Inflammation דלקת שאינה מבוקרת כראוי גורמת למחלה אוטואימונית- הגוף תוקף את עצמו, כאילו היה פתוגן זר.
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1 Inflammation דלקת- תגובת נגד של הגוף לנזק רקמתי (פציעה, כימיקלים מגרים, זיהומים מיקרוביולוגיים). המטרה- לסלק את מקור הגירוי ולגרום להחלמת הנזק. הדלקת מערבת תאי דם לבנים, ציטוקינים, פרוסטגלנדינים ועוד. סימני הדלקת: חום, אודם, נפיחות, כאב, איבוד התפקוד דלקת שאינה מבוקרת כראוי גורמת למחלה אוטואימונית- הגוף תוקף את עצמו, כאילו היה פתוגן זר.
2 constitutive COX-1/2/3 inducible Eicosanoids ARACHIDONIC ACID other lipoxygenases (12, 15) prostaglandin synthetase PGH 2 prostacyclin synthetase thromboxane synthetase 5-LOX LTB 4 5-HPETE LTA 2 HPETE (12,15) PGE 2 PGI 2 TXA 2 PGF 2 TXB 2 prostaglandins קרישת דם (טסיות) וזודילטציה עלייה בהפרשת ריר בקיבה כיווץ שריר חלק ברחם LTC 4 LTD 4 LTE 4 leukotrienes
3 PG analogs- Therapeutic indications PGE1: Alprostadil patency of ductus arteiosus, impotence. Side effects : pinal pain, priapism. Misoprostol- prevention of NSAID induced ulcers (citoprotective), Abortion. Side effects-diarrhea, CI in pregnacy. PGE2 : Dinoprostone- cervical opening, uterine emptying PGF2 : Carboprost- abortion Latanoprost- glaucoma. Side effects: iris pigmentation Travoprost, Bimatoprost - glaucoma PGI2: Epoprosterenol- Pulmonary hypertension (emergency) Common side effect- flushing
4 Non Steroidal Anti-inflammatory Drugs analgesic-antipyretics NSAIDs
5 Non steroidal anti-inflammatory drugs (NSAIDs) Inhibiting PGs synthesis Treatment of fever, pain, inflammation, rheumatoid arthritis, osteoarthritis, gout Low doses for fever and pain, higher doses for inflammation No similar structure
6 NSAIDs COX1 - Constitutive, antiplatelet, GIT protective COX2 - Inducible, inflammation COX nonselective inhibitors - PG, TXA2 synthesis
7 Actions of NSAIDs Anti-inflammatory (COX2) - PGs in tissue Analgesic (COX2) PGE2 - sensation of pain Antipyretic (COX2) - PGE2 - resets the thermostat in the hypothalamus GIT effects (COX1) PGs stimulate mucus synthesis and decrease HCl secretion - peptic ulcers Platelets (COX1) TXA2 promotes aggregation anticoagulant effect
8 Actions of NSAIDs Kidney (COX1+2) - PGs - changes in renal blood flow, nephritis. Uterus PGs - less smooth muscle constrictiondelays labor
9 NSAIDs Common side effects: Bleeding (TXA2) GIT bleeding, peptic ulcers ( citoprotective PG ) Renal and hepatic failure Drug interactions: Except for paracetamol, combination of NSAIDs shouldn t be given ( more side effects + interactions) NSAIDs inhibit Li secretion NSAIDs counteract some anti-hypertensive drugs (renal PGs) Use in pregnancy: not during the second half- ductus arteriosus premature closure and other fetal side effects
10 NSAIDs Non-selective NSAIDs (COX1 + COX2) Aspirin (non-reversible) Ibuprofen Naproxen Diclofenac Namubeton Etodolac (COX2 > COX1) Selective NSAIDs (COX2 only) Celecoxib No effect on platelets Less GIT side effects Increased risk of MI and stroke
11 Aspirin and salicilates Analgesia Anti-inflammation arthritis Antipyretic agent (*not under 16 years old Reye s syndrome) Prophylaxis of myocardial infarction Inflammatory bowl disease and Crohn s disease
12 Aspirin adverse effects Salicylism tinnitus, hearing Bleeding (GIT and other) Anaphylaxis ( especially in people with asthma, nose polyps) Reye syndrome in children with virus infection acid-base balance Hypoglycemia CNS coma very toxic at high doses
13 Non selective NSAIDs NSAIDs can worsen asthma Namubeton is the only non acid NSAIDs. Others- overdosealkaline urine
14 Paracetamol - Acetaminophen Pharmacology COX-3 inhibitor (???) in CNS no anti-inflammatory, platelet effect Analgesic, antipyretic safe in children with virus infection safe in pregnancy
15 Acetaminophen side effects Less side effects. Skin rash Renal dysfunction and tubular necrosis Overdose / renal failure/ dehydration: liver failure. Antidote: Acetylcysteine
16 Leukotrienes - Pharmacology Chemotaxis of white blood cells ( leuko ) Bronchoconstriction, mucus secretion Vasodilatation Coronary vasoconstriction
17 Leukotrien Antagonists Prevention of mild to moderate asthma LOX inhibitor Zileuton : low compliance (4/day) side effects: Hepatotoxicity. Drug interactions Theophilline, Warfarin LT competitive non-selective antagonists Zafirlukast, Montelukast Zafirlukast- Drug interactions (cyp)-phenytoin, warfarin, Lovastatin
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