Inflammation

Inflammation is the immune system’s response to infection, toxins, injury or irritation.

Inflammation continues beyond the need, or when it response doesn’t turn off appropriately
which can cause damage to healthy tissue.
Symptoms- Heat, Pain, Swelling, Redness, loss of Function

Inflammation: Three Phases Mediators of

 Acute inflammation
inflammation
 initial response to injury
 Autacoids release
 histamine
 serotonin
 bradykinin
 prostaglandins
 leukotrienes
 precedes immune response development
 Immune response
◦ activation of immune cells and responds to antigenic substances/ organisms
◦ acute or chronic inflammatory responses
 Chronic inflammation ;Mediators
  IL-1, IL-2, IL-3 (interleukins)
  GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor)
  TNF-a (tumor necrosis factor alpha)
  Interferons
  PDGF (platelet-derived growth factor)
 Phospholipase

----- Steroids

Arachidonic acid

Cyclooxygenase Lipoxygenases

NSAIDs ----- Lipoxygenase inhititors

-----

Prostaglandins
PMNs

PGF2α PGE2 PGI2

Lymphokines

algesic pyrexia vasodilation

The events of the inflammtory response and mechanisms of anti-flammatory

Effect of some of mediators in acute
inflammation
Mediator Vasodilation Vascular permeability Chemotaxis Pain

Histamine ++ ↑↑↑ - -

Serotonin +/- ↑ - -

Bradykinin +++ ↑ - +++

Prostaglandin +++ ↑ +++ +

Leukitrienes - ↑↑↑ +++ -

Consequences of inflammation
•Inflammatory disorders
•Autoimmune disorders
PID neparthritis psoriasis sarcoidosis
gout gastritis vasculitis atherosclerosis
lupus splenitis laryngitis allergic reactions
asthma sinusitis thyroiditis multiple sclerosis
eczema hepatitis prostatitis some myopathies
pleurisy hritis pharyngitis

Autoimmune disorders- An overactive immune response of the body against substances and
tissues normally present in the body. The body actually attacks its own cells. The immune system
mistakes some part of the body as a pathogen and attacks it
Crohn’s Disease Graves disease Ulcerative colitis Good pasture
syndrome
Dermato myositis Myasthenia gravis Multiple sclerosis Wegener's
granulomatosis
Diabetes mellitus Rheumatoid arthritis Celiac Disease Assitions disease
type-I
Approaches for treatement
 Block the mediators
◦ Prostaglandins
◦ Leukotrienes
◦ Cytokines
◦ TNF-α
Suppression of immune system
Note- In addition to this antihistaminics, kinin inhibitors, TNF-α, INF inhibition shown to be benificial for inflammatory
conditions.

Drug Categories:
Nonsteroidal antiinflammatory drugs –COX
Glucocorticoids - Infammatory genes & decreased transcription
Cytokines
Disease modifying antirheumatic drugs
Anti –gout drugs
Leukotriene inhibitors
TNF-α-inhibitors
Note: -Slow- acting anti rheumatic drugs, and non-opoid analgesics are some times included in this category as they act against
specific symptom of inflammation
Non steroidal anti-inflammatory
NSAID indications
• Analgesic
• Anti-inflammatory
• Antipyretic
• Anti-platelet
 Choice of different NSAIDS depend on
◦ Selectivity to COX-2
◦ Minimum adverse effects
◦ Patient related specifications
◦ Cost effectiveness
commonly used drugs

Non-steroids Steroids
◦ Aspirin and other
salicylates
◦ Ibuprofen
◦ Diclofenac sodium
◦ Naproxen
◦ Selective cox-2 inhibitor
 Aspirin and related drugs
Uses

◦ Analgesia/Anti-inflammatory Effects
  Aspirin in combination with opioid analgesics: effective management of some cancer pain.
anti-inflammatory effects of aspirin act to enhance opioid analgesia
  High-dose Salicylates have significant anti-inflammatory properties
rheumatic fever
rheumatoid arthritis
other inflammatory joint diseases
◦ Antipyretic Activity:  
◦ Antiplatelet:
◦ May reduce incidents of coronary artery thrombosis
Adverse
 effects
 Gastrointestinal Side Effects
 Central Nervous System Effects
 accumulation of salicylic acid derivatives + respiratory depression ® acidosis
 Leukotriene -mediated hypersensetivity reactions
  Aspirin - Not Effective for management of severe visceral pain, e.g. acute abdomen, pericarditis, myocardial infarction
(antiplatelet action may be useful), renal colic.
 Not typically recommended: in pregnant women
 Ibuprofen
Uses
◦ For the treatment of pain (muscular and rheumatic), sprains,
strains, backache and neuralgia
◦ Treatment of painful menstrual periods.  
◦ Temporary relief of fever.  
◦ Effective in the treatment of Alzheimer's disease
Adverse effects
◦ Common Side Effects stomach upset or irritation
◦ Infrequent Side Effects nausea and/or vomiting, constipation,
diarrhea
◦ Rare Side Effects skin irritations, drowsiness, gastrointestinal
bleeding
◦ Risks liver toxicity, stomach ulcers, allergic reactions
 
Diclofenac Sodium

potent cyclooxygenase inhibitor having

◦  anti-inflammatory
◦  analgesic
◦   antipyretic activity
Clinical Use/characteristics:
◦ Chronic inflammatory conditions:
  rheumatoid arthritis
  osteoarthritis
◦ Chronic musculoskeletal pain
◦ Ophthalmic solution: prevention of postoperative ophthalmic inflammation
 Adverse effects (frequency -20%)
◦ Gastrointestinal disturbance
◦ Occult GI bleeding
◦ Gastric ulceration
◦ Transaminitis (increase serum amino transferase) occurs more frequently with
diclofenac than with other NSAIDs
Steroids as anti-inflammatory
Inhibit phagocytosis
Inhibit synthesis of IL‑1, TNF, PGs LTs.
Inhibit antigen processing by macrophages
Stabilizes lysosomal membranes
Inhibits accumulation of neutrophils and
monocytes at inflammation site.
Inhibit phospholipase A .
2
Mechanism of glucocorticoid action
Disease modifying antirheumatic drugs
Examples
◦ DMARD
 Methotrexate
 Antimalarial drug: chloroquine
 Gold
 Penicillamine
 Steroids
 Acetaminophen
◦ L eukitriene antagonists
 Zafrilukast
 Montelukast
◦ Cytokine inhibitors
 TNF-inhibitor
 Infliximab
 Adalimumab
 Etanercept
 IL-inhibitor
 Ankinra
 Anti-gout drugs
•By increasing uric acid excretion (Uricosuric agents: probenecid,
sulfinpyrazone)
•By inhibiting leucocytes migration into the joint: Colchicine
)

•By a general anti-inflammatory and analgesic effect (NSAIDs).

•By inhibiting uric acid synthesis: Allopurinol(this is the main
prophylactic drug)