[PCOL] 3.2 Autacoids (Eicosanoids, Kinins)

Eicosanoids are derivatives of Arachidonic Acid. What enzyme catalyzes the initial rate-limiting step from Membrane Phospholipids to Arachidonic Acid, and which major drug class inhibits this enzyme?

A. Cyclooxygenase (COX); Inhibitor: NSAIDs

B. Lipoxygenase (LOX); Inhibitor: Zileuton

C. Phospholipase A2; Inhibitor: Glucocorticoids

D. Thromboxane Synthase; Inhibitor: Aspirin

C. Phospholipase A2; Inhibitor: Glucocorticoids

Explanation: Phospholipase A2 (PLA2) converts Membrane Phospholipids to Arachidonic Acid, the precursor of all Eicosanoids. Glucocorticoids inhibit this step.

The Lipoxygenase (LOX) pathway produces Leukotrienes. Which Leukotrienes are known as SRSA (Slow Reacting Substances of Anaphylaxis) and cause increased bronchial tone or bronchoconstriction?

A. LTB4

B. LTC4, LTD4, LTE4

C. Lipoxins

D. PGD2

B. LTC4, LTD4, LTE4

Explanation: LTC4, LTD4, and LTE4 are the SRSA that potently cause bronchoconstriction, a key feature of asthma and anaphylaxis.

Zileuton is a drug that specifically inhibits the formation of Leukotrienes. Which enzyme does Zileuton inhibit?

A. Cyclooxygenase (COX)

B. Phospholipase A2

C. Lipoxygenase (LOX)

D. Thromboxane Synthase

C. Lipoxygenase (LOX)

Explanation: Zileuton is a 5−Lipoxygenase inhibitor, thereby preventing the entire synthesis of Leukotrienes.

The COX pathway produces Prostaglandins and Thromboxanes. Which is the physiologic, constitutive enzyme responsible for cytoprotection in the GIT and is involved in maintenance functions?

A. COX−2 (Pathophysiologic)

B. COX−1 (Physiologic)

C. LOX

D. Phospholipase A2

B. COX−1 (Physiologic)

Explanation: COX−1 is constitutively expressed and produces Prostaglandins like PGE2 and PGI2 that are vital for stomach cytoprotection (mucus, HCO3) and renal blood flow.

NSAIDs primarily inhibit COX enzymes. What is the net result of COX inhibition on the Arachidonic Acid pathway, as indicated by the diagram's red arrow?

A. Increased Prostaglandin synthesis

B. Decreased Leukotriene synthesis

C. Shift of metabolism towards increased Leukotriene production

D. Inhibition of Phospholipase A2

C. Shift of metabolism towards increased Leukotriene production

Explanation: Blocking the COX pathway (NSAIDs) shunts more Arachidonic Acid to the LOX pathway, leading to Increased Leukotriene production (a pseudoprostaglandin effect). This can exacerbate asthma.

Which Prostaglandin and Thromboxane pair is responsible for Platelet Regulation and Vascular Tone and have opposite effects?

A. PGE2 (vasodilation) and PGF2α (vasoconstriction)

B. PGI2 (Inhibit Aggregation) and TXA2 (Promotes Aggregation)

C. PGD2 and LTC4

D. LTB4 and PGE1

B. PGI2 (Inhibit Aggregation) and TXA2 (Promotes Aggregation)

Explanation: PGI2 (Prostacyclin) is produced by endothelial cells and is a potent vasodilator and inhibitor of platelet aggregation, while TXA2 is produced by platelets and is a vasoconstrictor and promoter of aggregation (Clot).

Which Prostaglandin series is known to cause uterine contraction and is implicated in Dysmenorrhea?

A. PGI2 and PGE1 (Relaxation)

B. PGE2, PGF2α, and PGD2 (Contraction)

C. TXA2 and LTC4

D. LTB4 and Lipoxins

B. PGE2, PGF2α, and PGD2 (Contraction)

Explanation: PGE2, PGF2α, and PGD2 are potent uterotonic agents (Oxytocic) that cause uterine contraction and are responsible for menstrual cramps (Dysmenorrhea).

-Leukasts are drugs that block receptors for Leukotrienes. Which Leukotrienes are the primary targets of these receptor blockers (LTA4, LTD4, LTE4)?

A. LTB4 receptors

B. LTC4/D4/E4 receptors

C. TXA2 receptors

D. PGE2 receptors

B. LTC4/D4/E4 receptors

Explanation: Drugs ending in −lukast (e.g., Montelukast) are Leukotriene Receptor Antagonists that block the CysLT receptors responsible for the bronchoconstrictive effects of LTC4/D4/E4.

The acronym MEDAL is used to remember which class of drugs?

A. Serotonin Agonists

B. H1 Antagonists

C. Eicosanoid Synthesis Inhibitors

D. Prostaglandin Analogs and Related Drugs

D. Prostaglandin Analogs and Related Drugs

Explanation: MEDAL represents five Prostaglandin Analogs: Misoprostol, Epoprostenol, Dinoprostone, Alprostadil, and Latanoprost.

Misoprostol (Cytotec ) is a PGE1 analog with cytoprotective properties. What is its primary FDA−approved clinical use related to NSAID use?

A. Management of erectile dysfunction

B. Management of NSAID−induced peptic ulcers and gastritis

C. Acute management of pulmonary HTN

D. Lowering intraocular pressure (IOP)

B. Management of NSAID−induced peptic ulcers and gastritis

Explanation: Misoprostol replaces the cytoprotective Prostaglandins (PGE) whose synthesis is inhibited by NSAIDs.

Epoprostenol is a PGI2 (Prostacyclin) analog with potent vasodilating effects. What is its key clinical use?

A. Inducing abortion

B. Maintaining patency of Ductus Arteriosus

C. Acute management of primary pulmonary HTN

D. Treating glaucoma

C. Acute management of primary pulmonary HTN

Explanation: Epoprostenol's potent vasodilation effect in pulmonary circulation makes it a treatment for Pulmonary Arterial Hypertension (PAH).

Dinoprostone (PGE2 analog) and Carboprost Tromethamine (PGF2α analog) share which two related uterotonic clinical uses?

A. Erectile dysfunction and glaucoma management

B. NSAID ulcer Mgt and renal protection

C. Cervical ripening/labor induction and abortifacient

D. Pulmonary HTN and Ductus Arteriosus patency

C. Cervical ripening/labor induction and abortifacient

Explanation: PGE2 and PGF2α analogs are potent uterotonic agents used to ripen the cervix and to induce abortion.

Alprostadil is a PGE1 analog. What is its use in neonates with certain congenital heart defects?

A. To constrict the Ductus Arteriosus

B. To maintain patency of the Ductus Arteriosus (PDA)

C. To treat Pulmonary HTN

D. To close the Foramen Ovale

B. To maintain patency of the Ductus Arteriosus (PDA)

Explanation: PGE1 is a vasodilator that keeps the Ductus Arteriosus open (patent) in babies who need this shunt for blood flow until surgery.

Which drug is used to pharmacologically close the Ductus Arteriosus in neonates with Patent Ductus Arteriosus (PDA)?

A. Misoprostol

B. Alprostadil

C. Indomethacin

D. Dinoprostone

C. Indomethacin

Explanation: Indomethacin is a non−selective NSAID that inhibits Prostaglandin E2 (PGE2) synthesis, thereby allowing the Ductus Arteriosus to close.

Latanoprost (Xalatan ) is a PGF2α analog. What is its clinical use related to the eye?

A. Inducing bronchoconstriction

B. Management of glaucoma (lowering IOP)

C. Treating uveitis (inflammation)

D. Preventing platelet aggregation

B. Management of glaucoma (lowering IOP)

Explanation: PGF2α analogs like Latanoprost lower Intraocular Pressure (IOP) by increasing the outflow of aqueous humor, treating glaucoma.

Kinins (Bradykinin and Kallidin) are produced from which precursor molecules through the action of kallikrein?

A. Tryptophan and Tyrosine

B. Phospholipids and Arachidonic Acid

C. HMW and LMW Kininogen

D. Angiotensinogen

C. HMW and LMW Kininogen

Explanation: Kinins are formed from High Molecular Weight (HMW) and Low Molecular Weight (LMW) Kininogen by the enzymes plasma and tissue kallikrein.

Kinins are inactivated by Kininase II, which is identical to what enzyme in the Renin−Angiotensin System (RAS)?

A. Renin

B. Angiotensin Converting Enzyme (ACE)

C. Angiotensinase

D. Kallikrein

B. Angiotensin Converting Enzyme (ACE)

Explanation: ACE is synonymous with Kininase II, the enzyme that breaks down Bradykinin. This link explains why ACE Inhibitors cause Bradykinin accumulation.

ACE Inhibitors (ACEI) cause a rise in Bradykinin levels. What is the most common ADR related to this accumulation?

A. Hypotension

B. Angioedema

C. Dry cough

D. Hyperkalemia

C. Dry cough

Explanation: Increased Bradykinin in the lungs stimulates irritant receptors, leading to the dry, non−productive cough associated with ACEI.

What is the mechanism by which Kinins (Bradykinin and Kallidin) cause potent vasodilation (B2 receptor)?

A. Direct vasodilation of vascular smooth muscle

B. Inhibition of Sympathetic Nervous System

C. Release of Endothelium−Derived Relaxing Factor (EDRF →Nitric Oxide)

D. Blockade of Angiotensin II receptors

C. Release of Endothelium−Derived Relaxing Factor (EDRF →Nitric Oxide)

Explanation: Kinins bind to B2 receptors on endothelial cells, triggering the release of EDRF (NO), which causes arteriolar vasodilation.

Kinins contribute to the five cardinal signs of inflammation by causing which two effects?

A. Vasoconstriction and Bronchodilation

B. Bronchoconstriction and Decreased Capillary Permeability

C. Vasodilation and Increased Capillary Permeability

D. Vasodilation and Stimulation of Nerve Endings (Pain)

D. Vasodilation and Stimulation of Nerve Endings (Pain)

Explanation: Kinins contribute to swelling (Increased Capillary Permeability), redness and heat (Vasodilation), and Pain by directly stimulating nerve endings.

Which Angiotensin II Antagonist class reduces Angiotensin II's effects but leads to the beneficial accumulation of Bradykinin?

A. Angiotensin Receptor Blockers (ARBs)

B. Renin Inhibitors (Aliskiren)

C. ACE Inhibitors (ACEI)

D. Aldosterone Antagonists

C. ACE Inhibitors (ACEI)

Explanation: ACEI block the formation of Angiotensin II AND the breakdown of Bradykinin (via Kininase II inhibition), leading to increased Kinins.

What is the primary mechanism of Angiotensin II Receptor Blockers (ARBs) in lowering BP?

A. Inhibiting renin secretion

B. Preventing the conversion of Angiotensin I to Angiotensin II

C. Competitive binding to the AT1 receptor

D. Inhibiting aldosterone synthesis

C. Competitive binding to the AT1 receptor

Explanation: ARBs act as competitive antagonists at the AT1 receptor, blocking all of Angiotensin II's vasoconstrictive and salt−retaining effects.

Which Renin Inhibitor is mentioned as a drug that directly blocks the first step of the RAS cascade?

A. Candesartan

B. Losartan

C. Aliskiren (Rasilez)

D. Enalapril

C. Aliskiren (Rasilez)

Explanation: Aliskiren is a direct Renin Inhibitor, preventing Renin from converting Angiotensinogen to Angiotensin I.