LOCAL HORMONES AND MEDIATORS

Question 1

Where is histamine found in the body?

Answer 1

Tissues: Lungs, skin, GIT (especially high)
Cells: Mast cells, basophils, enterochromaffin-like cells (ECL in stomach), histaminergic neurons (brain)

Question 2

What are the four histamine receptors and their effects?

Answer 2

H1: Bronchoconstriction, vasodilation, increased permeability, pain/itching
H2: Gastric acid secretion, ↑ heart rate and cardiac output
H3 & H4: H3 modulates neurotransmitter release, H4 in inflammation

Question 3

What is the triple response of histamine?

Answer 3

Redness: Local vasodilation
Weal: Plasma leakage → swelling
Flare: Axon reflex → arteriolar vasodilation (CGRP)

Question 4

What are the uses and types of antihistamines?

Answer 4

H1 antagonists: Allergy relief, antiemetic; sedation (1st gen), less CNS entry (2nd gen)
H2 antagonists: ↓ gastric acid in ulcers/GERD (e.g. ranitidine, famotidine)
Agonists: Used in skin testing for allergies

Question 5

Common side effects of antihistamines?

Answer 5

Sedation, paradoxical excitement, anticholinergic effects, hypotension, dysrhythmias

Question 6

What enzymes synthesize prostanoids?

Answer 6

COX-1: Constitutive, housekeeping (GIT, kidney)
COX-2: Induced by inflammation, cytokines (IL-1, TNF-α)

Question 7

Major prostanoid effects?

Answer 7

PGD2: Bronchial/uterine relaxation
PGF2: Uterine contraction, bronchoconstriction
Short half-life

Question 8

Pharmacological interventions for prostanoids?

Answer 8

Agonists: Misoprostol, Latanoprost
Antagonists (NSAIDs): Aspirin, ibuprofen, celecoxib

Question 9

What synthesizes leukotrienes?

Answer 9

Lipoxygenase enzymes (esp. 5-LOX in WBCs, mast cells)

Question 10

Actions of leukotrienes?

Answer 10

LTB4: Neutrophil chemotaxis
LTC4, LTD4, LTE4: Bronchospasm, mucous secretion (spasmogens), vasodilation but coronary vasoconstriction

Question 11

Leukotriene-targeted drugs?

Answer 11

Zafirlukast, Montelukast (receptor antagonists)
Zileuton (5-LOX inhibitor)

Question 12

Where is serotonin produced?

Answer 12

GI tract (chromaffin cells), CNS, platelets

Question 13

Synthesis & degradation of serotonin?

Answer 13

Precursor: Tryptophan → 5-HTP → Serotonin
Degraded by MAO → 5-HIAA
Precursor to melatonin

Question 14

5-HT1:

Answer 14

CNS (inhibitory), used for migraine
Agonists: Triptans (sumatriptan, rizatriptan, etc.)

Question 15

5-HT2:

Answer 15

CNS excitation, vasoconstriction/dilation, uterine & bronchial contraction, platelet aggregation

Question 16

5-HT3:

Answer 16

Found in CTZ (chemoreceptor trigger zone), involved in vomiting
Antagonists: Ondansetron, granisetron → antiemetics

Question 17

5-HT4:

Answer 17

GI tract: ↑ motility
Agonist: Metoclopramide (non-selective)

Question 18

What are ergot alkaloids and their uses?

Answer 18

Mixed serotonin, dopamine, α-agonists
Ergotamine (migraine), bromocriptine (Parkinson’s)

Question 19

Migraine management?

Answer 19

Triptans (abortive), beta blockers, 5-HT2 antagonists, TCAs (prophylaxis)

Question 20

What is bradykinin and how is it formed?

Answer 20

A kinin peptide formed via protease cleavage of kininogens (kallikrein-kinin system)

Question 21

Bradykinin receptors and effects?

Answer 21

B1: Induced in inflammation
B2: Constitutive; vasodilation (via NO & PGI2), pain, spasmogenic

Question 22

Pharmacological agents?

Answer 22

Icatibant: B2 antagonist for hereditary angioedema
ACE inhibitors: ↑ BK, can cause dry cough

Question 23

Classes of cytokines?

Answer 23

Interleukins (IL-1, 2, 6, 8, 10, 17)
Chemokines (e.g. MCP-1, IL-8)
Interferons (IFN-α, β, γ)
Colony Stimulating Factors (G-CSF)

Question 24

Chemokines vs Interferons?

Answer 24

Chemokines: Direct immune cell migration (acute vs chronic response)
Interferons: Antiviral, antitumor (IFN-α, IFN-β, IFN-γ)

Question 25

What are neuropeptides and their functions?

Answer 25

Include Substance P, CGRP, endorphins Act in inflammation, vasodilation, pain transmission, smooth muscle contraction

Question 26

What is Nitric Oxide and how is it synthesized?

Answer 26

A gaseous signaling molecule from L-arginine via NO synthases (NOS) eNOS, nNOS: Constitutive (Ca²⁺-dependent) iNOS: Inducible (inflammatory cells, cytokine-driven, Ca²⁺-independent)

Question 27

Physiological effects of NO?

Answer 27

Vasodilation (via cGMP) Inhibits platelet aggregation, smooth muscle contraction ↑ COX-2 activity In CNS: Neurotransmitter, apoptotic mediator

Question 28

Pharmacological NO donors?

Answer 28

Nitroglycerin, Sodium nitroprusside, Inhaled NO (pulmonary hypertension) Used for angina, heart failure, ICU ventilation support

Question 29

Clinical considerations for NO?

Answer 29

NO deficiency in diabetes, smoking, hyperlipidemia Excess NO: Forms methemoglobin → hypoxia