Nsaids (Nouran Mohamed) MC PDF

NSAIDS (NON STEROIDAL ANTI-INFLAMMATORY DRUGS) Nouran Mohamed  For you “Greatness is a lot of small things done well. Day after day, workout after workout, obedience after obedience, day after day.”  Take breath and I love all of you very much OUTLINE ◦1-Introduction ◦2-pharmacodyn...

NSAIDS (NON STEROIDAL ANTI-INFLAMMATORY DRUGS) Nouran Mohamed  For you “Greatness is a lot of small things done well. Day after day, workout after workout, obedience after obedience, day after day.”  Take breath and I love all of you very much OUTLINE ◦1-Introduction ◦2-pharmacodynamics ◦3-pharmacokinetics ◦4-Drugs ◦5-prescriptions and questions ◦6-Applications Let`s start our journey ◦ ‫ركز معايا اوعدك مش هتزهق‬ ◦Remember to take breath and smile ◦ 1-Introduction ◦ Nsaids are anti- inflammatory + analgesic + antipyretic. ◦ Nsaids are also called non narcotic / nonopioid analgesics. ◦ Paracetamol not anti- inflammatory only analgesic and antipyretic ( I will explain the reason you will know soon) ◦ Remember ◦ Eicosanoids(Prostaglandins/Leukotriens/ThromboXanes/Prostacyc lins) ◦ prostanoids(PGs-TXs-PCs). INTRODUCTION ◦ -anti-inflammtory steroids=corticosteroids ◦ (difference between mechanism of corticosteroids and Nsaids). ◦ Remember ◦ -inflammation : is a normal part of the complex biological response of body tissues to harmful stimuli caused bay physical trauma , chemicals or microorganisms -inflammation is triggered by the release of chemical mediators from the injured tissues or migrating cells(mast cells) 2-PHARMACODYNAMICS (WHAT THE DRUG DOES TO THE BODY) NOTES ON THE PREVIOUS SLIDE ◦ Major roles of eicosanoids (very imp.) ◦ 1-prostaglandins (PGs) ◦ Modulate pain , inflammation , fever (Bad effect) ◦ Control acid secretion and mucus production in GIT ◦ Control renal blood flow. ◦ Control uterine contractions. NOTES ◦ 2-prostacyclin (PGI2) ◦ Inhibit platelet aggregation ◦ Induce vasodilation ◦ 3-Thromboxane A2 (TXA2) ◦ Induce platelet aggregation ◦ Induce vasoconstriction ◦ 4-leukotrienes (LTs) ◦ Powerful bronchoconstriction so take care Nsaids are C.I with asthmatic patients 2-PHARMACODYNAMICS PGE-2 is the mediator of pain and increase body temperature so when we decrease it the pain decrease and temp decreases. As it increases sensitization of nerve endings to histamine and bradykinin THE DIFFERENCE BETWEEN COX-1 AND COX-2 3-PHARMACOKINETICS (ADME) 'WHAT THE BODY DOES TO THE DRUG’ ◦-They are weak organic acids. ◦-good absorption and bioavalibility ◦-most of NSAIDs are excreted renally ◦-Most of Nsaids are high protein bound so take care of Drug interactions. DRUG INTERACTIONS WITH NSAIDS ◦ Take care side effects occur from drugs that have low plasma protein binding as Nsaids displace them. ◦ 1-Anti-coagulants (warfarin) so inc risk of bleeding. ◦ 2-phenytoin so inc CNS toxicity ◦ 3-oral hypoglycemics (inc. hypoglycemic risk) ◦ 4-methotrexate so increase toxicity. ◦ 5-Anti-hypertensives so may cause renal failure. ◦ 6-Antacids ( absorption of Nsaids inhibited by antacids) ◦ Remember they are weak acids LET`S START OUR DRUGS 1-SALICYLATES ASPIRIN (ACETYL SALICYLIC ACID) ◦ Remember Aspirin is unique bec. It is irreversible inhibitor of cox , but other Nsaids are reversible. ◦ the common use is anti-platelet aggreagation(75,81,100 mg). (low doses) (also analgesic and antipyretic) ◦ But considered as Nsaids at high dose 325 mg (analgesic , antipyretic and antiinflammatory).so take care about the dose. ◦ MOA :(irreversible inhibitor of COX due to formation of covalent bond with COX leading to inhibiting the formation of throboxanes which is resposible for platelets aggreagation and its effect last for 8- 10”age of platlets”) ◦ -pharmacokinetics(absorbed in stomach-metaboilsed mainly by liver- excreted by alkalinization). ASPIRIN Take care not for children bec. Of reyes syndrome  Aspirin toxicity -salicylism(mild form)cause headache,N&V, mental confusion, tinnitus severe form cause hallucinations ,confusion, respiratory failure leading to death -Reye’s syndrome(rare serious condition characterised by acute encephalopathy&hepatic dysfunction due to using aspirin during the viral infection “flu or chickenpox” leading to drop in blood glucose and increase in ammonia level. pharmacological action 1-anti-inflammatory 2-analgesic in high doses (decrease PGE2 leading to decrease pain sensation) PGE2 increase the sensitization of nerve endings to histamine and bradykinin and other chemical mediators 3-anti-pyretic (also due to decrease PGE2) Because PGE2 increase the set point of hypothalamus thermoregulatory center 4-anti-platelet in low doses (75, 81,100). 5- In low doses aspirin blocks secretion of uric acid at distal tubule so inc. uric acid level in blood , but in high doses aspirin blocks reabsorption of uric acid and increase its excretion. Recommendations ◦ The American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal–Fetal Medicine make the following recommendations: ◦ Low-dose aspirin (81 mg/day) prophylaxis is recommended in women at high risk of ◦ preeclampsia and should be initiated between 12 weeks and 28 weeks of gestation ◦ (optimally before 16 weeks) and continued daily until delivery. ◦ Low-dose aspirin prophylaxis should be considered for women with more than one of ◦ several moderate risk factors for preeclampsia. ◦ https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2018/07/low-dose-aspirin- use-during-pregnancy#:~:text=Low%2Ddose%20aspirin%20has%20been%20used%20during%20pregn  Side effects 1-ulceration and GIT bleeding due to decrease of beneficial PGs 2-decrease renal blood flow. Very imp counseling so we should take PPI (proton pump inhibitor) or synthetic PG analogue and taking with food or use selective COX-2 Note  category (NSAIDs) that are available without a prescription include ibuprofen, naproxen, and ketoprofen. All three are pregnancy category B in the first and second trimester, and category D in the third trimester *Lactation -Ibubrofen&indomethacin&naproxen are safe in lactating mother. -Nsaids displace bilirubin so C.I in neonates and breastfeeding mother and cause Kernicterus which causes neurological damage B- propionic acid derivative ◦Less GI side effects than Aspirin - Ibuprofen (brufen) max dose 1200 mg / day. - -Ketoprofen (Bi-alcofan) max dose 300 mg /day - Dexketoprofen - Naproxen (only Nsaid with single enantiomer). propionic acid derivative Ibuprofen + pseudoephedrine 200 , 400 , 600 mg C- acetic acid derivetives ◦ Indomethacin is one of the most potent Nsaids (potent analgesic/ anti-inflammatory and antipyretic). ◦ Diclofenac is unique and common Nsaids member as voltaren (diclofenac sodium) and cataflam (diclofenac potassium). (Duration) ◦ Aceclofenac (less GI side effect ) ex. Bristaflam ◦ Ketorolac ( the most potent and most effective Nsaid analgesic and should`nt be used more than 5 days ) ◦ 30 mg of ketorolac equal 10 mg of morphine. C- acetic acid derivetives C- acetic acid derivetives 12.5 and 25 mg for children but 50 mg for adults. (diclofenac sodium) Dolphin  D-ENOLIC ACID DERIVATIVE (OXICAMS) ◦ Long half-life , so used once daily except lornoxicam. ◦ Meloxicam has higher COX-2 selectivity.(semi-selective) lornoxicam Meloxicam Tenoxicam D-Enolic acid derivative (Oxicams) Piroxicam E- fenamic acid derivative (Mefenamic acid). ◦ Special for dysmenorrhea bec. It decreases uterine contractions. F- pyrazolone derivatives ◦ Metimazole (Novalgin) cause agranulocytosis used as analgesic , antipyretic and antispasmodic ◦ Agranulocytosis : A serious condition that occurs when there is an extremely low number of granulocytes (a type of white blood cell) in the blood. G- selective COX-2 inhibitors ◦ Less gastric ulceration & GIT symptoms than non selective ones. ◦ Lack anti-platelet effect as platelets only express COX-1 ◦ Rofecoxib was recently withdrawn from the market when an increased rate of myocardial infarction and stroke , there is now concern that all COX-2 inhibitors may increase risk of thrombtic events during chronic therapy ◦ A possible explanation may be that coxibs can inhibit endothelial prostaglandin synthesis but lack a compensatory effect on platelet thromoboxane synthesis. ◦ Celecoxib (Celebrex) one of Pfizer`s best selling drugs. G- selective COX-2 inhibitors PARACETAMOL ( TAKE CARE NOT ANTI- INFLAMMATORY). ◦ analgesic, antipyretic not anti-inflammatory ◦ Pharmacodynamics ◦ Act by inhibiting PG synthesis in the CNS ◦ It has no effect on COX enzyme in peripheral tissue. ◦ Thus lack anti-inflammatory effect Paracetamol -metabolism:mainly extensively metaboilsed in liver to N-acetyl-p- benzoquinone(NAPQI) by CYP450 -glutathione in liver eliminate the NAPQI -large doses of paracetamol cause acute hepatic necrosis as a result of glutathione depletion and xss of NAPQI -it can be prevent by early taking of methionine or acetylcysteine(sulfhydryl compounds). Paracetamol Paracetamol why not anti- inflammatory ? MOA of paracetamol 1-acting on COX-3 isoenzyme in brain and CNS ◦2-activation of descending serotonergic pathways ◦3-Inhibit reuptake of endocannabinoids which explain the relax, tranquility and euphoria reported by paracetamol users. Therapeutic uses 1-children in viral infections 2-pregnancy and breastfeeding woman 3-patient with cvs and GI complications 4-antipyretic 5-analgesic(for mild to moderate pain) 6-headache(especially with caffeine to enhance absorption and analgesic effect) paracetamol *Dose -maximum single adult dose (1 gm) -minimum dosing interval(4 hrs) -maximum daily dose (4 gm) plasters Enzyme replacement therapy Alpha amylase Trypsin + chymotrypsin  Take breath and I love all of you very much prescriptions ◦ Smile and answer Answer ◦ ambezim prescriptions Answer ◦ Alphintern ◦ brufen prescriptions Answer ◦ Winzoxib ◦ moveasy prescriptions Answer ◦ Winzoxib ◦ ferro Questions ◦ which of them has long duration ◦ Voltaren ◦ cataflam Answer ◦ Voltaren ( diclofenac sodium) questions ◦ (Bi-alcofan) max dose ……………………… Answer ◦300 mg /day. Questions ◦ We can take Nsaids before meals ◦ True ◦ False Answer ◦False Only 2 minutes please be patient we are about to fininish Drug eye Drug eye Drug eye Drug eye Egydose Egydose Egydose Thanks very much