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NSAIDs extra
- Can be used as anti-cancer drug but since most cells have prostaglandins side effects
- Higher the dose higher the side effect
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Nonsteroidal Anti-Inflammatory Drug Objectives
- Decrease inflammation
- Relieve mild-to-moderate pain (Analgesia)
- Decrease elevated body temperature (Antipresis)
- Decrease blood clotting (Anticoagulation)
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Why is Acetaminophen is not considered an NSAID
Bc not anti inflammatory or anticoagulant
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Prostaglandins
- Lipid-like compound that exhibits a wide range of physiologic activities
- Every cell except RBC’s produce prostaglandins
- --- so NSAID’s can affect most organs and tissues
- Pro inflammatory: trauma or change increases synthesis
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Thromboxane
- Derived from same precursor as prostaglandin; COX enzyme
- cause clot fomation
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Leukotrienes
- Mediate airway inflammation conditions (asthma, allergic reaction)
- Pro inflammatory
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Eicosanoids
Prostaglandins, thromboxanes, and leukotrienes
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Excessive Prostaglandin Synthesis Repercussions
- Local Inflammation
- ----PGE2 mediate local erythema and edema
- --------Increasing blood flow
- --------Increasing capillary permeability
- --------Increase permeability of histamine and bradykinin
- ----LTB4: leukotrienes
- --------Increase vascular permeability
- Pain
- ----Increase sensitivity of pain receptors
- Fever
- ----Pyrogenic: help produce elevated body temp during fever
- ----Promote fever by stimulating vagal afferent neurons
- Dysmenorrhea
- Thrombus formation (clot formation)
- ----TXA2: cause platelet aggregation
- Others:
- ----Hypertension
- ----Neoplasms (colon cancer)
- ----Respiratory dysfunction (asthma)
- ----Neurologic disorders (MS)
- ----Allergic encephalomyelitis
- ----Affect disorders
- ----Endocrine dysfunction (Bartter syndrome, DM)
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Mechanism of Action: NSAID’s
- Potent inhibitor of cyclooxygenase (COX enzyme)
- ----Blocks production of prostaglandins and thromboxanes
- COX-1 and COX-2 enzymes
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COX-1
needed for normal cellular activity and prostaglandin synthesis to help maintain function of organ
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COX-2
- produced from injured cells
- That’s why we have cox-2 inhibitors
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Aspirin
- Acetylsalicylic acid
- Best representative of an NSAID
- Inhibits prostaglandin synthesis
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Aspirin uses
- Pain and inflammation
- ----Headache
- ----Toothache
- ----Diffuse muscle aches
- ----Cramps with dysmenorrhea
- ----Pain following surgery
- ----Decrease need for opioids
- Fever
- ----Contradicted in children
- Vascular disorders
- ----Inhibits platelet clotting through inhibition of thromboxane biosynthesis
- --------Preventing MI, stroke
- Prevention of cancer
- ----Inhibit prostaglandins that promote tumor growth
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Aspirin Adverse effects
- GI problems
- ----hemorrhage and ulceration
- --------Due to loss of protective prostaglandins in mucosal lining
- Hepatotoxicity (high doses)
- Acute renal failure (ARF)
- Overdose
- Reye syndrome
- May delay healing
- ----Inhibition of prostaglandins retards bone healing and formation of new bone
- ----Inhibit synthesis and transport of CT components such as proteoglycans
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