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Common Non-communicable Diseases - ME2366 > L1 - Inflammation > Flashcards

L1 - Inflammation Flashcards

1
Q

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What is the “alarm” phase in the inflammatory response analogy?

A

The “alarm” phase represents the detection of damage or harmful stimuli (e.g., pathogens or injury), triggering the immune system to respond, much like emergency services being alerted to a fire.

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2
Q

What do the “emergency services” represent in the inflammatory response analogy?

A

Immune cells such as neutrophils and macrophages rushing to the site of damage or infection, beginning the fight against the harmful stimuli, much like firefighters attending the scene of a fire.

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3
Q

How is the “chaos” phase represented in the inflammatory response analogy?

A

The chaotic phase corresponds to the active inflammatory process: immune cells arrive in large numbers, barriers are created to contain the damage, and the area experiences redness, swelling, and heat due to increased blood flow and immune activity.

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4
Q

What does the “repair” phase signify in the inflammatory response analogy?

A

The repair phase involves the resolution of inflammation, replacement of damaged cells, and removal of debris, akin to rebuilding and cleaning up after a fire has been extinguished.

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5
Q

What do “false alarms” or “overreactions” represent in the inflammatory response analogy?

A

False alarms or overreactions represent inappropriate immune responses, such as allergies (exaggerated response to harmless substances) or autoimmunity (attacking the body’s own tissues).

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6
Q

Causes of inflammation - Infection & Microbial toxins

A
  • Bacterial
  • Viral
  • Fungal
  • Parasitic
  • Mild  Severe  Chronic
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7
Q

Causes of inflammation - Tissue Necrosis

A
  • Ischaemia
  • Trauma
  • Physical/chemical injury
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8
Q

Causes of inflammation
Immune reactions

A

Also referred to as hypersensitivity
* Autoimmune
* Allergens
* Microbes
* Typically associated with chronic
inflammation

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9
Q

Causes of inflammation
Foreign Bodies

A

Exogenous e.g splinters & sutures
* Endogenous e.g urate crystals (gout),
cholesterol (atherosclerosis)

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10
Q

What are Pattern Recognition Receptors (PRRs)?

A

PRRs are proteins expressed by immune cells that detect pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) to initiate an immune response.

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11
Q

What are PAMPs and DAMPs?

A

PAMPs (Pathogen-Associated Molecular Patterns): Molecules associated with pathogens (e.g., bacterial LPS, viral RNA).
DAMPs (Damage-Associated Molecular Patterns): Molecules released from damaged or dying cells (e.g., HMGB1, ATP).

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12
Q

What are the four main types of PRRs?

A

Toll-like receptors (TLRs)
Nod-like receptors (NLRs)
C-type lectin receptors (CLRs)
RIG-I-like receptors (RLRs)

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13
Q

Where are Toll-like receptors (TLRs) located?

A

TLRs can be found:

Extracellularly: On the cell surface, detecting microbial components like bacterial LPS.
Intracellularly: In endosomes, detecting viral RNA/DNA.

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14
Q

What is the function of TLRs?

A

TLRs recognise PAMPs and DAMPs, activating signalling pathways (e.g., NF-κB, MAPK) to promote cytokine release and inflammation.

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15
Q

What are Nod-like receptors (NLRs)?

A

NLRs are intracellular sensors of pathogens and cellular stress that form inflammasomes to activate inflammatory responses.

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16
Q

What is the role of inflammasomes formed by NLRs?

A

Inflammasomes activate caspase-1, which processes pro-inflammatory cytokines like IL-1β and IL-18 into their active forms.

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17
Q

What are C-type lectin receptors (CLRs)?

A

CLRs are surface receptors that recognise carbohydrate structures on pathogens like fungi, triggering antifungal immune responses.

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18
Q

What are RIG-I-like receptors (RLRs)?

A

RLRs are intracellular receptors that detect viral RNA in the cytoplasm and activate antiviral signalling pathways, including interferon production.

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19
Q

What is the difference between extracellular and intracellular PRRs?
A:

A

Extracellular PRRs: Detect pathogens in the extracellular environment (e.g., TLRs on the cell surface).
Intracellular PRRs: Detect pathogens or stress signals within the cytoplasm or endosomes (e.g., NLRs, RLRs, TLRs in endosomes).

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20
Q

How do PRRs contribute to inflammation?

A

By recognising PAMPs/DAMPs, PRRs activate signalling cascades that result in cytokine release, recruitment of immune cells, and promotion of inflammation.

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21
Q

What is an example of a PAMP detected by TLR4?

A

Lipopolysaccharide (LPS) from gram-negative bacteria.

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22
Q

What is an example of a DAMP detected by PRRs?

A

HMGB1 (High-Mobility Group Box 1) protein released from necrotic cells.

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23
Q

Why are PRRs important in immunity?

A

They are essential for early detection of pathogens and initiation of the innate immune response, bridging to adaptive immunity.

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24
Q

What is the role of inflammatory mediators in acute inflammation?

A

Inflammatory mediators are signalling molecules released by cells to initiate and regulate the inflammatory response.

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25
Q

Name key inflammatory mediators involved in the initiation of acute inflammation.

A

Histamine
Serotonin
Cytokines
Eicosanoids

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26
Q

What is the primary source and function of histamine in inflammation?

A

Source: Released by mast cells, basophils, and platelets.
Function: Increases vascular permeability and causes vasodilation, leading to redness and swelling.

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27
Q

What is the role of serotonin in acute inflammation?

A

Serotonin, released by platelets, promotes vasodilation and increased vascular permeability, similar to histamine.

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28
Q

What are cytokines, and how do they contribute to acute inflammation?

A

Definition: Small proteins (e.g., IL-1, IL-6, TNF-α) released by immune cells.
Function: Regulate inflammation by promoting immune cell recruitment, activating endothelial cells, and inducing fever.

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29
Q

What are eicosanoids, and what is their role in acute inflammation?

A

Definition: Lipid mediators derived from arachidonic acid.
Examples: Prostaglandins, leukotrienes, thromboxanes.
Function: Promote vasodilation, increase vascular permeability, and recruit immune cells.

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30
Q

Which cells release eicosanoids during acute inflammation?

A

Eicosanoids are produced by macrophages, neutrophils, mast cells, and endothelial cells.

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31
Q

How do histamine and serotonin differ in their inflammatory effects?

A

: Both increase vascular permeability, but histamine is primarily released by mast cells, while serotonin is released by platelets.

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32
Q

Why are cytokines like IL-1 and TNF-α critical in acute inflammation?

A

They amplify the inflammatory response by recruiting and activating immune cells and inducing systemic effects like fever.

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33
Q

What is the link between eicosanoids and pain during inflammation?

A

Prostaglandins sensitize nerve endings, contributing to the sensation of pain.

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34
Q

What is the purpose of vasodilation in acute inflammation?

A

Vasodilation increases blood flow to the affected area, causing redness and warmth and facilitating immune cell delivery.

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35
Q

Which inflammatory mediators are responsible for vasodilation?

A

Histamine
Serotonin
Cytokines (e.g., IL-1, TNF-α)
Eicosanoids (e.g., prostaglandins)

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36
Q

How does histamine induce vasodilation?

A

Histamine acts on H1 receptors on vascular smooth muscle, causing relaxation and increased vessel diameter.

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37
Q

What is the role of serotonin in vasodilation?

A

Serotonin, released from platelets during activation, induces vasodilation and enhances vascular permeability.

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38
Q

Which eicosanoids contribute to vasodilation, and how?

A

Prostaglandins (e.g., PGE2, PGI2) relax vascular smooth muscle, leading to increased blood flow and vasodilation.

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39
Q

How do cytokines like IL-1 and TNF-α influence vasodilation?

A

They indirectly promote vasodilation by stimulating endothelial cells to release nitric oxide (NO), a potent vasodilator.

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40
Q

What role do arterioles play in vasodilation during acute inflammation?

A

Arterioles are the primary site of vasodilation, increasing blood flow to capillaries in the affected tissue.

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41
Q

What visible clinical signs are associated with vasodilation?

A

Redness (erythema) and warmth due to increased blood flow.

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42
Q

What is the effect of vasodilation on immune cell recruitment?

A

Vasodilation enhances immune cell delivery by increasing blood flow to the site of injury or infection.

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43
Q

What is endothelial retraction in acute inflammation?

A

It is the temporary separation of endothelial cells, increasing vascular permeability to allow leukocytes, proteins, and fluid to move into the injured tissue.

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44
Q

Which inflammatory mediators trigger endothelial retraction?

A

Histamine
Bradykinin
Nitric Oxide (NO)
Complement components

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45
Q

What is the difference between endothelial retraction and endothelial injury?

A

Endothelial Retraction: Caused by chemical mediators, temporary and reversible.
Endothelial Injury: Caused by severe physical damage (e.g., burns), rapid onset, and long-lasting (hours to days).

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46
Q

How does endothelial retraction contribute to inflammation?

A

It increases vascular permeability, allowing immune cells (leukocytes), proteins (e.g., fibrinogen), and fluid to exit blood vessels and reach the site of injury.

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47
Q

What is the role of leukocytes in endothelial retraction?

A

Leukocytes migrate through the widened endothelial gaps to reach the inflamed tissue and combat infection or repair damage.

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48
Q

What role do proteins play in endothelial retraction?

A

Plasma proteins, such as fibrinogen and complement components, move into the tissue to help with clot formation and immune defence.

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49
Q

How does severe injury (e.g., thermal burns) affect the endothelium?

A

Severe injury causes direct endothelial damage, leading to sustained permeability and prolonged leakage of fluid and proteins into tissues.

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50
Q

What clinical signs result from endothelial retraction?

A

Swelling (oedema) and pain due to fluid accumulation and protein leakage into the interstitial space.

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51
Q

What is leukocyte adhesion in acute inflammation?

A

t is the process by which leukocytes attach to and migrate across the endothelium to reach inflamed tissues.

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52
Q

What are the four key steps of leukocyte adhesion?

A

Rolling
Integrin activation
Firm adhesion/spreading
Migration

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53
Q

What mediators are involved in leukocyte rolling?

A

P-selectin and E-selectin on endothelial cells bind to Sialyl-Lewis X-modified glycoproteins on leukocytes.

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54
Q

What activates integrins during leukocyte adhesion?

A

Cytokines and chemokines secreted by macrophages and endothelial cells activate integrins on leukocytes, increasing their affinity for endothelial ligands.

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55
Q

What is the difference between low-affinity and high-affinity integrins?

A

Low-affinity integrins: Allow leukocytes to roll along the endothelium.
High-affinity integrins: Enable firm adhesion and spreading on the endothelium.

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56
Q

What endothelial adhesion molecules bind to integrins on leukocytes?

A

ICAM-1 (Intercellular Adhesion Molecule-1)
PECAM-1 (CD31)

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57
Q

What triggers the expression of P-selectin, E-selectin, and ICAM-1 on endothelial cells?

A

Inflammatory signals like cytokines and microbes stimulate their upregulation on endothelial surfaces.

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57
Q

What role does PECAM-1 (CD31) play in leukocyte migration?

A

PECAM-1 facilitates leukocyte transmigration (diapedesis) through the endothelial junctions into the tissue.

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57
Q

How do macrophages contribute to leukocyte adhesion?

A

Macrophages release cytokines and chemokines that activate endothelial cells and leukocytes, promoting adhesion and migration.

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57
Q

What happens after leukocytes migrate into the tissue?

A

They phagocytose microbes, secrete inflammatory mediators, and assist in tissue repair.

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58
Q

What are vasoactive amines?

A

Vasoactive amines, like histamine, are molecules released during inflammation that alter vascular tone and permeability.

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59
Q

Where is histamine stored in the body?

A

Histamine is stored in mast cells, basophils, and platelets.

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60
Q

What triggers histamine release from mast cells?

A

Physical injury (e.g., trauma or heat)
IgE binding during allergic reactions
Complement proteins (C3a and C5a - anaphylatoxins)
Cytokines and neuropeptides

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61
Q

What are the primary effects of histamine during inflammation?

A

Vasodilation of arterioles
Increased vascular permeability in venules
Smooth muscle contraction in some tissues (e.g., bronchi)

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62
Q

What histamine receptor mediates its pro-inflammatory effects?

A

The H1 receptor mediates vasodilation, increased permeability, and smooth muscle contraction.

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63
Q

What is the role of histamine in vascular changes?

A

Causes endothelial retraction, leading to leakage of plasma and proteins.
Promotes redness (erythema) and swelling (oedema).

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64
Q

How long does histamine activity last in acute inflammation?

A

Histamine acts rapidly but is short-lived, as it is quickly degraded by enzymes like histaminase.

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65
Q

What is the systemic effect of histamine in severe allergic reactions?

A

Histamine release can cause anaphylaxis, characterised by widespread vasodilation, bronchoconstriction, and hypotension.

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66
Q

What pharmacological agents block histamine effects?

A

H1-receptor antagonists (e.g., loratadine) block inflammation and allergic symptoms.
H2-receptor antagonists (e.g., ranitidine) reduce gastric acid secretion.

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67
Q

Why is histamine considered a key mediator of acute inflammation?

A

Its rapid release and potent effects on blood vessels initiate early vascular changes essential for inflammation.

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68
Q

What is serotonin (5-HT), and where is it found?

A

Serotonin is a vasoactive amine primarily stored in enterochromaffin cells of the gut, platelets, and the CNS.

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69
Q

How is serotonin taken up into platelets?

A

Serotonin is taken up by platelets via the serotonin transporter (SERT).

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70
Q

What is the role of serotonin in the gastrointestinal (GI) tract?

A

Regulates gut motility by acting on smooth muscle.
Released into the gut lumen by enterochromaffin cells in response to stimuli.

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71
Q

What is serotonin’s function during inflammation?

A

Causes vasoconstriction or vasodilation depending on the vascular bed.
Enhances vascular permeability.
Promotes platelet aggregation during haemostasis.

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72
Q

How does serotonin contribute to platelet aggregation?

A

Serotonin is released from activated platelets, amplifying the aggregation response and contributing to clot formation.

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73
Q

What receptors mediate serotonin’s effects in inflammation?

A

Serotonin acts via 5-HT receptors, particularly 5-HT2 receptors, to modulate vascular tone and permeability.

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74
Q

What is serotonin’s role in capillary dynamics?

A

It influences capillary tone by inducing either constriction or relaxation, depending on the receptor subtype and local conditions.

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75
Q

How does serotonin act as a mediator of acute inflammation?

A

Released rapidly by platelets at sites of injury.
Initiates vascular changes and platelet aggregation.
Plays a secondary role compared to histamine.

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76
Q

Why is serotonin less studied as an inflammatory mediator compared to histamine?

A

A: Its effects are more localised and variable, and its primary role is in the GI tract and CNS rather than systemic inflammation.

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77
Q

What drugs affect serotonin pathways?

A

Selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine) block SERT in the CNS.
Antiplatelet agents (e.g., aspirin) reduce serotonin release from platelets.

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78
Q

What are eicosanoids, and what are they derived from?

A

Eicosanoids are lipid mediators derived from arachidonic acid, a polyunsaturated fatty acid found in cell membranes.

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79
Q

How is arachidonic acid released from cell membranes?

A

It is released by the enzyme phospholipase A2 (PLA2) in response to inflammatory stimuli.

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80
Q

What are the two main pathways for eicosanoid synthesis?

A

Cyclooxygenase (COX) pathway
5-Lipoxygenase (5-LOX) pathway

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81
Q

What does the COX pathway produce?

A

Produces prostaglandins, prostacyclins, and thromboxanes.

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82
Q

What are the functions of prostaglandins (PGs)?
A:

A

PGE2: Vasodilation, fever, and pain sensitisation.
PGI2 (prostacyclin): Vasodilation, inhibition of platelet aggregation.
PGF2α: Smooth muscle contraction.

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83
Q

What is the role of thromboxane (TXA2)?

A

Promotes platelet aggregation and vasoconstriction.

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84
Q

What does the 5-LOX pathway produce?

A

Produces leukotrienes (LTs) and lipoxins.

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85
Q

What are the functions of leukotrienes?
A:

A

LTB4: Chemotaxis and activation of neutrophils.
LTC4, LTD4, LTE4: Bronchoconstriction, increased vascular permeability (important in asthma and allergies).

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86
Q

What are the functions of lipoxins?

A

Anti-inflammatory mediators that promote the resolution of inflammation.

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87
Q

How do NSAIDs affect eicosanoid synthesis?

A

NSAIDs inhibit the COX enzymes (COX-1 and COX-2), reducing the production of prostaglandins and thromboxanes.

88
Q

What are the differences between COX-1 and COX-2?

A

COX-1: Constitutive, involved in maintaining homeostasis (e.g., gastric mucosal protection, renal blood flow).
COX-2: Inducible, upregulated during inflammation.

89
Q

What are the side effects of COX inhibition by NSAIDs?

A

COX-1 inhibition: Gastric ulcers, impaired platelet function.
COX-2 inhibition: Increased cardiovascular risk.

90
Q

What drugs target the 5-LOX pathway?

A

Zileuton: A 5-LOX inhibitor used in asthma treatment.
Leukotriene receptor antagonists (e.g., montelukast): Block the effects of LTC4, LTD4, LTE4.

91
Q

Why are eicosanoids important in inflammation?

A

They mediate key processes such as vasodilation, vascular permeability, leukocyte recruitment, pain, and fever.

92
Q

What are leukotrienes, and how are they synthesised

A

Leukotrienes are eicosanoids produced via the 5-lipoxygenase (5-LOX) pathway from arachidonic acid.

93
Q

Which cells produce leukotrienes?

A

LTB4: Produced mainly by neutrophils.
Cysteinyl leukotrienes (LTC4, LTD4, LTE4, LTF4): Produced by mast cells, macrophages, eosinophils, and basophils.

94
Q

What is the primary function of LTB4?

A

Acts as a potent chemoattractant, recruiting neutrophils to sites of inflammation.
Enhances neutrophil adhesion and activation.

95
Q

What are the roles of cysteinyl leukotrienes (LTC4, LTD4, LTE4)?

A

Cause bronchoconstriction.
Increase vascular permeability.
Contribute to mucus secretion.
Involved in asthma and allergic responses.

96
Q

What are the receptors for leukotrienes, and what do they mediate?
A:

A

BLT1 and BLT2: Receptors for LTB4, mediate neutrophil recruitment.
CysLT1 and CysLT2: Receptors for cysteinyl leukotrienes, mediate bronchoconstriction and inflammation.

97
Q

What are the therapeutic targets for leukotrienes?

A

5-LOX inhibitors (e.g., zileuton): Block leukotriene synthesis.
CysLT1 receptor antagonists (e.g., montelukast): Used in asthma to prevent bronchoconstriction and inflammation.

98
Q

What clinical conditions are leukotrienes most implicated in?

A

Asthma.
Allergic rhinitis.
Chronic obstructive pulmonary disease (COPD).

99
Q

What is LTB4, and what are its primary functions?

A

LTB4 is a leukotriene produced by neutrophils that acts as a potent chemoattractant, recruiting leukocytes to inflammation sites and enhancing their adhesion and activation.

100
Q

What are the two receptors for LTB4?

A

The two receptors for LTB4 are BLT1 and BLT2.

101
Q

What are the characteristics and functions of BLT1?
A:

A

Expressed: Predominantly on leukocytes.
Function: Facilitates chemotaxis and immune cell recruitment.
Affinity: High-affinity receptor for LTB4.
Signalling: Coupled to Gi/o proteins, leading to ↓cAMP and enhanced immune responses.

102
Q

What are the characteristics and functions of BLT2?

A

Expressed: Broadly in several tissues, including the gastrointestinal (GI) tract.
Function: Supports GI barrier integrity and function.
Affinity: Low-affinity receptor for LTB4.
Signalling: Coupled to Gi/q proteins, leading to ↓cAMP and ↑PLC activity.

103
Q

How does LTB4 affect intracellular signalling through BLT receptors?

A

BLT1: Activation decreases cAMP levels (↓cAMP) via Gi/o proteins, promoting immune cell activity.
BLT2: Activation involves decreased cAMP (↓cAMP) and increased phospholipase C (↑PLC) activity, contributing to tissue-specific responses.

104
Q

What roles do BLT1 and BLT2 play in health and disease?

A

BLT1: Critical in immune responses and inflammation, such as neutrophil recruitment in infections and autoimmune conditions.
BLT2: Plays a role in maintaining the GI barrier, potentially protecting against intestinal damage.

105
Q

Why is LTB4 a target for anti-inflammatory therapies?

A

LTB4 contributes to chronic inflammation and immune cell recruitment, making its receptors (BLT1/BLT2) potential targets for conditions like asthma, rheumatoid arthritis, and inflammatory bowel disease (IBD).

106
Q

What are the two cysteinyl leukotriene receptors, and what do they bind?

A

The two receptors are CysLT1 and CysLT2, which bind cysteinyl leukotrienes (LTC4, LTD4, LTE4).

107
Q

Where is CysLT1 expressed, and what are its primary functions?

A

Expressed on: Leukocytes and airway smooth muscle.
Functions:
Bronchoconstriction: Contributes to airway narrowing in asthma.
Leukocyte activation: Promotes immune cell recruitment and activity.

108
Q

Where is CysLT2 expressed, and what are its primary functions?

A

Expressed on: Leukocytes and vascular smooth muscle.
Functions:
Leukocyte activation: Enhances inflammatory responses.
Vasoconstriction: Constricts blood vessels, affecting blood flow and pressure.

109
Q

What role do cysteinyl leukotrienes (via CysLT1 and CysLT2) play in respiratory conditions?

A

They contribute to asthma and allergic rhinitis by promoting bronchoconstriction, mucus secretion, and immune cell recruitment to the airways.

110
Q

Why are CysLT1 receptors a therapeutic target in asthma?

A

Blocking CysLT1 receptors with leukotriene receptor antagonists (e.g., montelukast) reduces bronchoconstriction, airway inflammation, and symptoms of asthma and allergies.

111
Q

What is the difference in vascular effects between CysLT1 and CysLT2?

A

CysLT1: Primarily involved in bronchoconstriction.
CysLT2: Contributes to vasoconstriction, affecting blood vessel dynamics.

112
Q

What is the role of cyclooxygenase (COX) enzymes in prostaglandin synthesis?

A

Cyclooxygenase (COX) enzymes convert arachidonic acid into PGG2 and then into PGH2, which are precursors for various prostaglandins, thromboxanes, and prostacyclins.

113
Q

What are the key prostanoids derived from PGH2, and their synthesising enzymes?

A

Prostacyclin (PGI2): Synthesised by prostacyclin synthase.
Thromboxane A2 (TXA2): Synthesised by thromboxane synthase.
Prostaglandins (PGD2, PGE2): Synthesised by specific prostaglandin synthases.

114
Q

What are the primary effects of prostacyclin (PGI2)?
A:

A

Vasodilation: Expands blood vessels.
↓ Platelet aggregation: Prevents blood clot formation.

115
Q

What are the primary effects of thromboxane A2 (TXA2)?

A

Vasoconstriction: Narrows blood vessels.
↑ Platelet aggregation: Promotes blood clot formation.

116
Q

What are the effects of PGD2 and PGE2 in inflammation?

A

PGD2:
Vasodilation: Expands blood vessels.
Increased vascular permeability: Facilitates immune cell migration.
PGE2:
Vasodilation: Enhances blood flow to inflamed areas.
Vascular permeability: Contributes to redness and swelling.

117
Q

How do COX inhibitors (e.g., NSAIDs) affect this pathway?

A

They block COX enzymes, reducing the production of prostanoids (e.g., PGI2, TXA2), thereby decreasing inflammation, pain, and fever.

118
Q

What is the functional difference between PGI2 and TXA2 in vascular homeostasis?

A

PGI2: Promotes vasodilation and inhibits platelet aggregation (anti-thrombotic).
TXA2: Promotes vasoconstriction and enhances platelet aggregation (pro-thrombotic).

119
Q

What are the primary functions of COX-1 (constitutive COX)?

A

Gastric protection: Helps maintain the stomach lining.
Vascular homeostasis: Regulates blood flow and vessel function.
Platelet aggregation: Promotes blood clot formation.
Renal function: Supports kidney function, including maintaining blood flow.
Reproductive functions: Involved in processes like uterine contractions.

120
Q

What is the primary role of COX-2 (inducible COX)?

A

Site of Inflammation: Primarily expressed at sites of inflammation, where it is responsible for the production of prostaglandins that promote pain, fever, and swelling.

121
Q

Where are COX-1 enzymes constitutively expressed?

A

Brain: Involved in normal brain function.
Kidneys: Important for renal blood flow and function.
Bone: Plays a role in bone health and remodeling.

122
Q

How do COX inhibitors (NSAIDs) affect COX-1 and COX-2?
A:

A

COX-1 inhibitors reduce protective functions like gastric protection and renal blood flow.
COX-2 inhibitors primarily target inflammation but may carry a lower risk of gastric irritation

123
Q

What is the role of Phospholipase A2 (PLA2) in the production of arachidonic acid?

A

PLA2 is the most common enzyme that generates arachidonic acid.
It cleaves the phospholipid at the sn2 position, releasing arachidonic acid from membrane phospholipids.

124
Q

How does the alternate pathway generate arachidonic acid?

A

The alternate pathway involves Phospholipase C (PLC), which generates diacylglycerol (DAG).
DAG is then cleaved by DAG-lipase, releasing arachidonic acid by cutting at the sn2 position.

125
Q

What is the significance of arachidonic acid in eicosanoid biosynthesis?
A:

A

Arachidonic acid is a precursor to important eicosanoids like prostaglandins, thromboxanes, and leukotrienes, which are key mediators of inflammation and immune responses.

126
Q

What is the function of Tumour Necrosis Factor (TNF)?

A

TNF is a pro-inflammatory cytokine that plays a key role in systemic inflammation.
It is involved in fever induction, apoptosis, and the activation of immune cells such as macrophages and neutrophils.

127
Q

What are the major roles of Interleukin-1 (IL-1)?

A

IL-1 is a pro-inflammatory cytokine that helps in the regulation of immune and inflammatory responses.
It induces fever, endothelial activation, and stimulates the production of other cytokines, contributing to the acute phase response during inflammation.

128
Q

What are chemokines and how do they function?

A

Chemokines are a subgroup of cytokines that function as chemoattractants, guiding the movement of leukocytes to sites of infection or injury.
They bind to specific receptors on immune cells to mediate chemotaxis.

129
Q

Causes of chronic inflammation - Persistent infection

A
  • Hard to eradicate organisms
  • Mycobacteria e.g Tubercolosis
  • Viruses e.g Hepatitis B and C
  • Fungi e.g Aspergillosis
  • Parasites e.g Leishmaniasis
  • Evolution of acute inflammation e.g
    abscess
130
Q

Causes of chronic inflammation - Immune-mediated

A
  • Excessive/inappropriate immune activity
  • Target own tissues e.g rheumatoid
    arthritis
  • Unregulated responses e.g inflammatory
    bowel disease
  • Environmental allergens e.g asthma
131
Q

Causes of chronic inflammation - Prolonged ‘Toxin’ exposure

A

Exogenous e.g silica (silicosis)
* Endogenous e.g cholesterol and lipids
Causes of chronic inflammation

132
Q

What are the key features of acute inflammation?

A

Infiltration of immune cells such as neutrophils.
Tissue destruction due to the inflammatory response.
Healing attempts: The body tries to repair the damaged tissue.
Cuboidal epithelium may appear in damaged tissues as part of tissue repair.
Lung tissue may show signs of oedema, congestion, and infiltration of immune cells.

133
Q

What are the key features of chronic inflammation?
A:

A

Infiltration of immune cells: Chronic inflammation involves predominantly macrophages, lymphocytes, and plasma cells.
Fibrosis: Excessive collagen deposition leading to scar tissue formation.
Tissue destruction: Ongoing damage to tissues from prolonged inflammation.
Healing attempts: Ongoing attempts to repair the tissue, but this process may be impaired or incomplete, leading to chronic scarring and functional loss.

134
Q

How does chronic inflammation affect lung tissue?

A

Infiltration of immune cells such as macrophages and lymphocytes.
Fibrosis: Thickening and scarring of the lung tissue, which can impair lung function.
Tissue destruction: Continuous damage to alveolar structures.
Chronic lung diseases like chronic obstructive pulmonary disease (COPD) or pulmonary fibrosis may result from prolonged inflammation.

135
Q

What is the primary role of macrophages in inflammation?
A:

A

Phagocytosis: Macrophages engulf and digest pathogens, dead cells, and debris.
Cytokine production: They release inflammatory cytokines like TNF-α, IL-1, and IL-6, which modulate immune responses.
Tissue repair: Macrophages help in tissue repair by secreting growth factors and collagen.
Antigen presentation: They present antigens to T-cells, initiating adaptive immunity.

136
Q

How do macrophages contribute to acute inflammation?

A

Early response: Macrophages are among the first immune cells to respond to infection or injury.
Cytokine release: They release pro-inflammatory cytokines, such as TNF-α and IL-1, which promote vasodilation, recruit other immune cells, and amplify the inflammatory response.
Phagocytosis: Macrophages clear pathogens, dead cells, and debris from the inflamed tissue.

137
Q

How do macrophages contribute to chronic inflammation?
A:

A

Persistent activation: In chronic inflammation, macrophages are continuously activated and release pro-inflammatory cytokines, contributing to the cycle of ongoing inflammation.
Tissue damage: Prolonged macrophage activity leads to tissue damage and fibrosis through the release of matrix metalloproteinases (MMPs) and other damaging factors.
Macrophage polarization: In chronic inflammation, macrophages can become alternatively activated (M2), promoting tissue repair and fibrosis, but this can also lead to scar formation and impaired tissue function.

138
Q

What is the role of macrophages in tissue repair?

A

M2 polarization: Macrophages can polarize into an anti-inflammatory phenotype (M2) that promotes tissue healing and fibrosis.
Collagen secretion: They secrete growth factors (e.g., VEGF, TGF-β) and collagen to facilitate wound healing and tissue repair.
Resolution of inflammation: Macrophages also help to resolve inflammation by clearing apoptotic cells and initiating repair processes, including reepithelialization and revascularization.

139
Q

How do macrophages influence immune response during infection?

A

Innate immunity: As part of the innate immune system, macrophages act as first responders to pathogens.
Adaptive immunity activation: They present antigens to T-cells, bridging the innate and adaptive immune responses.
Cytokine production: Through cytokine release, they modulate the immune response, promoting either inflammation or resolution based on the context of the infection.

140
Q

What is the role of Th1 cells in inflammation?

A

Th1 cells activate M1 macrophages (classical macrophages) through the release of IFN-γ. M1 macrophages are involved in promoting inflammation, pathogen clearance, and tissue damage.

141
Q

What cytokine do Th1 cells release to activate macrophages?

A

Th1 cells release IFN-γ, which activates M1 macrophages, enhancing their pro-inflammatory and microbicidal activities.

142
Q

What is the role of Th2 cells in inflammation?

A

Th2 cells activate M2 macrophages (alternate macrophages) and recruit eosinophils to the site of inflammation, helping to regulate tissue repair and allergic responses.

143
Q

Which cytokines are released by Th2 cells?

A

Th2 cells release IL-4, IL-5, and IL-13, which promote M2 macrophage activation, eosinophil recruitment, and tissue repair.

144
Q

What is the role of Th17 cells in inflammation?

A

Th17 cells recruit neutrophils and monocytes to sites of infection or injury, playing a key role in defending against extracellular pathogens and promoting inflammation.

145
Q

What cytokine do Th17 cells release to recruit immune cells?

A

Th17 cells release IL-17 along with other cytokines, which stimulate the recruitment of neutrophils and monocytes to the site of inflammation.

146
Q

What is the role of eosinophils in inflammation?

A

Eosinophils are involved in IgE-mediated or parasite-mediated reactions. They release cytotoxic components, such as major basic protein, to kill parasites and modulate inflammation.

147
Q

What cytotoxic component do eosinophils release during inflammation?

A

Eosinophils release major basic protein, which is toxic to parasites and contributes to tissue damage during inflammatory responses.

148
Q

What is the role of mast cells in inflammation?

A

Mast cells bind IgE antibodies and release inflammatory mediators such as histamine and prostaglandins. They play a key role in allergic reactions and hypersensitivity responses.

149
Q

What inflammatory mediators do mast cells release?

A

Mast cells release histamine and prostaglandins, which contribute to vasodilation, increased vascular permeability, and other inflammatory responses.

150
Q

How do mast cells contribute to hypersensitivity reactions?

A

In hypersensitivity reactions, mast cells bind IgE antibodies and release histamine, prostaglandins, and other mediators that trigger inflammation and symptoms such as itching, swelling, and bronchoconstriction.

151
Q

What are anti-inflammatory drugs?

A

Anti-inflammatory drugs are medications that reduce inflammation by inhibiting the inflammatory process, typically targeting pathways like prostaglandin synthesis or immune cell activation

152
Q
A
153
Q

What are anti-histamines?

A

Anti-histamines are drugs that block the effects of histamine at histamine receptors, specifically the H1 receptors, which are involved in allergic responses and inflammation.

154
Q

What does the term ‘anti-histamine’ refer to?

A

The term ‘anti-histamine’ refers specifically to H1 receptor antagonists, not H2, H3, or H4 receptor antagonists, which have different roles in the body.

155
Q

What is the role of H1 receptors in inflammation?

A

H1 receptors mediate many symptoms of inflammation, including vasodilation, increased vascular permeability, and smooth muscle contraction. Activation of these receptors contributes to allergic responses, such as itching, swelling, and bronchoconstriction.

156
Q

How do H1 receptor antagonists (anti-histamines) work in inflammation?

A

H1 receptor antagonists block the binding of histamine to H1 receptors, reducing the symptoms of allergic reactions and inflammation, such as itching, redness, and swelling.

157
Q

What are common uses of H1 receptor antagonists?

A

H1 receptor antagonists are commonly used to treat allergic conditions such as hay fever, rhinitis, urticaria (hives), and as a treatment for some symptoms of allergic asthma.

158
Q

What are the issues with first-generation anti-histamines?

A

First-generation anti-histamines, such as cyproheptadine, cross the blood-brain barrier (BBB) and cause sedating effects, leading to drowsiness and reduced cognitive function.

159
Q

Why do first-generation anti-histamines cause sedation?

A

First-generation anti-histamines cross the BBB and block histamine receptors in the brain, which plays a role in maintaining wakefulness, resulting in sedation.

160
Q

What are the issues with second-generation anti-histamines?

A

Second-generation anti-histamines do not cross the BBB, reducing sedation, but they can be cardiotoxic, as seen with drugs like terfenadine, which can cause arrhythmias.

161
Q

What is the risk associated with terfenadine, a second-generation anti-histamine?

A

Terfenadine can be cardiotoxic, particularly at high doses, by interfering with cardiac potassium channels and leading to potentially dangerous arrhythmias.

162
Q

What are the advantages of third-generation anti-histamines?

A

Third-generation anti-histamines are considered ‘cardiosafe’ and are active metabolites of second-generation drugs, such as fexofenadine. They provide effective allergy relief with minimal risk of cardiovascular side effects.

163
Q

What is the significance of fexofenadine as a third-generation anti-histamine?

A

Fexofenadine is a metabolite of terfenadine that is safer, providing effective anti-histamine action without the cardiotoxic effects of its precursor, making it a safer option for long-term use.

164
Q

What are NSAIDs and COXIBs?

A

NSAIDs (non-steroidal anti-inflammatory drugs) are a class of drugs that inhibit cyclooxygenase (COX) enzymes, reducing inflammation, pain, and fever. COXIBs (COX-2 inhibitors) are a subtype of NSAIDs that selectively inhibit the COX-2 enzyme.

165
Q

What is the role of COX inhibitors in inflammation?

A

COX inhibitors reduce the production of prostaglandins, which are key mediators of inflammation, pain, and fever. This decreases inflammation and associated symptoms, such as swelling and pain.

166
Q

How do NSAIDs work in inflammation?

A

NSAIDs inhibit both COX-1 and COX-2 enzymes, reducing the production of prostaglandins that mediate inflammatory responses, pain, and fever.

167
Q

What is the difference between COX-1 and COX-2?

A

COX-1 is constitutively expressed in most tissues and is involved in maintaining normal physiological functions like protecting the gastric mucosa and regulating platelet aggregation. COX-2 is induced during inflammation and is responsible for producing prostaglandins involved in pain, fever, and swelling.

168
Q

What are COXIBs and how do they differ from traditional NSAIDs?

A

COXIBs, such as celecoxib, selectively inhibit the COX-2 enzyme, reducing inflammation with a lower risk of gastrointestinal side effects compared to traditional NSAIDs, which inhibit both COX-1 and COX-2.

169
Q

What is a potential side effect of NSAIDs that COXIBs help reduce?

A

Traditional NSAIDs, by inhibiting COX-1, can cause gastrointestinal irritation, ulcers, and bleeding. COXIBs selectively inhibit COX-2, reducing these gastrointestinal side effects while still providing anti-inflammatory benefits.

170
Q

What are the risks associated with COXIBs?

A

Although COXIBs reduce gastrointestinal side effects, they may increase the risk of cardiovascular events, such as heart attack and stroke, due to their effects on platelet aggregation and vascular health.

171
Q

How do COX-2 inhibitors contribute to adverse effects?

A

COX-2 inhibitors selectively block COX-2, reducing the production of PGI2 (prostacyclin), a protective prostaglandin that promotes vasodilation and inhibits platelet aggregation. This can increase the risk of cardiovascular events, such as heart attack and stroke.

172
Q

How does arachidonic acid metabolism affect renal perfusion?

A

Arachidonic acid is metabolised by COX enzymes into prostaglandins, including those that regulate renal blood flow. When NSAIDs inhibit COX-1 and COX-2, this reduces prostaglandin production, leading to decreased renal perfusion.

173
Q

How does decreased renal perfusion from NSAIDs affect blood pressure?

A

Reduced renal perfusion due to NSAIDs activates the renin-angiotensin-aldosterone system (RAAS), causing sodium and water retention, vasoconstriction, and increased blood pressure.

174
Q

What is the sequence of events leading to increased blood pressure with NSAID use?

A

NSAIDs reduce renal perfusion, which stimulates the RAAS. This results in fluid retention, vasoconstriction, and increased blood pressure, particularly in individuals with pre-existing cardiovascular or renal conditions.

175
Q

What is the role of COX inhibitors in inflammation?

A

COX inhibitors reduce the production of prostaglandins by inhibiting cyclooxygenase enzymes (COX-1 and COX-2), which are involved in inflammation, pain, and fever. This helps alleviate symptoms of inflammation and reduce pain.

176
Q

What are COXIBs?

A

COXIBs (COX-2 inhibitors) are a class of drugs that selectively inhibit the COX-2 enzyme, which is primarily involved in inflammation, without affecting COX-1, which plays a role in protecting the gastrointestinal tract.

177
Q

What are the main adverse effects of COXIBs?

A

The primary adverse effects of COXIBs include an increased risk of cardiovascular events (e.g., heart attack, stroke) due to reduced prostacyclin (PGI2) production, and potential renal issues like fluid retention and hypertension.

178
Q

How do COXIBs affect cardiovascular health?

A

COXIBs inhibit COX-2, reducing PGI2, which normally promotes vasodilation and inhibits platelet aggregation. The reduction of PGI2, combined with unopposed thromboxane A2 (TXA2) production from COX-1, can increase the risk of thrombotic events like heart attack and stroke.

179
Q

How do COXIBs contribute to renal adverse effects?

A

COXIBs, by inhibiting COX-2, can reduce the production of renal prostaglandins that help regulate blood flow and filtration in the kidneys. This can lead to decreased renal perfusion, fluid retention, and potential kidney impairment.

180
Q

Are COXIBs safer for the gastrointestinal system than traditional NSAIDs?

A

Yes, COXIBs are generally safer for the gastrointestinal system compared to traditional NSAIDs because they selectively inhibit COX-2, sparing COX-1, which is responsible for protecting the gastric mucosa. However, they still pose cardiovascular risks.

181
Q

What are glucocorticoids, and how do they act as anti-inflammatory steroids?

A

Glucocorticoids, such as hydrocortisone (cortisol), are steroid hormones that suppress inflammation by inhibiting the production of pro-inflammatory cytokines and mediators like prostaglandins and leukotrienes. They also reduce immune cell activity.

182
Q

How is hydrocortisone (cortisol) regulated in the body?

A

Hydrocortisone is produced by the adrenal glands in response to adrenocorticotropic hormone (ACTH) from the pituitary gland. ACTH stimulates the release of cortisol, which then exerts various metabolic and anti-inflammatory effects.

183
Q

What are the main therapeutic uses of glucocorticoids?

A

Glucocorticoids are used to treat a variety of inflammatory and autoimmune conditions, such as asthma, rheumatoid arthritis, and inflammatory bowel disease, due to their potent anti-inflammatory effects.

184
Q

What are the common side effects of glucocorticoids?

A

Common side effects include weight gain, fluid retention, hyperglycaemia (increased blood sugar), osteoporosis, increased susceptibility to infection, gastrointestinal ulcers, and mood changes such as anxiety or depression.

185
Q

How do glucocorticoids affect bone health?

A

Long-term use of glucocorticoids can lead to osteoporosis by inhibiting bone formation, reducing calcium absorption, and increasing bone resorption, which increases the risk of fractures.

186
Q

What is the effect of glucocorticoids on the immune system?

A

Glucocorticoids suppress the immune system by inhibiting the activation of T lymphocytes, reducing the production of cytokines, and preventing the accumulation of immune cells at sites of inflammation. This increases the risk of infections.

187
Q

How do glucocorticoids affect blood sugar levels?

A

Glucocorticoids can cause hyperglycaemia by promoting gluconeogenesis (glucose production) in the liver and reducing the effectiveness of insulin, which can lead to steroid-induced diabetes, particularly in long-term use.

188
Q

What are the long-term risks of glucocorticoid use?

A

Long-term glucocorticoid use increases the risk of systemic side effects, such as Cushing’s syndrome (characterized by obesity, moon face, and muscle wasting), adrenal suppression, hypertension, and mental health changes.

189
Q

What are Disease-Modifying Anti-Rheumatic Drugs (DMARDs)?

A

DMARDs are a group of drugs used to treat autoimmune diseases like rheumatoid arthritis by halting or reversing the progression of the disease. They have a slow onset of action, and their mechanisms of action are often not fully understood.

190
Q

What is the aim of using conventional synthetic DMARDs?

A

The aim of conventional synthetic DMARDs is to halt or reverse the progression of autoimmune diseases, reducing disease activity and preventing long-term joint damage.

191
Q

What are the key characteristics of conventional synthetic DMARDs?

A

Conventional synthetic DMARDs are a heterologous group of drugs with a slow onset of action. Their mechanisms of action vary and are often not fully understood.

192
Q

What are some examples of conventional synthetic DMARDs?

A

Examples include methotrexate, chloroquine (an anti-malarial), sulfasalazine (an NSAID), and cyclosporine (an immunosuppressant).

193
Q

How does methotrexate act as a DMARD?

A

Methotrexate is an anti-folate drug that inhibits the enzyme dihydrofolate reductase, reducing DNA synthesis in rapidly dividing cells, including immune cells, thereby suppressing inflammation and modulating the immune response.

194
Q

What is the role of chloroquine as a DMARD?

A

Chloroquine, an anti-malarial drug, modulates the immune system and reduces inflammation by inhibiting the activation of T lymphocytes and the production of cytokines, which are involved in the inflammatory process.

195
Q

How does sulfasalazine act in autoimmune diseases?

A

Sulfasalazine has both anti-inflammatory and immunomodulatory effects, possibly through the inhibition of cytokine production, though its exact mechanism in treating autoimmune diseases like rheumatoid arthritis remains unclear.

196
Q

How does cyclosporine work as a DMARD?

A

Cyclosporine is an immunosuppressant that inhibits T-cell activation by blocking calcineurin, a key enzyme in the activation of T cells, thereby reducing the immune response and inflammation in autoimmune diseases.

197
Q

How does methotrexate work as a disease-modifying anti-rheumatic drug (DMARD)?

A

Methotrexate inhibits dihydrofolate reductase (DHFR), blocking the conversion of dihydrofolate (DHF) to tetrahydrofolate (THF). This disrupts the synthesis of thymine and purines, essential for DNA synthesis, affecting rapidly dividing cells, such as immune cells and cancer cells.

198
Q

What is the role of tetrahydrofolate (THF) in the body?

A

Tetrahydrofolate (THF) is essential for the synthesis of thymine and purines, which are crucial for DNA synthesis and cell division.

199
Q

How does methotrexate affect purine synthesis?

A

Methotrexate inhibits enzymes involved in purine synthesis, including the conversion of glutamate, aspartate, and glycine to inosine monophosphate (IMP), a precursor to adenine and guanine, which are required for DNA replication.

200
Q

What are the effects of methotrexate on rapidly dividing cells?

A

Methotrexate targets rapidly dividing cells, such as immune cells and cancer cells, by interfering with DNA synthesis. This suppresses the immune response, reducing inflammation in autoimmune diseases like rheumatoid arthritis.

201
Q

Why does methotrexate cause bone marrow depletion?

A

Methotrexate affects rapidly dividing cells, including bone marrow cells, leading to bone marrow suppression. This can result in decreased production of blood cells, leading to conditions such as anaemia, leukopenia, and thrombocytopenia.

202
Q

What phases of the cell cycle does methotrexate affect?

A

Methotrexate primarily affects the S phase of the cell cycle, where DNA replication occurs, as it disrupts the synthesis of purines and thymine required for DNA synthesis.

203
Q

How does methotrexate impact immune cells?

A

Methotrexate reduces the proliferation of immune cells by inhibiting purine and pyrimidine synthesis, thereby modulating the immune response and reducing inflammation in autoimmune diseases.

204
Q

What are biologic DMARDs and how do they work?

A

Biologic DMARDs are drugs that target specific cytokines or leukocytes involved in the inflammatory process. They help to modulate the immune response and reduce inflammation in autoimmune diseases like rheumatoid arthritis.

205
Q

How are biologic DMARDs administered?

A

Biologic DMARDs are typically administered via subcutaneous (SC) or intravenous (IV) injection.

206
Q

What are the pharmacokinetic characteristics of biologic DMARDs?

A

Biologic DMARDs have variable pharmacokinetic profiles, meaning their absorption, distribution, metabolism, and elimination can differ depending on the specific drug and the individual patient.

207
Q

In what cases are biologic DMARDs typically used?

A

Biologic DMARDs are generally reserved for extreme cases, such as when other treatments have failed or the disease is severe and difficult to control.

208
Q

Why are biologic DMARDs considered expensive?

A

Biologic DMARDs are complex, biologically derived therapies that require costly production methods, making them more expensive compared to conventional synthetic DMARDs.

209
Q

What is the role of inflammation in the body?

A

Inflammation is a protective response designed to remove the cause of injury, such as pathogens, damaged cells, or harmful stimuli, and to initiate tissue repair.

210
Q

What are the two types of inflammation?

A

Inflammation can be either acute, which is a short-term response to injury, or chronic, which is a long-lasting inflammation often associated with diseases like rheumatoid arthritis.

211
Q

How do mediators influence inflammation?

A

Mediators, such as cytokines, prostaglandins, and leukotrienes, play key roles in both the progression and resolution of inflammation by regulating immune cell activity and the inflammatory response.

212
Q

What drives chronic inflammation?

A

Chronic inflammation is primarily driven by the activity of macrophages and lymphocytes, which continuously release pro-inflammatory cytokines and other mediators.

213
Q

How do anti-inflammatories work?

A

Anti-inflammatories target various aspects of the inflammatory process, such as the production of pro-inflammatory mediators, immune cell activity, and the resolution of inflammation.

214
Q

What types of anti-inflammatories are available?

A

There is a wide range of anti-inflammatories, including NSAIDs (nonsteroidal anti-inflammatory drugs), steroids (glucocorticoids), conventional synthetic DMARDs (csDMARDs), biologic DMARDs (bDMARDs), and antihistamines.

215
Q

What is the process of acute inflammation?
A: Acute inflammation is a rapid, short-term response to injury or infection that involves:

A

Vasodilation: Increased blood flow to the affected area, causing redness and heat.
Increased vascular permeability: Allows proteins, such as antibodies and clotting factors, to leak into tissues, causing swelling.
Leukocyte recruitment: White blood cells, particularly neutrophils, migrate to the site of injury via chemotaxis.
Phagocytosis: Neutrophils and macrophages engulf and digest pathogens or debris.
Resolution: Inflammation resolves when the cause of injury is removed, and tissue repair occurs.

216
Q

How do acute and chronic inflammation differ in terms of hallmarks?

A

Acute Inflammation: Characterised by a rapid onset, short duration, and prominent signs like redness, heat, swelling, pain, and loss of function. It primarily involves neutrophils and a strong inflammatory mediator response.
Chronic Inflammation: A prolonged, persistent inflammation that lasts for weeks to years. It is characterised by ongoing tissue damage, fibrosis, and the presence of macrophages, lymphocytes, and plasma cells. Chronic inflammation often leads to tissue remodelling and scarring.

217
Q

What are the roles of inflammatory mediators in the inflammatory process?

A

Cytokines (e.g., TNF-α, IL-1, IL-6): These are key regulators of inflammation, promoting immune cell recruitment and activation.
Prostaglandins and Leukotrienes: These lipid mediators cause vasodilation, increase vascular permeability, and contribute to pain and fever.
Histamine: Released from mast cells, it causes vasodilation and increased vascular permeability, contributing to the early stages of inflammation.
Chemokines: These attract specific immune cells to the site of injury or infection.

218
Q

What are the key cells involved in acute and chronic inflammation?

A

Acute Inflammation: Neutrophils are the first responders, followed by macrophages that clear debris and initiate tissue repair.
Chronic Inflammation: Macrophages and lymphocytes (T and B cells) are dominant. They release pro-inflammatory cytokines and contribute to tissue damage and fibrosis.

219
Q

How do anti-inflammatory therapeutics differ, and how are they used in treating inflammatory diseases?

A

NSAIDs: Inhibit cyclooxygenase (COX) enzymes, reducing the production of prostaglandins, which are responsible for pain, fever, and inflammation. They are used for short-term pain relief and inflammation management.
Steroids (Glucocorticoids): Suppress the immune system and reduce inflammation by inhibiting the production of cytokines and mediators. Used for both acute and chronic inflammatory diseases but have long-term side effects.
csDMARDs: Slow the progression of autoimmune diseases like rheumatoid arthritis by modulating immune cell function. These drugs have a delayed onset of action.
bDMARDs: Target specific cytokines or immune cells involved in inflammation (e.g., TNF inhibitors). Used for severe or refractory cases of autoimmune diseases.
Anti-histamines: Block histamine receptors to reduce allergic inflammation, primarily used in allergic reactions but also for other inflammatory conditions like rhinitis.

220
Q

How are anti-inflammatory therapies relevant in treating inflammatory diseases?

A

Anti-inflammatory drugs are crucial for managing diseases like rheumatoid arthritis, inflammatory bowel disease, and asthma by reducing inflammation, alleviating symptoms (e.g., pain, swelling), and preventing further tissue damage. The choice of therapy depends on the severity of the condition, the type of inflammation (acute or chronic), and the patient’s response to treatment.

221
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Common Non-communicable Diseases - ME2366 (8 decks)

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