Drugs acting to stop pain and inflammation

Drugs acting to stop pain and inflammation

Pain, inflammation and fever is mainly triggered by Autacoids

The major autacoids involved in pain, fever and inflammation are

histamines and

prostaglandins

Autacoids

The word autacoids comes from the Greek "Autos" (self) and "Acos" (relief, i.e. drug).

Autacoids are biological factors which act like local hormones, have a brief duration, act near the site of synthesis, and are not blood borne

Introduction

Agents that may induce release of autacoids include- Chemical irritants- UV light- Trauma- bacterial toxins- immune irritants

Major classes of autacoids

Biogenic AminesHistamineSerotonin (5 HT)

Class Example

Phospholipids Derived

Prostaglandins (Eicosanoids) , leukotrienes, Thromboxanes, Platelet activating factors(PAF)

PolypeptidesAngiotensin and Kinins (Bradykinin and Kallikidin)

Stopping pain, fever and inflammation

There are two main groups of pain killers

-Autacoids antagonists

-CNS acting nerve blockers (alpha 2 adrenergic drugs)

Autacoids antagonists

Antihistamines

ProstaglandinSynthesis inhibitors

Antihistamines (Antagonists)

Antihistamines act by blocking histamine receptors

There are four Histamine receptors designated as H1 H2, H3, and H4, each with different function

Only H1 is involved with pain All Histamines antagonists are

competitive blockers of histamine receptors

Histamine Receptors blockers

UIThioperamideH4 blockers

To treat neurodegenerative conditions

BurimamideImpromidineTheoperamide

H3 receptor blockers

To reduce Gastric acid release

CimetidineBurimamideMetiamideRanitidine

H2 receptor blockers

To treat allergic reactions

DiphenhydramineMepyramine maleatePromethazinehydrochloride

Pheniramine maleateAntazoline

H1 receptor blockers

Main functionsExamplesType

Non-Steroidal AntiinflammatoryDrugs (NSAIDs)

These are basically prostaglandin (PG) synthesis inhibitors

Remember that prostaglandin is an autacoid that will engineer pain stimuli

How is prodtaglandin synthesized

How is prodtaglandin synthesized

Common PG synthesis inhibitors

Aspirin Acetaminophen Phenylbutazone Dipyrone

Morden NSAIDs

Naproxen Flunixin meglumine (banamine) Meclofenamic acid Ibuprofein and indomethacin Orgotein Dimethyl sulphoxide (DMSO) Polysulfated glycosaminoglycans

(Adequan)

Mechanisms of Action of NSAIDs

Binding (reversibly and irreversibly) to cyclo-oxygenase (PG synthase)

- Aspirin – I rreversibly- Acetaminophen – reversibly- Phenylbutazone – I rreversibly- Dipyron- I rreversibly- Naproxein – I rreversibly- Flunixin – I rreversibly- Meclofenamic acid - I rreversibly

Mechanisms of Action of NSAIDs

Other mechanismsOrgotein – Breaks down superoxidefree radicals to peroxides

DMSO – I t also trap free radicals like superoxides

Adequan – Inhibits the loss of cartilaginous mucopolysaccharides

Alpha2-Adrenergic Agonists

Xylazine Detomidine