Anti Inflammatory Drugs
Anti Inflammatory Drugs
Anti Inflammatory Drugs
Anti-inflammatory drugs
II. Anti-allergic drugs
III. Immunomodulators
Plan of lecture:
Anti-inflammatory agents
Anti-allergic drugs
Immunomodulators
Inflammation
Inflammation is a complex protective response of the
organism to injury caused by damaging agents.
It is aimed at inactivation or removal of these agents and
promoting healing.
The traditional names for signs of inflammation come from
Latin:
Dolor (pain)
Calor (heat)
Rubor (redness)
Tumor (swelling)
Functio laesa (loss of function)
Mediators of inflammation
Prostaglandins
Gamma-Interferon
Bradykinin Tumor Necrosis Factor
Serotonin Transforming Growth Factor
Histamine Lymphotoxin
Interleukins-2 – 6, 10,
12,13
Platelet activating factor
The role of some prostaglandins
in the body
PGE 2 – vasodilation, bronchodilation, inhibition of
gastric acid secretion, stimulation of gastric mucus
secretion, sensitization of pain receptors to chemical
and mechanical stimuli, promotion of anterior pituitary
hormones release;
PGF2α - uterus contraction, bronchoconstriction,
decrease in intraocular tension;
TXA2 (thromboxane), produced by platelets, -
induction of platelet aggregation, vasoconstriction;
PGI 2 - inhibition of platelet aggregation, potent
vasodilation;
Cyclo-oxygenase (COX)
Exists in the tissue as constitutive isoform
(COX-1).
At site of inflammation, cytokines stim the
induction of the 2nd isoform (COX-2).
Inhibition of COX-2 is thought to be due to
the anti-inflammatory actions of NSAIDs.
Inhibition of COX-1 is responsible for their
GIT toxicity.
Most currently used NSAIDs are
somewhat selective for COX-1, but
selective COX-2 inhibitors are available.
NSAIDs – nonsteroidal
anti-inflammatory drugs
1. Nonsteroidal anti-
inflammatory drugs (NSAIDs)
Nonselective COX inhibitors
1. Salicylates 5. Antranilic acid
*Acetylsalicylic acid (Aspirin) derivatives
* Salicylamide *Mephenamic acid
2. Pyrazolone derivatives 6. Aryl – acetic acid
*Phenylbutazone derivatives
*Metamizol (Analginum) *Diclophenac sodium
3. Indole derivatives 7. Oxicam derivatives
*Indomethacin *Piroxicam
4. Propionic acid derivatives 8. Dihydropyrrolizine
carboxylic acid derivative
*Naproxen
*Ketorolac
Selective COX inhibitors
Preferential COX-2 inhibitors
Nimesulide
Meloxicam
Nabumeton
Selective COX-2 inhibitors
Celecoxib
Parecoxib
Rofecoxib
NB!!!These drugs cause little gastric
mucosa damage, they do not inhibit platelet
aggrigation!!!
Mechanism of action of NSAIDs
(Non-Steroidal Anti-Inflammatory Drugs)
A) Analgesic
B) Antipyretic
C) Anti-inflammatory
D)Acute gouty arthritis
E) Patent ductus arteriosus
Preparations of Ibuprofen
Oral preparations.
Topical cream for osteoarthritis.
A liquid gel for rapid relief of postsurgical
dental pain.
Intravenous route as In patent ductus
arteriosus
Adverse effects
1.Gastric upset (less
frequent than aspirin).
2.Fluid retention
3.Hypersensetivity reactions
4.Ocular disturbances
5.Rare hematologic effects
(agranulocytosis & aplastic
anaemia).
Contraindications
1. Peptic ulcer
2. Allergic patients to aspirin
3. Kidney impairment
4.Liver diseases
5.Pregnancy
6.Haemophilic patients
The concomitant administration of ibuprofen
antagonizes the irrevesible platelet inhibition
of ASPIRIN (limit cardioprotective effect of
aspirin).
Piroxicam
Mechanism of actions:
A) Non-selective inhibitors to
COX1 & COX2
B) Traps free radicals
C) Inhibits
polymorphonuclear
leukocytes migration
D) Inhibits lymphocyte
function.
Pharmacokinetics
Well absorbed orally
Half- Life 45 hours
Given once daily
Adverse effects
Less frequent gastric upset (20%).
Dizziness.
Tinnitus.
Headache.
Allergy.
Acetic acid derivatives
DICLOFENAC
Mechanism of action
Non-selective inhibitor to COX1 & COX2.
More potent as anti-inflammatory than
analgesic and antipyretics.
Clinical uses
DICLOFENAC
A) Any inflammatory conditions
B) Musculoskeletal pain
C) Dysmenorrhoea
D)Acute gouty arthritis
E) Fever
F) Locally to prevent or treat post opthalmic
inflammation
G) A topical gel for solar keratoses
Adverse effects
DICLOFENAC
Gastric upset
Renal impairment
Elevation of serum aminotransferase
Salt & water retention
Preparations of DICLOFENAC
Diclofenac with misoprostol decreases upper
gastrointestinal ulceration, but result in diarrhea.
Diclofenac with omeprazole to prevent recurrent
bleeding.
1% opthalmic preparation for postoperative
opthalmic inflammation.
A topical gel 3% for solar keratoses.
Rectal suppository as analgesic or for
postoperative nausea.
Selective COX 2 inhibitors
Advantages:
1. Highly selective inhibitors to COX2
enzyme.
2. Potent anti-inflammatory.
3. Have analgesic & antipyretic properties.
4. Highly bound to plasma proteins.
Selective Cox 2 inhibitors
5. Lower incidence of gastric upset.
6. No effect on platelet aggregation
(COX1).
7. Renal toxicities (they are not
recommended for patients with
severe renal insufficiency).
8. High incidence of cardiovascular
thrombotic events with some of them
as ROFECOXIB.
Selective Cox 2 inhibitors
9- They are recommended in
postoperative patients undergoing
bone repair.
10- Also, indicated in primary
familial adenomatous polyposis,
dysmenorrhea, acute gouty
arthritis, acute musculoskeletal
pain, ankylosing spondylitis.
SAIDs – steroidal
anti-inflammatory drugs
Steroidal anti-inflammatory drugs
1. Short-acting 3. Long-acting
glucocorticoids Betamethasone
(natural) Dexamethasone
Hydrocortisone Paramethasone
Cortisone 4.Topically acting
2. Intermediate-acting glucocorticoids
glucocorticoids Beclomethasone
Prednisone dipropionate
Prednisolone Budesonide
Methylprednisolone Fluocinolone
Triamcinolone acetonide
Fluocortolone
Preparations of SAIDs
Drugs Anti-inflam. Salt retaining Topical
Cortisol 1 1.0 1
Cortisone 0.8 0.8 0
Prednisone 4 0.8 0
Prednisolone 5 0.3 4
Methylpredni- 5 0 5
solone
Intermediate acting
Triamcinolone 5 0 5
Paramethasone 10 0 -
Fluoprednisolone 15 0 7
Preparations of SAIDs
Long acting
Betamethasone 25-40 0 10
Dexamethasone 30 0 10
Mineralocorticoids
Fludrocortisone 10 250 10
DOCA 0 20 0
MECHANISM OF ACTION Corticosteroids
OF SAIDs
Phospholipids
Phospholipase A2
Arachidonic acids
Lipoxygenase Cycylooxygenase
Prostaglandins,
Leukotriene Thromboxane,
Prostacyclins.
Clinical uses
of SAIDs
Adrenal insufficiency
Arthrities
Collagen diseases (systemic lupus erhymatosis, scleroderma)
Bronchial asthma
Severe allergic reactions
Autoimmune diseases
Skin diseases
Ulcerative colitis, Crohn’s disease
Cerebral edema
Organ transplantation and skin allograft
Septic shock
Main side effects of SAIDs
Susceptibility to infections
Delayed healing of wounds
Osteoporosis
Growth retardation in children
Peptic ulceration
Cushing habitus
Hyperglycaemia
Muscular weakness
Psychiatric disorders
Withdrawal syndrom
ANTI-ALLERGIC DRUGS
Allergy
An allergy is a hypersensitivity disorder of the immune
system.
Allergic reactions occur when a person's immune system
reacts to normally harmless substances in the
environment.
A substance that causes a reaction is called an allergen.
These reactions are acquired, predictable, and rapid.
Allergy is one of four forms of hypersensitivity and is
formally called type I (or immediate) hypersensitivity.
Allergic reactions are distinctive because of excessive
activation of certain white blood cells - lymphocytes
called B cells, whose role is production of antibodies,
called Immunoglobulin E (IgE).
Mast cells are activated and release mediator of allergy
(HISTAMINE) that results in an inflammatory response.
Clinical Symptoms
Associated With Histamine
Release
erythema, urticaria, and/or
mild/cutaneous itching
1. Antihistaminics
2. Corticosteroids
3. Mast cell stabilisers
4.Antileukotriene drugs
histaglobulin
Histamine-related Drugs
• Sedative/sleep aid
Second Generation:
!!!Non sedating!!!
Advantages of 2nd generation
antihistaminics