partial agonist at the serotonin 5-HT1A receptor.
• B. Potent antagonist at the histamine H1 receptor.
• C. Reversible inhibitor of MAO-A.
• D. Blocker of voltage-gated sodium channels.

Answer: A. Partial agonist at the serotonin 5-HT1A receptor.

16. The pharmacologic principle of “receptor desensitization” or “downregulation” is thought to be a key component of the long-term therapeutic effects of which drug class?

• A. Benzodiazepines
• B. Antihistamines
• C. SSRIs
• D. Stimulants

Answer: C. SSRIs

17. Paroxetine is a potent inhibitor of which cytochrome P450 enzyme, leading to a high potential for drug-drug interactions?

• A. CYP1A2
• B. CYP2C9
• C. CYP2D6
• D. CYP3A4

Answer: C. CYP2D6

18. Serotonin syndrome is a serious adverse effect caused by excessive serotonergic activity. The risk is highest when an SSRI is co-administered with which of the following?

• A. A beta-blocker
• B. An MAOI
• C. A proton pump inhibitor
• D. A statin

Answer: B. An MAOI

19. In overdose, TCAs can cause life-threatening cardiac arrhythmias due to the blockade of what?

• A. Voltage-gated potassium channels
• B. Voltage-gated calcium channels
• C. Voltage-gated sodium channels
• D. Muscarinic receptors in the heart

Answer: C. Voltage-gated sodium channels

20. Vortioxetine (Trintellix) is considered a “multimodal” antidepressant. What does this term imply about its pharmacology?

• A. It only comes in multiple dosage forms.
• B. It inhibits SERT and also acts as an agonist, partial agonist, or antagonist at several other serotonin receptor subtypes.
• C. It inhibits the reuptake of all three major monoamines equally.
• D. It must be taken multiple times per day to be effective.

Answer: B. It inhibits SERT and also acts as an agonist, partial agonist, or antagonist at several other serotonin receptor subtypes.

21. Desvenlafaxine is the active metabolite of venlafaxine. This pharmacokinetic property means that desvenlafaxine:

• A. Has a much longer half-life than venlafaxine.
• B. Is a more potent dopamine reuptake inhibitor.
• C. Bypasses the need for CYP2D6 metabolism to become active, potentially leading to a more predictable dose-response.
• D. Must be administered intravenously.

Answer: C. Bypasses the need for CYP2D6 metabolism to become active, potentially leading to a more predictable dose-response.

22. Which of the following best describes the pharmacological rationale for a cross-taper when switching between two SSRIs?

• A. It allows for immediate cessation of the first drug and initiation of the second at a full therapeutic dose.
• B. It minimizes the risk of withdrawal from the first drug while gradually introducing the second drug to ensure tolerability.
• C. It is only done to prevent hypertensive crisis.
• D. It ensures that both drugs reach peak concentration at the same time.

Answer: B. It minimizes the risk of withdrawal from the first drug while gradually introducing the second drug to ensure tolerability.

23. The pharmacodynamic profile of mirtazapine, with its potent H1 antagonism and lack of SERT inhibition, makes it a logical choice for depressed patients with which prominent symptom?

• A. Hypersomnia
• B. Insomnia
• C. Hypertension
• D. Weight loss

Answer: B. Insomnia

24. The concept of “potency” in pharmacology refers to:

• A. The maximum effect a drug can produce.
• B. The dose of a drug required to produce a specific effect.
• C. The half-life of a drug.
• D. The oral bioavailability of a drug.

Answer: B. The dose of a drug required to produce a specific effect.

25. The affinity of a drug for a receptor is a measure of:

• A. The drug’s ability to activate the receptor once bound.
• B. The drug’s rate of metabolism.
• C. The strength of the binding between the drug and the receptor.
• D. The drug’s ability to be absorbed from the gut.

Answer: C. The strength of the binding between the drug and the receptor.

26. Why do SNRIs like duloxetine have an indication for treating neuropathic pain, a feature generally not seen with SSRIs?

• A. The pain relief is mediated by dopamine reuptake inhibition.
• B. The inhibition of norepinephrine reuptake enhances the descending inhibitory pain pathways in the spinal cord.
• C. It is solely due to their anti-inflammatory properties.
• D. They block sodium channels in peripheral nerves.

Answer: B. The inhibition of norepinephrine reuptake enhances the descending inhibitory pain pathways in the spinal cord.

27. An “active metabolite” is a product of drug metabolism that:

• A. Is pharmacologically inert and ready for excretion.
• B. Also has pharmacological activity, which can contribute to the drug’s overall effect and duration of action.
• C. Is always more toxic than the parent drug.
• D. Cannot be eliminated from the body.

Answer: B. Also has pharmacological activity, which can contribute to the drug’s overall effect and duration of action.

28. Why is bupropion contraindicated in patients with a history of seizure disorders?

• A. It significantly lowers the seizure threshold, particularly at higher doses.
• B. It causes severe hyponatremia.
• C. It has potent anticholinergic effects.
• D. It is a known hepatotoxin.

Answer: A. It significantly lowers the seizure threshold, particularly at higher doses.

29. The term “pharmacodynamics” refers to:

• A. What the body does to the drug (absorption, distribution, metabolism, excretion).
• B. The process of developing a new drug.
• C. What the drug does to the body (mechanism of action, receptor binding, therapeutic effects).
• D. The study of the cost-effectiveness of a drug.

Answer: C. What the drug does to the body (mechanism of action, receptor binding, therapeutic effects).

30. Which antidepressant is also a potent inhibitor of CYP1A2 and is well-known for its interaction with theophylline and caffeine?

• A. Sertraline
• B. Fluvoxamine
• C. Citalopram
• D. Mirtazapine

Answer: B. Fluvoxamine

31. The primary pharmacological difference between a reversible MAOI and an irreversible MAOI relates to:

• A. The type of neurotransmitter they affect.
• B. Their route of administration.
• C. The duration of enzyme inhibition and the need for enzyme resynthesis for activity to return.
• D. Their ability to cross the blood-brain barrier.

Answer: C. The duration of enzyme inhibition and the need for enzyme resynthesis for activity to return.

32. The anxiolytic (anti-anxiety) effects of SSRIs are thought to be mediated by the long-term adaptation of which receptor system?

• A. The dopamine system
• B. The serotonin system, particularly involving 5-HT1A receptors
• C. The histamine system
• D. The cholinergic system

Answer: B. The serotonin system, particularly involving 5-HT1A receptors

33. The concept of “steady state” in pharmacokinetics is the point at which:

• A. The rate of drug absorption is zero.
• B. The drug is completely eliminated from the body.
• C. The rate of drug administration is equal to the rate of drug elimination over a dosing interval.
• D. The drug has reached its maximum possible therapeutic effect.

Answer: C. The rate of drug administration is equal to the rate of drug elimination over a dosing interval.

34. The “efficacy” of an antidepressant refers to:

• A. The dose required to see an effect.
• B. The drug’s ability to produce the maximum desired therapeutic response.
• C. The number of side effects it causes.
• D. The strength of its binding to the target transporter.

Answer: B. The drug’s ability to produce the maximum desired therapeutic response.

35. From a pharmacological standpoint, why is it not recommended to combine two SSRIs?

• A. They would cancel each other out due to opposing mechanisms.
• B. There is an increased risk of side effects, including serotonin syndrome, without any proven benefit in efficacy.
• C. It leads to a severe hypertensive crisis.
• D. They are metabolized by completely different enzymes.

Answer: B. There is an increased risk of side effects, including serotonin syndrome, without any proven benefit in efficacy.

36. A drug that binds to a receptor but produces an effect opposite to that of an agonist is called a(n):

• A. Partial agonist
• B. Non-competitive antagonist
• C. Inverse agonist
• D. Chemical antagonist

Answer: C. Inverse agonist

37. The noradrenergic activity of TCAs and SNRIs can sometimes cause which of the following side effects?

• A. Sedation
• B. Bradycardia
• C. Tachycardia and sweating
• D. Diarrhea

Answer: C. Tachycardia and sweating

38. Fluvoxamine, while an effective SSRI, is less commonly used for depression and more for obsessive-compulsive disorder (OCD) partly due to its:

• A. Lack of efficacy for depression.
• B. Very short half-life requiring multiple daily doses.
• C. Complex pharmacokinetic profile and high potential for drug-drug interactions via CYP inhibition.
• D. High cost and lack of availability.

Answer: C. Complex pharmacokinetic profile and high potential for drug-drug interactions via CYP inhibition.

39. A “black box warning” is the strongest warning issued by the FDA. The warning on antidepressants concerns:

• A. The risk of hypertensive crisis with tyramine.
• B. The risk of severe liver damage.
• C. The risk of increased suicidal thinking and behavior in younger populations.
• D. The risk of permanent cardiac damage.

Answer: C. The risk of increased suicidal thinking and behavior in younger populations.

40. The pharmacology of esketamine (Spravato) involves antagonism of which receptor, representing a different approach from monoamine-based therapies?

• A. Serotonin 5-HT2C receptor
• B. Dopamine D2 receptor
• C. NMDA glutamate receptor
• D. Alpha-1 adrenergic receptor

Answer: C. NMDA glutamate receptor

41. Which class of antidepressants is absolutely contraindicated with SSRIs and SNRIs due to the high risk of serotonin syndrome?

• A. Atypical antipsychotics
• B. Benzodiazepines
• C. Monoamine Oxidase Inhibitors (MAOIs)
• D. Mood stabilizers

Answer: C. Monoamine Oxidase Inhibitors (MAOIs)

42. The term “bioavailability” refers to the:

• A. Amount of drug that binds to plasma proteins.
• B. Fraction of an administered dose of unchanged drug that reaches the systemic circulation.
• C. Maximum concentration of the drug in the blood.
• D. Rate of drug metabolism by the liver.

Answer: B. Fraction of an administered dose of unchanged drug that reaches the systemic circulation.

43. The pharmacological action of TCAs at alpha-1 adrenergic receptors is responsible for which side effect?

• A. Tachycardia
• B. Sedation
• C. Dry mouth
• D. Orthostatic hypotension

Answer: D. Orthostatic hypotension

44. What is the pharmacological basis for the “discontinuation syndrome” seen with abrupt cessation of short half-life SSRIs like paroxetine?

• A. The rapid drop in synaptic serotonin levels before the brain has had time to re-adapt its receptor sensitivity.
• B. The formation of a toxic metabolite.
• C. A sudden increase in blood pressure.
• D. The unmasking of an underlying seizure disorder.

Answer: A. The rapid drop in synaptic serotonin levels before the brain has had time to re-adapt its receptor sensitivity.

45. Which of the following drugs is NOT considered a first-line pharmacological option for major depressive disorder?

• A. Sertraline (SSRI)
• B. Duloxetine (SNRI)
• C. Phenelzine (MAOI)
• D. Escitalopram (SSRI)

Answer: C. Phenelzine (MAOI)

46. In pharmacology, a “non-competitive antagonist” is a drug that:

• A. Binds to the same site as the agonist but can be overcome by increasing the agonist concentration.
• B. Binds to a different site on the receptor (an allosteric site) and changes the receptor’s conformation, preventing agonist activation.
• C. Binds to the agonist itself, inactivating it.
• D. Produces the opposite effect of the agonist.

Answer: B. Binds to a different site on the receptor (an allosteric site) and changes the receptor’s conformation, preventing agonist activation.

47. The pharmacokinetics of a drug with a high degree of plasma protein binding can be significantly altered by:

• A. Co-administration of another drug that competes for the same binding sites.
• B. Changes in dietary potassium.
• C. An increase in physical activity.
• D. A change in the time of day the drug is taken.

Answer: A. Co-administration of another drug that competes for the same binding sites.

48. Why is bupropion often considered a good option for patients who want to avoid weight gain or sexual side effects?

• A. It is a very weak antidepressant.
• B. Its pharmacological profile lacks significant serotonergic or histaminic activity.
• C. It is rapidly cleared from the body.
• D. It is only approved for smoking cessation.

Answer: B. Its pharmacological profile lacks significant serotonergic or histaminic activity.

49. The term “therapeutic index” is a pharmacological measure of a drug’s:

• A. Efficacy
• B. Potency
• C. Safety, comparing the dose that causes toxicity to the dose that produces a therapeutic effect.
• D. Half-life

Answer: C. Safety, comparing the dose that causes toxicity to the dose that produces a therapeutic effect.

50. The antidepressant effects of mirtazapine are also attributed to its blockade of which serotonin receptors?

• A. 5-HT1A and 5-HT1B
• B. 5-HT2A and 5-HT2C
• C. 5-HT4
• D. 5-HT6 and 5-HT7

Answer: B. 5-HT2A and 5-HT2C