[PCOL] 3.1 Autacoids (Histamine & Serotonin)

Autacoids are often referred to as "Paracrine /Local hormones" because their site of action is where?

A. Far away from the area of secretion (Systemic distribution)

B. Within the area of secretion

C. Only in the CNS

D. Only in Exocrine glands

B. Within the area of secretion

Explanation: Autacoids are endogenous compounds that act locally (Paracrine) at their site of secretion, unlike classical hormones that require systemic distribution.

Which amino acid is the precursor for the biosynthesis of Histamine?

A. L−Tyrosine

B. L−Tryptophan

C. L−Histidine

D. L−Arginine

C. L−Histidine

Explanation: Histamine is produced from the amino acid L−Histidine via decarboxylation.

The conversion of L−Histidine to Histamine is catalyzed by which enzyme and requires which vitamin as a cofactor?

A. Histidine Decarboxylase + Vitamin C

B. Monoamine Oxidase + Vitamin B12

C. Histidine Decarboxylase + Vitamin B6

D. Dopa Decarboxylase + Iron

C. Histidine Decarboxylase + Vitamin B6

Explanation: The reaction L−Histidine⟶Histamine is mediated by the enzyme Histidine Decarboxylase and requires Vitamin B6 (Pyridoxal phosphate) as a cofactor.

Which cell types account for approximately 70% of Histamine storage in the body?

A. Erythrocytes and Lymphocytes

B. Platelets and Neutrophils

C. Mast cells and Basophils

D. Enterochromaffin−like cells in the stomach

C. Mast cells and Basophils

Explanation: The majority of Histamine is stored in secretory granules of Mast cells (tissue location) and Basophils (blood location).

Histamine is released from mast cells and basophils via a process known as Degranulation. What is the release process called when it is IgE mediated and Ca

2+

dependent?

A. Anaphylactoid reaction

B. Neurogenic inflammation

C. Anaphylaxis

D. Phagocytosis

C. Anaphylaxis

Explanation: Anaphylaxis is the classic IgE−mediated hypersensitivity reaction (Type I), which triggers Ca

2+

influx into the mast cell, causing degranulation.

Histamine release that is Non−IgE mediated and Ca

2+

independent is called what?

A. Anaphylactoid reaction

B. Autoimmune disease

C. Allergy

D. Sympathetic release

A. Anaphylactoid reaction

Explanation: Anaphylactoid reactions mimic true Anaphylaxis but are triggered by direct drug-induced degranulation (e.g., from opioids or certain NMBs), and are Non−IgE and Ca

2+

independent.

In which organs or systems, besides Mast cells and Basophils, is Histamine found?

A. Liver and Kidneys

B. Stomach (Enterochromaffin−like cells) and CNS (Brain)

C. Skeletal muscles and Bone marrow

D. Pancreas and Thyroid

B. Stomach (Enterochromaffin−like cells) and CNS (Brain)

Explanation: Histamine is also synthesized and stored in enterochromaffin−like cells of the stomach (regulating acid secretion) and acts as a neurotransmitter in the brain (CNS).

Which drugs are classified as H3 Agonists?

A. Histamine, Betahistine

B. Indophenpropit, Thioperamide

C. R-alpha-methylhistamine, Imetine, Immepip

D. Doxapine, Clozapine

9899

C. R-alpha-methylhistamine, Imetine, Immepip

Explanation: R-alpha-methylhistamine, Imetine, and Immepip are examples of selective H3 receptor agonists.

Which H3 Antagonist is noted for being linked with the management of obesity?

A. Indophenpropit

B. Thioperamide

C. Clobenpropit

D. Histamine

B. Thioperamide

Explanation: Thioperamide is an H3 Antagonist that, by blocking the inhibitory H3 autoreceptor, increases Histamine release, which is linked to appetite suppression and the management of obesity.

Which two drugs are classified as both H4 Agonists and also H3 Antagonists and are often used to treat psychotic disorders?

A. Thioperamide, Indophenpropit

B. R-alpha-methylhistamine, Imetine

C. Doxapine, Clozapine

D. Betahistine, Histamine

C. Doxapine, Clozapine

Explanation: Doxapine and Clozapine are psychotropic drugs that have been found to act as H4 Agonists.

Which drug is listed as having dual activity as an H3 Antagonist and an H4 Agonist?

A. Indophenpropit

B. Thioperamide

C. Clobenpropit

D. Betahistine

C. Clobenpropit

Explanation: Clobenpropit is listed as having this dual activity, functioning as both an H3 Antagonist and H4 Agonist.

Which severe adverse drug reaction (ADR) is specifically noted for the H4 Agonist Clozapine?

A. Malignant hyperthermia

B. Agranulocytosis

C. Pulmonary fibrosis

D. Hepatotoxicity

B. Agranulocytosis

Explanation: Clozapine is specifically noted for the risk of Agranulocytosis (a severe drop in white blood cells), which requires close blood monitoring.

Histamine is generally considered Obsolete for therapeutic use, but it was formerly used as a diagnostic agent for which two conditions?

A. Obesity and Glaucoma

B. Acid peptic disease and Allergy

C. Airway hyperresponsiveness (Pulmonary challenge test) and Achlorhydria (Gastric acid secretion)

D. Hypertension and Symptomatic bradycardia

C. Airway hyperresponsiveness (Pulmonary challenge test) and Achlorhydria (Gastric acid secretion)

Explanation: Histamine's ability to cause bronchoconstriction and acid secretion was used diagnostically. It is replaced by Methacholine for Pulmonary challenge tests.

Achlorhydria is the absence of HCl. The management of this condition involves providing what concentration of HCl?

A. Acetic Acid (6%)

B. Dilute HCl (10%)

C. Concentrated HCl (30%)

D. Dilute HCl (6%)

B. Dilute HCl (10%)

Explanation: The notes indicate that Achlorhydria is managed by administering Dilute HCl (10%), as most diluted acids are 10% in concentration.

What is the standard concentration for most diluted acids mentioned in the notes, with the exception of Acetic Acid?

A. 6%

B. 10%

C. 25%

D. 100%

B. 10%

Explanation: Most diluted acids are 10% in concentration, except for Acetic Acid, which is 6%.

What is the dual mechanism of action (MOA) of Betahistine (Serc)?

A. H2 Agonist and H4 Antagonist

B. H1 Agonist and central H3 Antagonist

C. H1 Antagonist and H2 Antagonist

D. Non−selective Histamine release inhibitor

B. H1 Agonist and central H3 Antagonist

Explanation: Betahistine acts as an H1 agonist and a central H3 antagonist. The H3 antagonism increases Histamine release, which leads to vasodilation of the middle ear and resorption of endolymph hydrops.

What is the primary clinical use of Betahistine?

A. Management of allergic rhinitis

B. Management of gastroesophageal reflux disease (GERD)

C. Management of vertigo and Meniere's disease

D. Diagnosis of airway hyperresponsiveness

C. Management of vertigo and Meniere's disease

Explanation: Betahistine is used to manage vertigo associated with Meniere's Syndrome (inner ear fluid imbalance or endolymph hydrops).

Which drug is the Physiologic Antagonist to Histamine?

A. Cromolyn Sodium

B. Epinephrine

C. Ranitidine

D. Diphenhydramine

B. Epinephrine

Explanation: Epinephrine is the Physiologic Antagonist because its alpha and beta agonism (vasoconstriction, bronchodilation) produces effects opposite to those of Histamine.

Which two drug classes are the Pharmacologic Antagonists to Histamine?

A. H1 Antagonists and H2 Antagonists

B. Nedocromil and Cromolyn Sodium

C. AChE Inhibitors and NMDA Antagonists

D. Beta blockers and Calcium channel blockers

A. H1 Antagonists and H2 Antagonists

Explanation: H1 Antagonists (Antihistamines) and H2 Antagonists (Antacids) are the Pharmacologic Antagonists that competitively block Histamine receptors.

What is the mechanism of action of Nedocromil and Cromolyn Sodium?

A. H2 receptor blockade

B. Direct H1 agonism

C. Histamine Release Inhibitors (Mast cell stabilizers)

D. Anti−muscarinic activity

C. Histamine Release Inhibitors (Mast cell stabilizers)

Explanation: These drugs stabilize the mast cell membrane, preventing degranulation and the release of Histamine.

1st Generation H1 Antagonists are Sedating because they are Lipophilic. What are the three characteristic side effects related to their passage across the BBB and other receptor blockade?

A. Antimuscarinic effects (Alice in Wonderland), Sedation, Orthostatic hypotension

B. GI upset, Nausea, Vomiting

C. Rhabdomyolysis, Hyperkalemia, Fever

D. Tachycardia, Bronchodilation, Urinary retention

A. Antimuscarinic effects (Alice in Wonderland), Sedation, Orthostatic hypotension

Explanation: Due to Lipophilicity, they cause Sedation (central H1 block), Antimuscarinic effects (central and peripheral), and sometimes Orthostatic hypotension (alpha−1 blockade).

Which Ethanolamine derivative has the highest antimuscarinic effect and is the DOC (IV route) for acute dystonic crisis (severe torticollis)?

A. Promethazine

B. Doxylamine

C. Diphenhydramine (Benadryl)

D. Meclizine

C. Diphenhydramine (Benadryl)

Explanation: Diphenhydramine is used to manage Parkinsonism and acute dystonic crisis because of its potent central antimuscarinic effects.

Which Ethanolamine derivative is listed as the most sedating H1 blocker and is used primarily as a sleeping aid (Unisom tablet)?

A. Diphenhydramine

B. Dimenhydrinate

C. Carbinoxamine

D. Doxylamine

D. Doxylamine

Explanation: Doxylamine is noted for being the most sedating H1 blocker and is marketed specifically as a sleeping aid.

Which Piperazine derivative is the DOC for motion sickness?

A. Hydroxyzine

B. Meclizine (Bonamine)

C. Cyclizine

D. Pyrilamine

B. Meclizine (Bonamine)

Explanation: Meclizine is highly effective against motion sickness due to its combined H1 and antimuscarinic activity in the vestibular system.

Which Phenothiazine derivative is used as an Anesthetic adjunct to minimize Stage II anesthesia (emergence phenomenon) and has an additional MOA as a Na

+

channel blocker?

A. Chlorpheniramine

B. Promethazine (Phenergan)

C. Hydroxyzine

D. Cyproheptadine

B. Promethazine (Phenergan)

Explanation: Promethazine's sedative and Na

+

channel blocking effects make it useful as an anesthetic adjunct to reduce excitation during the induction phase.

Which Piperidine derivative has an additional MOA as a 5−HT Antagonist and is the DOC for the management of Serotonin Syndrome?

A. Meclizine

B. Cyproheptadine

C. Hydroxyzine

D. Brompheniramine

B. Cyproheptadine

Explanation: Cyproheptadine is the DOC for Serotonin Syndrome because its 5−HT Antagonist activity directly counteracts the excess serotonergic stimulation responsible for the syndrome's symptoms (muscle rigidity, hyperthermia).

What are the two primary reasons 2nd Generation H1 Antagonists are considered safer than 1st Generation drugs?

A. They are more lipophilic and do not block H1.

B. They do not cause Orthostatic hypotension and CNS effects.

C. They block alpha1, 5−HT, and Na

+

channels.

D. They are more potent for allergic rhinitis.

B. They do not cause Orthostatic hypotension and CNS effects.

Explanation: 2nd Generation drugs have a better safety profile because they are Less lipophilic and do not attach to alpha1, 5−HT, Na

+

, or CNS receptors (M1), avoiding sedation and peripheral side effects like Orthostatic hypotension.

Which structural class of 2nd Generation Antihistamines is considered Less sedating and includes the drug Cetirizine?

A. Piperidines

B. Ethanolamines

C. Piperazines

D. Alkylamines

C. Piperazines

Explanation: The Piperazine class, which includes Cetirizine (a metabolite of Hydroxyzine), is generally less sedating compared to the Non−sedating Piperidines.

Which structural class of 2nd Generation Antihistamines is considered Non−sedating and includes the drug Loratadine?

A. Piperazines

B. Piperidines

C. Phenothiazines

D. Ethylenediamines

B. Piperidines

Explanation: The Piperidine class, including Loratadine, Desloratadine, and Fexofenadine, is highly hydrophilic and characterized as Non−sedating.

2nd Generation Antihistamines are the only generation allowed for use by which profession due to their lack of CNS impairment?

A. Surgeons

B. Truck drivers

C. Pilots

D. Heavy machinery operators

C. Pilots

Explanation: Because they do not cross the BBB, 2nd Generation Antihistamines are the only type allowed to be used by pilots and patients who operate heavy machinery.

Which 2nd Generation Antihistamine has an additional MOA as a Mast cell stabilizer and is recommended for use 4-6 weeks before allergy season?

A. Fexofenadine

B. Ketotifen

C. Desloratadine

D. Bilastine

B. Ketotifen

Explanation: Ketotifen possesses dual activity (H1 Antagonist and Mast cell stabilizer), making it effective for seasonal allergic rhinitis when started prophylactically before allergen exposure.

Which drug combination, used for allergic symptoms, includes Levocetirizine (a 3rd Generation Piperazine) and Montelukast (a Leukotriene Receptor Antagonist)?

A. Co−Aleva (Ebastine+Betamethasone)

B. Co−Altria or Zykast

C. Claritin

D. Benadryl

B. Co−Altria or Zykast

Explanation: Zykast or Co−Altria is the brand name for the combination of Levocetirizine and Montelukast, addressing allergy symptoms via both Histamine and Leukotriene pathways.

3rd Generation Antihistamines are active metabolites of their 2nd Generation parent drugs. Match the 3rd Generation drug to its 2nd Generation precursor:

A. Fexofenadine ⟵ Loratadine; Desloratadine ⟵ Terfenadine

B. Levocetirizine ⟵ Fexofenadine; Desloratadine ⟵ Cetirizine

C. Fexofenadine ⟵ Terfenadine; Desloratadine ⟵ Loratadine

D. Levocetirizine ⟵ Loratadine; Fexofenadine ⟵ Cetirizine

C. Fexofenadine ⟵ Terfenadine; Desloratadine ⟵ Loratadine

Explanation: Fexofenadine is the metabolite of Terfenadine, and Desloratadine is the metabolite of Loratadine. Levocetirizine is the active enantiomer of Cetirizine.

What is the comparative Potency and Effectiveness noted between 1st Generation and 2nd Generation Antihistamines?

A. 1st gen is more potent and more effective for allergic rhinitis.

B. 2nd gen is more potent but less effective for allergic rhinitis.

C. 1st gen is more potent, but 2nd gen is less effective for allergic rhinitis.

D. 2nd gen is more potent and more effective for allergic rhinitis.

C. 1st gen is more potent, but 2nd gen is less effective for allergic rhinitis.

Explanation: 1st generation is noted to be more potent. However, 2nd generation is noted as less effective for allergic rhinitis compared to 1st generation, despite the safety trade-off.

Which H2 Antagonist is the Prototype and is characterized by a 5-C aromatic Imidazole ring with 2 N atoms?

A. Ranitidine

B. Famotidine

C. Nizatidine

D. Cimetidine (Tagamet)

D. Cimetidine (Tagamet)

Explanation: Cimetidine is the prototype H2 Antagonist and belongs to the Imidazole chemical class. It is also noted as the least potent (requiring the highest dose of 800 mg).

Which H2 Antagonist is chemically characterized by a Thiazole ring (5-C aromatic with 1 N and 1 S atom) and is the Most potent?

A. Cimetidine

B. Ranitidine

C. Famotidine (H2−Bloc)

D. Nizatidine

C. Famotidine (H2−Bloc)

Explanation: Famotidine is the most potent H2 Antagonist (only 40 mg needed) and is characterized by the Thiazole ring structure.

Which H2 Antagonist is chemically characterized by a Furan ring (5-C aromatic with 1 Oxygen atom)?

A. Ranitidine (Zantac)

B. Cimetidine

C. Famotidine

D. Nizatidine

A. Ranitidine (Zantac)

Explanation: Ranitidine is chemically a Furan derivative.

Which H2 Antagonist is noted for having almost 100% Oral Bioavailability (BA)?

A. Cimetidine

B. Ranitidine

C. Famotidine

D. Nizatidine (Axid)

D. Nizatidine (Axid)

Explanation: Nizatidine has very little first−pass metabolism, resulting in an Oral BA of almost 100%.

What is the primary Clinical Use of H2 Antagonists?

A. Management of acute allergic reactions

B. Management of vertigo and motion sickness

C. Management of acid peptic diseases (GERD, Dyspepsia, PUD)

D. Symptomatic relief of colds and rhinitis

C. Management of acid peptic diseases (GERD, Dyspepsia, PUD)

Explanation: H2 Antagonists block gastric acid secretion and are a cornerstone in the management of PUD, mild GERD, and acute GI ulcer bleeding (IV infusion).

H2 Antagonists are sometimes administered at bedtime for which adjunct purpose?

A. To potentiate antacid effect

B. As an adjunct anti−allergy medication

C. To prevent gastric polyps

D. To improve Vit B12 absorption

B. As an adjunct anti−allergy medication

Explanation: H2 receptors are involved in mast cell activation and vasodilation. H2 blockade can provide supplementary benefit in treating certain allergic conditions (in combination with H1 blockers).

Cimetidine's anti−androgenic $\text{ADR}$s are due to its additional MOA as what?

A. Enzyme inducer

B. Enzyme inhibitor

C. Alpha−1 blocker

D. Histamine release inhibitor

B. Enzyme inhibitor

Explanation: Cimetidine is a potent Enzyme inhibitor (CYP450), which leads to increased levels of other drugs, and it possesses anti-androgenic activity, resulting in Gynecomastia, sterility, and loss of libido.

Prolonged use of H2 Antagonists can lead to Vit B12 deficiency because reduced HCl production affects the activity of which enzyme?

A. Histidine Decarboxylase

B. Pepsin

C. Monoamine Oxidase

D. Cholinesterase

B. Pepsin

Explanation: Pepsin, which is activated by acidic pH (HCl), is essential for releasing Vit B12 from food proteins (Extrinsic factor) so it can be absorbed. Reduced HCl impairs Pepsin's function, causing Vit B12 deficiency.

Serotonin (5−HT) is synthesized from which precursor amino acid?

A. Tyrosine

B. Histidine

C. Tryptophan

D. Phenylalanine

C. Tryptophan

Explanation: Tryptophan is the precursor for Serotonin (5−Hydroxytryptamine), undergoing decarboxylation to form Tryptamine, followed by hydroxylation to form 5−HT.

Where is the majority (greater than 90%) of Serotonin stored in the body?

A. CNS neurons

B. Skeletal muscle

C. Platelets and Brain cells

D. Enterochromaffin cells (ECF) in the GIT

D. Enterochromaffin cells (ECF) in the GIT

Explanation: Over 90% of the body's Serotonin is found in the Enterochromaffin cells of the small intestine, where it regulates GI motility.

Serotonin is metabolized by MAO (Monoamine Oxidase) into which major inactive metabolite?

A. Melatonin (N−acetyl−5−methoxytryptamine)

B. Norepinephrine

C. 5−HIAA (5−hydroxyindole acetic acid)

D. Vanillylmandelic Acid (VMA)

C. 5−HIAA (5−hydroxyindole acetic acid)

Explanation: 5−HIAA is the major inactive metabolite formed when 5−HT is broken down by MAO.

Which Serotonin receptor is the only type that is Ligand Gated Ion Channel (all others are G−coupled)?

A. 5−HT1A

B. 5−HT2A

C. 5−HT3

D. 5−HT4

C. 5−HT3

Explanation: The 5−HT3 receptor is a Ligand Gated Ion Channel and is primarily located in the Area Postrema (CTZ), mediating Nausea and Vomiting.

Activation of the 5−HT2A receptor on Smooth Muscle and Platelets causes what two primary effects?

A. Nausea/Vomiting and Mood regulation

B. Peristalsis and Inhibition of 5−HT release

C. Contraction (Vasoconstriction, Uterine contraction, Bronchospasm) and Platelet Aggregation

D. Vasodilation and Thermoregulation

C. Contraction (Vasoconstriction, Uterine contraction, Bronchospasm) and Platelet Aggregation

Explanation: 5−HT2A is Gq−coupled, primarily causing smooth muscle Contraction in various tissues and mediating Platelet Aggregation.

Which Serotonin receptor is Presynaptic in the CNS and functions to inhibit further 5−HT release?

A. 5−HT1A

B. 5−HT1D

C. 5−HT3

D. 5−HT4

A. 5−HT1A

Explanation: 5−HT1A is an autoreceptor (Gi−coupled) that provides negative feedback on Serotonin-containing neurons to inhibit 5−HT release.

Serotonin causes Vasoconstriction in most blood vessels (via 5−HT1D and 5−HT2A receptors), EXCEPT in which two areas?

A. Peripheral blood vessels and Uterine arteries

B. Coronary arteries and Skeletal muscle arteries

C. Renal and Splenic arteries

D. Cerebral and Pulmonary arteries

B. Coronary arteries and Skeletal muscle arteries

Explanation: Serotonin causes vasodilation in normal Coronary and Skeletal muscle arteries, although it can cause profound vasoconstriction in diseased vessels.

Activation of the 5−HT4 receptor in the GIT leads to which Peripheral Effect?

A. Vomiting via CTZ

B. Decrease in acid secretion

C. Increased GI motility / Peristalsis

D. Decreased platelet aggregation

C. Increased GI motility / Peristalsis

Explanation: 5−HT4 receptors are located in the GIT plexus (Gs−coupled) and their activation increases ACh release and smooth muscle contraction, leading to Increased Peristalsis.

Which two classes of drugs are known to Inhibit 5−HT synthesis?

A. Reserpine and Triptans

B. Amphetamines and Parachlorophenylalanine

C. Ergotamine and Ergonovine

D. Buspirone and Repinotane

B. Amphetamines and Parachlorophenylalanine

Explanation: Amphetamines and Parachlorophenylalanine (PCPA) inhibit 5−HT synthesis. PCPA specifically inhibits tryptophan hydroxylase, the rate−limiting enzyme.

What is the MOA of Reserpine on Serotonin and Norepinephrine storage, and what is the resulting ADR?

A. Inhibits synthesis; ADR:Hypertensive crisis

B. Inhibits storage; ADR:Sympatholytic

C. Stimulates release; ADR:Serotonin syndrome

D. Blocks MAO; ADR:Depression

B. Inhibits storage; ADR:Sympatholytic

Explanation: Reserpine inhibits the vesicular monoamine transporter (VMAT), preventing storage of Serotonin and Catecholamines. This leads to their depletion and a Sympatholytic effect.

Buspirone (prototype) is a 5−HT1A Partial Agonist used for mood disorders. What is its primary Clinical Use as an Anxiolytic?

A. Treatment of severe mania

B. Management of Major Depressive Disorder (MDD)

C. Management of anxiety (anxiolytic)

D. Antipsychotic in schizophrenia

C. Management of anxiety (anxiolytic)

Explanation: Buspirone decreases 5−HT release in the CNS via presynaptic 5−HT1A autoreceptors, making it an effective Anxiolytic.

Repinotane is a 5−HT1A Partial Agonist with Anti−nociceptive activity. What is a key advantage it has over Opioids?

A. It does not cause nausea or vomiting.

B. It does not cause respiratory depression.

C. It has no ADR on cognition.

D. It is not metabolized by MAO.

B. It does not cause respiratory depression.

Explanation: Unlike Opioids, Repinotane achieves pain relief without the risk of fatal respiratory depression.

Triptans (Sumatriptan, Naratriptan, etc.) are 5−HT1B/1D Full Agonists used for acute migraine. What is their primary mechanism of action in the brain and vessels?

A. Inhibition of 5−HT release and vasodilation

B. Vasoconstriction of meningeal vessels and inhibition of neuropeptide release (CGRP)

C. Stimulation of CGRP release and vasodilation

D. Inhibition of MAO to increase Serotonin levels

B. Vasoconstriction of meningeal vessels and inhibition of neuropeptide release (CGRP)

Explanation: Triptans activate 5−HT1B/1D receptors. 5−HT1B causes vasoconstriction of dilated cranial vessels, and 5−HT1D inhibits the release of pro−inflammatory neuropeptides (CGRP, Substance P) from trigeminal nerves.

Which Triptan has the Least Bioavailability (20%) and which one has the Most Bioavailability (70%)?

A. Least:Rizatriptan; Most:Zolmitriptan

B. Least:Sumatriptan; Most:Naratriptan

C. Least:Naratriptan; Most:Sumatriptan

D. Least:Amlotriptan; Most:Rizatriptan

B. Least:Sumatriptan; Most:Naratriptan

Explanation: Sumatriptan has the Least BA due to high first−pass metabolism (MAO), while Naratriptan is the Most BA (70% and metabolized by CYP).

What are the two major $\text{ADR}$s and Contraindications of Triptans related to their vasoconstrictive effect?

A. Hypotension and Bronchospasm

B. Exacerbate HTN and precipitate Angina Pectoris

C. Rebound headache and GI discomfort

D. Sedation and Orthostatic hypotension

B. Exacerbate HTN and precipitate Angina Pectoris

Explanation: Triptans' vasoconstrictive MOA on 5−HT1B receptors can cause general vasoconstriction, making them dangerous for patients with uncontrolled HTN or Coronary Artery Disease (Angina Pectoris).

Ergotamine and Dihydroergotamine (DHEA) are 5−HT2A Agonists (Ergots) used to manage migraine and cluster headache. What is the maximum frequency of migraine treatment allowed to avoid rebound headache (medication overuse headache)?

A. Daily

B. Maximum of 2 doses per week

C. Twice a day

D. Only for post−partum bleeding

B. Maximum of 2 doses per week

Explanation: Ergots and Triptans should be limited to a maximum of 2 doses per week for migraine to prevent rebound headache (medication overuse headache).

What is the Triad of symptoms characteristic of Ergotism (St. Anthony's Fire) and what is the management for digital vasospasm?

A. Nausea, Vomiting, and Diarrhea; Mgt:Opioids

B. Paresthesia, HTN, and Digital vasospasm (necrosis); Mgt:Na Nitroprusside (IV)

C. Sedation, Confusion, and Fever; Mgt:Fluids

D. Headache, Photophobia, and Phonophobia; Mgt:Acetaminophen

B. Paresthesia, HTN, and Digital vasospasm (necrosis); Mgt:Na Nitroprusside (IV)

Explanation: Ergotism is a severe poisoning from ergots characterized by the Triad symptoms. The life−threatening vasospasm is managed with Na Nitroprusside (a potent vasodilator).

Which Ergot derivative is uteroselective and used to manage post−partum bleeding?

A. Ergotamine

B. Dihydroergotamine (DHEA)

C. Ergonovine

D. Sumatriptan

C. Ergonovine

Explanation: Ergonovine is highly uteroselective, causing strong uterine contraction and is used to manage post−partum hemorrhage (bleeding).

Which 5−HT2C Agonist was FDA approved for obesity, while Fenfluramine and Dexfenfluramine were withdrawn due to pulmonary HTN and cardiotoxicity?

A. Ketanserin

B. Lorcaserin

C. Alosetron

D. Ritanserin

B. Lorcaserin

Explanation: Lorcaserin is an FDA−approved 5−HT2C Agonist used as an appetite suppressant for obesity, unlike the older drugs Fenfluramine and Dexfenfluramine which were withdrawn due to serious cardiopulmonary ADRs.

Ketanserin and Ritanserin are 5−HT2A Antagonists. What are their two main clinical uses related to their effects on smooth muscle and platelets?

A. Management of IBS−C and GERD

B. Anti−emetic in chemotherapy

C. Preventing platelet aggregation and used as anti−HTN agents

D. Prophylaxis of migraine and inducing labor

C. Preventing platelet aggregation and used as anti−HTN agents

Explanation: 5−HT2A Antagonists block vasoconstriction and platelet aggregation effects mediated by 5−HT2A, making them useful as anti−HTN and anti−platelet agents.

Tetracyclic Ergoline alkaloids (Ergotamine, DHEA, Ergonovine) are 5−HT2A Agonists noted for causing Ergotism. What are the two main therapeutic uses of these drugs?

A. Anxiolytic and Anti−nociceptive

B. Acute migraine and cluster headache Mgt and Uterine atony/postpartum hemorrhage

C. Chemotherapy antiemetic and IBS−C Mgt

D. Appetite suppression and Antidepressant

B. Acute migraine and cluster headache Mgt and Uterine atony/postpartum hemorrhage

Explanation: Ergots are vasoconstrictors used for headache (Ergotamine, DHEA) and potent uterine contractors used for postpartum bleeding (Ergonovine).

5−HT3 Antagonists (The Setrons) block receptors in the CTZ and GIT. What is their primary clinical use?

A. Management of IBS with constipation (IBS−C)

B. Prophylaxis of migraine

C. Anti−emetic in chemotherapy (CA chemotherapy induced nausea and vomiting)

D. Management of HTN

C. Anti−emetic in chemotherapy (CA chemotherapy induced nausea and vomiting)

Explanation: 5−HT3 Antagonists are the most effective agents for preventing the severe nausea and vomiting caused by chemotherapy.

Which 5−HT3 Antagonist is not used as an anti−emetic but is used for the management of IBS with predominant diarrhea (IBS−D)?

A. Ondansetron

B. Palonosetron

C. Alosetron

D. Granisetron

C. Alosetron

Explanation: Alosetron reduces intestinal motility and visceral pain by blocking 5−HT3 receptors in the GIT, making it specific for IBS−D.

Ondansetron is associated with what serious ADR related to cardiac conduction?

A. Digital vasospasm

B. Retroperitoneal Fibrosis

C. QT interval prolongation →fatal arrhythmia

D. Hypertensive crisis

C. QT interval prolongation →fatal arrhythmia

Explanation: Ondansetron can prolong the QT interval, increasing the risk of Torsades de pointes and fatal arrhythmia.

Which 5−HT3 Antagonist is administered as a single IV dose and has effects that last for around 5 days?

A. Ondansetron

B. Palonosetron

C. Granisetron

D. Alosetron

B. Palonosetron

Explanation: Palonosetron is a long−acting 5−HT3 Antagonist that only requires a single IV dose to cover delayed nausea and vomiting for several days.

Tegaserod and Cisapride are 5−HT4 Partial Agonists, while Prucalopride is a Full Agonist. What is their common clinical use?

A. Acute migraine and cluster headache

B. Management of Irritable Bowel Syndrome with predominant constipation (IBS−C)

C. Anti−emetic for chemotherapy

D. Appetite suppression

B. Management of Irritable Bowel Syndrome with predominant constipation (IBS−C)

Explanation: 5−HT4 Agonists promote GI motility and peristalsis (prokinetic), making them effective for IBS−C and GERD.

Melatonin is primarily used for which two sleep−related conditions?

A. Acute migraine and tension headaches

B. Major depressive disorder (MDD) and anxiety

C. Sleep aid and to prevent jet lag disorder

D. IBS−C and GERD

C. Sleep aid and to prevent jet lag disorder

Explanation: Melatonin is the hormone that regulates sleep cycles (circadian rhythm), making it useful as a sleep aid and for managing jet lag.

Which two Melatonin Receptors mediate the effects of Melatonin?

A. MT−3 and MT−4

B. MT−1 and MT−2

C. 5−HT1A and 5−HT2C

D. MT−1 and 5−HT2A

B. MT−1 and MT−2

Explanation: Melatonin acts on MT−1 receptors to induce drowsiness/sleepiness and on MT−2 receptors to regulate the circadian rhythm.

Ramelteon is a Melatonin Agonist specifically approved for the treatment of which sleep disorder?

A. Narcolepsy

B. Sleep apnea

C. Insomnia

D. Restless legs syndrome

C. Insomnia

Explanation: Ramelteon is a Melatonin receptor agonist used to treat Insomnia (specifically sleep onset difficulty).

Agomelatine is used to treat Major Depressive Disorder (MDD). What is its dual mechanism of action (MOA)?

A. 5−HT1A agonist and H3 antagonist

B. Melatonin agonist and 5−HT2C antagonist

C. MAO inhibitor and 5−HT3 antagonist

D. Melatonin agonist and D2 antagonist

B. Melatonin agonist and 5−HT2C antagonist

Explanation: Agomelatine works as a Melatonin agonist to resynchronize the circadian rhythm and as a 5−HT2C antagonist to increase Norepinephrine and Dopamine release in the frontal cortex, providing an antidepressant effect.