ANTIINFLAMMATION DRUGS:

CORTICOSTEROID AND NON STEROID

ANTIINFLAMMATORY DRUGS (NSAIDs)

Desak Ketut Ernawati PhD Apt

 OVERVIEW
• Stages of inflammation
• Types of anti-inflammatory drugs
• Corticosteroid
• Non Corticosteroid/ NSAIDs
 Sign and symptoms of inflammation

• Calor  heat
• Rubor  redness
• Dolor  pain
• Tumor  swelling
• Functio laesa  less function
 Stages of inflammation
• Minutes after Calor, rubor,
injury
Vascular • Release dolor, tumor, FL
mediator

• Hours to days Fever, increase

• Mediators secretion
Exudate invades the
bloodstreams

• Last until
Tissue healing is Tenderness and
complete
repair • New cells swelling
Classifications of anti-inflammatory drugs

• Corticosteroids
• Non Corticosteroid anti-inflammatory drugs
(NSAIDs)
• Anti-histamines
• Leukotriene inhibitors
Corticosteroids
 Adrenal cortex releases steroid hormons

• Mineralocorticoid (aldosterone)  salt

retaining activity  synthesized at zona
glomerulosa
• Glucocorticoid (cortisol)  affect
carbohydrate and protein metabolism 
synthesized at zona fasciculata and reticularis
 Mineralocorticosteroids
• Aldosterone and fludrocortisone
• Fludrocortisone is given with hydrocortisone
in adrenal insufficiency (Addison’s diseases)
 Glucocorticoids
• Have high affinity for the receptors
• Less rapidly inactivated
• Have little or no salt retaining properties
• MOA: complex of receptor-glucocorticoid
enter the nucleus and binds to steroid
response elements on target DNA
 Glucocorticoids
• Metabolic effects
inhibits protein synthesis and stimulate
protein catabolism to amino acid
• Anti-inflammatory and immunosuppresive
effects
suppress inflammatory response – inhibits all
inflammation mediators (PG, Leucotriene, PAF)
suppress Phospholipase A2, COX2, IL2
 Glucocorticoids
• Hydrocortisone
• Prednisone/Prednisolone/Methylprednisolone
• Betamethasone
• Dexamethasone
• Beclomethasone
• Budesonide
• Triamcinolone
 Dosage forms
Oral Parenteral Topical
Dexamethasone Cortisone Hydrocortisone
Betamethasone Dexamethasone Triamcinolone
Prednisone Methylprednisolone
Prednisolone Hydrocortisone
 Adverse drug reactions
• Metabolism effects
- moon faces (fats quickly cause a rounded
face)
- fat redistributed in the trunk
- hyperglycemia – diabetes
- increase bone catabolism - osteoporosis
- protein loss on muscle – weakness
 Adverse drug reactions
• Adrenal suppression
• Infections
• Fluid retention
– Hypokalemia and hypertension
 Adverse drug reactions
• After 1 week
- acne
- sodium and fluid retention
- difficulty in swelling
- emotionally changed
• After a month of therapy
- weight gain
- fat redistribution
- bruise easily
- loss of muscle mass
NSAIDs
 NSAID
• Group of drugs which are structurally different
with various effects as analgesic, antipyretic
and anti- inflammation.
• Since the activities are similar, the choice is
based on farkin properties and SE
• Mostly acts on COX (cyclooxygenase) –
2 isoenzymes COX1 ( stomach and kidney) &
COX 2 (inflammation)
Mechanism of Action
Mechanism of Action
 Actions of some eicosanoids
Eicosanoid Effects Clinical uses
Prostaglandins
PGE2 Vasodilation, Oxytoxic
bronchodilatation, oxytoxic
PGE1, analog misoprostol Increase bicarb and mucus Prevention of NSAID
secretion in stomach induced ulcers
PGF2 Vasoconstriction, None
bronchoconstriction,
oxytoxic
Prostacylin (PGI2) Prevent Platelet Severe Pulmonary
aggregation, vasodilation Hypertension
Thromboxane (TXA2) Facilitates Platelet None
aggregation
Leucotrienes Bronchoconstriction None
 MoA
• Antiinflammatory: inhibit prostaglandin (which
produce vasodilation and increase in vascular
permeability)
• Analgesics: peripheral and central actions
associated with anti-inflammation effects
• Antipyretics: during fever, IL1 is released from
leucocytes and acts directly to
thermoregulatory centre in the hypothalamus.
This rises prostaglandin in the brain.
Color atlas of pharmacology, 2003
 MoA
• prostaglandin has the role to reduce gastric acid secretion,
prostaglandine increase blood flow to mucosa and to enhance
synthesis of mucus. Inhibition on prostaglandine  damage
to gastric mucose (gastrointestinal toxicity)  used of
misoprostol (analog prostaglandin)
• Prostaglandin is a powerful vasodilator synthesis in renal medulla
and glomerulli, control renal blood flow and control excretion of
salt and water  inhibition caused sodium retention and reduce
blood flow and renal failure (renal toxicity)
• Lack of broncodilatating effect of prostaglandin and induce
leucotriene (pseudoalergenic)  asthma attach in predisposed
patients
Color atlas of pharmacology, 2003
Introductory of clinical pharmacology
PHARMACODYNAMIC INTERACTION NSAIDs WITH OTHER DRUGS

• NSAIDs + hypotensive drugs ( β-blockers, ACE-inhhibitors, diuretics

) = ↓ hypotensive effect
• NSAIDs + ethanol = ↑risk of bleeding from gastrointestinal tract
• NSAIDs + ticlopidine or clopidogrel = ↑risk of bleeding
• NSAIDs + lithium = ↑lithium toxicity
• NSAIDs + cylosporine or ACE-inhibitors or takrolimus=
↑nephrotoxicity of drugs
• NSAIDs + fluoroquinolons = ↑ toxic action of fluoroquinolons on
CNS
• NSAIDs +oral antidiabetic drugs =↑ risk of hypoglycemia
• NSAIDs + cumarines = ↑risk of bleeding from gastrointestinal tract
 PHARMACOKINETIC INTERACTION NSAIDs WITH OTHER DRUGS

• NSAIDs + oral antidiabetic drugs = ↑ risk of hypoglycemia

• NSAIDs + cumarines =↑risk of bleeding
• NSAIDs + corticosteroids = ↑risk gastropathy and bleeding from
gastrointestinal tract
• NSAIDs + aminogycosides = ↑ ototoxicity and nephrotoxicity of
aminogycosides
• NSAIDs + fenytoine or valproinic acid = ↑action of fenytoine or valproinic
acid
• NSAIDs + metotrexat or digoxin = ↑action and ↑ toxicity metotrexat or
digoxin
• NSAIDs + tricycles antidepressive drugs neuroleptics or antiarrhytmic
drugs or
selective serotonin reuptake inhibitors ( SSRI ) = ↑ action of drugs
 Aspirin
• Thrombocytes: thromboxane enhance
thrombocyte aggregation while prostacyclin
lowering it. Low dose of aspirin inhibits
thromboxane irreversibly  thrombocyte
aggregation lessen  anticoagulant
• Low dose as analgesic; high dose as anti
inflammation agents
• May cause Reye’s syndrome in child with viral
infection
 Propionate Derivates
• Inhibits PG – Cox 1 and 2
• Ibuprofen, ketoprofen, naproxen, fenoprofen
• Analgesic and antipyretic in chronic
rheumatoid arthritis
• Reversible COX inhibitor
 Antranilinic acid derivate
• Inhibits PG – Cox 1 and 2
• Mefenamic acid
• Mostly as analgesic with no anti-inflammatory
effect
• ADE: diarrhea, anemia hemolytic
 Oxicam Derivate
• Piroxicam
• Inhibit PG synthesis – Cox 1 and 2
• Used for rheumatoid arthritis , OA
• T1/2 = 50 hours ~ once daily
 Indole acetic acid
• Indometasin
• More potent antiinflammatory agent than
aspirin
• Farkin: quickly absorbed, metabolised in the
liver
• SE: nausea, vomiting, GI disturbance, diarhae
 Paracetamol/Acetaminophen
• Inhibit prostaglandine at CNS
• Less effect on COX peripheral
• Quickly absorbed and metabolised in liver 
conjugated to glucoronide and hidroxilised to N-
acethyl benzokuineimin
• High dose of paracetamol may result in liver
necrosis due to N-acethyl benzokuineimin
bonded with sulfhidril in the liver.
• Excreted in the urine
 Selective COX2 Inhibitor
• Celecoxib
• Acts specifically on COX2
• Theoretically less effects on gastrointestinal
toxicities
 NSAID and CV Risk

J Am Coll Cardiol. 2004;43(4):519-525. doi:10.1016/j.jacc.2003.09.043

 Consideration in using NSAID
• Patient with risk of CV disease (stroke, heart attack)
• Increased with higher doses
• NSAIDs in CI in patient after cardiac by pass surgery
• Should not be used in patient with cerebrovascular
bleeding/other bleeding disorders
• Unintended reaction with other blood thinner
• Refer patients to doctor, pharmacist